Vitamin E - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

VITAMIN E A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Vitamin E: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84234-5 1. Vitamin E-Popular works. I. Title.

iii

Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

iv

Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on vitamin E. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

v

About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

vi

About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON VITAMIN E ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Vitamin E...................................................................................... 9 E-Journals: PubMed Central ....................................................................................................... 67 The National Library of Medicine: PubMed ................................................................................ 70 CHAPTER 2. NUTRITION AND VITAMIN E .................................................................................... 117 Overview.................................................................................................................................... 117 Finding Nutrition Studies on Vitamin E .................................................................................. 117 Federal Resources on Nutrition ................................................................................................. 123 Additional Web Resources ......................................................................................................... 124 CHAPTER 3. ALTERNATIVE MEDICINE AND VITAMIN E .............................................................. 129 Overview.................................................................................................................................... 129 National Center for Complementary and Alternative Medicine................................................ 129 Additional Web Resources ......................................................................................................... 146 General References ..................................................................................................................... 165 CHAPTER 4. DISSERTATIONS ON VITAMIN E ................................................................................ 167 Overview.................................................................................................................................... 167 Dissertations on Vitamin E ....................................................................................................... 167 Keeping Current ........................................................................................................................ 169 CHAPTER 5. CLINICAL TRIALS AND VITAMIN E........................................................................... 171 Overview.................................................................................................................................... 171 Recent Trials on Vitamin E ....................................................................................................... 171 Keeping Current on Clinical Trials ........................................................................................... 177 CHAPTER 6. PATENTS ON VITAMIN E........................................................................................... 179 Overview.................................................................................................................................... 179 Patents on Vitamin E................................................................................................................. 179 Patent Applications on Vitamin E............................................................................................. 213 Keeping Current ........................................................................................................................ 243 CHAPTER 7. BOOKS ON VITAMIN E .............................................................................................. 245 Overview.................................................................................................................................... 245 Book Summaries: Federal Agencies............................................................................................ 245 Book Summaries: Online Booksellers......................................................................................... 246 The National Library of Medicine Book Index ........................................................................... 249 Chapters on Vitamin E .............................................................................................................. 250 Directories.................................................................................................................................. 253 CHAPTER 8. MULTIMEDIA ON VITAMIN E.................................................................................... 255 Overview.................................................................................................................................... 255 Video Recordings ....................................................................................................................... 255 Bibliography: Multimedia on Vitamin E ................................................................................... 256 CHAPTER 9. PERIODICALS AND NEWS ON VITAMIN E................................................................. 257 Overview.................................................................................................................................... 257 News Services and Press Releases.............................................................................................. 257 Newsletter Articles .................................................................................................................... 262 Academic Periodicals covering Vitamin E................................................................................. 262 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 263 Overview.................................................................................................................................... 263 U.S. Pharmacopeia..................................................................................................................... 263 Commercial Databases ............................................................................................................... 264 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 267

viii Contents

Overview.................................................................................................................................... 267 NIH Guidelines.......................................................................................................................... 267 NIH Databases........................................................................................................................... 269 Other Commercial Databases..................................................................................................... 272 The Genome Project and Vitamin E .......................................................................................... 272 APPENDIX B. PATIENT RESOURCES ............................................................................................... 277 Overview.................................................................................................................................... 277 Patient Guideline Sources.......................................................................................................... 277 Finding Associations.................................................................................................................. 280 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 283 Overview.................................................................................................................................... 283 Preparation................................................................................................................................. 283 Finding a Local Medical Library................................................................................................ 283 Medical Libraries in the U.S. and Canada ................................................................................. 283 ONLINE GLOSSARIES................................................................................................................ 289 Online Dictionary Directories ................................................................................................... 290 VITAMIN E DICTIONARY......................................................................................................... 291 INDEX .............................................................................................................................................. 393

1

FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with vitamin E is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about vitamin E, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to vitamin E, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on vitamin E. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to vitamin E, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on vitamin E. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

3

CHAPTER 1. STUDIES ON VITAMIN E Overview In this chapter, we will show you how to locate peer-reviewed references and studies on vitamin E.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and vitamin E, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “vitamin E” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Effects of Vitamin E on Cardiovascular and Microvascular Outcomes in High-Risk Patients with Diabetes: Results of the HOPE Study and MICRO-HOPE Substudy Source: Diabetes Care. 25(11): 1919-1927. November 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular (CV) events and of microvascular complications in people with diabetes. However, data from randomized clinical trials are limited. This article reports on a study that evaluated the effects of vitamin E supplementation on major CV outcomes and on the development of nephropathy (kidney disease) in people with diabetes. The Heart Outcomes Prevention Evaluation (HOPE) trial is a randomized

4

Vitamin E

clinical trial which evaluated the effects of vitamin E and of ramipril in patients at high risk for CV events. The study was designed to recruit a large number of people with diabetes, and the analyses of the effects of vitamin E in this group were preplanned. There were 3,654 people with diabetes in the study. Vitamin E had a neutral effect on the primary study outcome, on each component of the composite primary outcome, and on all predefined secondary outcomes. The authors conclude that the daily administration of 400 IU vitamin E for an average of 4.5 years to middle aged and elderly people with diabetes and CV disease or additional coronary risk factors has no effect on CV outcomes or nephropathy. 2 figures. 2 tables. 26 references. •

Should You Take Vitamin E? Source: Health. p. 129-132, 136. November/December 2000. Summary: Researchers are studying whether taking vitamin E can reduce heart disease risk, lower cataract risk, and prevent Alzheimer's disease, but an Institute of Medicine expert panel has decided not to recommend taking vitamin E for any condition. According to the panel, 'a large and growing body of experimental evidence suggests that high intakes of vitamin E may lower the risk of some chronic diseases, especially heart disease.[but] the limited and discordant clinical trial evidence available precludes recommendations at this time of higher vitamin E intakes.' Panel members also said that taking up to 1,100 IU is safe even though current recommendations are 20 IU (international units). J. Michael Gaziano, a vitamin E researcher at Harvard Medical School, noted that some of the remaining questions about vitamin E are likely to be answered in the next few years. He emphasized that if researchers did not believe that there was 'a chance that vitamin E offered real benefits,' they would not be spending their time and money investigating it. Sidebars provide information on taking vitamin E supplements and the vitamin E content of various foods.

•

Is the Placebo Control Obsolete in a World After Donepezil and Vitamin E? Source: Archives of Neurology. 55(11): 1420-1424. November 1998. Summary: This article addresses how known effective therapies for Alzheimer's disease (AD) should guide the choice of proper control processes in future AD clinical trials, particularly in light of the effective therapeutic drugs for AD produced from research on donepezil and vitamin E. It explains how the ethics of research involving the cognitively impaired sets standards for appropriate research risks and benefits that may outweigh the reasons for placebo control. It discusses choosing the best research design between placebo or active control to help assure the research community that a trial will change clinical practice and is potentially beneficial to subjects. The issue of informed consent, and proxy consent, when a cognitively impaired subject would be participating in an AD research trial also is addressed. The authors reveal that state legislation forbids AD research involving proxy consent 1) if the research risk is judged to be too high or 2) the possibility of direct benefit to the patient is too low or nonexistent. They then presents a way that risk and benefit assessment can settle clinical uncertainties: the condition of equipoise, where caregivers, patients or patient advocates, and the medical community negotiate clinical trial design. 35 references.

•

High-Dose Vitamin E Supplementation Normalizes Retinal Blood Flow and Creatinine Clearance in Patients with Type 1 Diabetes Source: Diabetes Care. 22(8): 1245-1251. August 1999.

Studies

5

Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a study that determined the effectiveness of vitamin E treatment in normalizing retinal blood flow and renal function in patients who had type 1 diabetes for less than 10 years. The 8-month randomized double-masked placebocontrolled crossover trial evaluated 36 people who had type 1 diabetes and 9 people who did not have diabetes. Subjects were randomly assigned to either 1,800 IU vitamin E per day or placebo for 4 months and followed, after treatment crossover, for a further 4 months. Retinal blood flow was measured using video fluorescein angiography, and renal function was assessed using normalized creatinine clearance from timed urine collections. After vitamin E treatment, serum levels of vitamin E were significantly elevated in both people who had type 1 diabetes and control patients. Glycosylated hemoglobin was not affected by vitamin E treatment. The baseline retinal blood flow of patients who had diabetes was significantly decreased compared with that of people who did not have diabetes. After vitamin E supplementation, the retinal blood flow of patients who had diabetes was significantly increased and was comparable with that of the people who did not have diabetes. In addition, vitamin E treatment significantly normalized elevated baseline creatinine clearance in people who had diabetes. The article concludes that oral vitamin E treatment appears to be effective in normalizing retinal hemodynamic abnormalities and improving renal function in people who have had type 1 diabetes for less than 10 years. This suggests that vitamin E supplementation may provide an additional benefit in reducing the risks for developing diabetic retinopathy or nephropathy. 3 figures. 2 tables. 37 references. (AA-M). •

Vitamin E for Alzheimer's Disease (Cochrane Review) Source: Cochrane Database of Systematic Reviews. 4: CD002854. 2001. Summary: This article presents a systematic review of vitamin E treatment for people with Alzheimer's disease (AD). The Cochrane Dementia Group Register of Clinical Trials was searched to identify all unconfounded, double blind, randomized trials in which treatment with vitamin E at any dose was compared with placebo for patients with AD. Only one trial was found which met the inclusion criteria. In this study of 341 participants, the primary outcome was survival time to one of four endpoints: death, institutionalization, loss of two out of three basic activities of daily living, or severe dementia. The total numbers in each group who reached the primary endpoint within 2 years were reported for participants completing the study. Results suggested some benefit from vitamin E compared with placebo (58 percent versus 74 percent reaching endpoint). However, more participants taking vitamin E experienced a fall (16 percent compared with 5 percent for placebo). Results for specific endpoints and for secondary outcomes could not be interpreted. The authors conclude there is insufficient evidence of the efficacy of vitamin E as a treatment for AD. 3 tables, 38 references.

•

Vitamin E Reduced Secondary Cardiovascular Disease Events in Patients Receiving Long-term Hemodialysis Source: ACP Journal Club. p. 91. May-June 2001. Contact: Available from American College of Physicians-American Society of Internal Medicine (ACP-ASIM). 190 North Independence Mall West, Philadelphia, PA 191061572. Summary: This brief article reports on a study of the impact of vitamin E on cardiovascular disease in patients receiving long term hemodialysis. The randomized,

6

Vitamin E

blinded, controlled trial included 196 patients (mean age 65 years, 69 percent men) with cardiovascular disease (CVD, including myocardial infarction, ischemic stroke, angina pectoris, transient cerebral ischemia, or peripheral vascular disease) who were stable on hemodialysis. After stratification by sex and age, patients at each center were allocated to 800 IU (international units) of vitamin E to be taken at night (n = 97) or to placebo (n = 99). All cause mortality was 31 percent in the vitamin E group and 29 percent in the placebo group. CVD mortality (including sudden death) was 9 percent in the vitamin E group and 15 percent in the placebo group. Fewer total CVD events and myocardial infarctions (MI, heart attack) occurred in the vitamin E group than in the placebo group. The article includes a brief commentary on the research study; the commentary author notes that in three studies, no conclusive evidence has arisen to show that vitamin E supplements reduce the risk for secondary CVD events. Both the researchers and the commentary author call for a larger trial to continue evaluating the potential impact of vitamin for risk reduction for CVD death and fatal and nonfatal MIs. 1 table. 3 references. •

Should High-Dose Vitamin E Supplementation Be Recommended to Diabetic Patients? (editorial) Source: Diabetes Care. 22(8): 1242-1244. August 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This editorial addresses the issue of whether high-dose vitamin E supplementation should be recommended to people who have diabetes. There is no clear evidence as to whether oxidative stress plays any role in the development of complications in people who have diabetes. Many animal studies demonstrate a reduction in oxidative stress and complications after antioxidant supplementation. Studies of vitamin E supplementation in people who have diabetes have not provided any conclusive results. Vitamin E supplementation of people who have diabetes has been shown to decrease or have no effect on blood glycated hemoglobin, to reduce or have no effect on triglyceride levels, and to lower levels of lipid peroxides and thromboxane-B2 and the oxidative susceptibility ex vivo to low density lipoprotein. However, one study has for the first time determined the effect of vitamin E supplementation on retinal blood flow and renal hyperfiltration in people who have type 1 diabetes. Results show that high-dose vitamin E supplementation for a short duration of 4 months normalizes retinal blood flow and renal hyperfiltration in people who had type 1 diabetes for less that 10 years and no or minimal diabetic retinopathy or microalbuminuria. The most important issue resulting from this study is whether highdose vitamin E supplements, such as the 1,800 IU used in the study, should be recommended to people who have diabetes. An additional issue is whether there are subsets of people who have diabetes who would be more likely to show beneficial effects of vitamin E or other antioxidant intervention. There is currently no data for or against concerns for a high dose of vitamin E supplementation. A long term clinical trial with a larger patient population is needed to assess the efficacy of vitamin E supplementation. 35 references.

•

Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease Source: New England Journal of Medicine. 336(17): 1216-1222. April 24, 1997.

Studies

7

Summary: This journal article describes a placebo-controlled trial of selegiline (a selective monoamine oxidase inhibitor), alpha-tocopherol (vitamin E), or both as a treatment for Alzheimer's disease (AD). Patients with AD of moderate severity were recruited from 23 centers participating in the Alzheimer's Disease Cooperative Study. They were randomly assigned to receive selegiline (10 mg/d), alpha-tocopherol (2,000 IU/d), both selegiline and alpha-tocopherol, or placebo for 2 years. The primary outcome measure was the time to occurrence of one of the following end points: death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia defined as a Clinical Dementia Rating of 3. A comparison of the baseline characteristics of the four treatment groups revealed a higher Mini-Mental State Examination score in the placebo group. After controlling for this difference, there were significant delays in the time to primary outcome for patients treated with selegiline (median of 655 days), alpha-tocopherol (670 days), and combination therapy (585 days), as compared with placebo (440 days). The authors conclude that treatment with selegiline or alpha-tocopherol may delay clinically important functional deterioration in patients with moderately severe AD. An editorial commentary, written by Drs. David A. Drachman and Paul Leber, is included in the same journal issue. 1 figure, 5 tables, appendix, 34 references. •

Addition of Vitamin E to Donepezil as a Treatment for Alzheimer's Disease Source: Alzheimer's Reports. 2(3): 143-146. 1999. Summary: This journal article describes a study comparing donepezil alone and donepezil with vitamin E in the treatment of mild to moderate Alzheimer's disease (AD). Nineteen patients with probable AD, mean age 73.63 years, were randomly assigned to receive either 5 mg of donepezil alone or 5 mg of donepezil plus 1,200 mg of vitamin E daily for 12 weeks. All participants were assessed at 6 and 12 weeks with the Mini-Mental State Examination, Clinical Global Improvement scale, Empirical Behavioral Pathology in Alzheimer's disease scale, and a measure of extrapyramidal symptoms. No significant differences in efficacy or safety were found between the two treatment regimens. Patients with behavioral symptoms were more likely to improve on the combined regimen, but the difference was not significant and was lost after week 12. The authors conclude that the combined therapy should be studied for a longer period of time. 2 tables, 12 references

•

Association of Vitamin E and C Supplement Use With Cognitive Function and Dementia in Elderly Men Source: Neurology. 54: 1265-1272. March 2000. Summary: This journal article explores whether the use of vitamin E and C supplements protects against subsequent development of dementia and poor cognitive functioning. The sample included 3,385 Japanese- American men, from the Honolulu-Asia Aging Study, whose use of vitamin E and C supplements had been ascertained. Participants were divided into five cognitive functioning-type groups consisting of Alzheimer's disease (AD), vascular dementia (VaD), mixed or other types of dementia, poor cognitive functioning without dementia, and cognitively intact. A protective effect for VaD and other dementia was found in men who reported taking both vitamin E and C supplements. No protective effect was found for AD. Among men without dementia, the use of either vitamin E or C supplements was significantly associated with better cognitive functioning, and the use of both supplements had borderline significance. 4 tables, 46 references.

8

•

Vitamin E

Molecular Mechanisms of Vitamin E Transport Source: in McCormick, D.B., Bier, D.M., and Goodridge, A.G., eds. Annual Review of Nutrition. Palo Alto, CA: Annual Reviews Inc. 1999. Volume19: 343-355. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax (415) 424-0910. PRICE: $53.00. ISBN: 0824328167. ISSN: 01999885. Individual article reprints available from Annual Reviews Preprints and Reprints. (800) 347-8007 or (415) 259-5017. E-mail: [email protected]. Base price $13.50 per article. Summary: This review article (from an Annual Review of Nutrition monograph) focuses on molecular mechanisms of vitamin E transport. The authors describe how interactions by investigators from various scientific disciplines using stable isotopes, molecular biology tools, and sophisticated genetic studies of humans with vitamin E deficiency have led to a better understanding of these mechanisms. The chapter provides an overview of studies using deuterated tocopherols that demonstrated that the plasma preference for alpha tocopherol is dependent on metabolic processes in the liver; the isolation, molecular biology, and function of the alpha tocopherol transfer protein; and studies that demonstrated that patients who were vitamin E deficient as a result of no known cause had defective alpha tocopherol transfer protein genes. 2 figures. 45 references.

•

Effects of Long-Term Supplementation with Moderate Pharmacologic Doses of Vitamin E are Saturable and Reversible in Patients with Type 1 Diabetes Source: American Journal of Clinical Nutrition. 72(5): 1142-1149. November 2000. Contact: Available from American Journal of Clinical Nutrition. Production Office, 9650 Rockville Pike, Bethesda, MD 20814. (301) 530-7038. Fax (301) 571-8303. Website: www.ajcn.org. Summary: Vitamin E supplementation has been proposed as adjunctive therapy to counteract the increased LDL (low density lipoproteins, a type of blood fat or lipid) oxidation in diabetes and thus prevent or delay cardiovascular complications. This article reports on a study undertaken to investigate the effect of a moderate pharmacologic dose of vitamin E for less than one year in patients with type 1 diabetes. The study was double blind and the subjects were randomly assigned to 2 groups: the supplemented group (group S, n = 22) received vitamin E three times for day for 1 year and the placebo group received a placebo for 6 months followed by vitamin E three times per day for an additional 6 months. Serum vitamin E (levels of the vitamin in the blood) doubled after 3 months of supplementation. Although lipid profiles, glycated hemoglobin, and blood biochemistry values did not change significantly, copper induced in vitro peroxidizability of LDL and VLDL decreased after 3 months of supplementation. Vitamin E supplementation for an additional 3 to 9 months resulted in no further changes in serum vitamin E and lipoprotein peroxidizability. Values returned to baseline after supplementation ended. The authors conclude that because the improvement in lipoprotein peroxidizability is saturable and reversible, life long supplementation with vitamin E should be considered in patients with type 1 diabetes. 2 figures. 63 references.

Studies

9

Federally Funded Research on Vitamin E The U.S. Government supports a variety of research studies relating to vitamin E. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to vitamin E. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore vitamin E. The following is typical of the type of information found when searching the CRISP database for vitamin E: •

Project Title: A PHASE 1B STUDY OF IPA IN AD Principal Investigator & Institution: Galasko, Douglas R.; Associate Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 30-SEP-1991; Project End 30-JUN-2006 Summary: Oxidative damage is widespread in the brain in Alzheimer's Disease (AD) and may be related to amyloid-beta (Abeta) toxicity. Clinical and epidemiological evidence suggests that antioxidants such as vitamin E and vitamin C may lower the risk of AD or delay clinical milestones. Indole-3-propionic acid (IPA) is a highly potent, naturally occurring antioxidant that also inhibits fibril formation by Abeta. The objectives of this proposal are to conduct a phase IB study of IPA in patients with AD to assess its safety and tolerability. In addition, levels of biological markers related to oxidative damage and to AD will be measured, to assess central and peripheral biological activity of IPA. A 12 week, double blind, placebo-controlled multi-center study will be conducted. Patients will be assigned in a 4:1 ratio to receive IPA (40 patients total) or an identical placebo (10 patients) and will receive treatment for 12 weeks. Treatment during the first 4 weeks will be a low dose, followed by 4 weeks of a medium dose and 4 weeks of a higher dose. The primary outcome measure will be safety, assessed by frequencies of clinical and biochemical adverse events. Secondary outcome measures will be changes in levels of biological markers in plasma (8,12isoprostane-F2) and cerebrospinal fluid (8,1-isoprostane-F2, tau and Abeta42) from baseline to 12 weeks. Pharmacokinetic information will be assessed using measures of plasma and CSF levels of IPA in relation to doses of IPA. Pharmacokinetic information will be assessed using measures of plasma and CSF levels of IPA in relation to doses of IPA. Clinical measures of cognition (ADAScog) and function (ADCS-ADL) will be used as further assessments of safety or of possible beneficial short-term effects on AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

10

•

Vitamin E

Project Title: ALCOHOL INDUCED IMMUNOMODULATION--RETROVIRAL CARDIOPATH Principal Investigator & Institution: Watson, Ronald R.; Professor; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 03-JUL-1999; Project End 30-JUN-2004 Summary: Cardiomyopathy and left ventricular dysfunction are prevalent in people with AIDS or chronic alcohol use. However almost nothing is known of the combined effects of retroviral infection plus alcohol on heart disease. Our murine retrovirus infection mimics much of the cytokine dysregulation found during HIV infection, prompting inflammatory damage for cardiac toxicity. We found that alcohol consumption exacerbated many immune, oxidative, and nutritional defects due to murine retrovirus infection. We found that alcohol + retrovirus exposure was particularly toxic, increasing Th2 and reducing Th1 cytokines, dramatically lowering cardiac vitamin E, increasing oxidation of cardiac lipids and synergistically promoting severe heart damage due to Coxsackie B3 infection. Our overall hypothesis is that the combination of ethanol + retroviral infection induces immune dysfunction and oxidation for increased cardiovascular disease. These effects should promote growth and pathogenesis of cardiotrophic pathogens. This hypothesis will be investigated using Coxsackie B infection of mice during retrovirus and/or ethanol exposure. Left ventricular function will be quantitated in vivo with interventricular catheter to define the ventricular dysfunction and characterize the effects of alcohol. We will determine the contribution of the inflammatory response, induced by alcohol and/or retroviral exposure, to myocardial ischemic events and infarctions. We will assert the immune mechanisms involving PMNs in amplifying ischemic injury during cocaine plus retroviral exposure. We will assess leukocyte adhesion and localization, plateletleukocyte interactions, and blocking these cells' function with drugs to understand their role in ischemia and heart pump dysfunction induced by cocaine and/or retrovirus exposure. We will assert the cardiotoxic effects of alcohol exposure prior to as well as post retrovirus infection. Our model studies will increase understanding of etiology of alcohol + retrovirus-induced immune dysfunction in cardiac pathology. We will limit the deleterious cardiac effects of retroviral infection and alcohol exposure with our proven methods that prevented much of the cytokine dysregulation and oxidative damage to the heart: T-cell receptor Vbeta 8.1, multiple antioxidant, and vitamin E supplementation. We hypothesize that our treatments will restrict cytokine dysregulation and thus cardiotoxicity in retrovirally-infected, alcohol-exposed mice. Such studies could provide the basis for their application to reduce heart disease in alcohol-abusing, HIV-infected patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ALZHEIMER'S DISEASE IN DOWN SYNDROME: ANTIOXIDANT TRIAL Principal Investigator & Institution: Lott, Ira T.; Pediatrics; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The objective of this pilot clinical trial is to obtain information on the tolerability, safety, and efficacy of a high potency combinatorial supplement in the treatment of Alzheimer disease (AD) in Down syndrome (DS). Individuals with DS have an increased incidence of AD and evidence of oxidative stress in brain. The DS population is an excellent candidate for antioxidant intervention. The

Studies

11

trial will conform to a double-blind, placebo-controlled, and repeated analysis of variance design. The supplement will consist two cellular antioxidants (vitamins E 900 IU/day and C 200 mg/day) and a mitochondrial antioxidant (alpha-lipoic acid 600 mg/day). The clinical diagnosis of AD in DS will be made by the investigators utilizing their previous experience with DSM-IV criteria for dementia in DS. There are three specific aims: 1) to determine whether cognitive measures are improved by antioxidant supplementation. Outcome measures have been shown to have reliability and validity for DS. They comprise three informant scales (Dementia Rating Scale for Persons with Mental Retardation, Neuropsychology Behavior and Affect Profile, Vineland Adaptive Scales) and three direct assessments (Severe Impairment Battery, Brief Praxis Test, and the FULD-Object/Memory Test-modified); 2) to determine whether plasma biomarkers of lipid oxidative damage (malondialdehyde, isoprostanes), protein oxidative damage (carbonyl group formation), levels of beta-amyloid, and vitamin E levels will be altered in subjects receiving the diet; and 3) to determine the safety and tolerability of the antioxidant supplementation utilizing checklists for adverse events, clinical chemistries, and measures of medication compliance. All study measures will be obtained at baseline and at 6-month intervals for a total of 24 months of treatment. All study patients will be on an acetylcholinesterase inhibitor. Power analysis configured on the primary outcome measures supports a study group of 30 treated and 30 placebo randomized patients. Database management will facilitate analysis of the 24-month observations. The data from this study is intended to provide information relevant to the indications for a multicenter definitive clinical trial of antioxidants in DS. Since the process resulting in AD in DS is age dependent across the lifespan, a positive result from this pilot trial may have implications for utilizing high potency combinatorial antioxidants at earlier age epochs in DS. The pilot trial should also contribute information as to the possible role of antioxidants in the treatment or prevention of AD in the general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIOXIDANT & HYPERGLYCEMIA INDUCED PROCOAGULANT STATE Principal Investigator & Institution: Boden, Guenther; Professor of Medicine; Medicine; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Diabetes is associated with an increased incidence and prevalence of premature atherosclerotic vascular disease and mortality. The reason for this is not well understood, but is likely to be related, at least in part, to a procoagulant state existing in diabetes. We have recently shown that prolonged hyperglycemia/hyperinsulinemia (about 200 mg/dl x 18-72 h) but not euglycemiahyperglycemia activated the tissue factor (TF) pathway of blood coagulation in healthy young men as evidenced by a rise in plasma factor VIla and factor VII coagulant activity and by elevated TF pathway inhibitor and FVHL This suggested an enhanced potential for acute thrombosis during hyperglycemia when coagulation mechanisms are triggered by intense exposure to tissue factor, such as during plaque rupture. In the proposed project, we plan to test the hypotheses that 1) selective hyperglycemia is as effective as hyperglycemia-hyperinsulinemia in activating the TF pathway; 2) hyperglycemia induces expression of IF in monocytes; 3) in non-diabetic subjects, hyperglycemia mediated activation of the TF pathway of blood coagulation can be prevented or reduced with antioxidants; 4) that the procoagulant state in diabetes is, at least partially, caused by hyperglycemia and can be reduced by either strict glycemic control or with antioxidants (at co-existing hyperglycemia). We will test these hypotheses 1) in obese

12

Vitamin E

and non-obese non-diabetic and obese diabetic subjects by determining effects of prolonged (48 h) hyperglycemia (about 200 mg/d1) on IF pathway factor (VIla, VIIc, TF pathway inhibitor) and other coagulation proteins (factor VIII) and markers of thrombin generation (prothrombin fragment 1+2, thrombin-antithrombin complex) with and without administration of antioxidants (Vitamin C or Vitamin E) and 2) in patients with Type II diabetes by determining effects of strict euglycemic control (for 5 days) on IF pathway activity. We believe that this model of prolonged hyperglycemia (with or without hyperinsulinemia) is uniquely suited to study in vivo effects of therapeutic interventions, including lowering of blood glucose and administration of antioxidant vitamins, on the TF pathway of blood coagulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIOXIDANT INTERACTIONS OF SELENIUM AND VITAMINS Principal Investigator & Institution: May, James M.; Associate Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2002 Summary: The goal of this project is to define a role for selenium in preventing oxidant damage, both in vitro and in vivo. Selenium, by as yet unknown mechanisms, has long been known to "spare" vitamin E from oxidative loss in animal dietary studies. Vitamin E, or alpha-tocopherol, is the primary chain-breaking antioxidant in lipoproteins and cell membranes that must be recycled from its oxidized form. Recycling of alphatocopherol is thought to be mediated, at least in part, by vitamin C, or ascorbic acid. This project will test hypotheses that the selenoenzyme thioredoxin reductase and other selenoproteins are crucial in recycling ascorbic acid, in preserving alpha-tocopherol and in preventing lipid peroxidative damage in cells and in animals. Accelerated lipid peroxidation has been associated with several human diseases, including atherosclerosis, inflammatory conditions, and Alzheimer's disease. There are three specific aims. Studies in the first aim will examine the mechanisms by which thioredoxin reductase regenerates ascorbic acid from its oxidized forms, and will establish the extent to which such recycling occurs in cultured human hepatoma cells (HepG2). A novel role for low molecular weight selenoproteins to enhance the ability of thioredoxin reductase to recycle ascorbate will be examined, and there are plans to purify and characterize one or more of these proteins from rat liver. Studies in the second aim will test the hypothesis that thioredoxin reductase both spares alpha-tocopherol and prevents lipid peroxidation by reducing lipid hydroperoxides in lipid bilayers. The relative contributions of thioredoxin reductase and the glutathione peroxidases to such protection will be assessed using the differential sensitivity of these enzymes to selenium deficiency in HepG2 cells. In the third aim, a dietary model of combined nutrient deficiency in guinea pigs will be established to examine the extent to which selenium can prevent oxidative loss of both ascorbate and alpha-tocopherol. Like humans, guinea pigs cannot synthesize ascorbic acid. Thus, use of ascorbate-deficient animals will provide the means to test in vivo whether selenium preserves ascorbate, and whether this contributes to selenium-dependent sparing of alpha-tocopherol and to prevention of lipid peroxidation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ANTIOXIDANTS AND FEMALE HORMONES IN THE ETIOLOGY OF RA Principal Investigator & Institution: Karlson, Elizabeth W.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115

Studies

13

Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: The candidate is an Instructor in Medicine in the Department of Medicine, Division of Rheumatology, Immunology and Allergy at the Brigham and Women's Hospital and Harvard Medical School. Her research area is the epidemiology of rheumatic diseases, and the social and biological determinants of outcome in rheumatic diseases. Dr. Matthew Liang, Director, Multipurpose Arthritis and Musculoskeletal Diseases Center (MAMDC), Professor of Medicine at Harvard Medical School and Professor of Health Policy and Management at Harvard School of Public Health, will be her sponsor and co-mentor along with Drs. Frank Speizer, Charles Hennekens, Walter Willett and Meir Stampfer from the Channing Laboratory and Division of Preventive Medicine. The research training program consists of the two studies described below, Research Seminars in the MAMDC, Channing Laboratory and Division of Preventive Medicine, courses at the Harvard School of Public Health, and close review by an Advisory Committee. The goal of the proposed studies is to define the role of dietary and hormonal risk factors in the development of rheumatoid arthritis (RA) in women. Specifically, it will test the potential protective role of antioxidants and N-3 fatty acids on the risk of RA, whether postmenopausal estrogen reduces risk and whether menopause increases risk of RA. The study utilizes information from two separate, complementary cohorts, the Nurses' Health Study, a prospective cohort of 121,700 women aged 30-55 years at baseline, followed since 1976, and the Women's Health Study, a randomized, double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 female health professionals, aged 45 years and older. RA will be confirmed by a screening questionnaire regarding rheumatic symptoms and review of medical records. The study will identify potentially modifiable risk factors for primary prevention of RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIOXIDATIVE ROLE OF GPX1 IN VIVO OF TRANSGENIC MICE Principal Investigator & Institution: Lei, Xingen; Animal Science; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-AUG-2002 Summary: Cellular glutathione peroxidase (GPX1) is the first identified and a major selenium (Se)-dependent enzyme, its activities in tissues have been used to determine dietary Se requirements of humans and animals. Because we still do not know the metabolic functions of GPX1, these allowances for Se are not well founded physiologically. We propose to use both GPX1 overexpressing and knockout mouse models to determine whether GPX1 is a major selenoperoxidase against various forms of oxidative stress in vivo, and whether the antioxidative function of GPX1 is affected by dietary vitamin E and/or other selenoperoxidases. Our long-term objective is to elucidate the physiological role of GPX1 gene expression in Se nutrition. We will conduct nine major experiments to determine the role of GPX1 in protecting against acute, chronic, and metabolic oxidative stress and the interaction of GPX1 with vitamin E and other selenoperoxidases in this regard. The acute oxidative stress will be generated by administration of lethal and sublethal doses of pro-oxidant compounds, the chronic oxidative stress by feeding dietary polyunsaturated fatty acids, and the metabolic oxidative stress by aging and pregnancy. We will determine the physiological or pathological responses of whole body which include survival time, clinic signs, tissue lesions, growth and reproductive performance, and general health. We will measure the biochemical changes of various tissues which include antioxidant status, peroxidation of protein and lipid, damage of DNA, and mRNA and activity expression of GPX1 and

14

Vitamin E

several other Se-dependent or independent enzymes. We will also test the predisposed oxidative status of isolated hepatocytes and thymocytes. Our key approach will be to compare the differences in these responsess between the GPX1 overexpressing. GPX1 knockout, and their respective control mice, and to compare the effect of various dietary levels of vitamin E and Se on the role of GPX1. Our study will illustrate unequivocally the antioxidative role of GPX1 and its interaction with vitamin E and other selenoperoxidases in vivo at the gene expression level. These results can be applied to accurately assess dietary Se needs and facilitate other usage of Se for optimal health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIPROLIFERATIVE TOCOTRIENOLS

&

APOPTOTIC

MECHANISMS

OF

Principal Investigator & Institution: Sylvester, Paul W.; School of Pharmacy; University of Louisiana at Monroe 700 University Ave Monroe, La 71209 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant) : Tocotrienols, a subclass of compounds in the vitamin E family, significantly inhibits mitogen-induced proliferation and initiates apoptosis in preneoplastic and neoplastic mammary epithelial cells. These findings are particularly interesting because they were observed using treatment doses that had little or no effect on normal mammary epithelial cells growth or viability. In contrast, studies investigating the anticancer activity of tocopherols, the other vitamin E subclass, have shown for the most part, negative results. Determining the mechanism(s) mediating the antiproliferative and apoptotic effects of tocotrienols would provide essential information necessary for understanding the potential health benefits of these compounds in preventing and/or reducing the risk of breast cancer in women. The following aims are designed to determine the mechanism(s) mediating the antiproliferative and apoptotic effects of tocotrienols in normal and neoplastic mammary epithelial cells, with the goal of providing useful insights for basing effective strategies for use of tocotrienols in the prevention and treatment of breast cancer in women. 1) To determmentionedine tissue distribution and cellular concentrations of specific tocotrienols and correlate these findings with treatment effects on mitogenesis and apoptosis in normal, preneoplastic and neoplastic mammary epithelial cells in animals fed tocotrienol-supplemented diets. Absorption and distribution of tocopherols and tocotrienols is limited by the specificity and saturability of specific carrier protein and transport mechanisms within the body; 2) To determine the intracellular mechanism(s) mediating tocotrienol suppression of EGF-dependent mitogenic signaling in isolated normal, preneoplastic and neoplastic mammary epithelial cells in vitro. Since the initial events associated with EGF-dependent mitogenesis in mammary epithelial cells include protein kinase C, adenylate cyclase and cAMP-dependent protein activation, and tocotrienols have been shown to inhibit activation of these proteins in other cells types, it is possible that the antiproliferative effects of tocotrienols results from the inhibition of these mitogenic-signaling pathways; 3) To determine the intracellular signaling pathways responsible for mediating tocotrienol-induced apoptosis in normal, preneoplastic and neoplastic mammary epithelial cells. Various signaling pathways mediate vitamin E-dependent apoptosis in different cell types. Studies will be conducted to identify those apoptotic signaling pathways involved in tocotrienol-induced apoptosis, and whether or not similar signaling pathways are involved in mediating tocotrienol-induced apoptosis in, preneoplastic and neoplastic mammary epithelial cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

Project Title: ASCORBATE CHARACTERIZATION B561

HOMEOSTASIS:

15

FUNCTIONAL

Principal Investigator & Institution: Asard, Han; University of Nebraska Lincoln 14Th and R Sts Lincoln, Ne 68588 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Vitamin C (ascorbate) is essential in eukaryotic cells as an antioxidant and enzyme cofactor. It protects against cancer and aging by preventing DNA oxidation. Ascorbate is intimately involved in cellular redox homeostasis through its interactions with NADH, glutathione and vitamin E metabolisms. In spite of its importance, there remain significant gaps in our understanding of ascorbate metabolism and regulation. A class of membrane proteins, cytochrome b561s, mediating ascorbate-dependent transmembrane electron transfer, has recently been identified in mammals and plants. Little is known about their biochemical properties or precise physiological functions. In mammals cytochrome b561 isozymes are involved in iron uptake and neuropeptide hormone biosynthesis. In humans and mice the cytochrome b561 protein family includes four proteins. Because of the implications to human biology, Mus musculus is an ideal model system to thoroughly characterize members of this family of redox proteins. Biochemical, molecular and cell biological approaches will be integrated to provide a detailed understanding of the physiological functions and properties of two cytochrome isozymes, likely to mediate important and diverse electron transfer reactions, by addressing the following questions: 1) What are the biochemical and physicochemical properties of these cytochrome b561s? We will characterize the biochemical and physicochemical properties of recombinant mouse cytochrome 13561isozymes and test the hypothesis that these proteins transport electrons across membranes using ascorbate as an electron donor. 2) What are the tissue expression patterns and subcellular distribution of cytochrome b561s? The isozyme-specific tissue expression patterns and subcellular Iocalizations of the cytochrome b561s reflect their physiological functions. We will examine the tissue and subcellular distribution of two cytochrome b561s from mice. 3) What proteins interact with cytochrome b561s? The working hypothesis is that cytochrome b561 isozymes interact with other proteins. These interactions will be explored by using the yeast two-hybrid system. The proposed studies will establish the groundwork for understanding the physiological roles of cytochromes b561. Based on the importance of ascorbate to mammalian physiology, these studies will provide fundamentally new insights into redox metabolism in eukaryotic cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGIC ACTIVITY OF BETA-CAROTENE METABOLITES Principal Investigator & Institution: Russell, Robert M.; Associate Director; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-MAY-1991; Project End 31-AUG-2006 Summary: (provided by applicant): Understanding the mechanism(s) of anticarcinogenic and procarcinogenic effects of beta-carotene is important due to continuing interest in the potential use of carotenoids as chemopreventive agents -- and the conflicting results of observational studies vs. intervention trials. In the last grant period, our studies indicate that a biologic basis for the harmful effect of beta-carotene supplementation in smokers is related to the high dosage used and the enhanced formation of reactive beta-carotene metabolites in the free-radical-rich, but antioxidantpoor environment of the lungs of cigarette smokers. A mechanism to explain the

16

Vitamin E

instability of the beta-carotene molecule is that exposure of lung cells to smoke results in increased lung cell oxidative stress, thereby causing decreased tissue levels of other important antioxidants, such as ascorbate and alpha-tocopherol, which have a stabilizing effect on unoxidized beta-carotene. In the present grant, we propose to conduct an intervention to investigate possible protective effects of a rational combination of linked antioxidants (beta-carotene, vitamins C and E) against cigarette smoke-induced lung lesions in the ferret model. These studies will provide important information on the potential future use of rational antioxidant combinations against lung cancer as well as other tissue. Our specific aims are as follows: 1) To determine the effectiveness of beta-carotene in both physiologic (low) and pharmacological (high) doses in the presence of vitamins C and E as anti-proliferative agents in the smokeexposed ferret by examining A) lung cell proliferation indices (cyclin D1, proliferative cellular nuclear antigen PCNA), and the appearance of squamous metaplasia; B) lung retinoid concentrations and retinoid target gene expressions (RARbeta, MAP kinase phosphatase-1, and Bax-1); C) the Jun N-terminal kinase-dependent (JNK) signaling pathway; and D) apoptosis (Caspase 3 and TUNEL); 2) To determine if there is a dosedependent relationship between beta-carotene intake in the presence of vitamins C and E and oxidative stress by examining A) beta-carotene, vitamin E and vitamin C concentrations in both plasma and lung tissue; and B) the degree of oxidative stress status by measuring isoprostane and malondialdehyde levels in both plasma and lung tissue of ferret; and 3) To determine if vitamins C and E will inhibit the formation of oxidative metabolites from beta-carotene via in vitro incubation studies using the postnuclear fraction of ferret lungs. We will also determine whether beta-carotene 9?10?dioxygenase in the ferret lung is involved in metabolism of beta-carotene into apocarotenals by examining A) expression of beta-carotene 9?10'?-dioxygenase in the ferret lung tissue after treatment with smoke, pharmacological beta-carotene supplementation, or a combination of both in vivo; and B) whether additional supplementation of vitamins C and E in the smoke-exposed ferret with or without beta-carotene supplementation will regulate the expression of beta-carotene 9?10?-dioxygenase and prevent the destruction of beta-carotene both in vivo and in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOLOGY OF 12-LIPOXYGENASE ISOZYMES Principal Investigator & Institution: Funk, Colin D.; Professor of Pharmacology; Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Atherosclerosis, chronic inflammatory process progressing from fatty lesions to fibrous and unstable plaques, is the major underlying factor in most cases of coronary heart disease. Clinical disease as a result of atherosclerotic disease remains as the leading determinant for the extensive mortality and morbidity. and exorbitant health care costs in our society. The "LDL oxidation" hypothesis has gained general acceptance as a leading player in atherogenesis and it is recognized that oxidized LDL exhibits many pro-atherogenic properties. properties. The factors that initiate LDL, oxidating in vivo are poorly understood. However, circumstantial evidence has placed the 12/15lipoxygenase in the context of atherosclerosis. Thus, in the first specific aim, the role of 12/15- lipoxygenase in mouse models of atherosclerosis (apoB editing catalytic polypeptide-1 (apobec-1)/LDL-receptor deficient and apoE deficient) will be assessed by quantitating lesion development throughout the aorta by the "en face" method using appropriately crossbred 12/15-lipoxygenase deficient mice. The combined effects of the anti-oxidant vitamin E with 12/15-lipooxygenase deficiency will also be examined.

Studies

17

Total cholesterol, triglycerides, lipoprotein profiles and oxidative stress markers known as isoprostanes will be measured and correlated with lesion development. If specific 12/15-lipoxygenase inhibitors are ultimately to be used in atherosclerotic disease management they will need to be effective in limiting, or causing regression of, preexisting lesion. By using an inducible 12/15-lipoxygenase gene disruption strategy in mice with atherosclerosis at various stages this important matter will be addressed. In specific aim 2, the subset of macrophages expressing 12/15- lipoxygenase will be characterized and purified. The effects of lipid loading and factors regulating 12/15lipoxygenase gene expression will be determined. In specific aim 3, the novel 12(R)lipoxygenase will be characterized and its relevance to atherosclerosis and LDL oxidation discerned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN MACROPHAGES AND REPRODUCTIVE AGING Principal Investigator & Institution: Naftolin, Frederick; Obstetrics and Gynecology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: The aging female rat's reproductive life ends when she can no longer produce a surge of gonadotrophin in response to the midcycle surge of estrogen (positve feedback). Normally, this hypothalamic aging is gradual, marked by peroxidase accumulation in astroglia in the hypothalamus. We have shown a relationship between estrogen-induced synaptic retraction, elaboration of glial processes and positive feedback. To explain this aging, we propose that in the cycling rat, resident brain macrophages in the arcuate nucleus are repeatedly activated by estrogen and produce free radicals that, in turn, disables hypothalamic function. In testing this hypothesis: 1) In cycling female rats, we will characterize the physiological mid cycle activation of arcuate nucleus macrophages and determine the morphological relationship between synaptic plasticity of arcuate nucleus synapses/neurons, astrocytes and brain macrophages using light and electron microscopic immunolabeling for the neuronal marker microtubule-associated protein 2 (MAP 2), the astroglia marker glial fibrillary acidic protein (GFAP), the macrophage marker OX42, and, the appearance of a cell adhesion molecule 1 (I-CAM-1) to mark activated macrophages. 2) We propose to delay the onset of reproductive senescence in normally aging rats with the administration of vitamin E, an anti-oxidant that previously has been shown to suppress free radical production in the central nervous system. The reproductive cycles of normally aging animals will be monitored by vaginal smears and blood LH measurements. At three distinct aging milestones (3 months old, 11 months old and 15 months), control and vitamin E-treated females will be studied by light- and electron microscopic immunocytochemistry for brain macrophage markers in combination with quantitative synaptology will be carried out. The failure of reproduction is normally evident by eleven months and completed by 15 months. Thus, we will characterize aging functionally and morphologically and determine the protective effect of vitamin E. 3) To determine in vitro the cellular basis of activation of brain macrophages by estrogen, we will treat primary cultures of microglia, astrocytes, and, neuronal cell lines that express alpha, beta or alpha/beta estrogen receptors, alone and in combination, assess the effects of estrogen, alone or with vitamin E or superoxide dismutase on these. We will assess production of reactive oxygen species in these cultures by in-situ chemiluminescence and histochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

18

•

Vitamin E

Project Title: CELLULAR VITAMIN E STATUS AND INTEGRIN FUNCTION Principal Investigator & Institution: Keaney, John F.; Professor; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-DEC-2004 Summary: This proposal is based upon the hypothesis that leukocyte and platelet vitamin E content is an important determinant of vascular inflammation through its action on beta 2 and beta 3 integrin function. This hypothesis is important because experimental, clinical and pathologic studies have established a role for inflammation in vascular disease such as atherosclerosis and the response to arterial injury. Inflammatory cell-cell and cell-matrix interactions are orchestrated by cell adhesion molecules and considerable experimental effort has demonstrated that the balance between vascular cell antioxidant status and oxidative stress is involved in the regulation of vascular cell adhesion molecules. However, the effect of antioxidant status on leukocyte and platelet integrin counter-receptors for these vascular cell adhesion molecules has been largely overlooked. Preliminary data from our laboratories indicates that vitamin E potently inhibits the function of beta 2 integrins in monocytes and beta 3 integrins in platelets. The goal of this proposal, therefore, is to define the role of cellular vitamin E, the principal lipid-soluble antioxidant in humans, on integrin function in leukocytes and platelets. The primary experimental models for this proposal will be cultured human monocytic cells (U937 and THP-1) and neutrophils, as well as freshly isolated human platelets. To achieve the goal of this project, we will finish characterizing inhibitor action of vitamin E on beta 2 integrin-dependent monocyte adhesion using agonists relevant to vascular disease including oxidants. The characterization will be extended to human neutrophils and platelets, two important mediators of vascular inflammation and the response to injury. Once this characterization is established, the investigators will investigate candidate mechanisms focusing primarily on intracellular calcium transients and protein kinase C phosphorylation status, two vitamin E targets identified in our preliminary data. Finally, the PIs will establish the physiologic relevance of their findings by testing the activity of vitamin E on vascular inflammation and neointimal growth using a newly developed murine model of arterial injury that we have established to be dependent on platelet deposition and beta 2 integrin function. Collectively, these studies should shed light on the control of vascular inflammation and provide the insights necessary to design important new strategies for the modulation of vascular disease, an important source of morbidity and mortality in the world today. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: CHEMICAL TOXICITY AND VITAMIN E REGULATION Principal Investigator & Institution: Reed, Donald J.; Director, Envir. Hlth. Scies. Ctr.; Biochemistry and Biophysics; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: The long range objectives of this research project with intact mice and rats are to (1) elucidate the mechanisms of in vivo protective systems which are dependent on vitamin E, (2) relate these protective systems to mechanisms of chemically induced toxicity including oxidative stress and damage, and (3) investigate the interactions of these protective systems using intact animals for interorgan considerations. In Specific Aim l, studies are proposed to elucidate the mechanism by which vitamin E is secreted into the bile under both physiologic and pathologic conditions, including chemically altered bile secretion. We will determine the extent to which vitamin E secreted into the bile is reabsorbed under both normal and pathologic conditions to test the hypothesis

Studies

19

that canalicular mdr2 P-glycoprotein is important in the biliary secretion of vitamin E. We will use the recently developed mdr2 knockout mice, which lack phospholipids in their bile, to investigate the relationship between vitamin E status and phospholipid homeostasis. In addition, as part of specific aim l we will study the relationship between vitamin E status, and the biliary secretion of vitamin E, and GSH homeostasis using the gamma-glutamyl transpeptidase (GGT) knockout mice recently developed in the laboratory of Dr. Michael Lieberman, Baylor University. A collaborative study with Dr. Daniel Liebler, University of Arizona, is proposed in Specific Aim 2 to investigate the in vivo consumption and oxidation products of vitamin E. Our hypothesis is that the oxidation product profile of vitamin E will vary with the mechanism of oxidative challenge and the GSH status of the animal; certain oxidation products, which can be detected in the blood, may serve as biomarkers of the extent of hepatic oxidative stress. These experiments are expected to provide a better understanding of the possible in vivo "sparing" effect of GSH and vitamin E under pathologic conditions. In Specific Aim 3 we will use a strain of Wistar rats which are unable to produce vitamin C to investigate the turnover of vitamin E and oxidation products formed under both normal metabolic and oxidative stress conditions; we will use diets which provide 3 levels of both vitamin E and vitamin C. Our hypothesis is that vitamin C status will have an effect on the turnover of vitamin E, as well as the quantity and species of vitamin E oxidation products, when comparing animals with low v.s. high tissue vitamin E levels under pathologic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMOPREVENTION OF ORAL CANCER: MODEL STUDIES Principal Investigator & Institution: El-Bayoumy, Karam E.; Director of Research; Institute for Cancer Prevention 1 Dana Rd Valhalla, Ny 10595 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2002 Summary: Although primary prevention by tobacco use cessation and by moderation in alcohol intake should be the most successful strategy for control of head and neck cancer, the evaluation of complementary approaches, such as chemoprevention, is very important as a means toward achieving this goal. Natural and synthetic analogs of vitamin A (retinoids), beta-carotene, vitamin E and selenium are featured in the reported studies of chemoprevention of head and neck cancer. Literature data appear to support the notion that the chemopreventive efficacy of a mixture of vitamins and minerals is superior to a single agent. Data showing a reduction in the incidence and mortality rates of oral and other head and neck cancers as a result of large-scale intervention trials with chemopreventive agents are lacking. At this time, it appears premature to suggest supplementation of specific chemopreventive agents as a routine strategy to prevent head and neck cancer. Therefore, the basis of the present investigation is to systematically determine the efficacy of relevant agents, individually and in combination; initially, in well-defined animal model assays and with delineation of the mechanisms of action involved in etiology and prevention. We demonstrated the utility of the lacZ transgenic mouse for investigations involving initiation pf carcinogenesis of the oral cavity by synthetic 4-nitroquinoline-N-oxide (4-NQO), as well as carcinogens present in tobacco and its pyrolysis products (4-(methylnitrosamino)-1(3-pyridyl)-1-butanone [NNK] and benzo(a)pyrene [BaP]). We also demonstrated that a diet supplemented with a synthetic organoselenium compound (1,4phenylenebis(methylene)selenocyanate, p-XSC)) or with vitamin E and C in several organs, including oral tissues, can inhibit mutagenesis to varying extents and the system can be used to evaluate other chemopreventive agents. In addition, we have shown that,

20

Vitamin E

in F344 rats, p-XSC can inhibit tumors of the tongue and block the cell proliferation induced by 4-NQO. Furthermore, results obtained in our laboratory, as well as in others, clearly demonstrate that a form of selenium compound, not selenium per se, is critical in cancer chemoprevention. On the basis of our preliminary results and those reported in the literature, we hypothesize that the combination of selenium in the form of p-XSC or the naturally-occurring Se-methylselenocysteine (MSC), vitamin A, and E should prove to be highly promising cocktail for chemoprevention of cancer of the oral cavity. Specifically, this cocktail will inhibit oxidative damage, cell proliferation and COX-2 activity; this will result in induction of apoptosis and inhibition of tumorigenesis. To test our hypothesis, our specific aims are: 1. To determine the inhibition of mutagenesis induced by 4-NQO and BaP in the oral cavity of the lacZ transgenic mouse by selenium (MSC and p-XSC), vitamin A, and E individually and in combination. 2. To determine the chemopreventive efficacy of the most effective cocktail (developed in Aim 1) against the development of tumors of the tongue induced by 4-NQO and BaP in male F344 rats, and in female B6C3F mice, respectively. 3. To examine the effect of the cocktail on critical intermediate biomarkers (cell proliferation, oxidative, DNA damage, COXactivities, and apoptosis) in the tongue of the rat and mouse. The results of this project will provide insights regarding the feasibility of using the most effective cocktail in future clinical trials toward chemoprevention of oral cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL STUDIES OF MITOCHONDRIAL DISEASE Principal Investigator & Institution: Johns, Donald R.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from The Applicant's Abstract): Mitochondrial diseases have protean clinical manifestations, including the nervous system and eye. We identified a novel mitochondrial disease, Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoplegia (SANDO), which is associated with multiple mitochondrial DNA (mtDNA) deletions. Sensory ataxia is prominent in two other neurologic diseases, Friedreich's ataxia and ataxia with vitamin E deficiency, caused by neuronal oxidative stress. Leber's hereditary optic neuropathy (LHON) was the first disease to be associated with mtDNA point mutations. There have been tremendous diagnostic advances in LHON, but little therapeutic progress. Three primary LHON-associated mtDNA mutations account for the majority of LHON cases. Tobacco and alcohol act as interacting epigenetic factors in LHON. Cybrids are cytoplasmic hybrid cell lines, formed by the fusion of the same recipient nucleus with different donor mutant mitochondria, that are cellular models of mtDNA-mediated disease. Oxidative stress is a critical cellular imbalance between prooxidant species and antioxidant defenses. The hypothesis to be tested is that disruption of mitochondrial energy production (via mtDNA point mutations or multiple deletions) renders neurons more sensitive to oxidative stress and is a unifying feature of LHON and SANDO. We propose studies with the following specific aims: 1. To develop an in vitro cybrid cellular therapeutic model of LHON to facilitate the testing of novel therapeutic hypotheses and guide future rational therapy; 2. To define the epigenetic risk factors that interact with LHONassociated mtDNA mutations. Clinical epidemiology (retrospective & prospective) studies of our extensive population of molecularly-confirmed LHON patients will be performed; 3.To perform preventive and therapeutic clinical trials in molecularlyconfirmed LHON patients and their at-risk maternal relatives; 4. To refine and expand the molecularly-proven SANDO clinical phenotype. The ultimate goal of this patient-

Studies

21

oriented research, is to advance the prevention and treatment of LHON, SANDO, and other mitochondrial diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL STUDIES OF NONALCOHOLIC STEATOHEPATITIS Principal Investigator & Institution: Sanyal, Arun J.; Associate Professor; Internal Medicine; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 20-MAY-2002; Project End 30-APR-2007 Summary: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in North America. It is characterized histologically by either a fatty liver alone or steatohepatitis. There is increasing evidence that NAFLD is associated with insulin resistance. Insulin resistance is associated with increased peripheral lipolysis and fatty acid delivery to the liver for uptake, oxidation and resterification to triglycerides. Recent studies also indicate that NAFLD is associated with increased hepatic oxidant stress. However, the underlying dietary, psychological and social factors predisposing to development of insulin resistance and NAFLD have not been characterized. Also, the pathogenetic mechanisms natural history and health impact of NAFLD, particularly non-alcoholic steatohepatitis (NASH) are not fully known. Furthermore, there is no established treatment of NASH. The research plan includes: (1) An outline of the structure of a large database, to be used by a clinical network for studies on NAFLD, is described. Justification for the specific information to be entered is provided: (2) Studies are proposed to test two hypotheses: (a) that the rate of progression of hepatic fibrosis accelerates after the development of bridging fibrosis in patients with NASH, and (b) specific social and psychological factors contribute to the behavioral profile associated with insulin resistance as well as the likelihood of success of diet and exercise interventions in improving insulin resistance in such patients. These will be studied by (a) comparing the rates of progression of fibrosis by one grade in patients with NASH with or without bridging fibrosis over a 3 year period, and (b) determination of eating and exercise behaviors, personality traits and psychopathology in those with NASH and comparison to a control group of patients with hepatitis C. Also, the relationship of these factors with the physiologic and histologic abnormalities present and the success of diet a nd exercise counseling will be assessed. (3) It is hypothesized that a twopronged treatment approach correcting insulin resistance with an insulin sensitizer, pioglitazone, and treating oxidant stress with vitamin E is superior to vitamin E alone for the treatment of NASH. A prospective, randomized short-term ( 1 year duration) clinical trial to test this hypothesis is proposed. The primary endpoint is the necroinflammatory grade. Both studies will require participation of the network. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: COHORT STUDY OF DIETARY SUPPLEMENTS AND CANCER RISK Principal Investigator & Institution: White, Emily; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 23-JUL-1999; Project End 30-APR-2004 Summary: Vitamin and mineral supplements are among the most commonly used drugs in the U.S. Neither chemoprevention trials nor observational studies have established the benefits or risks of supplemental use. The aim of this proposal is to investigate the association of intake of supplemental vitamin C, vitamin E, calcium and multivitamins with total cancer incidence. To meet this aim, a cohort will be recruited within the 13 counties of western Washington State, and followed for a mean of 2 1/4 years. A

22

Vitamin E

mailing will be sent to 300,000 men and women age 50-74 using names obtained from a commercial mailing list, which will include a recruitment letter targeting supplemental users and a questionnaire. The recruitment procedures have been tested, and should yield 35,000 male respondents and 40,000 female respondents with 75% of respondents having used at least one dietary supplement in the prior 10 years. The questionnaire solicits detailed information on supplement use over the last 10 years, and information on covariates that may be associated with supplement use and with future risk of cancer (e.g., medical history, cancer risk factors, cancer screening, reasons for supplement use). The questionnaire also incorporates a food frequency questionnaire, with additional items on supplemented foods. A second mailing to respondents 2-4 months later will supply a tape measure for anthropometric measures and brushes for collection of DNA from cheek cells. Studies to quantify the relative validity of our primary exposure measures will be conducted. Endpoint information will be efficiently and accurately collected by linking participant identifiers to the system Washington SEER cancer registry and the Washington State death tapes. Out-migration from the attachment areas of these files will be monitored by linkage to the National Change of Address tape. Longer term follow-up of this cohort will allow the investigation of the association of supplements with specific cancers (lung, prostate, breast and large bowel) and with total mortality, and will allow investigation of gene-supplement interactions. If supplements are harmful or of no use, this information would be important for the large number of Americans taking supplements. If a beneficial effect is found, it could be translated into highly cost effective cancer control measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--CELL BIOLOGY AND IMMUNOTOXICOLOGY Principal Investigator & Institution: Leid, Mark; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 01-NOV-1975; Project End 31-MAR-2006 Summary: The Cell Biology and Immunotoxicology Research Core serves as a biologically oriented complement to the Chemical/Analytical Cores of the OSUEHS Center to provide a focus of relevance to human health for application of the chemical and physical approaches and expertise available within the other Cores. Thus the Core provides a medium for the initiation of research projects in directions that otherwise may not have been pursued. Core leadership has changed from Dr. Barnes (who left OSU in 1997) to Dr. Leid. Drs. Bayne, Kerkvliet and Reed continue to be in this Core and are joined by recent Center investigators: Drs. Greenwood, Hagen, Ishmael and Vella. Dr. Hedstrom (Associate member of Center) also remains associated with this research core. In addition, there are 2 postdoctoral, 17 graduate students and 12 research assistants. The objectives of this Core are to provide an intellectual resource for pursuits into cellular signaling and hormonal/cytokine control of growth, differentiation, early development and mechanisms of cell death. Specific projects by investigators of this Core include: analysis of T cells with regard to TCDD or Ah receptor and peroxisome proliferators; immunomodulation by xenobiotics; oxidative stress, including mitochondrial dysfunction, glutathione and protein thiols, with regard to cell death and immunotoxicity; age-related effects on mitochondrial functions. This Core serves as a biologically oriented complement to the Chemical/Analytical Cores to provide "a focus of relevance to human health for application of chemical and physical approaches". This Core has assisted with 97 publications since 1995 with about 16 being collaborative studies. Eight past collaborative projects are listed [Dr. Kerkvliet (4); Dr. Barnes (2); Dr. Reed (1);and Dr. Leid (1)]. Future plans include additional joint projects with the more

Studies

23

recent Center investigators, e.g., projects between Drs. Ishmael and Leid (cloning PAR. alpha transcriptional coactivators); Drs. Kerkvliet and Ishmael (new cell cultures models to assess cell cycle after exposure to nongenotoxic carcinogens); Drs. Reed and Hagen role of glutathione, iron and vitamin E on myocytes; Drs. Kerkvliet, Reed and Hagen (role of glutathione and vitamin E in apoptosis of lymphocytes); Drs. Kerkvliet, Vella, Leid and Hedstrom (TCDD effects on dendritic cells). Drs. Kerkvliet and Vella will provide the immunological expertise for this Core with Drs. Leid and Reed providing biochemical and molecular expertise. This Core provides biological bridging with the other Cores and Center investigators with support for experimental design fostered through workshops and monthly laboratory meetings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CREATION OF A MULTIETHNIC DIETARY SURVEY FOR ELDERS Principal Investigator & Institution: Gustafson, Deborah R.; Nutrition and Food Sciences; Utah State University Logan, Ut 84322 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-DEC-2003 Summary: Cancer rates differ dramatically among various ethnic subgroups in the United States (U.S.). Although cancer rates have typically been lower among Native American populations, recent data indicate that these numbers are increasing. Changing patterns of dietary intake may account for some of these differences. Since cancer is a disease of aging, accurate and reliable measurements of dietary intake among the elderly are very important in estimating diet and cancer relationships. This knowledge will facilitate the development and evaluation of culturally-specific cancer control programs. There is a dearth of dietary assessment tools available for assessing intakes of elderly in the U.S., particularly elderly of various ethnic backgrounds. The goal of this project is to formulate a dietary survey that will accurately and reliably assess dietary intakes of elderly Native American (Navajo and Ute) and Caucasian populations in Utah. Completion of this project will form an excellent basis for future dietary data collection efforts among the elderly. Four sequential objectives are described in this proposal: 1) Determine the food sources of cancer-related nutrients, e.g., vitamin C, betacarotene, vitamin E, folate, and fiber, in the diets of Native American and Caucasian elderly adults who over 50 years of age using 24 hour recall methods. 2) Compose a relevant food list for the creation of a multi-ethnic food frequency questionnaire-based dietary assessment strategy for Native American and Caucasian elderly. 3) Modify the PicSort dietary assessment method to assess the frequency of intake of cancerpreventive nutrients and foods in the elderly. Focus groups will be used to assess its utility. 4) Determine traditional plant and animal food sources among Navajo and Ute to provide a basis for cancer risk reduction food-based interventions based on traditional foodways. Focus groups will be conducted to accomplish this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DIABETIC NEUROPATHY: IMPLICATIONS FOR WOUND REPAIR Principal Investigator & Institution: Gibran, Nicole S.; Associate Professor; Surgery; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 30-SEP-1999; Project End 31-AUG-2007 Summary: (provided by applicant): This proposal explores cell signaling pathways that occur between cutaneous sensory nerve fibers and endothelial cells in response to cutaneous injury. Our previous data suggest that nerve-derived neuropeptides contribute to the normal wound repair process. In contrast, non-healing chronic ulcers

24

Vitamin E

associated with diabetes mellitus are characterized by microangiopathy and decreased innervations. Based on encouraging data during the past funding period we continue to explore our hypothesis that in patients with diabetes mellitus, hyperglycemia and hyperlipidemia impair microvascular endothelial cell response to nerve-derived neuropeptides and endothelial cell production of necessary inflammatory mediators. These abnormalities contribute to impaired response to cutaneous injury. We will test our hypothesis by addressing the following Aims: Aim 1: To determine the effects of hyperglycemia and matrix glycosylation on microvascular endothelial cells responses. Hyperglycemia can directly alter cellular responses and can indirectly alter cellular response by extracellular matrix molecule glycosylation. We will determine whether hyperglycemia and/or matrix molecule glycosylation alters SP-induced endothelial cell mediator synthesis, cytoskeleton organization, integrin expression and intracellular signaling. Aim 2: To determine the effect of elevated fatty acid levels on endothelial cell responses. Hyperlipidemia is strongly associated with complications in diabetes mellitus. We will determine whether elevated fatty acids alone or as Triglycerides alter SP-induced endothelial cell mediator synthesis, cytoskeleton organization, integrin expression or intracellular signaling. Aim 3: To determine the anti-oxidant regulation of microvascular endothelial cell response to hyperglycemia & hyperlipidemia. Oxidative stress due to hyperlipidemia may alter cellular response to injury. We will continue our studies of effects of antioxidants, vitamin E, vitamin C and n-acetyl cysteine on cellular responses under hyperlipidemic and hyperglycemic conditions. Aim 4: To determine whether restoration of neuropeptide activity improves wound repair in diabetic mice. We will use several approaches to evaluate the roles of neuropeptides in wound repair. Using an excisional wound repair model in hyperglycemic db/db mice, we will replace substance P and inhibit neutral endopeptidases activity. We will also test the effects of antioxidants in this murine wound model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIET AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE Principal Investigator & Institution: Camargo, Carlos A.; Director; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2003 Summary: Chronic obstructive pulmonary disease (COPD) morbidity and mortality are rising, a trend that is unique among the top five causes of death in the USA. Despite the enormity of the problem, there are relatively few epidemiologic studies on COPD risk factors besides cigarette smoking. The proposed study examines the relationship between dietary factors and COPD among participants in the Nurses' Health Study, an ongoing prospective cohort study of 121,700 women, ages 39-64 in 1985. This cohort has been followed by means of biennial questionnaires which inquire about a variety of topics, including dietary intake (using a validated semi-quantitative food frequency questionnaire) and physician diagnosis of COPD. In 1998, all participants with a history of COPD were sent a supplementary questionnaire regarding specifics of COPD diagnosis and related topics. The primary aim of the proposed study will be to examine the relation of dietary factors to risk of newly-diagnosed COPD during 1985-1998. During this time period, there were approximately 2,100 cases of "confirmed" COPD (i.e., physician diagnosis and pulmonary function tests [PFTs] at time of diagnosis or abnormal FEV-1 in past year) and "probable" COPD (i.e., physician diagnosis and recent respiratory symptoms, but PFTsnot known). Preliminary data support the validity of these case definitions, and this will be examined further by reviewing 600 medical records. Likewise, potential under-diagnosis will be examined in a random sample of

Studies

25

past and current smokers who have never reported COPD or asthma. The specific dietary hypotheses are that high intakes of antioxidants (e.g., vitamin C, vitamin E, and carotenoids), magnesium, potassium, and n-3 polyunsaturated fatty acids (e.g., fish oils) decrease risk of COPD, whereas high intakes of specific fatty acids (e.g., linoleic acid) increase risk. The cohort size and 13-year follow-up provide greater than 90 percent power to detect a trend across quintiles of dietary intake. In 1998, among approximately 2,400 prevalent cases with diet data, study investigators will address a secondary aim: to determine the relation of dietary factors to COPD severity during 1998-2000. COPD severity will be assessed by self-report of current medications, recent symptoms, activity limitations, and health care utilization (e.g., emergency room or urgent office visits for COPD exacerbations). The rising prevalence of COPD, particularly among women, along with its high societal cost, make COPD prevention an important public health goal. The proposed study is cost-effective, as it makes use of an existing cohort, and it will provide information that could have direct clinical application to reduce risk of COPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIET AND GENETIC RISKS FOR LUNG CANCER Principal Investigator & Institution: Patterson, Ruth E.; Associate Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 05-MAR-2001; Project End 31-DEC-2002 Summary: (Applicant's Description) This proposal is for an investigation into the associations of diet, and interactions of diet and genetic polymorphisms, with the risk of lung cancer. Data are from 18,314 men and women enrolled in a chemoprevention trial of beta-carotene and retinol (CARET). After a mean of 7.4 years of follow up, CARET has endpoint data on almost 800 cases of lung cancer. Dietary intake was measured with a food frequency questionnaire. Serum micronutrient and genetic polymorphisms have been analyzed for 388 lung cancer cases and 753 controls. Our specific aims are: 1. To better understand the association of fruit and vegetable intake with the reduced risk of lung cancer. Fruit and vegetable intake will be measured as: (i) servings per day (total and grouped by phytochemical content), (ii) micronutrient associated with fruits and vegetables, including vitamins C and E, folate, and carotenoids, and (iii) serum carotenoids and vitamin E. 2. To examine whether the associations of fruit and vegetable intake with lung cancer risk are modified by genotypes of carcinogen metabolizing enzymes (i.e., CYP2D6, CYP2El, CYP1Al, GSTM1, GSTT1, and EH). We will conduct cohort analyses for dietary intake data and case control analyses for laboratory based studies. Although the baseline dietary data have been collected and the laboratory analyses (for serum micronutrients and genotypes) have been completed, there are no CARET investigators with expertise in nutrition science who are funded to conduct these analyses and write the associated manuscripts. Therefore, to meet the specific aims proposed above, we request support for nutritional epidemiologists, a statistician, molecular biologist, and the staff support needed to publish the findings. This work addresses important questions about the etiology and prevention of lung cancer, and can be completed with a modest amount of funding in addition to what has already been invested in this large chemoprevention trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DIETARY OXALATE AND KIDNEY STONE FORMATION Principal Investigator & Institution: Assimos, Dean G.; Professor; Neurology; Wake Forest University Health Sciences Winston-Salem, Nc 27157

26

Vitamin E

Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Calcium oxalate kidney stone formation affects a significant number of individuals in the United States and contributes billions of dollars to health care costs. Urinary oxalate excretion plays a major role in the formation of these calculi as it influences the supersaturation of urine with calcium oxalate, a prerequisite for calcium oxalate stone formation. Recent investigations have shown that a significant amount of urinary oxalate is derived from dietary sources. Therefore, reducing oxalate consumption or its absorption from the intestinal tract may prove to be useful methods for limiting an individual's risk of forming stones. Experiments with cultured cells and animal models have demonstrated that oxalate has the potential to damage renal tissue through the generation of chemicals called oxygenated free radicals. This process may play a causative role in calcium oxalate stone formation. Therefore, attenuating this response may also limit stone generation.There are three specific aims in this research proposal. The first is to compare the response of stone forming and nonstone forming adults to dietary oxalate. The second aim is to compare renal oxalate clearance in both of the aforementioned groups. These studies will determine whether there are any differences in the renal handling of oxalate between these two groups. The third aim is to determine whether urinary oxalate excretion and renal proximal tubular cell injury can be reduced with calcium supplements, vitamin E supplements, administration of oxalate degrading bacteria, or a combination of all three of these regimens. All of these studies will be conducted in our General Clinical Research Center where carefully controlled diets can be administered. Various responses will be assessed including gastrointestinal oxalate absorption, urinary supersaturation, oxalate excretion, oxidative stress and markers of renal proximal tubular cell injury. These studies will aid in the development of strategies to prevent kidney stone formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIFFERENTIAL GENE EXPRESSION INDUCED BY ANTIOXIDANTS Principal Investigator & Institution: Kim, Jeri; Genitourinary Medical Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Prostate cancer is the most common cancer in American men other than skin cancer. Despite screening and detection advances, the prostate cancer mortality rate, while declining, has not fallen dramatically, and both localized and metastatic disease continues to challenge surgical, chemotherapeutic, radiotherapeutic, and hormonal interventions. Researchers have responded by initiating chemoprevention trials to cut incidence. Secondary end-point findings in randomized trials indicate the ability of vitamin E and selenium to reduce prostate cancer incidence. The aims of this study are: 1) to identify genes differentially induced by the antioxidants l-selenomethionine (selenium) and alpha-tocopherol (vitamin E), singly and in combination, in normal and cancerous prostate cells from radical prostatectomy specimens using laser capture microdissection (LCM) and oligonucleotide microarrays; and 2) to validate changes of expression in identified genes that may serve as markers for future clinical trials. Already under study is modulation of glutathione peroxidase, NF-kB, cyclooxygenase-2, p53, and Ki-67, and markers of apoptosis in patients who are treated with selenium, vitamin E, or a combination before prostatectomy. Using core biopsies of radical prostatectomy specimens from the 38 evaluable patients participating in that study, we will use LCM to generate tissue samples whose cancerous and normal cells will be studied for gene expression profiling using oligonucleotide probe arrays. Statistical methods encompass gene image analysis, and we will use a computer

Studies

27

implementation of gene shaving, which relies on repetitive calculation of gene clusters' largest principal components, to characterize both genes and tumors. One of the developers of this computer implementation will collaborate on this project. The expression changes of selected genes will be validated with real-time polymerase chain reaction and immunohistochemistry. With these methods it is possible to characterize alterations in specific genes known to regulate cell cycle, apoptosis, angiongenesis, and differentiation and to correlate those findings to others related to selected biomarkers (SBs). Once characterized, these SBs will widen the scope and enhance the feasibility of prostate cancer trials, creating broader opportunities for advances toward successful prevention, effective treatment, and eventual cure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF HIV PROTEASE INHIBITORS ON ENDOTHELIAL DYSFUNC Principal Investigator & Institution: Mcclure, Harold M.; Associate Director; Microbiology and Immunology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 12-SEP-2000; Project End 30-JUN-2005 Summary: (Adapted from the applicant's abstract) To define the role of HIV protease inhibitors in endothelium-dependent vasorelaxation and endothelial morphology. Hypothesis 1: protease inhibitors may impair endothelium-dependent vasorelaxation and endothelial morphology. A novel artery culture perfusion model (C. Chen R01) and a rhesus macaque model (H. McClure R01) of SHIV infection will allow analysis of vessel contraction and relaxation, endothelial cell morphology and substructures Endothelium- dependent relaxation will also be tested by high-resolution ultrasonography of the brachial artery in humans receiving and not receiving therapy (J Lennox R01). 2) To determine the effect of HIV protease inhibitors on NO production, eNOS activity and expression. Hypothesis 2: protease inhibitors may affect NO production, eNOS activity and expression. Studies will determine NO production, eNOS activity, eNOS gene expression, cell metabolism, eNOS transcription rate, and eNOS mRNA stability in the artery culture and macaque models (Chen, McClure. eNOS activity will also be measured in humans either receiving or not receiving protease inhibitors, and in the presence of absence of endothelial dysfunction (Lennox). 3) To determine the effect of HIV protease inhibitors may superoxide anion (O2) production, NADH oxidase activity, and peroxynitrite formation. Hypothesis 3: protease inhibitors may affect on O2 production, NADH oxidase activity, and peroxynitrite formation. Analyses in artery perfusion culture and endothelial cell cultures will include O2 production, NADH oxidase activity, Cu/An SOD expression (Chen). Cu/SOD expression, peroxynitrite formation, lipid peroxidation, will be measured in macaques (Chen/McClure) and in humans (Lennox). 4) To develop strategies to prevent HIV protease inhibitor-associated endothelial dysfunction. Hypothesis 4: administration of Larginine as an NO donor or vitamins E and C as O2 production, NADH oxidase activity in vitro (C Chen), Cu/Zn-SOD expression, peroxynitrite formation and lipid peroxidation, and plasma levels of vitamin C and vitamin E in macaques and humans (Chen/McClure, Lennox); and changes in brachial artery ultrasound findings (Lennox). Collaborative applications (Basic science-C. Chen; Clinical science-Jeffrey Lennox; and Non-human primates-Harold McClure) are submitted. Together, the integrated basic science, non-human primate and human investigations offer a multi disciplinary approach to the understanding and prevention of protease inhibitor-associated vascular complications.

28

Vitamin E

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF LIPIDS ON VASCULAR GRAFT HEALING Principal Investigator & Institution: Graham, Linda M.; Professor; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from Applicant's Abstract): Prosthetic grafts are used widely in vascular reconstructive surgery, but their long-term patency is limited, perhaps due to altered cell function caused by oxidized low density lipoprotein (oxLDL). In preliminary studies they have shown that: 1) graft material stimulates monocytic cells to oxidize LDL in vitro, 2) this oxLDL inhibits endothelial cell (EC) migration in vivo. This contributes to the prolonged thrombogenicity and eventual failure of these grafts. The goal of this project is to determine the effect of lipids, especially oxidized lipids, on EC migration on prosthetic grafts. To test their hypothesis, the effect of oxidized lipids on EC migration and the mechanism by which oxLDL inhibits EC migration will be studied. The investigators will first investigate the role of reactive oxygen species (ROS) in oxLDL's inhibition of EC migration. They will characterize the effect of oxLDL on superoxide production by EC, assessing the effect of ROS on EC migration, and determining the ability of antioxidants to restore EC migration in the presence of oxLDL. Since ROS alter membrane fluidity and changes in fluidity affect migration, they will investigate the effect of oxLDL on EC membrane fluidity. They will also evaluate the ability of vitamin E and other antioxidants to prevent changes in membrane fluidity and preserve EC migration. The effect of oxLDL on EC migration on ePTFE graft material in vitro will be studied, and the ability of vitamin E or superoxide dismutase to restore migration determined. Finally, they will study the effect of hypercholesterolemia on EC ingrowth onto prosthetic grafts implanted in rabbits, and assess the ability of vitamin E to preserve endothelial migration. The proposed studies will investigate the role of lipids and lipoproteins, and their oxidatively modified derivatives, in the failure of synthetic vascular grafts to endothelialize. Studies will also address the efficacy of treatment with dietary antioxidants to control lipid oxidation and promote graft healing. This will lead to a better understanding of the role of lipids in the pathophysiology of graft failure. Ultimately, this may lead to methods to promote endothelialization of prosthetic grafts and prolong patency of small-diameter vascular grafts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ESOPHAGEAL ADENOCARCINOGENESIS AND ITS PREVENTION Principal Investigator & Institution: Yang, Chung S.; Professor Ii & Chair; Chemical Biology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2003; Project Start 01-APR-1998; Project End 31-JAN-2008 Summary: (provided by applicant): The long-term goal of this project is to provide a mechanistic basis for the prevention of esophageal adenocarcinoma (EAC). In the previous grant period, a surgical model esophagogastroduodenal anastomosis (EGDA) was developed and characterized. Our results helped us to develop the present hypothesis that reactive oxygen species and excessive arachidonic acid metabolites, which are produced due to reflux-induced inflammation, are major factors driving esophageal adenocarcinogenesis. In this application, we plan to test this hypothesis and examine related chemoprevention approaches with the following specific aims: 1. To test the hypothesis that oxidative stress is a major driving force for esophageal adenocarcinogenesis by studying the effect of antioxidant nutritional status (by

Studies

29

manipulating dietary levels of vitamin E) or supplementation with N-acetyl cysteine on EAC formation and related biochemical and histological changes in the rat EGDA model. 2. To examine the contribution of aberrant arachidonic acid (AA) metabolism, especially the overproduction of prostaglandin E2 and leukotriene B4, to esophageal adenocarcinogenesis by analyzing key enzymes, metabolites, and receptors in rat tissues. Functional studies in explant and cell cultures will be carried out with respective enzyme inhibitors and receptor antagonists for selecting potential chemopreventive agents. 3. To determine the effectiveness of specific inhibitors of AA metabolism and receptor antagonists (identified in Aim 2) as chemopreventive agents against tumorigenesis in the rat EGDA model. The effects of these agents on short-term biochemical markers and inflammation will be correlated with inhibition of tumorigenesis to gain mechanistic information. Combination of agents will be studied systematically to develop effective chemopreventive approaches.These studies are expected to fully elucidate the roles of oxidative stress and aberrant AA metabolism in the formation of EAC and help develop effective agents for its prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ESTROGEN, VITAMIN E, AND COGNITIVE CHANGE IN WOMEN Principal Investigator & Institution: Dunn, Julie E.; Research Scientist; New England Research Institutes, Inc. 9 Galen St Watertown, Ma 02472 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Primary Aims of this study will determine: 1. Effects of vitamin E supplement use (VitE) on cognitive function (CF) and 3-year change in cognitive function in women age 60 and over. Hypotheses: a) Vit E supplement users will have higher scores at baseline and less decline over 3 years on visual memory tests, compared to non-users. 2. Effects of estrogen replacement therapy (ERT) on CF measures over 3 years in women age 60 and over. Hypotheses: ERT users will have higher scores at baseline and three years on verbal memory tests than non-users. Secondary Aims will determine: 1. Effects of plasma alpha-tocopherol (a-tc) levels on CF over 3 years. Hypothesis: a-tc levels will be directly related to visual memory scores at 0 and 3 years. 2. Effects of Apolipoprotein E (ApoE) genotype on change in CF over 3 years and upon VitE and/or ERT effects: Hypotheses: a) test scores will be more likely to decline in women with one or more E4 alleles. b) associations of VitE and/or ERT with CF test scores(Aims 1 &2 above) may differ between those with and without ApoE in those with ApoE e4. Background: Cognitive loss in later life is associated with increased mortality and disability, and reduced quality of life, and may represent an early stage of dementia, possibly amenable to treatment. VitE and ERT are under study as possible means to prevent or delay progression of Alzheimer's disease (AD) and both are biologically plausible as neuroprotective agents. Less is known of their ability to preserve CF in non-demented individuals. Equivocal results of previous studies may be due to nonuniform methodology and use of non-specific or less sensitive CF tests. Methods: 575 women age 60+ will be recruited from Women's Health Initiative (WHI) Observational Study and Diet Modification Control enrollees. ERT history and vitamin supplement and medication data, already collected for WHI, will be updated. Blood samples will be collected for plasma VitE measurement and ApoE genotyping. CF will be assessed with a battery of neuropsychological tests performed on 2 occasions, 3 years apart. Tests will include measures of memory, language, visual-perceptual ability and attention, as well as assessments of functional ability and depressive symptoms. Primary analyses will specifically include tests of verbal memory, which may be more

30

Vitamin E

sensitive to ERT effects, and visual memory, which may be most sensitive to effects of age. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE-DIET INTERACTIONS AND HEART DISEASE Principal Investigator & Institution: Campos, Hannia; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Evidence is building from epidemiological and laboratory investigations to support the hypothesis that genetic variation can modulate the effect of dietary intake on metabolic parameters to promote atherosclerosis and increase the incidence of coronary heart disease (CHD). Technological advances in molecular and nutritional epidemiology now make it possible to study gene-diet interactions and CHD in human populations at a new level of sophistication. The overall goal of this project is to carry out a population-based case-control study in 2,150 cases of myocardial infarction and 2,150 matched controls from Costa Rica, to test specific hypotheses relating gene-diet induced atherosclerosis susceptibility (GDAS) markers to CHD. Twelve GDAS markers were selected for this study. GDAS markers are defined as common genetic variants that modulate the effect of intake of specific fatty acids, tocopherols, and carotenoids on atherosclerosis. We will determine whether carriers of the GDAS marker variants are at increased risk of CHD compared to wild type homozygotes when exposed to high intakes of lauric 12:0, myristic 14:0, and palmitic 16:0, and trans fatty acids particularly 18:2 trans from partially hydrogenated soybean oil. We will study whether high intakes of alpha-linolenic acid, vitamin E, carotene, particularly alpha- carotene, lutein, and lycopene reduce the risk of CHD, and whether the GDAS marker variants alleles lessen this protective effect. In secondary analyses, we will test the hypotheses that the GDAS variant alleles influence the effect of dietary fiber, cholesterol, physical activity, and smoking on CHD. Haplotypes of metabolically related GDAS markers that are better predictors of CHD than individual markers alone will be established, and for each haplotype, we will determine specific adverse dietary patterns. Dietary exposure variables will be evaluated by simultaneous analyses of a semi-quantitative food frequency questionnaire, and biochemical measures of intake including adipose tissue tocopherols and carotenoids by HPLC, and fatty acids, including trans isomers of partially hydrogenated soybean oil by GC. This study will provide the most complete data set to study numerous hypotheses relating genes, diet, and CHD, and could lead to specific targeted interventions for reducing the development of CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HUMAN BREAST CANCER CELL GROWTH INHIBITION BY VITAMIN E Principal Investigator & Institution: Kline, Kimberly; Professor; Human Ecology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JUL-2005 Summary: (Applicant's Abstract) Goals are to investigate the mechanisms of action of VES (vitamin E succinate; RRR-alpha-tocopheryl succinate), a potent inducer of apoptosis in human breast cancer cells but not normal mammary epithelial cells. The applicant's studies show that VES can restore both transforming growth factor-beta (TGF-beta) and Fas/CD95 impaired anti-proliferative and death signaling in human breast cancer cells that are resistant to these two important cell homeostatic signaling

Studies

31

pathways. In this competing continuation application the applicant proposes to investigate critical signaling events involved in VES initiated apoptosis in human MDAMB-435 breast cancer cells. Normal human mammary epithelial cells (HMECs) and immortalized, non-tumorigenic human mammary epithelial MCF-10A cells which are insensitive to VES induced apoptosis but responsive to both TGF-beta and Fas induced cell fates will be studied for comparative purposes. Aim 1 will characterize components of the TGF-beta signal transduction pathway contributing to VES-induced apoptosis. Aim 2 will characterize Fas signal transduction events involved in VES induced apoptosis. Aim 3 will investigate the decision phase of apoptosis in VES treated cells with emphasis on Bax and mitochondrial mediated events that produce downstream execution phase mediators. Comparisons between VES and ligand (TGF-beta1 and antiFas agonistic antibody) mediated events in MDA-MB-435, HMECs and MCF-10A cells will address the molecular basis of VES's selective ability to induce apoptosis in cancer cells but not in normal or immortalized but non-tumorigenic cells. Expectations are that data generated will increase basic knowledge about TGF-beta and Fas signaling in normal and cancer cells and will provide a better understanding of how VES, a potent pro-apoptotic agent, induces cell death. Part of the significance of these mechanistic studies lies in the potential use of agents like VES for chemotherapy of human breast cancer. This possibility has been strengthened by the recent demonstration that a VES ether analog is a potent, orally active chemotherapeutic agent in a preclinical xenograft model of human breast cancer. Another aspect of the significance of these type studies lies in the belief that better understanding of signaling events will lead to the identification of critical intracellular signal transduction molecules which can be targeted for design of mechanism-based drugs to achieve improved cancer cell killing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LC/MS OF LARGE ATHEROGENIC LIPID OXIDATION PRODUCTS Principal Investigator & Institution: Byrdwell, William C.; Chemistry and Biochemistry; Florida Atlantic University Boca Raton, Fl 33431 Timing: Fiscal Year 2003; Project Start 12-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Triacylglycerols (TAG) contain sites of unsaturation that are susceptible to oxidation when exposed to air, or when heated. These TAG form a variety of primary oxidation products that contain fatty acids with multiple functional groups, such as hydroperoxides, epoxides, ketones and alcohols. Fatty acid oxidation products have been shown to represent a significant atherosclerotic risk. Oxidation products have been shown to be incorporated into brush border cells, and then into lowdensity lipoprotein (LDL). New analytical methodologies that the P.I. is pioneering have allowed large, high molecular weight (MW) TAG oxidation products (TAGOX), made from the joining together of several oxidized TAG, to be directly identified for the first time. These large, oligomeric TAGOX deserve further study because they are routinely consumed as part of the typical American diet, yet they have never before been characterized. We propose to use liquid chromatography coupled with electrospray ionization-mass spectrometry (ESI-MS) for analysis of the large oxygen-containing oligomers produced by heated oils. We will characterize intact oligomers containing two (dimers), three (trimers) or four (tetramers) triacylglycerols covalently bonded together. These molecules contain oxygen functional groups that are reactive and could allow oxidized fatty acids to be incorporated into biological tissue, such as low-density lipoprotein (LDL). We will analyze oxidation products from triolein (the major component in olive and canola oils) heated for 0 hr., 1 hr., 3 hr., and 6 hr. to determine the onset and extent of degradation due to oxidation. We will examine heated oil

32

Vitamin E

samples treated with 0 ppm, 100 ppm, and 400 ppm alpha tocopherol (vitamin E) to demonstrate that oxidation can be significantly reduced by incorporation of antioxidants. This research will represent the first time that the specific molecular species of high molecular weight oxidation products have been directly identified. We propose to use LC/MS to study the products formed by model oils and also the products extracted from potato chips fried in the heated oils. The characterization of these high molecular weight oxidized oligomers will provide unprecedented insight into the mechanisms by which dietary oils are oxidized and made available for incorporation into biological tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPOPROTEIN METABOLISM

STRUCTURE/FUNCTION

IN

CHOLESTEROL

Principal Investigator & Institution: Young, Stephen G.; Professor; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2001; Project Start 01-FEB-1989; Project End 31-JAN-2004 Summary: This is the second renewal of this Program Project Grant, which has focused on the structure and function of key proteins in lipoprotein metabolism and atherosclerosis. During the next 5 years, our goals will be: 1) To identify the structural domains of apolipoproteins that regulate lipid transport; 2) To contribute to the understanding of the involvement of apo-B-containing lipoproteins in atherogenesis; and 3) To more fully understand the physiologic roles of lipoproteins and apolipoproteins in metabolism, including the roles of lipoproteins in embryonic development and in cardiac physiology. Four projects and four cores have been assembled, which interact closely and contribute significantly to each other. The research program is multi- disciplinary and relies on state-of-the-art technology, including X-ray crystallography, transgenic and gene-targeted mouse models, cellular biology, and ultrastructural biology. "Influence of Apolipoprotein E structure on Function," uses X-ray crystallography and biochemical approaches to determine the three- dimensional structure of apo-E and to determine how the three-dimensional structure affects lipoprotein metabolism. "Cellular Mechanism for Lipoprotein Retention in the Artery Wall," will test the hypothesis that proteoglycan binding sites in apo-B play a crucial role in the retention of lipoproteins in the artery wall and the development of atherosclerosis. "Alpha-TTP and Vitamin E in Development and Disease," explores the role alpha-tocopherol transfer protein and vitamin E in metabolism and atherosclerosis. The Cores (Animal Model; Histology, Atherosclerosis, Ultrastructure; Cell Culture and Protein Production; Administration) will provide the common services that are necessary for accomplishing the goals of the Program Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPOPROTEINS, OXIDATAIVE DAMAGE, AND RESPONSES TO DIET Principal Investigator & Institution: Rainwater, David L.; Scientist; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Lipid and lipoprotein phenotypes and markers of oxidative damage are among the strongest, most consistent predictors of cardiovascular disease (CVD). With a few notable exceptions, the genes that govern variation in these important risk factor phenotypes are poorly characterized, and it appears that there may be many novel

Studies

33

genes involved which were not previously suspected. The overarching goal of this project is to search the genome for quantitative trait loci (QTLs) that influence markers of lipoprotein metabolism and oxidative damage, to locate and identify these genes, and ultimately to better understand the metabolic processes involved. The traits that we will assess include lipid and lipoprotein measures of LDLs and HDLs and plasma indicators of oxidative damage. In addition, we will focus on identifying the effects ofgenotype x environment interactions on these CVD traits, specifically, responses to changing levels of dietary components, such as fat, cholesterol, and the antioxidant vitamin E, and also age-related changes. Exploiting our existing resources (i.e., pedigreed baboons, statistical genetic tools, frozen samples from previous diet studies, and availability of genotypes for the microsatellite markers comprising the baboon linkage map) plus data from a new dietary challenge experiment, we propose the following specific aims: (1) to detect, map, and statistically characterize QTLs that affect lipid and lipoprotein phenotypes on different diets, (2) to determine the extent to which genes affect indicators of oxidative damage, (3) to determine the pleiotropic effects of genes that influence lipoprotein phenotypes and oxidative damage indicators, (4) to determine the effects of genes on long-term longitudinal changes in CVD risk factors (by means of rechallenging baboons that had previously undergone the dual dietary challenge experiment), and (5) to determine the effects of genes on responses of oxidative damage indicators to a high dose of vitamin E (by means of adding a new diet to the rechallenge protocol). Accomplishing these specific aims will enable us to detect, locate, and characterize genes that govern variation in well established CVD risk factors. Based on the close phylogenetic relationship of baboons and humans, the results from our studies will provide insights into the genes that underlie the onset and progression of atherosclerosis in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM ANTIOXIDANTS

OF

APOPTOSIS:

POLYAMINES

AND

Principal Investigator & Institution: Adebodun, Foluso A.; North Carolina Agri & Tech St Univ 1601 E Market St Greensboro, Nc 27411 Timing: Fiscal Year 2001; Project Start 01-JUN-1977; Project End 31-JUL-2005 Summary: (provided by applicant): Apoptosis is a natural form of cell death by which damaged, defective or otherwise incompetent cells are efficiently removed without inflammation in multicellular organisms. The understanding of the mechanism and regulation of this active physiological process offers new possibilities for the manipulation of apoptosis for cancer therapy and prevention. Based on the hypothesis that a defective regulation of apoptosis may play a significant part in the etiology of cancer, this research project will use nuclear magnetic resonance (NMR) and other biophysical and biochemical techniques to determine the contributions of polyamines to the mechanism of apoptosis, and assess any contributions of polyamines to the mechanism of glucocorticoid resistance in human leukemic cells. The hypothesis that polyamines, due to their ability to promote cellular proliferation, may provide a mechanism for therapeutic resistance by inhibiting apoptotic cell death will be tested. The effects of intracellular level of polyamine on the activities of caspases, phospholipid metabolism and DNA fragmentation, which are key factors in apoptosis, will be determined. Using NMR and 15N-labeled polyamines, the metabolism of polyamines will be measured, and the connection between polyamine and the activity of transglutaminase (an enzyme involved in the crosslinking of proteins during apoptosis) will be evaluated as well as the time-scale of the actions of polyamines. Since

34

Vitamin E

intracellular pro-oxidant states are known contributing factors to cell proliferation and carcinogenesis, the assumption that antioxidants may be required during apoptosis to enhance apoptotic efficiency will also be tested by this research. The contributions of common vitamin antioxidants (e.g., vitamin A, vitamin C, and vitamin E) to the mechanism of apoptosis and glucocorticoid resistance, and the extent of the involvement of oxidative stress in the mechanism of apoptosis and glucocorticoid resistance will be evaluated by specifically determining the effects of these antioxidants on phospholipid metabolism, cellular activity of caspases, the level of DNA degradation, the level of intracellular free Ca(II), cell membrane potential, and cellular energy state. The ability of antioxidants to work synergistically with glucocorticoid to induce apoptosis or reduce resistance will also be evaluated. One glucocorticoid-sensitive and three different glucocorticoid-resistant variants will be used. The results obtained for all the four cell lines will be analyzed for the roles of polyamines and antioxidants in apoptosis, and for new insight into the mechanisms of apoptosis and glucocorticoid resistance in leukemic cell lines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS AND PREVENTION OF ETOPOSIDE INDUCED LEUKEMIA Principal Investigator & Institution: Yalowich, Jack C.; Associate Professor of Pharmacology; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: (Applicant's Abstract) Etoposide (VP-16)-related secondary leukemias (tAML) occur in up to 10 percent of drug-treated patients and are most frequently associated with MLL gene translocations at 11q23. Delineating the mechanism(s) of VP16-mediated leukemogenesis is an important goal in oncology and is the major focus of this project. Our central hypothesis is that redox cycling of VP-16 initiated by myeloperoxidase (MPO) amplifies the genotoxicity and carcinogenicity of this agent in myeloid precursors which contain high MPO activity. We propose that MPO converts VP-16 to free radical species and oxidized metabolites that induce oxidative DNA damage and initiate recombinogenic events specifically in myeloid precursor stem cells leading to the chromosomal translocations responsible for t-AML. We further hypothesize that antioxidants such as vitamin C or vitamin E homologues will protect against oxidative DNA damage and may prevent t-AML by reducing levels of VP-16 free radical species produced by MPO. Peroxidative activation of the VP-16 E-ring phenol to form phenoxyl and semiquinone radicals, and orthoquinones results in increased DNA strand breakage. It is not known whether enhanced DNA cleavage occurs by interaction of VP-16 oxidation products directly with DNA, by redox cyclegenerated reactive oxygen species (ROS), and/or by enhanced inhibition/poisoning of DNA topoisomerase II (topo II). We propose to characterize the precise mechanism(s) by which activation of VP-16 to free radical forms enhances its DNA damaging activity specifically in genomic regions of the MLL gene known to contain breakpoints associated with t-AML. Specific aims are to: 1. Determine the role of MPO and the bioreductive enzyme NAD(P)H:quinone oxidoreductase (NQO1) in VP-16 metabolic activation, generation of ROS, and oxidative DNA damage in cultured human leukemia cells (HL60, K562) and in normal human CD34+ progenitor cells. 2. Develop an antioxidant recycling system to decrease MPO-generated phenoxyl radicals of VP-16 and attenuate VP-l6-induced oxidative DNA damage. 3. Characterize chemical

Studies

35

modifications in topo II upon interaction with oxidatively activated VP-16 that may be responsible for increased DNA strand breakage/recombination events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICRONUTRIENT METABOLISM IN HIV+AND HIV-DRUG USERS Principal Investigator & Institution: Forrester, Janet E.; Assistant Professor; Family Medicine & Cmty Health; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Summary: (provided by applicant) The proposed research, to be done in HIV-infected drug abusers, is in response to a research program on the medical and health consequences of drug abuse and a program at NIDA on metabolic and endocrine complications of drug substance abuse and HIV infection. Poor serum/plasma micronutrient status is common in drug abusers with and without HIV. Low micronutrient levels have been associated with adverse outcomes in HIV infection. Previous studies suggest that poor nutritional status among drug abusers cannot be attributed entirely to dietary intake. Little research has been published on non-dietary mechanisms by which drug abusers, with and without HIV, may develop low blood levels of micronutrients. Non-dietary factors affecting micronutrient status may include malabsorption, abnormal metabolism, increased excretion, and increased requirements. Malabsorption, liver, and renal dysfunction are all common among drug abusers. Furthermore, drug abusers often smoke cigarettes and abuse alcohol, which are known to affect the metabolism of some micronutrients. Here, we propose to examine some aspects of micronutrient metabolism to identify mechanisms contributing to low blood levels. We will focus on the antioxidant micronutrients vitamins A and E, the carotenoids, selenium and zinc, which are metabolically related to one another. Specifically we will: 1) Determine the prevalence of low to marginal serum levels of the micronutrients vitamin A, beta-carotene, vitamin E, selenium and zinc among three groups: drug abusers with HIV, drug abusers without HIV and non-drug abusers with HIV. 2) Determine the association between malabsorption and serum icronutrient levels (listed in specific aim 1). 3) Determine the association between levels of transportation factors and serum micronutrient levels. 4) Determine the role of liver or renal dysfunction in the association between micronutrient transport factors and low to marginal serum micronutrient levels. The proposed study will build on the existing BIENESTAR study (NIDA DA11598), and complement the ongoing TANG study (NIDA DA10252). The long term goal of this research is to develop effective interventions to improve the nutritional status and health outcomes of drug abusers with and without infectious diseases, including HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PROGRAM

MINORITY

BASED

COMMUNITY

CLINICAL

ONCOLOGY

Principal Investigator & Institution: Conrad, Marcel E.; Professor of Medicine; Mobile Infirmary Medical Center 3 Mobile Infirmary Circle, Ste 3 Mobile, Al 36607 Timing: Fiscal Year 2001; Project Start 14-SEP-1990; Project End 31-MAY-2003 Summary: The University of South Alabama (USA) has been a designated MBCCOP since the inception of the program. The grant supports the administration and data management of cancer treatment protocols, cancer control programs and cancer prevention trials at USA. In addition, it supports limited travel of faculty to national research base meetings and the cost of transporting specimens to designated

36

Vitamin E

laboratories as required by protocols. USA is currently involved and has membership in the Southwest Oncology Group (SWOG), the National Surgical Adjuvant Breast and Bowel Program (NSABP), the Radiation Therapy Oncology Group (RTOG), the Pediatric Oncology Group (POG), the MD Anderson program (MSKCC) and The University of Rochester. We are participants in the P1-Breast Cancer Prevention Trial (BCPT) and the Study of Tamoxifen and Roloxafine (STAR) program and the Prostate Cancer Prevention Trial (PCPT). We plan to participate in the Prostate Prevention Trial utilizing vitamin E and selenium. Currently, over 450 living cancer patients are in active follow up. USA keeps about 185 active Investigative Review Board (IRB) approved protocols for eligible patients at any given time. Approximately ten percent of newly diagnosed cancer patients become participants of cancer treatment protocols at USA. We do not engage in any studies sponsored by pharmaceutical firms. Approximately one half of patients placed on cancer treatment protocols are minority individuals with the majority being African American. We have no difficulty in recruiting minority patients for cancer treatment protocols. However, it is difficult to recruit minority patients to cancer prevention trials and cancer control programs which involve either a procedure or a medication with potential side effects. Most minority subjects recruited to cancer prevention studies are from upper socioeconomic and educated groups. Recruitment occurs through appropriate radio, newspaper, health fairs, churches and social organizations. Population surveys at USA suggest that 'fatalism' plays an important role in delayed diagnosis and failure to use cancer preventative means. USA is the only University hospital with a 150 mile radius of Mobile Alabama in the Gulf Coast. It serves the urban population of a Gulf Coast Port City and a surrounding rural southern population of patients from South Alabama, Southern Mississippi and the panhandle of Florida. The University hospital has 840 beds with 32 beds in a designated adult oncology unit. Approximately 475 new cancer patients are seen yearly at this facility with half of them from minority populations. With increasing numbers of oncologists in the region and development of radiation treatment facilities in the community hospitals, cancer patient accrual has not increased at USA in recent years. To solve this problem it is planned to construct a USA Cancer Hospital and treatment facility largely using existent buildings, and assume responsibility for oncologic care at a community hospital. Further, we are involving former fellows and associates in Biloxi and Mobile for participation in the STAR trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODIFYING OXIDATIVE DAMAGE IN WAVE Principal Investigator & Institution: Steffes, Michael W.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: Supplemental vitamin E has been associated with a reduced risk of recurrent myocardial infarctions, with efficacy related to dosage and the duration of treatment. Its effects may be enhanced by vitamin C, an antioxidant that can regenerate vitamin E activity. Theoretically vitamin E and C (VitE/C) accumulate in the vascular wall with a concurrent reduction in oxidative damage, a primary feature of atherosclerotic lesions. Estrogen/hormone replacement therapy (HRT) also may reduce oxidative damage, and it may enhance the effect of vitamin E and C. These hypotheses are supported by studies defining oxidation-dependent accumulation of lipids in developing atherosclerosis; the detection of oxidative damage products, such as oxidized-LDL particles, in human atherosclerotic lesions; and clinical studies associating antioxidant or

Studies

37

estrogen supplementation with reductions in oxidative damage cardiovascular disease. Nevertheless, no human studies have evaluated the effect of long-term VitE/C treatment, which has been reported as being the most effective prevention factor by epidemiologic studies, on specific. biochemical markers of oxidative damage and concurrently their association with recurrent cardiovascular disease. In addition, no studies have characterized the effect of long-term HRT on markers of oxidative damage or HRT's potential synergistic effect with VitE/C therapy. We propose assaying specific biochemical measures of oxidative damage (all markers at closeout and nitrotyrosine and chlorotyrosine also at baseline) in the Women's Angiographic Vitamin and Estrogen (WAVE) Trial, which randomized 420 38-86 year old women with a prior cardiovascular disease event to placebo, VitE/C, HRT or the combination of VitE/C and HRT. WAVE will determine the efficacy of these treatments on quantitative angiographic evaluation of minimal coronary artery diameter performed at baseline and at the final visit to be completed during the first 10 months of 2001. We will measure oxidation products from several classes of compounds (lipids by F2-isoprostanes, proteins by nitrotyrosine and chlorotyrosine, and DNA by 8-hydroxy-2'-deoxyguanosine), thereby studying several major pathways that may lead to atherogenesis. In addition, inflammation with Creactive protein, platelet activation with p-selectin, altered lipid metabolism with a lipid profile and other characteristics of the study population will be integrated into the assessment of oxidative damage in WAVE. By measuring these various factors and by assessing oxidative damage in several classes of compounds, we can test the relationships among specific pathways of oxidative damage, supplemental VitE/C and/or HRT and other risk factors upon the progression of established macrovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR EFFECTS OF NUTRITION SUPPLEMENTS IN PROSTATE Principal Investigator & Institution: Haqq, Christopher M.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2003; Project Start 10-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Prostate cancer remains the most common and second most fatal cancer among men in the United States. The long term goal of this study is to identify the mechanism of action for nutritional supplements that protect men from developing prostate cancer. Future prostate cancer prevention trials depend on identification of these pathways to facilitate drug development. Specific Aim 1: Gene expression patterns from prostate biopsies among men on nutritional supplements vs. placebo will be compared. Men will be randomized to take placebo, lycopene or fish oil supplements and prostate biopsies will be taken at initiation of the study and at three months. The primary outcome measure is a two-fold up or two-fold down change in gene expression, pre- and post-intervention; the proportion of men with this outcome will be compared between intervention and placebo groups. Using these criteria, we will identify candidate molecular targets for nutrition response pathways deserving further study. Specific Aim 2: Baseline gene expression patterns from initial prostate biopsies will be correlated with self-reported dietary intake. Based on previous epidemiologic, in vitro, and in vivo studies, we hypothesize that higher intakes of total energy, fat/meat/animal products, dairy/calcium, and lower intakes of fish, vegetables, tomatoes/lycopene, vitamin E, and selenium will be associated with particular gene expression profiles. Specific Aim 3: Nutritional supplementation, self-reported diet and gene expression patterns will be correlated with clinical progression of prostate cancer

38

Vitamin E

among men following a watchful waiting protocol. After the three-month intervention, we will follow each subject for up to an additional nine months (12 months total) for clinical progression of his prostate cancer (i.e. based on PSA kinetics, pathology, etc). Men will have standard clinical exams quarterly, and we will query each patient's physician regarding the status of the patient's prostate tumor at three-month intervals. Our laboratory has developed considerable expertise in genome-wide analysis of clinical needle biopsies from men with prostate cancer using a faithful RNA amplification method. The MENS study will use gene expression profiling in the context of a prospective randomized cohort study. Statistical methods will be used to combine epidemiologic dietary information with gene expression data, and to correlate nutritional interventions with gene expression data. Results will be confirmed with an independent assay of gene expression levels, quantitative polymerase chain reaction using the same clinical samples. Post trial follow-up of patients will determine the outcome of watchful waiting, and the correlation of gene expression in patients who do and do not exhibit clinical progression may lead to development of targeted therapeutics for prostate cancer. The DNA, serum, tissue samples and dietary data collected in this trial will be available for other planned future collaborative studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTICENTER KNEE OSTEOARTHRITIS STUDY Principal Investigator & Institution: Torner, James C.; Professor and Head; Epidemiology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2008 Summary: (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis and disease in the knee is a leading cause of disability. Most epidemiologic studies of knee OA have focused on radiographic disease, but symptomatic OA should be a major focus of studies on preventing OA, because symptomatic disease causes disability and has formidable societal and public health impacts. OA is potentially preventable, but only a limited number of mostly nonmodifiable risk factors has been identified, even though modifiable risk factors such as particular activities, muscle weakness, proprioceptive deficits, micronutrient deficiencies and structural factors have been proposed and may affect substantially the risk of disease. Prevention opportunities are most relevant and are most likely to be used by those who already have disease or who are at highest risk of getting it. This proposal introduces four new approaches into the epidemiologic study of knee osteoarthritis: l.a focus on symptomatic disease, 2. a comprehensive evaluation of risk factors including modifiable ones, 3. a focus on those who would really benefit from prevention opportunities, those who already have disease or those who are at high risk of getting it and 4. the incorporation of more comprehensive and reproducible imaging than has previously been used including, state of the art radiographic techniques and MRI. MRI provides rich information on structural factors in which abnormalities may affect the risk of disease. The overall objective of this study is to evaluate longitudinally the effects of three groups of factors: biomechanical factors (squatting,kneeling, stair climbing, quadriceps weakness and proprioceptive deficits), bone and structural factors (bone density,bone marrow and meniscal lesions on MRI) and micronutrient deficiencies (vitamin C, E and D) on the occurrence and progression of symptomatic and radiographic knee OA in a populationbased sample of men and women aged 50 to 79. We propose to recruit a communitybased sample of 3,000 men and women likely to either have knee OA or be at high risk of OA. High-risk groups will include those who are overweight, those with knee symptoms or those with a history of knee injuries or operations. Subjects will be

Studies

39

evaluated with symptom questionnaires, radiographs and MRI?s and will be followed 36 months for the development or progression of symptomatic or radiographic OA. Analyses will focus on the relation of these important risk factors and OA outcomes. This large, multifaceted and comprehensive study of persons with knee OA, or at high risk of disease, offers to address definitively the relation of potentially important risk factors to the development or progression of a major disabling disease and to provide new insights into disease biology and potential opportunities for prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MULTI-CENTER OSTEOARTHRITIS STUDY Principal Investigator & Institution: Nevitt, Michael C.; Professor; Epidemiology and Biostatistics; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-JUN-2008 Summary: (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis, and disease in the knee or hip are leading causes of disability. Most epidemiologic studies of knee and hip OA have focused on radiographic disease, but symptomatic OA should be a major focus of studies on preventing OA, because symptomatic disease causes disability and has formidable societal and public health impacts. OA is potentially preventable, but only a limited number of mostly nonmodifiable risk factors has been identified, even though modifiable risk factors such as particular activities, muscle weakness, proprioceptive deficits, micronutrient deficiencies and structural factors have been proposed and may affect substantially the risk of disease. Prevention opportunities are most relevant and are most likely to be used by those who already have disease or who are at highest risk of getting it. This proposal introduces four new approaches into the epidemiologic study of knee osteoarthritis: l.a focus on symptomatic disease, 2. a comprehensive evaluation of risk factors including modifiable ones, 3. a focus on those who would really benefit from prevention opportunities, those who already have disease or those who are at high risk of getting it and 4. the incorporation of more comprehensive and reproducible imaging than has previously been used including, state of the art radiographic techniques and MRI. MRI provides rich information on structural factors in which abnormalities may affect the risk of disease. The overall objective of this study is to evaluate longitudinally the effects of three groups of factors: biomechanical factors (squatting, kneeling, stair climbing, wearing high heeled shoes, quadriceps weakness and proprioceptive deficits), bone and structural factors (bone density, bone marrow and meniscal lesions on MRI) and micronutrient deficiencies (vitamin C, E and D) on the occurrence and progression of symptomatic and radiographic knee OA in a population-based sample of men and women aged 50 to 79. Although the focus of this project is knee OA, we also incorporate a study of hip OA. We propose to recruit a community-based sample of 3,000 men and women likely to either have knee OA or be at high risk of OA. High risk groups will include those who are overweight, those with knee symptoms and those with a history of knee injuries or operations. Subjects will be evaluated with symptom questionnaires, radiographs and MRI?s and will be followed 36 months for the development or progression of symptomatic or radiographic OA. Analyses will focus on the relation of these important risk factors and OA outcomes. This large, multifaceted study offers to address definitively the relation of potentially important risk factors to the development or progression of a major disabling disease and to provide new insights into disease biology and potential opportunities for disease prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

40

•

Vitamin E

Project Title: MULTICENTER OSTEOARTHRITIS STUDY (MOST) Principal Investigator & Institution: Lewis, Cora Elizabeth.; Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2008 Summary: (provided by applicant): Osteoarthritis (OA) is the most common form of arthritis and disease in the knee is a leading cause of disability. Most epidemiologic studies of knee OA have focused on radiographic disease, but symptomatic OA should be a major focus of studies on preventing OA, because symptomatic disease causes disability and has formidable societal and public health impacts. OA is potentially preventable, but only a limited number of mostly nonmodifiable risk factors has been identified, even though modifiable risk factors such as particular activities, muscle weakness, proprioceptive deficits, micronutrient deficiencies and structural factors have been proposed and may affect substantially the risk of disease. Prevention opportunities are most relevant and are most likely to be used by those who already have disease or who are at highest risk of getting it. This proposal introduces four new approaches into the epidemiologic study of knee osteoarthritis: l.a focus on symptomatic disease, 2. a comprehensive evaluation of risk factors including modifiable ones, 3. a focus on those who would really benefit from prevention opportunities, those who already have disease or those who are at high risk of getting it and 4. the incorporation of more comprehensive and reproducible imaging than has previously been used including, state of the art radiographic techniques and MRI. MRI provides rich information on structural factors in which abnormalities may affect the risk of disease. The overall objective of this study is to evaluate longitudinally the effects of three groups of factors: biomechanical factors (squatting,kneeling, stair climbing, quadriceps weakness and proprioceptive deficits), boneand structural factors (bone density,bone marrow and meniscal lesions on MRI) and micronutrient deficiencies (vitamin C, E and D) on the occurrence and progression of symptomatic and radiographic knee OA in a populationbased sample of men and women aged 50 to 79. We propose to recruit a communitybased sample of 3,000 men and women likely to either have knee OA or be at high risk of OA. High risk groups will include those who are overweight, those with knee symptoms or those with a history of knee injuries or operations. Subjects will be evaluated with symptom questionnaires, radiographs and MRI?s and will be followed 36 months for the development or progression of symptomatic or radiographic OA. Analyses will focus on the relation of these important risk factors and OA outcomes. This large, multifaceted and comprehensive study of persons with knee OA, or at high risk of disease, offers to address definitively the relation of potentially important risk factors to the development or progression of a major disabling disease and to provide new insights into disease biology and potential opportunities for prevention Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MULTICENTER VITAMIN E TRIAL-PERSONS WITH DOWN SYNDROME Principal Investigator & Institution: Dalton, Arthur J.; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, Ny 10314 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the application) There is evidence from a multicenter clinical trial that vitamin E slows the rate of clinical deterioration in individuals with moderately severe Alzheimer s disease (AD). The AD Cooperative Study (ADCS) is now mounting a large study to test the effects of vitamin E in persons at the earliest stage of

Studies

41

cognitive deterioration. Older individuals with Down syndrome (DS) are at very high risk for AD. Most individuals with DS develop functional decline and show neuropathological evidence of AD by the sixth decade. The applicants propose an international multicenter randomized double-blind study to determine whether vitamin E supplementation will slow the rate of cognitive/functional decline in individuals with DS. Subjects with DS who are at least 50 years of age will be randomized into two treatment groups: vitamin E 2000 IU plus a multivitamin per day or placebo plus multivitamin. The multivitamin contains vitamin E 15 IU. The treatment period will be three years with evaluation visits every six months. The primary outcome measure will be a three year change score on a cognitive/functional measure that was derived for this purpose from the DYSPRAXIA Scale for Adults with Down Syndrome. Secondary outcome measures will include additional cognitive tests as well as informant-based measures of function and behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NATURAL VITAMIN E FORMS AS ANTI-INFLAMMATORY DRUGS Principal Investigator & Institution: Ames, Bruce N.; Professor; Children's Hospital & Res Ctr at Oakland Research Center at Oakland Oakland, Ca 94609 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Chronic inflammation constitutes one of the major etiologies of degenerative diseases including cancer, and cardiovascular and neurodegenerative diseases; chronic inflammation also contributes to rheumatoid arthritis, asthma and hepatitis. These diseases are among the leading causes of death and disability in the world. During inflammation, several pro-inflammatory mediators including prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), as well as cytokines, such as TNF-alpha, play central roles in regulating inflammatory response and inflammationmediated damage. Vitamin E comprises eight structurally related molecules, alpha,beta-, gamma-, delta-tocopherol, and alpha-,beta-, gamma-, delta -tocotrienol. Among them, only alpha -tocopherol (alphaT) has been extensively studied. Recent studies indicate that other forms of vitamin E have unique properties, which are not shared by alphaT, but are important to human disease prevention and therapy. GammaTocopherol (gammaT) and its metabolite, but not aT, exhibit anti-inflammatory effects by inhibiting cyclooxygenase (COX)- catalyzed formation of PGE2. In a rat inflammation model, gammaT inhibits not only PGE2, but also LTB4, and TNF-alpha. These results suggest that gammaT may be superior to some commonly used non-steroid antiinflammatory drugs (NSAIDs), such as COX inhibitors, most of which only inhibit the COX-mediated pathway. Preliminary studies also indicate that delta- tocopherol and gamma-tocotrienol, compared with gammaT, are even stronger inhibitors of the COXcatalyzed formation of PGE2. These observations led to the current hypothesis that certain forms of vitamin E and their combinations have unique pharmaceutical utility as anti-inflammatory drugs, or as supplements that complement and improve current treatments for inflammatory diseases. This hypothesis will be tested by pursuit of the following Specific Aims in cell culture and animal experiments: 1. Investigate in vitro anti-inflammatory properties of individual vitamin E forms and their combinations; 2. Investigate and compare in vivo anti-inflammatory activities of individual vitamin E forms and their combinations; and 3. Investigate the potentially improved effects of combining certain forms of vitamin E and NSAIDs, such as aspirin, in a rat inflammation model. Our studies may lead to the discovery of novel and better therapy for treating and preventing inflammatory diseases, and provide the scientific rationale, the experimental evidence and the biochemical basis for future human studies.

42

Vitamin E

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL CEHC DERIVATIVES FOR NEUROINFLAMATION Principal Investigator & Institution: Wechter, William J.; Encore Pharmaceuticals, Inc. 1401 Research Park Dr, Ste 400 Riverside, Ca 925072145 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Vitamin E (alpha-tocopherol) formulations constitute a multi-million dollar US market. Tocopherol supplements are widely used for presumptive health benefits and antioxidant properties; but these supplements are almost exclusively restricted to a-tocopherol. Tocopherol biology is complicated by the fact that other tocopherol forms (beta-, gamma-, and delta-tocopherol), structurally distinct from a-tocopherol, exist as part of the natural human diet. Moreover tocopherols are metabolized in vivo to yield carboxyethyl-hydroxyl chromane (CEHC) products that have been insufficiently studied. Recent studies suggest that gamma-tocopherol and its analogs possess anti-inflammatory and other activities that could be harnessed therapeutically. Scientists at the Oklahoma Medical Research Foundation (OMRF) have established a partnership with Encore Pharmecuticals, Inc. for the purpose of developing novel tocopherol-based structures with superior anti-inflammatory and other activities. We have begun to systematically evaluate structure-activity relationships among natural tocopherol analogs, their CEHC metabolites, and synthetic derivatives, with the goal of determining features that impart biological potency. The ultimate purpose of this endeavor is to develop novel, patentable compounds that inhibit neuroinflammatory reactions within the centralnervous system. Toward this end we propose the following SPECIFIC AIMS. SPECIFIC AIM 1: An initial series ofeleven new CEHC derivatives will be synthesized in order to determine whether rational derivatization of the 3, 4 and 5 positions of the chromane head group will improve bioactivity. Derivatives will be designed to combine beneficial features of the best firstgeneration molecules; and to systematically test the significance of substituent electronics, sterics and polarity on compound bioactivity. SPECIFIC AIM 2: The compounds synthesized under SPECIFIC AIM I will be evaluated for antagonism of TNFa-stimulated microglial activation using an established EOC-20 microglial cell culture assay. Nitrite output and prostaglandin E2 (PGE2) production will be used as indicators of anti-neuroinflammatory activity. Efficacy of CEHC derivatives will be compared with that of benchmark nonsteroidal anti-inflammatory drugs. The goal of this Phase I application is to identify two lead CEHCs for treating neuroinflammatory disease. During Phase II these lead agents will be further evaluated in a murine model for amyotrophic lateral sclerosis (ALS), the G93A-SOD1 transgenic mouse, which demonstrates a robust neuroinflammatory disease profile. Success in the G93A-SOD1 mouse model and confirmatory testing in a relevant mouse model of Alzheimer's disease (AD) will justify pursuit of investigational new drug (IND) status. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: NUTRITION, VIRAL MUTATION AND HOST DEFENSE Principal Investigator & Institution: Beck, Melinda A.; Associate Professor; Pediatrics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Emerging viruses is a term used to describe viruses that have newly appeared in the population or that are rapidly expanding their range. It

Studies

43

is important to understand the underlying mechanisms involved in the emergence of new viral pathogens or old viral pathogens with altered pathogenic potential. We have demonstrated that the nutritional status of the host is a driving force for the emergence of new viral variants. Influenza viral infection of a host deficient in selenium (Se), an essential component of the antioxidant enzymes glutathione peroxidases and thioredoxin reductse, leads to increased lung pathology compared to infected Seadequate hosts. Influenza viruses isolated from Se-deficient hosts developed specific mutations in the viral genome, resulting in a more pathogenic strain of virus. This mutated influenza virus strain was more virulent than the original virus; infection of hosts with normal Se status resulted in enhanced pathology and severe morbidity. The goal of this proposal is to understand the mechanism(s) involved in the role of host nutritional status in promoting viral mutation. Because the mechanism(s) involved are likely to be multi-factorial, we have designed our project to examine 3 different viewpoints: host cellular responses, viral responses, and host inflammatory/innate immune responses. This approach recognizes that the virus itself may be affected by the nutritional status of the host, that the cellular machinery required for viral replication may be affected by the host nutritional status, and finally that the immune response against the virus may also be influenced by host nutritional status. Using murine models as well as a unique in vitro system of differentiated primary human airway epithelial cells, we can address the following questions: 1) How is the natural course of influenza virus evolution altered in the Se-deficient host? 2) How does the host respond to the mutated virus in comparison with the wild type virus? 3) What is the minimum level of host Se required to prevent the mutations from occurring? 4) Does excess vitamin E compensate for a lack of Se in preventing the viral mutations? 5) Does a host deficiency in other antioxidant nutrients (e.g. vitamin C) lead to viral mutations9 6) Can the innate immune response and/or host cellular redox status be correlated with the induction of viral mutations in the Se-deficient host? Taken together, this interdisciplinary project will provide new information on the role of nutrition in driving viral mutations that may ultimately be used in predicting and/or preventing new viral outbreaks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ORAL ANTIOXIDANT/ANTICYTOKINE THERAPY FOR ALD Principal Investigator & Institution: Hill, Daniell B.; Associate Professor of Medicine; Medicine; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Alcoholic liver disease (ALD) remains the leading major cause of liver disease and liver related mortality in the United States. Alcohol metabolism and ALD are associated with lipid peroxidation and oxidative stress with decreased levels of nutritional antioxidants such as reduced glutathione (GSH) and vitamin E. Animal studies have clearly shown that treatment with GSH precursors, such as N-.acetylcysteine (NAC) and S-adenosyl- L-methionine (Adomet or SAMe), ameliorates alcohol/endotoxin liver injury. We postulate that chronic alcohol abuse causes increased gut permeability and endotoxemia, depletion of nutritional antioxidants (e.g., GSH, Vit E), generation of reactive oxygen intermediates, activation of NFKB, increased TNF production, increased IL-8 production with neutrophil infiltration, Adomet deficiency, mitochondrial GSH depletion, increased susceptibility to hepatic TNF cytotoxicity, and liver injury. We have chosen a combination of two nutritional supplements which inhibit cytokine production in effector cells (e.g. Kupffer cells) and which attenuate liver metabolic abnormalities and enhance cytoprotection in target cells (e.g. hepatocytes). Because there is no ideal model system and animal studies

44

Vitamin E

to date all support beneficial effects of Adomet/NAC therapy, we are proposing human studies. The two agents to be used, NAC and SAMe, are already commercially available as over-the-counter nutritional supplements. The specific objectives of this proposal are to: I) Determine an oral dose of Adomet in stable alcoholic cirrhotics that when given for 21 days significantly improves methionine clearance, increases Adomet levels, and attenuates cytokine production; 2) Determine in stable alcoholic cirrhotics an oral dose of NAC that when given for 21 days significantly increases whole blood GSH levels and decreases cytokine production; and 3) Determine in stable alcoholic cirrhotics whether giving Adomet and NAC together for a 21 day period provides a degree of improvement in methionine clearance, whole blood GSH values and cytokine levels at least as significant as with either drug alone, and determine that this combination is well tolerated. The data from these studies will be useful in designing clinical trials using these agents in the treatment of acute alcoholic hepatitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FIBROSIS

OVERCOMING

NUTRIENT

MALABSORPTION

IN

CYSTIC

Principal Investigator & Institution: Clark, William A.; Yasoo Health, Inc. 2109 W Market St, Ste 122 Johnson City, Tn 37602 Timing: Fiscal Year 2001; Project Start 25-SEP-2001; Project End 31-DEC-2002 Summary: In cystic fibrosis (CF), pancreatic insufficiency and a diminished bile acid pool cause malabsorption of vitamin E, carotenoids and other fat-soluble antioxidants, which contributes to resulting oxidative stress and poor nutritional status, both of which are associated with increased risk of disease, neurological dysfunction and reduced quality of life. The object of this study is to determine the feasibility of using an oral liquid formulation of micellar-like vehicles to overcome malabsorption of important nutrients and antioxidants and therefore improve oxidation and nutrition status. The researchers intend to study a unique generally regarded as safe (GRAS) molecule as the delivery vehicle for fat-soluble nutrients and antioxidants. The formulation will be optimized for physical and chemical stability, and for taste acceptable to children and young adults. Although tested first in cystic fibrosis patients, this technology could be useful to other fat malabsorbers. The technology is based on d-alpha-tocopheryl polyethylene glycol 1000 succinate or TPGS. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATION RISK FACTORS AND IMT PROGESSION IN FH Principal Investigator & Institution: Hopkins, Paul N.; Research Associate Professor; Internal Medicine; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Verbatim from the application): In 346 patients with heterozygous FH we found 20-fold higher incidence rates of early coronary artery disease (CAD) compared to a general population. Yet, clinical disease onset varied greatly in these FH patients. We examined a comprehensive battery of suggested risk factors in these FH patients, and found only factors implicated in the LDL oxidation hypothesis appeared to be associated with CAD risk. We therefore hypothesize that factors related to LDL oxidation (rather that factors unrelated to the inherently high LDL in FH) are the major determinants of CAD risk among FH patients. Our experience from this study and from others suggests that change in repeated carotid intima-medial thickness (IMT)

Studies

45

measurements, as opposed to a single measurement, will provide a good index of ongoing atherosclerosis progression and risk related to oxidant stress. Though evidence supports a major role for oxidized lipids in atherogenesis, this has not been critically examined in patients with FH. We propose a 5-year study, now including a vitamin intervention component, to determine IMT progression rate among 200 patients with familial hypercholesterolemia. In addition to state-of-the-art IMT determination we will measure coronary calcification by spiral CT, brachial artery flow-mediated dilation, and perform high resolution MR angiography of the carotid tree. Using a random effects model, rate of change of these non-invasive measures of disease burden will be related to previously identified risk factors (including ultracentrifuged lipids and LDL apoB, plasma Lp(a), and total homocysteine) and oxidation-related risk factors (plasma concentration of F2-isoprostanes; susceptibility of LDL to copper-induced oxidation; dietary intake and plasma levels of vitamin E, vitamin C, and carotenoids; as well as plasma platelet-activating factor acetylhydrolase and paraoxonase). Our major hypothesis is that IMT progression will be strongly related to the balance of pro-oxidant and antioxidant factors. The newly added imaging techniques will allow us to compare and contrast results using these endpoints as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND HEMODIALYSIS ACCESS FAILURE Principal Investigator & Institution: Weiss, Miriam F.; Professor; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) Antioxidant treatment of human disease has met with mixed success. Factors that lead to oxidative stress in living systems are complicated, and as a result, the actions of antioxidants may seem paradoxical. There is a great deal of evidence for increased oxidative stress in uremia. The rationale for this proposal stems from emerging evidence for efficacy of vitamin E in uremia. The investigators believe that intimal hyperplasia in hemodialysis vascular access represents a unique model of oxidative damage to vascular tissue. Complications of hemodialysis access are a major cause of morbidity and the most frequent single reason for hospitalization among patients with end stage renal disease (ESRD). In vivo and in vitro, oxidative stress stimulates cell growth factors and regulatory mechanisms that lead to the characteristic lesion of access failure, intimal hyperplasia. The central hypothesis to be tested by this project is that oxidative stress is a major (and modifiable) pathogenetic trigger for vascular access complications in patients with ESRD. In elucidating the roles of oxidative stress in the pathophysiology of access failure, the goal is to discover diagnostic factors that can lead to accurate indications for antioxidant therapy. In testing antioxidant medication, the investigators hope to slow progression of intimal hyperplasia in hemodialysis access. Because antioxidant therapy is not currently routine in patients with uremia, the proposal is a pilot study. Data obtained in these specific aims will be used to design large-scale testing of the efficacy of vitamin E (alpha-tocopherol). Specific Aim A: To identify predictors of vascular access venous outflow stenosis or thrombosis, focusing on circulating and histologic markers indicative of the effects of oxidative stress. Specific Aim B: To determine the efficacy of chronic administration of an antioxidant (alpha-tocopherol) in the prevention of intimal hyperplasia and thrombosis of the hemodialysis access. Specific Aim C: To compare the success rates of prophylactic angioplasty when non-invasive techniques demonstrate decreased flow in the hemodialysis access in alpha-tocopherol-treated versus placebotreated patients.

46

Vitamin E

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND VASCULAR SMOOTH MUSCLE CELL GROWTH Principal Investigator & Institution: Berk, Bradford C.; Professor & Chairman; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-APR-1995; Project End 30-NOV-2002 Summary: (Adapted from Investigator's Abstract): The major goal of this renewal proposal is to define the mechanisms by which oxidative stress regulates vascular remodeling. Oxidative stress may cause cardiovascular disease by oxidation of LDL and the vessel itself. Studies with vitamin E suggest that harmful effects of oxidative stress may be reversed as shown by the reduction in myocardial infarction in the CHAOS study. They propose that the effects of oxidative stress on vascular remodeling are mediated by redox sensitive protein kinases in endothelial cells (EC) and vascular smooth muscle cells (VSMC). Specifically, they believe that the beneficial effect of "outward" remodeling (increase in vessel and lumen size) are inhibited by increased production of reactive oxygen species (ROS). This hypothesis is based on three findings obtained during the previous two years of grant support. 1) They found a 3-fold increase in ROS production 2 weeks after coronary balloon injury. 2) They showed that vitamins C and E caused outward vessel remodeling which correlated with decreased ROS production by the injured vessel. 3) They defined several signal events stimulated by ROS and identified two members of Mitogen Activated Protein(MAP) kinase family ERK1/2 and the Big MAP Kinase (BMK-1)-as redox sensitive kinases. They now propose to investigate the role of BMK1 as an important redox-sensitive kinase involved in vascular remodeling. They have focused on BMK1 because it is the only redox sensitive kinase that is specifically activated by ROS and not by growth factor and cytokines; our data suggest that BMK1 is regulated by c-Src which may be a key mediator of redox-sensitive signal transduction; their data suggest that BMK1 to be highly regulated in both EC and VSMC; and it is likely that BMK1 plays an essential role in the changes in gene expression that accompany oxidative stress. The following Aims are proposed. Aim 1: Characterize the effect of vessel redox state on vascular remodeling in the rat carotid artery by using vitamin E deficient rats to increase ROS production. Aim 2: Determine the signal transduction events activated by steady and oscillatory flow in EC that stimulate BMK1 focusing on the role of c-Src and Rho. Aim 3: Determine the signal transduction events activated by ROS which stimulates BMK1 in VSMC focusing on the role of c-Src. Aim 4: Evaluate the role of BMK1 in vascular remodeling in the rat carotid by dominant inhibition using adenoviral gene transfected antisense oligonucleotide techniques. these studies should provide insight into the mechanisms by which ROS regulate remodeling and aid development of new therapeutic approaches to limit restenosis and atherogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: OXIDATIVE STRESS AND VITAMIN E REQUIREMENTS Principal Investigator & Institution: Traber, Maret G.; Professor of Nutrition; None; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (Scanned from the applicant's description): Cigarette smoking is associated with a higher risk for chronic diseases, such as heart disease and cancer; oxidative damage is one of the contributing causes of these increased risks. Free radical products

Studies

47

from cigarette smoking and from activated neutrophils contribute to the observed oxidative damage. Vitamin E is the most potent, lipid soluble antioxidant in plasma, and exposure of human plasma to smoke in vitro results in depletion of vitamin E. Smokers' plasma contains low ascorbic acid levels, low to normal vitamin B levels and increased lipid peroxidation products. However, to date, there is no direct evidence in humans that vitamin E prevents oxidative damage. Our specific goal is to evaluate whether antioxidant supplementation might ameliorate some of the oxidative damage that results from cigarette smoking. We propose the following: 1) Cigarette smoking increases oxidative damage and thus, increases vitamin B turnover. 2) In subjects taking vitamin C supplements, increased vitamin C levels decrease oxidative damage and reduce vitamin E radicals, thus protecting vitamin E and decreasing vitamin B turnover. 3) Oxidation products resulting from cigarette smoking induce a protective mechanism that causes more vitamin E to be secreted from the liver into the plasma. These hypotheses will be addressed in three trials. In Trial 1, vitamin B kinetics will be measured in smokers and non-smokers using vitamin B labeled with stable isotopes to determine whether smokers have increased vitamin B fractional catabolic rates (FCRs). In Trial 2, the same group of subjects (after a washout period) will be given vitamin C supplements, 500 mg twice a day for 1 month prior to and then during the vitamin B kinetics study. We will assess whether vitamin C supplements decrease vitamin E FCRs. In Trial 3, three different forms of vitamin E, labeled with differing amounts of deuterium, will be administered to assess whether hepatic secretion of the only regulated form of vitamin B (RRR-a-tocopherol) is increased in response to the oxidative stress of smoking. Markers of lipid peroxidation (plasma lipid hydroperoxides and F2isoprostanes) and plasma ascorbic acid will be measured throughout all three trials to document levels of oxidative damage. These proposed studies will further our goal of understanding the role of vitamin E in the amelioration of oxidative damage in aging and in chronic diseases, such as heart disease, diabetes and cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS IN ALCOHOLIC CARDIOMYOPATHY Principal Investigator & Institution: Lui, Charles Y.; Associate Professor of Medicine; To Be Determined; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Alcoholism is one of the top public health problems in the U S Although alcohol abuse can cause cardiac muscle dysfunction with a relatively high prevalence, the early disease states usually go unrecognized clinically, since patients seldom experience any symptom of congestive heart failure When the extent of cardiac dysfunction becomes clinically evident, the disease has invariably resulted in a severely enlarged heart (dilated cardiomyopathy) commonly described as alcohol-induced heart muscle disease or alcoholic cardiomyopathy Experimental data generally supports the notion that alcohol is the sole causative agent in the development of this disease. However, there is a growing body of evidence to suggest that cardiomyopathy, regardless of etiology, is directly or indirectly related to an increased oxidative stress to the heart as a common final pathway. Since selenium and vitamin deficiencies are common among alcoholics, possibly as a result of malnutrition and/or malabsorption, it is hypothesized that alcoholic cardiomyopathy is caused by long-term alcohol abuse in the setting of nutritional deficiency involving both selenium and vitamin E. Since selenium and vitamin E are important anti-oxidants, a deficiency state involving these two anti-oxidants will result in a decrease in anti-oxidant defense. Alcohol consumption is well recognized to be associated with an increase in free radical

48

Vitamin E

production. Under these two specific nutritional deficiency states, the resultant decrease in anti-oxidant defense may not be adequate in quenching/removing the free radicals generated from high alcohol intake. This resultant increase in oxidative stress may damage various organs such as the heart leading to cardiac contractile dysfunction manifested clinically as congestive heart failure. Therefore, the present study is designed to confirm such hypothesis by feeding rats long-term high-dose alcohol and diets deficient in selenium and/or vitamin E. Pressure-volume conductance and histological studies will be performed when echocardiographic study indicates a decrease. Biochemical and molecular studies of the cardiomyopathic heart will then be performed in cardiac function and ventricular enlargement after 40 weeks of feeding. They include measuring 4-hydroxy-2-nonenal, a major product and biomarker of lipid peroxidation. To investigate if increased apoptosis occurs as a result of increased oxidative stress, two consecutive measurements of apoptotic index and caspase 3 release will be conducted first when hypertrophy is detected from serial echocardiography and again with the development of alcoholic cardiomyopathy. The results obtained from this study will not only provide unique information regarding the pathogenetic mechanism involved in the development of alcoholic cardiomyopathy, but may also yield a new model of alcoholic cardiomyopathy suitable for future studies to evaluate therapeutic options such as selenium-, vitamin E supplementation, specific anti-metabolites of alcohol, specific antilipid peroxidation inhibitor or specific anti-apoptosis agent for preventing the development of alcoholic cardiomyopathy as well as reversing the far more prevalent yet frequently undiagnosed stage of alcoholic cardiomyopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHWAYS BIOMOLECULES

FOR

THE

INFLAMMATORY

DAMAGE

OF

Principal Investigator & Institution: Heinecke, Jay W.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-AUG-2002 Summary: (provided by applicant): Oxidants generated by activated white blood cells are critical to host defenses against microorganisms. However, overproduction of reactive species can damage host tissue. Indeed, white blood cells represent the cellular hallmark of inflammation, and oxidants have been implicated in tissue injury in inflammatory diseases ranging from atherosclerosis to neurodegenerative disorders to cancer.We have investigated four phagocyte-dependent pathways that oxidatively damage proteins in vitro. The pathways and their characteristic products are: myeloperoxidase and 3-chlorotyrosine; tyrosyl radical and o,o-dityrosine; hydroxyl radical and ortho-tyrosine; and reactive nitrogen species and 3-nitrotyrosine.Using two clinically relevant models of inflammation, we will study genetically engineered mice whose phagocytes are unable to produce specific oxidants. In the proposed research, we will ask three related questions. First, we will identify the pathways that generate chlorotyrosine, dityrosine, ortho-tyrosine, and nitrotyrosine in viva. The experiments will reveal whether a genetic deficiency of any of these oxidant-generating systems inhibits production of any of the chemical markers, thereby determining which pathway generates a particular marker in viva.Second, we will determine whether tissue, plasma, and urinary levels of the oxidized amino acids change in parallel. We will also investigate the absorption, metabolism, and urinary excretion of the oxidized amino acids. These experiments will determine whether plasma and urinary levels of these well-characterized products can be used as noninvasive markers of oxidative stress.Third, we plan to determine whether two proposed antioxidants-vitamin C or

Studies

49

vitamin E- inhibit oxidative stress in our models of inflammation. Collectively, the proposed experiments will identify the oxidative pathways that cause phagocytes to damage tissues and will test the hypothesis that levels of oxidized amino acids in urine and plasma indicate levels of oxidative stress in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDIATRIC TRIALS IN NON-ALCOHOLIC STEATOHEPATITIS (NASH) Principal Investigator & Institution: Lavine, Joel E.; Professor and Vice Chair; Pediatrics; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 30-APR-2007 Summary: (provided by the applicant) Pediatric hepatologists in the Joint Program in Pediatric Gastroenterology, Hepatology and Nutrition at the University of California, San Diego propose their inclusion as a Clinical Center in the "Clinical Research Network in Non-Alcoholic Steatohepatitis". Although NASH generally is regarded as a common condition in adults, recent research reveals that NASH is one of the most common causes of liver disease in 10-18 year olds. This application proposes UCSD participation as a center on the basis of past experience of the Principal Investigator with pediatric NASH, the number of children available to our center for studies, and the ethnic diversity of our population based on our unique geographic location. Cooperation of UCSD adult hepatologists and Scripps Clinic hepatologists for referral of adult patients with NASH will allow participation in proposals initiated by other centers in the clinical research network which focus on adults. Our NIH-funded General Clinical Research Center will facilitate all facets of proposed studies. Our application provides a template for preparation of a multicenter database and tissue/serum bank to study pediatric NASH, based on knowledge and experience of the presentation and proposed pathophysiology of the condition. Two proposals are detailed in this application. The first is a prospective, multi-center, epidemiologic analysis of factors associated with the development of NASH in obese children, evaluating the role of age, race and gender. Potential factors involved in pathogenesis will be assessed with respect to pubertal development, insulin resistance, increased exposure to mediators of inflammation, and increased indicators of oxidative stress. The second study is a prospective, multi-center, randomized, double-blind trial evaluating treatment of childhood NASH with Vitamin E versus placebo. Children randomized to placebo will serve as a long-term cohort to understand the natural history of this untreated condition with early onset. The treated children, who in previous open-label pilot studies have been shown to normalize serum markers of liver damage, will be rigorously studied to determine if antioxidant therapy improves outcome as assessed by changes in liver histology and markers found associated with NASH pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PHOSPHOLIPID METABOLISM IN DIABETIC NEUROPATHY Principal Investigator & Institution: Eichberg, Joseph; Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2001; Project Start 01-JUL-1982; Project End 31-MAR-2004 Summary: (Taken from application) The goal of this project is to carry out studies that will evaluate the hypothesis that abnormalities in signal transduction mechanisms, especially those involving metabolism of phospholipids and their component fatty acids are critically involved in the complex events comprising the pathogenesis of

50

Vitamin E

experimental diabetic neuropathy. The mechanism by which aldose reductase inhibitors and antioxidants, especially RRR -alpha-tocopherol (Vitamin E), exert their beneficial effects on diabetic nerve will also be studied. The specific aims of this project are as follows: 1.Investigation of the possible relationship between arachidonic acid (AA) metabolism, the polyol pathway and antioxidant treatment in human primary and tumor-derived (NF1T) Schwann cell lines, as well as in primary neonatal rat and human fetal Schwann cells by examining the effects of aldose reductase and sorbitol dehydrogenase inhibitors as well as Vit E and N-acetylcysteine, on arachidonyl containing molecular species (ACMS) levels and arachidonate turnover. 2. Exploration of the mechanism underlying reduced ACMS levels and altered AA turnover in NF1T cells grown in elevated glucose by : a) measurement of free fatty acid and acyl CoA levels; b) assay of delta-6 desaturase activity; c) assay of PLA2 activity; d) determination of NADP+/NADPH ratio e) identification of AA metabolites i.e. prostaglandins and HETEs, released from the cells and the ability of the cells to synthesize these compounds. 3. Complementary experiments will be performed by feeding normal and streptozotocin -induced diabetic rats diets supplemented with : a) an aldose reductase inhibitor; b) Vit E; c) both agents together; d) a Vit E deficient diet. The effects of these dietary regimens on nerve ACMS, DAG levels and PKC activity will be assessed. These analyses will be correlated with morphological examination and nerve conduction velocity measurements. In addition it will determine whether ACMS levels are reduced in normal and transgenic mice that express human aldose reductase. 4. Investigations on the expression of several antioxidant enzymes in nerve and dorsal root ganglia from normal and STZ-induced diabetic rats with respect to their mRNA levels and protein, as well as enzyme activities. The enzymes will include Mn superoxide dismutase, glutathione peroxidase and catalase. The impact of Vit E supplementation and imposition of a Vit E deficiency on expression and activity of the enzymes will also be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHYSICIANS HEALTH STUDY II: PREVENTION TRIAL OF VITAMINS Principal Investigator & Institution: Gaziano, J Michael.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This proposal seeks 5 years of funding to continue the vitamin E (400 IU on alternate days), vitamin C (500 mg daily), and multivitamin (Centrum Silver daily) components of the Physicians' Health Study (PHS) II, extending average treatment and follow-up from 3.7 to 8.2 years. The PHS Ills an ongoing randomized, double-blind, placebo-controlled trial using a factorial design to evaluate the roles of Vitamin E, vitamin C, a multivitamin, and p-carotene in chronic disease prevention among 14,642 U.S. male physicians aged 50 years and older who have demonstrated excellent morbidity and mortality follow-up and high compliance. The PHS Ills uniquely positioned to clarify ambiguities regarding the roles of vitamin E in the primary prevention of prostate cancer and cardiovascular disease (CVD) among those at usual risk; the role of a multivitamin and vitamin C in the prevention of cancer and CVD; and all three agents in the prevention of eye disease and declines in cognitive function. After reviewing the progress of the trial and the unblinded data, the Data and Safety Monitoring Board unanimously recommended an extension beyond the trial's scheduled termination of funding in December 2002. The primary rationale for the Board's recommendation was the likelihood, at the end of current funding, of

Studies

51

ambiguous results due to insufficient numbers of endpoints and an inadequate latent period, which they feared could result in considerable clinical confusion. Because recruitment and 3.7 years of treatment and follow-up have been supported by nearly $20,000,000 of industry funds, the proposal to extend PHS II represents an extremely cost-efficient way to provide either clear positive or definitive null results on which sound clinical and public health recommendations can be Dased for the use of these commonly consumed vitamin supplements. Given the gaps in knowledge this study is intended to address, we believe the proposed extension of this primary prevention trial in men at usual risk is timely, important, and will complement other ongoing clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PIOGLITAZONE IN ALZHEIMER'S DISEASE PROGRESSION Principal Investigator & Institution: Geldmacher, David S.; Neurology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 30-JUN-2002 Summary: Alzheimer's disease (AD) is a major public health problem and there is an urgent need for more effective therapies. Activation of the brain's microglial immune cells and subsequent inflammatory processes are now recognized as playing an important role in the progression of AD. Laboratory evidence strongly suggests that agonists of Peroxisome Proliferator Activated Receptor-gamma (PPARgamma) act to downregulate the transduction of inflammatory signals in microglia exposed to ADrelated amyloid peptide. Therefore, agents that activate PPARgamma have great potential for reducing the progressive neuronal loss in AD. Drugs of the thiazolidinedione class, developed to reduce insulin resistance in type II diabetes mellitus have significant PPARgamma activation, suggesting that they may be useful for treating AD progression. Of this class, the most favorable clinical experience and safety profile exists for pioglitazone (PGZ). This application proposes a double-blind, placebo controlled, parallel group, pilot study to determine the safety and tolerability of PGZ in patients with AD. Another goal of the study is assess how clinical measures might demonstrate sensitivity to the potential effect of PGZ in slowing AD progression. Since there are no prior data for PGZ effects in AD, efficacy measures from this pilot will be used primarily to inform effect-size determinations for future studies. Thirty patients diagnosed with probable AD by NINCDS-ADRDA criteria, at a mild or moderate level of severity (CDR = 1-2) will be enrolled. One-half of the subjects will be randomized to receive PGZ at the best tolerated dose of 15, 30, or 45mg daily; the others will receive placebo. All subjects will take Vitamin E 200mg daily. Subjects will be followed for safety and tolerability at monthly intervals for 1 year, then again at 15 and 18 months. All adverse events will be recorded and compared between treatment groups. Human subjects' safety will monitored by an independent and unblinded safety committee. Efficacy measures will be the Alzheimer's Disease Assessment Scale- cognitive score (ADAS-cog), the Clinical Dementia Rating-Sum of Boxes score (CDR-SB), and the Clinician's Interview-based Impression of Change (CIBIC-Plus). Secondary measures will include the Neuropsychiatric Inventory, Nurse's Observation Scale for Geriatrics (NOSGER) and the ADFACS scale for activities of daily living. Comparison of mean differences (using last observation carried forward imputation techniques) and survival analyses will be employed to assess for group differences in clinical measures AD of progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

52

•

Vitamin E

Project Title: PREVENTION OF ALZHEIMER'S BY VITAMIN E AND SELENIUM Principal Investigator & Institution: Markesbery, William R.; Professor of Pathology & Neurology; Sanders-Brown Ky Res Ctr/Aging; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2006 Summary: Alzheimer's disease (AD), is a major health problem in the United States, where it affects approximately four million older individuals. There is no effective treatment of AD and prevention is the key to this disorder. Oxidative stress, in the form of lipid, protein, carbohydrate and DNA oxidation plays a significant role in the pathogenesis of neuron degeneration in AD and serves as a potential therapeutic target for slowing the onset or preventing the disease. The present application, termed PREADVISE, is based on the hypothesis that early treatment with vitamin E and selenium (Se) in the presymptomatic stage of the disease may delay the onset or prevent AD. These two agents have strong antioxidant properties and have not been used together in a large human study. This proposed evaluation of AD prevention will be added to the Selenium and Vitamin E Chemoprevention Trial (SELECT), a NCIsupported, phase III, double-blind, placebo-controlled 2X2 factorial study that assesses the combined and single effect of these two antioxidants on the reduction of the incidence of prostate cancer in 32,400 healthy men 55 or older (50 or older if African American). The duration of SELECT will be 12 years with a five-year uniform accrual period. PREADVISE is open to men 65 or older (60 or older if a minority) and it is estimated that 10,368 participants will be enrolled. They will be randomized to one of four arms: vitamin E plus Se, vitamin E plus Se placebo, Se plus vitamin E placebo, or vitamin E and Se placebos. They will undergo a memory impairment screening examination as part of the initial and annual SELECT evaluation, and those that fall below the cutoff point will undergo a more thorough cognitive evaluation using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery of cognitive tests. Participants who fail the CERAD battery will receive a thorough dementia medical evaluation for diagnosis and be reviewed in a consensus conference by neurologists and a neuropsychologist with lengthy experience in dementia. It is estimated that the relative risk for AD (relative risk 0.60) is detectable with 80 percent power in this trial. The study offers an inexpensive opportunity to evaluate the longterm effect of two antioxidant agents in slowing the onset or preventing AD in a large number of subjects. The study also will evaluate the sensitivity and specificity of the screening measure in a matched sample of normals. In addition, it will evaluate the effect of antioxidant therapy in a group of 200 elderly longitudinally followed normal controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PRIMARY PREVENTION VERSUS SCREENING FOR PROSTATE CANCER Principal Investigator & Institution: Etzioni, Ruth B.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The objective of this research is to provide a quantitative framework for researchers and policy makers developing prevention and screening strategies to control prostate cancer. Research into prostate cancer prevention is expanding and maturing. The Prostate Cancer Prevention Trial (PCPT), a phase III trial of finasteride as a possible preventive agent, is scheduled for completion in 2004. A

Studies

53

second Phase III prostate cancer prevention trial is currently under way to test the efficacy of selenium and vitamin E in preventing the disease. At the same time, ProstateSpecific Antigen (PSA) screening has become common practice in the US. Data on PSA utilization and prostate cancer incidence over the past decade are consistent with rapid dissemination of the test for early detection purposes. How should limited health care dollars be allocated when both screening and prevention are available for control of prostate cancer? The central theme of this proposal is that computer modeling provides an appropriate and powerful means to answer this important and timely question. Our primary Specific Aim is to develop a comprehensive computer model of prostate cancer prevention and screening at the level of the individual. The model will add a primary prevention component and an economics front end to an established model of prostate cancer natural history and PSA screening developed by the study investigators. For any strategy combining a specific screening schedule with a primary preventive agent, the model will project the years of life saved, the costs of the strategy less any savings in treatment costs, and the incremental cost per year of life saved. Our second Specific Aim is to use the model together with data from the PCPT to project the incremental costs and benefits of different strategies combining finasteride with PSA screening. In addition to illustrating the utility of our model, this aim will also allow us to estimate the cost-effectiveness of finasteride as a preventive agent for prostate cancer. As part of this aim, we will use the PCPT data to estimate the effects of finasteride on disease natural history, including disease onset, tumor metastasis, and PSA growth rates. The modeling infrastructure developed through the proposed work will be applicable to any potential preventive agent. The final model will be made available to investigators through a dedicated website which will allow users to run the model with their own settings for key cost and efficacy parameters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSPECTIVE STUDY OF DIET AND PROSTATE CANCER Principal Investigator & Institution: Giovannucci, Edward; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 23-AUG-1991; Project End 31-MAR-2006 Summary: (provided by Applicant) This project aims to identify dietary, hormonal, and genetic factors related to prostate cancer in the Health Professionals Follow-Up Study (HPFS). In spite of the slow progression rates of most prostate cancers, a subset of patients will experience a more aggressive and generally fatal course. The heterogeneity in biologic potential for progression among tumors is likely related to acquired molecular characteristics. Thus, we will try to link dietary and hormonal factors that are related to aggressive behavior in prostate cancer to specific molecular characteristics that determine biologic potential, including cell proliferation, differentiation, apoptosis, inflammation, and angiogenesis. We will also examine whether identified dietary and other modifiable risk factors can, in the post-diagnostic period, influence the risk for PSA relapse among men treated with apparently organ-confined prostate cancer. Because our ultimate goal is to provide feasible approaches for prevention, in addition to many aims geared towards understanding the disease (hormones, genetic factors, total energy intake), the focus of many of our aims is on modifiable factors (aspirin, calcium, omega-3 fatty acids, lycopene (tomatoes), and vitamin E). Among 47,000 HPFS men free of cancer at baseline in 1986, we anticipate 4,124 new cases of prostate cancer by 2004, including 573 metastatic cases. We also plan to acquire tumor blocks from 1,732 prostatectomy cases. The sources of the exposure data in the HPFS are (1) questionnaire, including diet, (2) plasma samples (insulin-like growth factors, sex hormones, vitamin

54

Vitamin E

D, carotenoids), and (3) blood and buccal cell DNA for MnSOD, vitamin D and androgen receptor CAG polymorphisms. The outcome data will be based on (1) medical record and pathology report review for initial diagnosis and relapse (PSA failure), and (2) tissue blocks for microvessel density, VEGF, COX-2, PTEN loss, proliferation, and apoptosis. Stratified analysis and multivariate analysis will be used to control for potential confounding factors. This project is likely to yield important new findings that may help our understanding of modifiable risk factors for prostate cancer incidence, progression, and relapse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEINS OF NORMAL AND CATARACTOUS LENSES Principal Investigator & Institution: Giblin, Frank J.; Professor; None; Oakland University Rochester, Mi 483094401 Timing: Fiscal Year 2001; Project Start 01-AUG-1977; Project End 31-DEC-2002 Summary: (provided by applicant): The objective of the proposed work is to evaluate oxidative stress as a factor in the development of human senile cataract. Emphasis will be placed on studying the mechanism of formation of nuclear cataract, a major cause of loss of lens transparency in the aging human. The hypothesis to be tested is that molecular O2 and UVA light can each contribute to cataract formation in regions of the lens where antioxidant levels are low. Although a number of lens and non-lens studies have implicated UVA radiation as being biologically toxic, the role of this major component of sunlight in cataractogenesis is currently unclear. To investigate oxidative mechanisms in the lens, the PI will use two in vivo guinea pig models involving treatment of the animals with hyperbaric 02 (HBO) and/or UVA light. Each model produces an increase in the level of lens nuclear light scattering combined with damage to nuclear fiber cell membranes. The PI and his collaborators will employ a variety of techniques including SDS-PAGE, HPLC, laser methods in vivo and in vitro, mass spectrometry and infrared spectroscopy to investigate oxidative effects on lens proteins and membrane lipids, and to identify crystallins that have precipitated in the lens because of in vivo oxidative stress. The studies are designed to determine the relative contributions of lens membrane damage and crystallin modifications to the observed loss of nuclear transparency, and to identify reactive species of oxygen that may be involved. In addition, possible HBO-induced myopia in the guinea pig lens will be investigated, and a mouse/vitamin E-deficient/HBO model will be used to search for a link between poor nutrition occurring early in life and subsequent nuclear cataract. In vitro HBO and UVA methods will complement in vivo studies as a means of elucidating oxidative, as well as protective, mechanisms. In the in vitro work, roles for alphacrystallin and protein-thiol mixed disulfides in preventing crystallin precipitation in 02stressed lenses will be evaluated, and the mechanism of UVA blockage of pentose shunt activity in H202-challenged cultured lenses will be determined. Quantitative measurement of UVA-induced generation of H202, superoxide anion and singlet oxygen during in vitro irradiation of guinea pig lens proteins will aid in elucidating in vivo mechanisms. Molecular methods will be employed to investigate possible up-regulation of particular lens antioxidant enzymes for the two in vivo models, and for evaluating antioxidant polyphenol compounds as possible anticataract agents. Overall, the studies will provide valuable information on protecting the lens against 02- and UVA-induced damage, and on guarding against the formation of maturity-onset cataract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

55

Project Title: RANDOMIZED TRIALS OF VITAMIN SUPPLEMENTS AND EYE DISEASE Principal Investigator & Institution: Christen, William G.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-1986; Project End 30-JUN-2003 Summary: This application proposes to conduct randomized, double-blind placebocontrolled trials to test the hypothesis that supplementation with antioxidant vitamins reduces the risk of age-related macular degeneration (AMD) and cataract. This proposal includes continuation of current ongoing investigations conducted as part of the Physicians' Health Study (PHS) and expansion of these studies to include women in the newly established Women's Health Study (WHS). The PHS is a randomized, doubleblind, placebo-controlled trial of aspirin use in reducing cardiovascular disease, and beta-carotene in reducing cancer, among 22,071 male U.S. physicians aged 40 to 84 years in 1982. The WHS is a randomized, double- blind, placebo-controlled trial of betacarotene and vitamin E in the primary prevention of cancer and cardiovascular disease, and low-dose aspirin in the prevention of cardiovascular disease, among over 40,000 female U.S. nurses, aged 50 or older in 1992, with enrollment to begin in the summer of 1992. All self-reports of cataract and AMD will be confirmed by medical record review. The primary aims are to determine through randomized comparisons l) whether betacarotene supplementation reduces the risk of AMD in men and women, 2) whether betacarotene supplementation reduces the risk of cataract in men and women, 3) whether vitamin E supplementation reduces the risk of AMD in women, 4) whether vitamin E supplementation reduces the risk of cataract in women, and 5) whether alternate day, low-dose aspirin reduces the risk of cataract in women. It is expected that by the end of the follow-up period there will be approximately 1,660 incident cases of cataract and 600 incident cases of AMD in the PHS, and 1,150 incident cases of cataract and 480 incident cases of AMD in the WHS. The primary analysis for the randomized studies involving beta-carotene, vitamin E, and aspirin treatment will be incidence of AMD or cataract in the treatment and placebo groups. Survival analysis will be used to determine whether there is a difference in time to AMD or cataract diagnosis. The incidence of AMD and cataract will also be investigated prospectively for other antioxidants including vitamins A, C, and E (in men). Other potential risk factors for AMD and cataract which will also be investigated prospectively include systemic hypertension cardiovascular disease, blood cholesterol, blood pressure cigarette smoking, alcohol intake, height body mass index, and diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: REDOX INTERACTIONS OF DT DIAPHORASE AND VITAMIN E Principal Investigator & Institution: Liebler, Daniel C.; Professor; Pharmacology and Toxicology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 11-FEB-2000; Project End 31-JAN-2003 Summary: NAD(P)H:quinone oxidoreductase (NQO1, EC 1.699.2, DT-diaphorase) is a ubiquitous enzyme that carries out 2-electron reduction of numerous quinone substrates and is induced in antioxidant responses. Although a "physiologic" substrate for NQO1 had been obscure, we observed recently that NQO1 reduces the endogenous alphatocopherol (alphaTH, vitamin E) oxidation product alpha- tocopherolquinone (TQ) to alpha-tocopherolhydroquinone (TQH2), which can, in turn, regenerate alphaTH from the alpha- tocopheroxyl radical. An alphTH regenerating system is thought to be an essential contributor to cellular antioxidant protection. We hypothesize that an essential

56

Vitamin E

function of NQO1 is to supply reducing equivalents to redox cycles of alphaTh, thus sustaining cellular antioxidant protection against propagation of oxidative damage in membranes. This action may involve either reduction of one-electron oxidized tocopheroxyl radicals or 2- electron oxidized tocopherones either by NQO1 itself or by TQH2. To test these hypotheses, we propose: Aim 1) To characterize the participation of TQH2 and NQO1 in a one-electron alphaTH redox cycle. Reduction of the tocopheroxyl radical to alphaTH either directly by NQO1 or via TQH2 will be studied in liposome and membrane systems. Aim 2) To characterize the participation of TQH2 and NQO1 in a two-electron alphaTh redox cycle. Reduction of 8a-substituted tocopherones to alphaTH either directly or via TQH2 will be studied in liposome and membrane models. Aim 3) To characterize the impact of NQO1 on alphaTh redox status and antioxidant turnover in intact cells. These studies will employ CHO cells and human cell lines expressing NQO1 polymorphisms. The levels and distribution of alphaTH and its oxidation products will be measured as a function of NQO1 activity in cells subjected to oxidative stress. These studies will clarify the endogenous antioxidant role of NQO1 and determine how the antioxidant chemistry of alphaTH, Nature's most ubiquitous membrane antioxidant, is tied to cellular metabolic redox balance. Answers to these questions are essential to improving our understanding of the interplay between cellular antioxidant defenses and their roles in human health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATORS OF FETAL RODENT PULMONARY HYPOPLASIA Principal Investigator & Institution: Schnitzer, Jay J.; Associate Visiting Surgeon; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 05-JUL-2001; Project End 31-MAR-2006 Summary: Infants with congenital diaphragmatic hernia (CDH) die from inadequate lung function, which is a combination of 1) pulmonary hypertension of the newborn. The pulmonary hypoplasia is characterized by immature, small lungs. We have demonstrated the efficacy of prenatal glucocorticoid therapy in accelerating pulmonary maturation in CDH lung in fetal rats and sheep. We have further shown that prenatally administered antioxidants , particularly vitamin E, accelerate prenatal growth of CDHassociated hypoplastic lungs in vitro and in vivo. We have demonstrated significant differences in the levels of mitogen- activated protein (MAP) kinase phosphorylation (extracellular signal regulated protein kinases, ERK-1 and -2) between CDH and normal fetal lungs, and have shown increased phosphorylation towards that observed normally, in CDH lungs after treatment with vitamin E in vivo. We hypothesize that important regulators and pathways of normal and hypoplastic fetal lung growth converge on the mitogen-activated protein (MAP) kinase pathways. We further hypothesize that antioxidants stimulate hypoplastic fetal lung growth via the MAP kinase cascade, and, in particular, via up-regulation of the MAP kinase kinases (MEK +) and Raf-1. We propose to define the molecular mechanism(s) in the rodent responsible for the salutary effects of the anti-oxidants and define the modulators of signal transduction pathways responsible for CDH- associated pulmonary hypoplasia. We will reestablish that the observed stimulation of embryonic lung growth by antioxidants occurs via a reductant mechanism and determine where antioxidants impact the MAP kinase pathways. We will establish the role of other candidate genes and pathways in fetal lung hypoplasia, define whether differences exist in gene expression patterns in the various rodent CDH models, and study in the rodent model worthy candidate genes identified in Projects I, II, and IV. We hope that these studies will provide new insights

Studies

57

into the mechanisms of prenatal lung growth control. These, in turn, can provide a platform for the future development of prenatal targeted therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ANTIOXIDANTS IN OVARIAN THECAL HYPERPLASIAR Principal Investigator & Institution: Duleba, Antoni J.; Associate Professor and Clinic Chief; Obstetrics and Gynecology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2006 Summary: This proposal is designed to test the hypothesis that (i) oxidants increase and antioxidants decrease the size and steroidogenic capability of the ovarian thecalinterstitial (T-I) compartment and (ii) insulin, insulin-like growth factor I (IGF- I) and tumor necrosis factor alpha (TNF-alpha) stimulate growth of T-I cells by inducing oxidative stress. We propose that, under pathological conditions, excessive oxidative stress on T-I cells may contribute to the development of polycystic ovary syndrome (PCOS). This hypothesis is based on evidence indicating that other disorders associated with insulin resistance and hyperinsulinemia, such as syndrome X, are characterized by increased oxidative stress and reduced radical-trapping, antioxidant capacity. We propose that insulin and insulin-like growth factors (IGFs) increase oxidative stress and thus cause relative depletion of antioxidants such as vitamin E. Conditions associated with hyperinsulinemia and/or increased bioavailable IGFs are also characterized by increased proliferation of several mesenchymal tissues including vascular smooth muscle and skin fibroblasts. Similarly, women with PCOS have insulin resistance, compensatory hyperinsulinemia, and increased levels of free IGF- I. Our studies have shown that insulin and IGFs promote proliferation and decrease apoptosis of T-I cells; these effects likely contribute to hyperplasia of T-I cells, a characteristic feature of PCOS. Our preliminary data demonstrate that in vitro administration of vitamin E succinate and other antioxidants inhibit proliferation of T-I cells in a dose-dependent fashion. In contrast, induction of modest oxidative stress stimulates proliferation. The specific aims of this proposal are: (i) to study the effects of oxidants and antioxidants on T-I proliferation, steroidogenesis, and apoptosis; and (ii) to evaluate the role of insulin, IGFI and TNF-alpha in the generation of reactive oxygen species in cultures of T-I cells. These aims will be addressed by experiments on rat T-I cell cultures. The relevance of the key findings to the human ovary will be tested. The results of these studies will provide a new insight into the role of oxidative stress and antioxidants, especially vitamin E, on the growth and function of ovarian mesenchyme. Ultimately, this study may shed new light on the pathophysiology of PCOS and thus provide an impetus towards development of new diagnostic and therapeutic approaches, including the possible therapeutic use of antioxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: SCOR IN MOLECULAR MEDICINE AND ATHEROSCLEROSIS Principal Investigator & Institution: Witztum, Joseph L.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 23-APR-1997; Project End 31-MAR-2007 Summary: (provided by the applicant): Despite recent advances in lifestyles and hypolipidemic therapy, atherosclerosis remains the major cause of morbidity and mortality. Among the many factors that go "beyond cholesterol," much evidence supports the oxidation of LDL (OxLDL) as playing a key role in the atherogenic process.

58

Vitamin E

While the original interest in OxLDL occurred because it led to rapid macrophage uptake and foam-cell formation, almost 20 years later it is now clear that OxLDL and its many oxidatively modified products contribute to atherogenesis by its proinflammatory, immunogenic and cytotoxic properties, consistent with the concept that atherosclerosis is a chronic inflammatory process that involves complex interactions between the endogenous cells of the artery and cells recruited from the blood, chiefly monocytes and T cells. The goal of the La Jolla SCOR is to investigate mechanisms by which oxidation influences these processes and specifically focuses on the role of monocyte/macrophages and the role of T cells and immune responses. Because the recruitment of monocytes into the artery is rate limiting, we will study the extracellular and intracellular mechanisms for the regulation of chemokine receptors and adhesion molecules which determine rates of recruitment and retention. We will utilize new methods to quantify the rates of recruitment of monocytes into lesions and the impact of various interventions, such as such as deletion of CCR2, or MCP-1, or the use of vitamin E or agonists for PPARgamma. We will study the structure and function of receptors involved in the binding and internalization of OxLDL, including CD36, and CD68, and define ligands on OxLDL and apoptotic cells for these receptors. Nuclear receptors such as PPARs, LXRs and possibly ESRs appear to play pivotal roles in expression of genes known to affect atherogenesis, such as scavenger receptors, cytokines, and cholesterol homeostasis. We will determine the molecular mechanisms by which activation of these receptors modulate macrophage gene expression, and determine the role of each receptor in vivo in inflammation and atherosclerosis models through the use of novel gene targeted murine models. Oxidation of LDL renders it immunogenic and we will determine the consequences to atherogenesis of the immune response. In particular, we will determine the mechanisms by which immunization of mice with OxLDL ameliorates atherosclerosis and specifically determine the role of T cells in this process. We will utilize immunological techniques to measure the relative rates of oxidation of LDL in vivo in animals and determine the impact of various interventions, such as vitamin E. Finally, we will determine the epidemiologic relationship of various plasma markers of OxLDL, including a measure of OxLDL (mmLDL) itself, with respect to clinical and morphological measures of atherosclerosis and the ability of these measures to predict disease. In summary, the La Jolla SCOR proposes a multi-disciplinary approach that focus on the consequences to atherogenesis of the immune response to OxLDL and on the effects of OxLDL on monocyte/macrophage biology. These insights may lead to novel approaches to the treatment and prevention of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SOUTHWEST ONCOLOGY GROUP--CCOP RESEARCH BASE Principal Investigator & Institution: Coltman, Charles A.; Chairman; Ctrc Research Foundation 7979 Wurzbach Rd, Ste 500 San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 30-SEP-1983; Project End 31-MAY-2006 Summary: (Applicant?s Description) The Southwest Oncology Group has evolved since its inception in 1956 into an adult multi-disease, multi-modality clinical research organization. This organization has grown to include 31 Full Member Institutions, 27 Community Clinical Oncology Program (CCOP) institutions, including 3 MinorityBased (MB) CCOPs, 4 Pilot Program CCOPs and 1 Pilot Program MBCCOP, 25 Urologic Cooperative Outreach Program (UCOP) institutions, and a network of approximately 1,434 Affiliate Program (AFFIL) investigators at 245 Affiliate institutions. In addition, 13 Group institutions also participate in the CTEP Minority Initiative program, which serves to enhance minority accrual in cancer clinical trials. More than 4,000

Studies

59

investigators, representing all research modalities, are members of the Group and actively participate in the registration of patients to cancer treatment and cancer control and prevention protocols. In addition, the Southwest Oncology Group coordinates two large intergroup chemoprevention trials funded by the Division of Cancer Prevention (DCP), the Prostate Cancer Prevention Trial (PCPT) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). More than 200 PCPT institutional sites affiliated with the Southwest Oncology Group and two other cooperative groups participate in this trial. Currently, over 200 institutional sites affiliated with the Southwest Oncology Group, 4 other cooperative groups, the Veterans Affair Cooperative Studies Group and the Canadian Urologic Oncology Group have been chosen to participate in the SELECT trial. The Southwest Oncology Group is also committed to representative accrual of women and minority patients and subjects to Group clinical trials. To this end, the Group has developed an extremely active Committee on Women and Special Populations, which serves to evaluate and enhance the accrual of women, minorities and special populations (e.g., elderly) to Group trials, identify and address special concerns regarding women?s health issues in the cooperative group setting, and act as a direct liaison with women?s and minority health groups, such as the Office of Research on Women?s Health (ORWH) and the Office of Research on Minority Health (ORMH). The Southwest Oncology Group has continued to pursue the goals of the National Cancer Institute CCOP and MB-CCOP program through innovative membership and cancer prevention and control programs, extensive training and educational opportunities for the Group membership, and unsurpassed excellence in patient accrual and quality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES ON ENDOTHELIAL DYSFUNCTION IN HEART FAILURE Principal Investigator & Institution: Katz, Stuart D.; Associate Professor of Internal Medicine; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1995; Project End 31-AUG-2001 Summary: (Adapted from the application): The applicant has previously demonstrated that impaired endothelium-dependent vasodilation in response to hormonal agonists and shear stress in patients with heart failure is attributable to reduced synthetic activity of the L-arginine-nitric oxide metabolic pathway and that endothelial dysfunction in heart failure is reversible with physical training. These findings indicate that endothelial dysfunction is a modifiable determinant of reduced aerobic capacity in heart failure and thereby is a target for therapy. We now propose: 1) to perform controlled clinical trials to determine whether specific therapies which decrease oxidative stress (Vitamin C, Vitamin E), increase L-arginine availability (supplemental oral L-arginine), or increase cGMP-mediated vasodilation (sildenafil) chronically enhance endothelial function in patients with heart failure; 2) to determine the role of endothelial dysfunction in disease progression with serial assessment of endothelial function in a large population of ambulatory patients with heart failure; and 3) to identify specific cellular mechanisms which contribute to impaired nitric oxide synthesis in heart failure with studies in cell culture. In clinical studies, endothelial function will be assessed non-invasively with a battery of tests for physiological testing of flow-mediated nitric oxide-induced vasodilation (Doppler ultrasonography and venous occlusion plethysmography) and determination of nitric oxide metabolism (isotope tracer techniques with '5N-L-arginine and measurement of nitric oxide production in expired gases). In laboratory studies, PKC and PKBIAkt activation, eNOS-calveolin-1 interactions, and regulation of substrate availability for eNOS (L-arginine transport and ADMA metabolism) will be investigated

60

Vitamin E

with molecular biology techniques in cultured human endothelial cells incubated with autocrine/paracrine factors and serum from normal subjects and patients with heart failure. The hypotheses to be tested are: 1) endothelial dysfunction is reversible with chronic interventions to decrease oxidative stress, increase availability of L-arginine, and enhance cGMP-dependent vasodilator effector mechanisms in vascular smooth muscle; 2) endothelial dysfunction is linked to disease progression in heart failure; and 3) reduced synthetic activity of the L-arginine-nitric oxide metabolic pathway in heart failure is attributable serum-induced decreases in PKC isoform or PKB/Akt activation, increased inhibitory eNOS-caveolin-1 interactions, or reduced substrate availability for eNOS (due to decreased L-arginine transport or decreased ADMA metabolism). Proposed studies will provide new data to develop novel therapeutic strategies to improve outcome in patients with heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUPPLEMENTAL SE AND VITAMIN E AND PULMONARY FUNCTION Principal Investigator & Institution: Cassano, Patricia A.; Div/Nutritional Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This proposed project is a randomized clinical trial testing whether supplementation with selenium and/or vitamin E affects pulmonary function. There is compelling evidence from observational epidemiologic studies that high antioxidant intakes are associated with reduced risks of chronic obstructive disease (COPD) and increased lung function. This proposal is an ancillary study to the multisite selenium and Vitamin E Cancer Prevention Trial (SELECT), a 4-arm placebo-controlled, double-blinded randomized trial in 32,400 men testing whether daily supplementation with vitamin E (400mg alpha-tocopherol), selenium (200 micrograms selenomethionine) or both vitamin E and selenium can prevent prostate cancer. We will enroll 3,000 SELECT participants for this respiratory ancillary study, and extend data collection to include pulmonary function, respiratory disease, and respiratory symptoms. We also will collect biological measures of nutrient exposure (serum vitamin E and selenium) and plasma lipids (total and high-density lipoprotein cholesterol) on all participants and oxidant burden (urinary F2-isoprostane) on a sub sample of heavy smokers and men with COPD. The primary outcome will be change between baseline and year 3 in forced expiratory volume in the first second (FEV1). FEV1 is a valid and reliable measure of respiratory function that strongly predicts COPD and mortality. Extensive data on diet and dietary supplement use are being collected by the SELECT parent study. All specific aims examine pre-specified contrasts between the 4 arms of the SELECT randomized trial. The underlying hypothesis is that antioxidants will reduce the age related decline in FEV1, and thus at the 3-year follow-up FEV1 will be higher in the groups receiving antioxidant supplements compared to controls. A secondary aim considers whether the effect of supplementation is greater among smokers (high burden of exogenous oxidants) who, by purposive selection of the study sites, will comprise 25% of the sample. The proposed study addresses important and timely questions about diet and lung disease, and makes cost efficient use of the research infrastructure of SELECT. This study could have enormous public health significance, because supplementation with antioxidant nutrients would be an inexpensive and practicable means to reduce morbidity and mortality from pulmonary disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

61

Project Title: TCDD-INDUCED OXIDATIVE STRESS Principal Investigator & Institution: Hassoun, Ezdihar A.; Pharmacology; University of Toledo 2801 W Bancroft St Toledo, Oh 43606 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 30-MAY-2004 Summary: In this project, we propose that subchronic exposure to 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD), induces oxidative stress with the production of oxidative tissue damage and changes in the antioxidant defense mechanisms and the aminergic systems in various regions of the brain. We also propose that antioxidants, such as vitamin E succinate and ellagic acid provide protection against these effects. To test this hypothesis, groups of female Sprague Dawley rats will be treated p.o., with daily doses of TCDD for 13 weeks and will then be sacrificed at the end of this period. Various regions of the brain will be dissected and assayed for the determination of the biomarkers of oxidative stress, as well as the levels of different monoamines and their metabolites. The formation of reactive oxygen species in brain tissues will be determined using the cytochrome c reduction assay, and the induction of the processes of lipid peroxidation and DNA-single strand breaks (SSB) will be measured using the thiobarbituric acid reactive substances (TBARS) assay and the alkaline elution technique, respectively. The levels of glutathione and the activities of various antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and catalase will be also determined, using established biochemical assays. The levels of different biogenic amines in the brain regions will be determined using high performance liquid chromatography (HPLC). The protective effects of selected antioxidants, namely vitamin E succinate and ellagic acid against TCDD-induced oxidative stress in the brains of mice, will also be assessed. The results of the study will help future investigations of the body functions that are associated with the affected brain regions, which will provide tools for early detection of TCDD-intoxication. Furthermore, the study will be the first to investigate the protection by antioxidants against TCDD-induced effects on the brain, which may lead to new preventive measures against TODD-induced brain damage in exposed human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TRIAL OF ASPIRIN AND VITAMIN E IN WOMEN Principal Investigator & Institution: Buring, Julie E.; Professor of Ambulatory Care and Prevent; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-FEB-1991; Project End 31-AUG-2004 Summary: This application proposes to extend the Women's Health Study (WHS) for an additional 3 years of randomized treatment and follow-up. The WHS is an ongoing randomized, double-blind, placebo-controlled, 2x2 factorial trial evaluating the balance of benefits and risks of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer among 39,876 U.S. female health professionals aged 45 and older. Its goal is to provide either clear positive results or definitive null results on which sound clinical and public health recommendations for the use of low-dose aspirin and vitamin E can be made. Based on a review of the unblinded data, both the clinical and methodologic members of the trial's Data and Safety Monitoring Board unanimously recommended an extension of both randomized components beyond the trial's scheduled termination in August 2001. The primary rationale for the Board's recommendation was the likelihood of ambiguity at the scheduled end of the trial regarding the findings of both agents on both endpoints, ambiguity that could result in considerable clinical confusion. Three additional years will help clarify these

62

Vitamin E

ambiguities, more conclusively determine the balance of benefits and risks of these agents for the primary prevention of cardiovascular disease, and allow an adequate latent period to elapse for assessing the effects of both agents on cancer, thus providing clear clinical recommendations for health care providers and patients. The Women's Health Study is in a unique position to answer these important questions. Average duration of treatment is 6 years; morbidity and mortality follow-up rates are 98 percent and 100 percent, respectively. Compliance with both agents at 72 months is 75.6 percent. Pilot data indicate that 97 percent of compliers would definitely be willing to continue the trial for 3 additional years or would consider continuing. This trial is cost effective, at 75 dollars per randomized participant per year in direct costs. Given the gaps in knowledge this study is intended to address, as well as the certain intense interest in its findings by the medical, lay, and regulatory communities, the proposed extension of this trial in women is timely and important. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ULTRAFINE PARTICLE EXPOSURE IN HUMANS Principal Investigator & Institution: Frampton, Mark W.; Associate Professor; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Hypotheses: Exposure to ambient air particles is associated with increased risk for cardiovascular mortality, cardiac arrhythmias, and myocardial infarction, but the mechanisms are unknown. Dysfunction of the vascular endothelium is critically linked to the pathogenesis of atherosclerotic vascular disease, and factors affecting myocardial repolarization influence the susceptibility to arrhythmias. We will test the hypotheses that: 1) inhalation of ultrafine particles alters endothelial function in nonsmokers and smokers, and 2) inhalation of ultrafine particles alters ventricular repolarization. Specific Aims: 1) Determine in nonsmokers the effects of inhalation of clean air and 50 pg/rn3 carbon UFP on endothelial function, leukocyte activation, and leukocyte oxidant production. 2) Determine in current smokers the effects of inhalation of clean air and 50 pg/rn3 carbon UFP on endothelial function, leukocyte activation, and leukocyte oxidant production. 3) Identify effects of inhalation of clean air and 50 pg/rn3 carbon UFP on cardiac repolarization in nonsmokers and smokers. Methods: Forty-eight healthy nonsmokers will undergo exposures to air and 50 pg/rn3 carbonaceous UFP for 2 hours with intermittent exercise, in a double-blind, randomized, two period crossover study design. Subject groups will be stratified by both age and gender. Before and at intervals after exposure, phlebotomy will be performed and endothelial function will be assessed using flow mediated vascular dilatation of the forearm (FMD). Continuous 24-hour 12-lead ECG monitoring will be obtained with each exposure, and analyzed for changes in ventricular repolarization, heart rate, and heart rate variability. Primary outcomes will be changes in FMD and the duration of ventricular repolarization as measured by the corrected QT interval on the ECG. Secondary outcomes will include markers of blood leukocyte activation and expression of adhesion molecules, plasma endothelins and nitric oxide, heart rate and heart rate variability, and additional measures of cardiac repolarization. Following completion of these studies in nonsmokers, an identical study protocol will be undertaken in current smokers. In both studies we will determine by correlation analysis whether blood markers of systemic inflammation or blood vitamin E levels at baseline influence the cardiovascular responses to UFP. These studies will identify key mechanisms for the cardiovascular effects of exposure to ambient air particles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

63

Project Title: ULTRASOUND, INTESTINAL AND CARDIAC FUNCTION IN RATS Principal Investigator & Institution: Baldwin, Ann L.; Professor; Physiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Environmental factors in animal facilities can cause distress if not properly controlled. Noise is particularly important because it has nonauditory effects that alter the physiology of the whole body. Studies on the effect of lowfrequency sounds on rodents have established that both physiological and behavioral responses are common. A stress response in rats is produced, as indicated by a rapid transient increase in plasma corticosterone, and gastrointestinal, cardiac and immunological functions are also affected. Rats are extremely sensitive to sounds in the ultrasonic range (12-40kHZ) and these are routinely encountered in animal facilities. It is likely that ultrasound has similar effects, but no data are available. It is essential that environmental stressors in animal facilities are minimized, not only for animal welfare, but because the results of biomedical research depend on the animals showing standard responses to clearly defined experimental procedures. The purpose of this study is to test the hypothesis that: exposure of research rats to daily periods of ultrasound affects gastrointestinal and cardiac function and that antioxidants reduce these effects. The applicant's long-term goal is to convince scientists to demand better environments for their animals. The specific aims of this study are to: 1. Determine whether subjecting rats to a short period of daily ultrasound increases: a) Production of reactive oxidant species (ROS) in the intestinal mucosa, and epithelial disruption; b) Particulate uptake from the intestinal lumen by M cells in the mucosa, thus overtaxing the immune system; e) Mesenteric microvascular permeability, thus reducing selective barriers to transvascular exchange; d) Increases heart rate but decreases heart rate variability, both markers of stress. 2. Determine whether dietary vitamin E and/or lipoic acid reduce the deleterious effects of ultrasound as demonstrated in Aim 1. Production of reactive oxygen species (ROS) will be assessed using a fluorescent probe; epithelial sloughing and mucosal mast cell degranulation by microscopy. Lack of selective exclusion of foreign particles by the M cells will be tested by orally administering polystyrene particles and measuring their concentrations in Peyer's patches and lymph nodes. Microvascular endothelial leakage and mesenteric mast cell degranulation will be assessed using intravital epifluorescence microscopy and image analysis. The effects of noise-induced stress on heart rate, heart rate variability and cardiac performance will be determined in conscious, freely moving rats by radiotelemetry. Rat behavior, another indicator of stress, will be assessed by videotaping pairs of rats in their cages before and after ultrasound. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: UNDERSTANDING COUPLED TRANSFERS OF ELECTRONS AND PROTONS Principal Investigator & Institution: Mayer, James M.; Professor; Chemistry; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-FEB-1995; Project End 31-MAR-2007 Summary: (provided by applicant): Many biochemical processes involve the coupled transfer of electrons and protons. This is a key step, for instance, for a range of enzymes (e.g., cytochrome c oxidase, photosystems I and II, cytochromes P450) and in the trapping of reactive oxygen species (e.g., by vitamin E and superoxide dismutases). The goal of the proposed research is to develop a fundamental and predictive understanding

64

Vitamin E

of these processes. This understanding will be valuable in a range of biochemical systems, much as the current knowledge of pure electron transfer has been very valuable. The proposed work encompasses a variety of compounds, reactions, and techniques to uncover the essential features of the chemistry. Hydrogen atom transfer reactions are a primary focus of the proposal, building on the recent discovery that a range of H-atom transfer reactions follow the Marcus cross relation. The Marcus approach enables prediction of reaction rates and provides a new fundamental intuition for these reactions, based on driving force and intrinsic barriers. The intrinsic barriers can be measured through studies of self-exchange rates, which will be determined for a number of compounds. The relationship between the intrinsic barriers for electron, proton, and hydrogen atom transfer will be examined. Extensions to hydride transfer reactions are discussed, including possible application of the Marcus approach. New chemical systems will be developed in which an intramolecular proton transfer is coupled to intermolecular electron transfer. Such proton-coupled electron transfer (PCET) processes are very common, as in the oxidation of the tyrosine Z-histidine unit in photosystem II. It will be determined whether proton transfer precedes, succeeds, or is concerted with electron transfer in such systems. The reasons for adopting one mechanism or another will be probed, using the intrinsic barriers and thermodynamics of the reactions. Chemical reactions that involve metal peroxide complexes will also be examined, both reactions of isolated peroxides and reactions that could form O-O bonds. The proposed work takes a broad view - studying iron, cobalt, manganese, ruthenium and osmium systems and a variety of types of reactions - in order to provide new and valuable insights into the various kinds of proton-coupled electron transfer that occur in biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN E AND ATHEROSCLEROSIS IN LDLR-/-MICE Principal Investigator & Institution: Meydani, Mohsen; Professor of Nutrition; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Recent human trials report that for patients with established atherosclerotic lesions, vitamin E (E) treatment does not reverse this process, thus concluding that E supplementation does not reduce mortality from coronary heart disease (CHD). Yet, much convincing epidemiological and experimental evidence indicates the potential preventive rather than therapeutic effect of E supplementation on reducing the risk of arteriosclerosis and CHD. To date, no controlled studies have been conducted to demonstrate the preventive role of E supplementation started at an early age on arteriosclerosis. We hypothesize that "supplementation with vitamin E from an early age prevents or retards the development of atherosclerosis and the risk of CHD in individuals with either Western dietary habits (high fat/cholesterol) or a reduced intake of fat and cholesterol." Since long-life E supplementation studies on humans is not practical, we propose testing this hypothesis on a LDL-receptor deficient (LDLR-/-) mouse by feeding mice: a) moderate or b) high fat/cholesterol diet from the age of 5 wks and supplementing both groups' diets with E starting from ages 5 weeks, 6 and 12 mo, to the age of 18 mo. The extent of aortic lesions will be examined by en face microscopic examination, immunohistochemistry, and molecular techniques. The presence and extent of oxidized LDL, macrophages, T cells, and smooth muscle cell populations, as well as endothelial cells expression of adhesion molecules, ICAM-1, VCAM-1, and PCAM-1, will be measured by immunohistochemistry, while aortic expression of mRNA for adhesion molecules as well as inflammatory cytokines and chemokines will be

Studies

65

measured by using RT-PCR analysis. In addition, gene chip microarray techniques will be used to determine responsive genes to dietary interventions. The study's results will provide valuable information on the potential preventive role of E supplementation started early in life compared to middle and later ages in reducing the risk of atherosclerosis, the leading cause of morbidity and mortality from CHD in the US. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN E AND INFECTION IN THE ELDERLY Principal Investigator & Institution: Meydani, Simin N.; Professor of Nutrition & Immunology; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 15-MAY-1997; Project End 30-APR-2004 Summary: (Adapted from the Applicant's Abstract): Infections in general, and respiratory infections (RI) in particular, are highly prevalent in nursing homes, and are one of the major causes of morbidity and mortality in the elderly. The increased incidence of infections in the elderly is multifactorial. A major contributing factor, however, is the well-described decline in cellular and humoral immunity with age. Higher mortality and morbidity, as well as a lesser degree of self-sufficiency, have been reported in elderly people with impaired immune response. The applicants have shown that short- and long-term supplementation with vitamin E significantly improves immune response in elderly humans. Furthermore, preliminary results appear to show that vitamin E-supplemented older individuals had a 30% lower incidence of selfreported infectious diseases compared to a placebo group. Old mice supplemented with vitamin E also have lower lung viral titer following influenza infection compared to old mice consuming an adequate level of vitamin E. It is therefore hypothesized, in this application, that supplementation with vitamin E will enhance the immune response of elderly individuals residing in long-term care facilities; and that this, in turn, will reduce the incidence and severity of RI, which should result in a lower number of sick days and less antibiotic use. The Specific Aims of the project are to determine the effect of one year of vitamin E supplementation on the incidence of RI, total number of sick days and antibiotic use, and in vivo and in vitro indices of cell-mediated immunity. The study will attempt to test the impact of a vitamin E intervention, using clinical and immunological endpoints, in a population of vulnerable long-term nursing home residents. The results are intended to provide basic and applied insight into the mechanisms involved, the goals to be realized, and ways to sharpen the intervention and enhance its impact. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: VITAMIN E DEFICIENCY: OXIDANT INDUCED GENE EXPRESSION Principal Investigator & Institution: Gohil, Kishorchandra; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) The long-term objectives of this research are to define molecular mechanisms underlying interactions of dietary antioxidants with cellular and environmental oxidants in vivo by the application of global gene expression analysis. The availability of transgenic mice with selective deletion of the gene for alphatocopherol (a-TC) transfer protein, and the resulting depletion of tissue a-TC (vitamin E), offers a unique opportunity to rigorously examine the role of a major dietary antioxidant of biological membranes and lipoproteins in normal physiology. In addition, its potential role as a dietary supplement to intervene in the pathogenesis of chronic

66

Vitamin E

diseases triggered by oxidant pollutants in the environment can also be tested. The specific aims of this proposal are to: (1) define and compare the mRNA expression profiles of lungs and livers from a-tocopherol transfer protein knockout (TTP-KO) and wild type mice; (2) assay the changes in mRNA expression profiles of lungs and livers in response to a photochemically-generated environmental oxidant, ozone, in TTP-KO and wild type mice; and (3) evaluate the changes in the expression of proteins encoded by selected mRNAs, identified through specific aims 1 and 2, by immunoblot and immunohistochemical analysis. The proposed research will identify, for the first time, the genomic response in vivo to silencing of a gene whose product plays a significant role in the homeostasis of a primary antioxidant in membranes lipoproteins. In addition, global gene expression analysis will also identify the molecular targets of a- TC that may not be directly related to the scavenging of reactive oxygen species and the molecular response to depletion of TTP not directly related to the transfer of a-TC. Gene expression analysis following exposure to an environmental oxidant, ozone, whose primary target is the membrane milieu, will identify the "transcriptional" response in vivo to oxidative stress inflicted by an environmental pollutant and the role of a dietary antioxidant, vitamin E, on oxidant-induced changes in gene expression in the target tissues. The analysis of proteins encoded by selected mRNAs will establish the potential functional implications of changes in the mRNAs detected by analysis with gene arrays. These molecular data may provide the basis for designing more effective protocols for dietary interventions with antioxidants that might ameliorate lung diseases induced by environmental oxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VITAMIN MECHANISMS

E

NEUROPROTECTION:

NOVEL

MOLECULAR

Principal Investigator & Institution: Sen, Chandan K.; Associate Professor; Surgery; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Neuroprotective properties of vitamin E have been established from the study of alpha-tocopherol, one of 8 members of the vitamin E family broadly categorized as tocopherols and tocotrienols. This proposal is based on a striking observation that alpha-tocotrienol, but not aipha-tocopherol, confers potent neuroprotection at nanomolar concentrations through regulation of signal transduction pathways independent of its antioxidant property. Thus, it was found that at 50-100 nM (one-tenth of plasma-concentration in supplemented humans) alpha-tocotrienol prevented glutamate-induced death of cultured HT4 cells as well as that of both immature and mature primary cortical neurons. Murine HT hippocampal neuronal cells, lacking intrinsic excitotoxicity-pathway, have been validated as a model to characterize oxidative glutamate toxicity. Neuroprotective effects of alpha-tocotrienol were also observed when homocysteic acid or buthionine sulfoximine (inhibitor of GSH synthesis) was used to challenge HT4 or primary rat fetal cortical neurons. Tocotrienols occur naturally and has been safely consumed by humans, particularly in Southeast Asia, for years. We observed that dietary alpha-tocotrienol contained in palm oil fed to pregnant rats reaches the brain of mother rats. Availability of this form of vitamin E is multi-fold higher in fetal brain compared to that of the mother. The objective of this proposal is to characterize the mechanisms by which alpha-tocotrienol exerts its neuroprotective action using pharmacological, biochemical and genetic approaches. In addition, the dogma that the neuroprotective function of vitamin E is solely mediated by its antioxidant property will be revisited. A commonly used criterion to establish the

Studies

67

involvement of reactive oxygen species (ROS) in a cell-response system is sensitivity of that system to antioxidants. It is often ignored that antioxidant molecules may have potent antioxidant-independent properties. Our working hypothesis is that elevated levels of extracellular glutamate trigger the following events: i) activation of pp6O c-Src, extracellular signal regulated kinase (ERK) and 12-lipoxygenase (LOX), and ii) depletes [GSH]i resulting in high [ROS]i, high [Ca2+]i, mitochondrial dysfunction eventually causing neuronal death. Tocotrienol controls these responses at two levels: early and late. In a time frame where >90 percent of the cells are dead after 12h of glutamate challenge, inhibition of inducible c-Src, ERK and 12-LOX activation within the first 1 h of glutamate treatment by nM (50-250) alpha-tocotrienol constitutes one of the early control mechanisms that is antioxidant-independent. Depletion of [GSH]i, elevation of [ROSJ]i and subsequent mitochondrial dysfunction are all tightly linked and are subject to late-control by higher (= or> 1 micromolar) concentrations of alpha-tocotrienol by virtue of its antioxidant property. This study will lay the foundation for a safe and efficient approach to prevent death and secure normal functioning of neurons under challenging conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “vitamin E” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for vitamin E in the PubMed Central database: •

[alpha]-Tocopherol modulates the low density lipoprotein receptor of human HepG2 cells. by Pal S, Thomson AM, Bottema CD, Roach PD.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156638

•

[alpha]-Tocopherol transfer protein stimulates the secretion of [alpha]-tocopherol from a cultured liver cell line through a brefeldin A-insensitive pathway. by Arita M, Nomura K, Arai H, Inoue K.; 1997 Nov 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24987

•

[gamma]-Tocopherol and its major metabolite, in contrast to [alpha]-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. by Jiang Q, ElsonSchwab I, Courtemanche C, Ames BN.; 2000 Oct 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17228

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

68

Vitamin E

•

[gamma]-Tocopherol Detoxification of Nitrogen Dioxide: Superiority to [alpha]Tocopherol. by Cooney RV, Franke AA, Harwood PJ, Hatch-Pigott V, Custer LJ, Mordan LJ.; 1993 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45961

•

[gamma]-Tocopherol traps mutagenic electrophiles such as NOx and complements [alpha]-tocopherol: Physiological implications. by Christen S, Woodall AA, Shigenaga MK, Southwell-Keely PT, Duncan MW, Ames BN.; 1997 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20349

•

An unusual vitamin E constituent ([alpha]-tocomonoenol) provides enhanced antioxidant protection in marine organisms adapted to cold-water environments. by Yamamoto Y, Fujisawa A, Hara A, Dunlap WC.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60838

•

Autoxidation of Lipids and Antioxidation by [alpha]-Tocopherol and Ubiquinol in Homogeneous Solution and in Aqueous Dispersions of Lipids: Unrecognized Consequences of Lipid Particle Size as Exemplified by Oxidation of Human Low Density Lipoprotein. by Ingold KU, Bowry VW, Stocker R, Walling C.; 1993 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45596

•

d-[alpha]-Tocopherol Inhibition of Vascular Smooth Muscle Cell Proliferation Occurs at Physiological Concentrations, Correlates with Protein Kinase C Inhibition, and is Independent of Its Antioxidant Properties. by Tasinato A, Boscoboinik D, Bartoli G, Maroni P, Azzi A.; 1995 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40322

•

Delayed-onset ataxia in mice lacking [alpha]-tocopherol transfer protein: Model for neuronal degeneration caused by chronic oxidative stress. by Yokota T, Igarashi K, Uchihara T, Jishage KI, Tomita H, Inaba A, Li Y, Arita M, Suzuki H, Mizusawa H, Arai H.; 2001 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65004

•

Effect of alpha-tocopherol on pulmonary antioxidant defence system and lipid peroxidation in cigarette smoke inhaling mice. by Koul A, Bhatia V, Bansal MP.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60661

•

Enhanced Formation of [alpha]-Tocopherol and Highly Oxidized Abietane Diterpenes in Water-Stressed Rosemary Plants. by Munne-Bosch S, Schwarz K, Alegre L.; 1999 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59469

•

Gamma ([gamma]) tocopherol upregulates peroxisome proliferator activated receptor (PPAR) gamma ([gamma]) expression in SW 480 human colon cancer cell lines. by Campbell SE, Stone WL, Whaley SG, Qui M, Krishnan K.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=222914

•

Growth Factors and Vitamin E Modify Neuronal Glutamate Toxicity. by Schubert D, Kimura H, Maher P.; 1992 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49898

Studies

69

•

High dietary level of synthetic vitamin E on lipid peroxidation, membrane fatty acid composition and cytotoxicity in breast cancer xenograft and in mouse host tissue. by Cameron IL, Munoz J, Barnes CJ, Hardman WE.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153528

•

Human Plasma Vitamin E Kinetics Demonstrate Rapid Recycling of Plasma RRR[alpha]-Tocopherol. by Traber MG, Ramakrishnan R, Kayden HJ.; 1994 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44946

•

Increased atherosclerosis in hyperlipidemic mice deficient in [alpha]-tocopherol transfer protein and vitamin E. by Terasawa Y, Ladha Z, Leonard SW, Morrow JD, Newland D, Sanan D, Packer L, Traber MG, Farese RV Jr.; 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17661

•

Isolation of an Arabidopsis mutant lacking vitamin E and identification of a cyclase essential for all tocopherol biosynthesis. by Porfirova S, Bergmuller E, Tropf S, Lemke R, Dormann P.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129473

•

Long-term vitamin E supplementation fails to reduce lipid peroxidation in people at cardiovascular risk: analysis of underlying factors. by Chiabrando C, Avanzini F, Rivalta C, Colombo F, Fanelli R, Palumbo G, Roncaglioni MC.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134477

•

Nitration of [gamma]-tocopherol and oxidation of [alpha]-tocopherol by copper-zinc superoxide dismutase /H2O2 /NO2 [minus sign]: Role of nitrogen dioxide free radical. by Singh RJ, Goss SP, Joseph J, Kalyanaraman B.; 1998 Oct 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23652

•

Occurrence of alpha-tocopherolquinone and alpha-tocopherolquinol in microorganisms. by Hughes PE, Tove SB.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=220420

•

On the Mechanism of the Anticlotting Action of Vitamin E Quinone. by Dowd P, Zheng ZB.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41118

•

Oxidative Susceptibility of Low Density Lipoprotein Subfractions is Related to their Ubiquinol-10 and [alpha]-Tocopherol Content. by Tribble DL, Berg JJ, Motchnik PA, Ames BN, Lewis DM, Chait A, Krauss RM.; 1994 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43118

•

Reduced Activity of Geranylgeranyl Reductase Leads to Loss of Chlorophyll and Tocopherol and to Partially Geranylgeranylated Chlorophyll in Transgenic Tobacco Plants Expressing Antisense RNA for Geranylgeranyl Reductase. by Tanaka R, Oster U, Kruse E, Rudiger W, Grimm B.; 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59307

•

The Roles of Coenzyme Q10 and Vitamin E on the Peroxidation of Human Low Density Lipoprotein Subfractions. by Alleva R, Tomasetti M, Battino M, Curatola G, Littarru GP, Folkers K.; 1995 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40990

70

Vitamin E

•

The uptake of tocopherols by RAW 264.7 macrophages. by Gao R, Stone WL, Huang T, Papas AM, Qui M.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139959

•

Ubiquinol-10 Protects Human Low Density Lipoprotein More Efficiently Against Lipid Peroxidation Than Does [alpha]-Tocopherol. by Stocker R, Bowry VW, Frei B.; 1991 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51081

•

Vitamin C and Vitamin E in Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in Choline Deficient Diet Fed Rats. by Oliveira CP, Gayotto LC, Tatai C, Nina BI, Lima ES, Abdalla DS, Lopasso FP, Laurindo FR, Carrilho FJ.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=270010

•

Vitamin E inhibits CD95 ligand expression and protects T cells from activationinduced cell death. by Li-Weber M, Weigand MA, Giaisi M, Suss D, Treiber MK, Baumann S, Ritsou E, Breitkreutz R, Krammer PH.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151103

•

Vitamin E Prevents Oxidative Modification of Brain and Lymphocyte Band 3 Proteins during Aging. by Poulin JE, Cover C, Gustafson MR, Kay MM.; 1996 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39293

•

Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model. by Factor VM, Laskowska D, Jensen MR, Woitach JT, Popescu NC, Thorgeirsson SS.; 2000 Feb 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15777

•

Vitamin E succinate inhibits the function of androgen receptor and the expression of prostate-specific antigen in prostate cancer cells. by Zhang Y, Ni J, Messing EM, Chang E, Yang CR, Yeh S.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124244

•

Vitamin E supplementation and macular degeneration: randomised controlled trial. by Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ.; 2002 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116664

•

Vitamin E-deficient diets enriched with fish oil suppress lethal Plasmodium yoelii infections in athymic and scid/bg mice. by Taylor DW, Levander OA, Krishna VR, Evans CB, Morris VC, Barta JR.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174576

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater 6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

Studies

71

number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with vitamin E, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “vitamin E” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for vitamin E (hyperlinks lead to article summaries): •

A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Author(s): Desnuelle C, Dib M, Garrel C, Favier A. Source: Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases. 2001 March; 2(1): 9-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11465936&dopt=Abstract

•

A family with spinocerebellar ataxia type 8 expansion and vitamin E deficiency ataxia. Author(s): Cellini E, Piacentini S, Nacmias B, Forleo P, Tedde A, Bagnoli S, Ciantelli M, Sorbi S. Source: Archives of Neurology. 2002 December; 59(12): 1952-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470185&dopt=Abstract

•

A pilot study on the relation between cisplatin neuropathy and vitamin E. Author(s): Bove L, Picardo M, Maresca V, Jandolo B, Pace A. Source: J Exp Clin Cancer Res. 2001 June; 20(2): 277-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11484987&dopt=Abstract

•

A prospective study on supplemental vitamin e intake and risk of colon cancer in women and men. Author(s): Wu K, Willett WC, Chan JM, Fuchs CS, Colditz GA, Rimm EB, Giovannucci EL. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1298-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433706&dopt=Abstract

72

Vitamin E

•

A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Author(s): Malmberg KJ, Lenkei R, Petersson M, Ohlum T, Ichihara F, Glimelius B, Frodin JE, Masucci G, Kiessling R. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 June; 8(6): 1772-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060616&dopt=Abstract

•

A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formation. Author(s): Sparrow JR, Vollmer-Snarr HR, Zhou J, Jang YP, Jockusch S, Itagaki Y, Nakanishi K. Source: The Journal of Biological Chemistry. 2003 May 16; 278(20): 18207-13. Epub 2003 March 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646558&dopt=Abstract

•

Alpha-tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial. Author(s): Tornwall ME, Virtamo J, Haukka JK, Albanes D, Huttunen JK. Source: Atherosclerosis. 2001 July; 157(1): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427217&dopt=Abstract

•

Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Author(s): Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu CR, Liu CH, Hwang J, Selzer RH, Azen SP; VEAPS Research Group. Source: Circulation. 2002 September 17; 106(12): 1453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234947&dopt=Abstract

•

Alpha-tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: a review. Author(s): Prasad KN, Kumar B, Yan XD, Hanson AJ, Cole WC. Source: Journal of the American College of Nutrition. 2003 April; 22(2): 108-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672706&dopt=Abstract

•

Alteration of Vitamin E levels in patients with pancreatic adenocarcinoma. Author(s): Wang DF, Qu XC, Dai ZQ. Source: Di Yi June Yi Da Xue Xue Bao. 2002 March; 22(3): 210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390764&dopt=Abstract

Studies

73

•

An argument for Vitamin E supplementation in the management of systemic inflammatory response syndrome. Author(s): Bulger EM, Maier RV. Source: Shock (Augusta, Ga.). 2003 February; 19(2): 99-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578114&dopt=Abstract

•

An update: vitamin E supplementation and heart disease. Author(s): Blumberg JB. Source: Nutrition in Clinical Care : an Official Publication of Tufts University. 2002 March-April; 5(2): 50-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134710&dopt=Abstract

•

Analysis of glutathionyl hemoglobin levels in diabetic patients by electrospray ionization liquid chromatography-mass spectrometry: effect of vitamin E administration. Author(s): Naito C, Niwa T. Source: J Chromatogr B Biomed Sci Appl. 2000 September 1; 746(1): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11048744&dopt=Abstract

•

Antioxidant capacity in Fasciola hepatica patients before and after treatment with triclabendazole alone or in combination with ascorbic acid (vitamin C) and tocofersolan (vitamin E). Author(s): Rehim WM, Sharaf IA, Hishmat M, el-Toukhy MA, Rawash NA, Fouad HN. Source: Arzneimittel-Forschung. 2003; 53(3): 214-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705178&dopt=Abstract

•

Antioxidants and the response of skin to oxidative stress: vitamin E as a key indicator. Author(s): Packer L, Valacchi G. Source: Skin Pharmacology and Applied Skin Physiology. 2002 September-October; 15(5): 282-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239421&dopt=Abstract

•

Antioxidative properties of coenzyme Q10 and vitamin E in exposure to xylene and gasoline and their mixture with methanol. Author(s): Piotrowska D, Dlugosz A, Pajak J. Source: Acta Pol Pharm. 2002 November-December; 59(6): 427-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669764&dopt=Abstract

74

Vitamin E

•

Arachidonate cascade, apoptosis, and vitamin E in peripheral blood mononuclear cells from hemodialysis patients. Author(s): Maccarrone M, Manca-di-Villahermosa S, Meloni C, Massoud R, Mascali A, Guarina R, Finazzi-Agro A, Taccone-Gallucci M. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 September; 40(3): 600-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200813&dopt=Abstract

•

Assessment of DNA strand breakage by the alkaline COMET assay in dialysis patients and the role of Vitamin E supplementation. Author(s): Kan E, Undeger U, Bali M, Basaran N. Source: Mutation Research. 2002 September 26; 520(1-2): 151-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297155&dopt=Abstract

•

Ataxia with isolated vitamin E deficiency: a clinical, biochemical and genetic diagnosis. Author(s): Alex G, Oliver MR, Collins KJ. Source: Journal of Paediatrics and Child Health. 2000 October; 36(5): 515-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11036814&dopt=Abstract

•

Ataxia with vitamin E deficiency and severe dystonia: report of a case. Author(s): Roubertie A, Biolsi B, Rivier F, Humbertclaude V, Cheminal R, Echenne B. Source: Brain & Development. 2003 September; 25(6): 442-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907280&dopt=Abstract

•

Baseline ophthalmic findings in the vitamin E, cataract and age-related maculopathy (VECAT) study. Author(s): Robman LD, Tikellis G, Garrett SK, Harper CA, McNeil JJ, Taylor HR, McCarty CA. Source: Australian and New Zealand Journal of Ophthalmology. 1999 December; 27(6): 410-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641899&dopt=Abstract

•

Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia. Author(s): Green D, O'Driscoll G, Rankin JM, Maiorana AJ, Taylor RR. Source: Clinical Science (London, England : 1979). 1998 September; 95(3): 361-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9730857&dopt=Abstract

Studies

75

•

Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Author(s): Gurney ME, Cutting FB, Zhai P, Doble A, Taylor CP, Andrus PK, Hall ED. Source: Annals of Neurology. 1996 February; 39(2): 147-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8967745&dopt=Abstract

•

Benefits of vitamin E supplementation to Norplant users--in vitro and in vivo studies. Author(s): Subakir SB, Setiadi E, Affandi B, Pringgoutomo S, Freisleben HJ. Source: Toxicology. 2000 August 7; 148(2-3): 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10962136&dopt=Abstract

•

Beta carotene, vitamin E, and lung cancer. Author(s): Ballmer PE, Stahelin HB. Source: The New England Journal of Medicine. 1994 September 1; 331(9): 612-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8047093&dopt=Abstract

•

Beta carotene, vitamin E, and lung cancer. Author(s): Pryor WA. Source: The New England Journal of Medicine. 1994 September 1; 331(9): 612; Author Reply 613. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8047092&dopt=Abstract

•

Beta-carotene, vitamin C, and vitamin E and cardiovascular diseases. Author(s): Dagenais GR, Marchioli R, Yusuf S, Tognoni G. Source: Current Cardiology Reports. 2000 July; 2(4): 293-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10953262&dopt=Abstract

•

Beta-carotene, vitamin C, and vitamin E: the protective micronutrients. Author(s): Charleux JL. Source: Nutrition Reviews. 1996 November; 54(11 Pt 2): S109-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9110586&dopt=Abstract

•

Beyond cholesterol reduction in coronary heart disease: is vitamin E the answer? Author(s): Cockcroft J, Chowienczyk P. Source: Heart (British Cardiac Society). 1996 October; 76(4): 293-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8983670&dopt=Abstract

•

Bioavailability of vitamin E as function of food intake in healthy subjects: effects on plasma peroxide-scavenging activity and cholesterol-oxidation products. Author(s): Iuliano L, Micheletta F, Maranghi M, Frati G, Diczfalusy U, Violi F. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 October; 21(10): E34-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597949&dopt=Abstract

76

Vitamin E

•

Bioavailability of vitamin E. Author(s): Cohn W. Source: European Journal of Clinical Nutrition. 1997 January; 51 Suppl 1: S80-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9023489&dopt=Abstract

•

Bioconversion of vitamin E acetate in human skin. Author(s): Nabi Z, Tavakkol A, Dobke M, Polefka TG. Source: Current Problems in Dermatology. 2001; 29: 175-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225197&dopt=Abstract

•

Biokinetics in humans of RRR-alpha-tocopherol: the free phenol, acetate ester, and succinate ester forms of vitamin E. Author(s): Cheeseman KH, Holley AE, Kelly FJ, Wasil M, Hughes L, Burton G. Source: Free Radical Biology & Medicine. 1995 November; 19(5): 591-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8529918&dopt=Abstract

•

Biological effects of oxidant stress in haemodialysis: the possible roles of vitamin E. Author(s): Galli F, Canestrari F, Buoncristiani U. Source: Blood Purification. 1999; 17(2-3): 79-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10449865&dopt=Abstract

•

Biological variability in serum vitamin E concentrations: relation to serum lipids. Author(s): Maes M, Weeckx S, Wauters A, Neels H, Scharpe S, Verkerk R, Demedts P, Desnyder R. Source: Clinical Chemistry. 1996 November; 42(11): 1824-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8906083&dopt=Abstract

•

Bioreactivity and biocompatibility of a vitamin E-modified multi-layer hemodialysis filter. Author(s): Galli F, Rovidati S, Chiarantini L, Campus G, Canestrari F, Buoncristiani U. Source: Kidney International. 1998 August; 54(2): 580-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9690226&dopt=Abstract

•

Biphasic action of vitamin E on the growth of human oral squamous carcinoma cells. Author(s): Elattar TM, Virji AS. Source: Anticancer Res. 1999 January-February; 19(1A): 365-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10226568&dopt=Abstract

Studies

77

•

Blood antioxidants (vitamin E and beta-carotene) in long-term low density lipoprotein apheresis. Author(s): Assogba U, Lepage S, Bruckert E, Bonnefont-Rousselot D, Dairou F, de Gennes JL, Delattre J. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1995 March 31; 235(2): 147-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7554269&dopt=Abstract

•

Blood oxidative stress and lipoprotein oxidizability in haemodialysis patients: effect of the use of a vitamin E-coated dialysis membrane. Author(s): Bonnefont-Rousselot D, Lehmann E, Jaudon MC, Delattre J, Perrone B, Rechke JP. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 December; 15(12): 2020-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11096149&dopt=Abstract

•

By the way, doctor. I take vitamin E pills, but I've heard they can cause bleeding. Is this anything to worry about? Author(s): Bistrian B. Source: Harvard Health Letter / from Harvard Medical School. 2002 December; 28(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499152&dopt=Abstract

•

Characterization of the vitamin E-binding properties of human plasma afamin. Author(s): Voegele AF, Jerkovic L, Wellenzohn B, Eller P, Kronenberg F, Liedl KR, Dieplinger H. Source: Biochemistry. 2002 December 10; 41(49): 14532-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463752&dopt=Abstract

•

Clinical trials of vitamin E in coronary artery disease: is it time to reconsider the lowdensity lipoprotein oxidation hypothesis? Author(s): Heinecke JW. Source: Current Atherosclerosis Reports. 2003 March; 5(2): 83-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573190&dopt=Abstract

•

Clinical trials with vitamin E in cardiovascular disease: are they meaningful? Author(s): Violi F, Micheletta F, Iuliano L. Source: Thrombosis and Haemostasis. 2001 October; 86(4): 1121-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11686337&dopt=Abstract

78

Vitamin E

•

Clinicopathological report of retinitis pigmentosa with vitamin E deficiency caused by mutation of the alpha-tocopherol transfer protein gene. Author(s): Pang J, Kiyosawa M, Seko Y, Yokota T, Harino S, Suzuki J. Source: Japanese Journal of Ophthalmology. 2001 November-December; 45(6): 672-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754917&dopt=Abstract

•

Co- and multimedication in users of ASA and vitamin E drugs in the Federal Republic of Germany. Results of the Federal Health Surveys 1984-1999. Author(s): Melchert HU, Knopf H, Pabel E, Braemer-Hauth M, Du Y. Source: Int J Clin Pharmacol Ther. 2001 November; 39(11): 488-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11727969&dopt=Abstract

•

Cognitive function in elderly people is influenced by vitamin E status. Author(s): Ortega RM, Requejo AM, Lopez-Sobaler AM, Andres P, Navia B, Perea JM, Robles F. Source: The Journal of Nutrition. 2002 July; 132(7): 2065-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097694&dopt=Abstract

•

Combination therapy of donepezil and vitamin E in Alzheimer disease. Author(s): Klatte ET, Scharre DW, Nagaraja HN, Davis RA, Beversdorf DQ. Source: Alzheimer Disease and Associated Disorders. 2003 April-June; 17(2): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794389&dopt=Abstract

•

Combined intralesional interferon alpha 2B and oral vitamin E in the treatment of Peyronie's disease. Author(s): Novak TE, Bryan W, Templeton L, Sikka S, Hellstrom WJ. Source: J La State Med Soc. 2001 July; 153(7): 358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11519219&dopt=Abstract

•

Combined treatment with vitamin E and colchicine in the early stages of Peyronie's disease. Author(s): Prieto Castro RM, Leva Vallejo ME, Regueiro Lopez JC, Anglada Curado FJ, Alvarez Kindelan J, Requena Tapia MJ. Source: Bju International. 2003 April; 91(6): 522-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12656907&dopt=Abstract

•

Combined vitamin E and vitamin C supplement use and risk of cardiovascular disease mortality. Author(s): Simon JA. Source: Archives of Internal Medicine. 2002 December 9-23; 162(22): 2630; Author Reply 2630. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456238&dopt=Abstract

Studies

79

•

Comments on the new dietary reference intake for vitamin E. Author(s): Bieri JG. Source: The American Journal of Clinical Nutrition. 2002 April; 75(4): 781; Author Reply 781-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916770&dopt=Abstract

•

Comparing beta-carotene, vitamin E and nitric oxide as membrane antioxidants. Author(s): Schafer FQ, Wang HP, Kelley EE, Cueno KL, Martin SM, Buettner GR. Source: Biological Chemistry. 2002 March-April; 383(3-4): 671-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033456&dopt=Abstract

•

Comparison of a vitamin E-rich diet and supplemental vitamin E on measures of vitamin E status and lipoprotein profile. Author(s): McGavin JK, Mann JI, Skeaff CM, Chisholm A. Source: European Journal of Clinical Nutrition. 2001 July; 55(7): 555-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11464229&dopt=Abstract

•

Comparison of the antioxidant effects of equine estrogens, red wine components, vitamin E, and probucol on low-density lipoprotein oxidation in postmenopausal women. Author(s): Bhavnani BR, Cecutti A, Gerulath A, Woolever AC, Berco M. Source: Menopause (New York, N.Y.). 2001 November-December; 8(6): 408-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723413&dopt=Abstract

•

Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: a randomized trial. Author(s): Strauss JS, Gottlieb AB, Jones T, Koo JY, Leyden JJ, Lucky A, Pappas AA, McLane J, Leach EE. Source: Journal of the American Academy of Dermatology. 2000 November; 43(5 Pt 1): 777-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050580&dopt=Abstract

•

Contraction-induced muscle damage is unaffected by vitamin E supplementation. Author(s): Beaton LJ, Allan DA, Tarnopolsky MA, Tiidus PM, Phillips SM. Source: Medicine and Science in Sports and Exercise. 2002 May; 34(5): 798-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11984298&dopt=Abstract

•

Coxsackievirus B3-resistant mice become susceptible in Se/vitamin E deficiency. Author(s): Beck MA, Williams-Toone D, Levander OA. Source: Free Radical Biology & Medicine. 2003 May 15; 34(10): 1263-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12726914&dopt=Abstract

80

Vitamin E

•

Cytochrome P450 omega-hydroxylase pathway of tocopherol catabolism. Novel mechanism of regulation of vitamin E status. Author(s): Sontag TJ, Parker RS. Source: The Journal of Biological Chemistry. 2002 July 12; 277(28): 25290-6. Epub 2002 May 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997390&dopt=Abstract

•

Cytokines and NASH: a pilot study of the effects of lifestyle modification and vitamin E. Author(s): Kugelmas M, Hill DB, Vivian B, Marsano L, McClain CJ. Source: Hepatology (Baltimore, Md.). 2003 August; 38(2): 413-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883485&dopt=Abstract

•

Cytotoxicity in ciprofloxacin-treated human fibroblast cells and protection by vitamin E. Author(s): Gurbay A, Garrel C, Osman M, Richard MJ, Favier A, Hincal F. Source: Human & Experimental Toxicology. 2002 December; 21(12): 635-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12540033&dopt=Abstract

•

D-alpha-tocopheryl succinate (vitamin E) enhances radiation-induced chromosomal damage levels in human cancer cells, but reduces it in normal cells. Author(s): Kumar B, Jha MN, Cole WC, Bedford JS, Prasad KN. Source: Journal of the American College of Nutrition. 2002 August; 21(4): 339-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166531&dopt=Abstract

•

Diet supplementation with vitamin E, vitamin C and beta-carotene cocktail enhances basal neutrophil antioxidant enzymes in athletes. Author(s): Tauler P, Aguilo A, Fuentespina E, Tur JA, Pons A. Source: Pflugers Archiv : European Journal of Physiology. 2002 March; 443(5-6): 791-7. Epub 2002 January 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11889577&dopt=Abstract

•

Dietary intake of vitamin E and folic acid in a defined population in Sri Lanka. Author(s): Mendis S, Bulugahapitiya DU, Ranatunga PK, Gunawardene PR, Kandegedera PG. Source: Ceylon Med J. 1999 March; 44(1): 25-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10643094&dopt=Abstract

•

Dietary intakes and serum concentrations of vitamin E and total carotenoids of healthy adults with severe physical disabilities are lower than matched controls. Author(s): Burri BJ, Neidlinger TR. Source: Journal of the American Dietetic Association. 2002 December; 102(12): 1804-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487545&dopt=Abstract

Studies

81

•

Dietary reference intakes for the antioxidant nutrients: vitamin C, vitamin E, selenium, and carotenoids. Author(s): Monsen ER. Source: Journal of the American Dietetic Association. 2000 June; 100(6): 637-40. Erratum In: J Am Diet Assoc 2000 September; 100(9): 1008-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10863565&dopt=Abstract

•

Dietary vitamin E and Parkinson's disease: something to chew on. Author(s): Olanow CW. Source: Lancet. Neurology. 2003 February; 2(2): 74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849259&dopt=Abstract

•

Dietary vitamin E and selenium and toxicity of nitrite and nitrate. Author(s): Chow CK, Hong CB. Source: Toxicology. 2002 November 15; 180(2): 195-207. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324194&dopt=Abstract

•

Dietary vitamin E and T cell-mediated function in the elderly: effectiveness and mechanism of action. Author(s): Serafini M. Source: International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience. 2000 July-August; 18(4-5): 40110. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817923&dopt=Abstract

•

Different isoforms of tocopherols enhance nitric oxide synthase phosphorylation and inhibit human platelet aggregation and lipid peroxidation: implications in therapy with vitamin E. Author(s): Li D, Saldeen T, Romeo F, Mehta JL. Source: Journal of Cardiovascular Pharmacology and Therapeutics. 2001 April; 6(2): 15561. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509922&dopt=Abstract

•

Direct evidence for bioconversion of vitamin E acetate into vitamin E: an ex vivo study in viable human skin. Author(s): Baschong W, Artmann C, Hueglin D, Roeding J. Source: J Cosmet Sci. 2001 May-June; 52(3): 155-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11413495&dopt=Abstract

82

Vitamin E

•

Direct evidence for recycling of myeloperoxidase-catalyzed phenoxyl radicals of a vitamin E homologue, 2,2,5,7,8-pentamethyl-6-hydroxy chromane, by ascorbate/dihydrolipoate in living HL-60 cells. Author(s): Kagan VE, Kuzmenko AI, Shvedova AA, Kisin ER, Li R, Martin I, Quinn PJ, Tyurin VA, Tyurina YY, Yalowich JC. Source: Biochimica Et Biophysica Acta. 2003 March 17; 1620(1-3): 72-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595076&dopt=Abstract

•

Do fish oils or vitamin E reduce morbidity and mortality after myocardial infarction? Author(s): Rand PJ, Schooff M. Source: The Journal of Family Practice. 1999 November; 48(11): 847-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907618&dopt=Abstract

•

Docosahexaenoic acid and vitamin E can reduce human monocytic U937 cell apoptosis induced by tumor necrosis factor. Author(s): Yano M, Kishida E, Iwasaki M, Kojo S, Masuzawa Y. Source: The Journal of Nutrition. 2000 May; 130(5): 1095-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801904&dopt=Abstract

•

Does vitamin E beneficially affect muscle pains during HMG-Co-enzyme-Areductase inhibitors without CK-elevation? Author(s): Sinzinger H. Source: Atherosclerosis. 2000 March; 149(1): 225. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799017&dopt=Abstract

•

Does vitamin E decrease heart attack risk? summary and implications with respect to dietary recommendations. Author(s): Traber MG. Source: The Journal of Nutrition. 2001 February; 131(2): 395S-7S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11160568&dopt=Abstract

•

Does vitamin E protect against cognitive changes as we age? Author(s): Tangney CC. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 October; 17(10): 806-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684384&dopt=Abstract

•

Does vitamin E supplementation prevent cardiovascular events? Author(s): Manson JE, Bassuk SS, Stampfer MJ. Source: Journal of Women's Health (2002). 2003 March; 12(2): 123-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741415&dopt=Abstract

Studies

83

•

Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderatesevere Alzheimer's disease. Author(s): Onofrj M, Thomas A, Luciano AL, Iacono D, Di Rollo A, D'Andreamatteo G, Di Iorio A. Source: Clinical Neuropharmacology. 2002 July-August; 25(4): 207-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151908&dopt=Abstract

•

Donepezil, rivastigmine, and vitamin E in Alzheimer disease: a combined P300 eventrelated potentials/neuropsychologic evaluation over 6 months. Author(s): Thomas A, Iacono D, Bonanni L, D'Andreamatteo G, Onofrj M. Source: Clinical Neuropharmacology. 2001 January-February; 24(1): 31-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11290880&dopt=Abstract

•

Dual effect of glucose on LDL oxidation: dependence on vitamin E. Author(s): Otero P, Herrera E, Bonet B. Source: Free Radical Biology & Medicine. 2002 October 15; 33(8): 1133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374625&dopt=Abstract

•

Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. Author(s): Graat JM, Schouten EG, Kok FJ. Source: Jama : the Journal of the American Medical Association. 2002 August 14; 288(6): 715-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169075&dopt=Abstract

•

Effect of oral vitamin E supplementation in children with cholestasis. Author(s): Roongpraiwan R, Suthutvoravut U, Feungpean B, Phuapradit P. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549795&dopt=Abstract

•

Effect of vitamin E on resistance vessel endothelial dysfunction induced by methionine. Author(s): Raghuveer G, Sinkey CA, Chenard C, Stumbo P, Haynes WG. Source: The American Journal of Cardiology. 2001 August 1; 88(3): 285-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11472709&dopt=Abstract

•

Effect of vitamin E supplementation on circulating cell adhesion molecules pre- and post-coronary angioplasty. Author(s): Ferns GA, Forster LA, Williams JC, Tull SP, Verma PK, Starkey B, Gershlick AH. Source: Annals of Clinical Biochemistry. 2000 September; 37 ( Pt 5): 649-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11026517&dopt=Abstract

84

Vitamin E

•

Effect of vitamin E treatment on the oxidative damage occurring in Henoch-Schonlein purpura. Author(s): Erdogan O, Oner A, Aydin A, Isimer A, Demircin G, Bulbul M. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 May; 92(5): 546-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839282&dopt=Abstract

•

Effects of a vitamin E-bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients. Author(s): Usberti M, Gerardi G, Micheli A, Tira P, Bufano G, Gaggia P, Movilli E, Cancarini GC, De Marinis S, D'Avolio G, Broccoli R, Manganoni A, Albertin A, Di Lorenzo D. Source: Journal of Nephrology. 2002 September-October; 15(5): 558-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455724&dopt=Abstract

•

Effects of a vitamin E-modified dialysis membrane and vitamin C infusion on oxidative stress in hemodialysis patients. Author(s): Eiselt J, Racek J, Trefil L, Opatrny K Jr. Source: Artificial Organs. 2001 June; 25(6): 430-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453871&dopt=Abstract

•

Effects of combined in vivo treatment of transplantable solid mammary carcinoma in wistar rats using vitamin E and cysteine peptidase inhibitors from human placenta. Author(s): Saleh Y, Siewinski M, Sebzda T, Grybos M, Pawelec M, Janocha A. Source: Journal of Experimental Therapeutics & Oncology. 2003 March-April; 3(2): 95102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822515&dopt=Abstract

•

Effects of erythropoietin and vitamin E-modified membrane on plasma oxidative stress markers and anemia of hemodialyzed patients. Author(s): Usberti M, Gerardi G, Bufano G, Tira P, Micheli A, Albertini A, Floridi A, Di Lorenzo D, Galli F. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 September; 40(3): 590-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200812&dopt=Abstract

•

Effects of metabolic control on vitamin E nutritional status in children with type 1 diabetes mellitus. Author(s): Campoy C, Baena RM, Blanca E, Lopez-Sabater C, Fernandez-Garcia JM, Miranda MT, Molina-Font JA, Bayes R. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 February; 22(1): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553954&dopt=Abstract

Studies

85

•

Effects of vitamin C and vitamin E on in vivo lipid peroxidation: results of a randomized controlled trial. Author(s): Huang HY, Appel LJ, Croft KD, Miller ER 3rd, Mori TA, Puddey IB. Source: The American Journal of Clinical Nutrition. 2002 September; 76(3): 549-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197998&dopt=Abstract

•

Effects of vitamin E and prostaglandin E2 on expression of CREB1 and CREB2 proteins by human T lymphocytes. Author(s): Valenti A, Venza I, Venza M, Fimiani V, Teti D. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2000; 49(3): 363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043924&dopt=Abstract

•

Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy. Author(s): Lonn E, Yusuf S, Hoogwerf B, Pogue J, Yi Q, Zinman B, Bosch J, Dagenais G, Mann JF, Gerstein HC; HOPE Study; MICRO-HOPE Study. Source: Diabetes Care. 2002 November; 25(11): 1919-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401733&dopt=Abstract

•

Effects of vitamin E on the endothelium: equivocal? Alpha-tocopherol and endothelial dysfunction. Author(s): Visioli F. Source: Cardiovascular Research. 2001 August 1; 51(2): 198-201. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470458&dopt=Abstract

•

Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity. Author(s): Pathak A, Roth P, Piscitelli J, Johnson L. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 July; 88(4): F324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819167&dopt=Abstract

•

Effects of vitamin E supplementation on blood antioxidants levels in patients with Behcet's disease. Author(s): Kokcam I, Naziroglu M. Source: Clinical Biochemistry. 2002 November; 35(8): 633-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498998&dopt=Abstract

86

Vitamin E

•

Enhanced susceptibility to oxidation and diminished vitamin E content of LDL from patients with stable coronary artery disease. Author(s): Haidari M, Javadi E, Kadkhodaee M, Sanati A. Source: Clinical Chemistry. 2001; 47(7): 1234-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427454&dopt=Abstract

•

Evaluation of the local effects of vitamin E (E-Mousse) on free radicals in diabetic microangiopathy: a randomized, controlled trial. Author(s): Ruffini I, Belcaro G, Cesarone MR, Geroulakos G, Di Renzo A, Milani M, Coen L, Ricci A, Brandolini R, Dugall M, Pomante P, Cornelli U, Acerbi G, Corsi M, Griffin M, Ippolito E, Bavera P. Source: Angiology. 2003 July-August; 54(4): 415-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934761&dopt=Abstract

•

Evidence for oxidative activation of c-Myc-dependent nuclear signaling in human coronary smooth muscle cells and in early lesions of Watanabe heritable hyperlipidemic rabbits: protective effects of vitamin E. Author(s): de Nigris F, Youssef T, Ciafre S, Franconi F, Anania V, Condorelli G, Palinski W, Napoli C. Source: Circulation. 2000 October 24; 102(17): 2111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044429&dopt=Abstract

•

Exercise and vitamin E intake are independently associated with metabolic abnormalities in human immunodeficiency virus-positive subjects: a cross-sectional study. Author(s): Gavrila A, Tsiodras S, Doweiko J, Nagy GS, Brodovicz K, Hsu W, Karchmer AW, Mantzoros CS. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1593-601. Epub 2003 Jun 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802761&dopt=Abstract

•

Failure of high-dose vitamin E to correct ceruloplasmin ferroxidase deficiency in cigarette smokers. Author(s): Pacht ER, Davis WB. Source: Am Rev Respir Dis. 1990 November; 142(5): 1063-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2240829&dopt=Abstract

•

Failure of supplementation with vitamin E to prevent bronchopulmonary dysplasia in infants less than 1,500 g birth weight. Author(s): Watts JL, Milner R, Zipursky A, Paes B, Ling E, Gill G, Fletcher B, Rand C. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1991 February; 4(2): 188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2044736&dopt=Abstract

Studies

87

•

Failure of vitamin E to protect cultured human arterial smooth muscle cells against oxysterol-induced cytotoxicity. Author(s): Zhou Q, Wasowicz E, Kummerow FA. Source: Journal of the American College of Nutrition. 1995 April; 14(2): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7790692&dopt=Abstract

•

Familial ataxia with isolated vitamin E deficiency not due to mutation of alpha-TTP. Author(s): Shiojiri T, Yokota T, Fujimori N, Mizusawa H. Source: Journal of Neurology. 1999 October; 246(10): 982. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10552255&dopt=Abstract

•

Familial isolated vitamin E deficiency. Extensive study of a large family with a 5-year therapeutic follow-up. Author(s): Amiel J, Maziere JC, Beucler I, Koenig M, Reutenauer L, Loux N, Bonnefont D, Feo C, Landrieu P. Source: Journal of Inherited Metabolic Disease. 1995; 18(3): 333-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7474901&dopt=Abstract

•

Fanconi anemia lymphocytes: effect of DL-alpha-tocopherol (Vitamin E) on chromatid breaks and on G2 repair efficiency. Author(s): Pincheira J, Bravo M, Santos MJ, de la Torre C, Lopez-Saez JF. Source: Mutation Research. 2001 January 5; 461(4): 265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104902&dopt=Abstract

•

Fish oil supplementation with and without added vitamin E differentially modulates plasma antioxidant concentrations in healthy women. Author(s): Turley E, Wallace JM, Gilmore WS, Strain JJ. Source: Lipids. 1998 December; 33(12): 1163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9930401&dopt=Abstract

•

Free radical activity and loss of plasma antioxidants, vitamin E, and sulfhydryl groups in patients with burns: the 1993 Moyer Award. Author(s): Nguyen TT, Cox CS, Traber DL, Gasser H, Redl H, Schlag G, Herndon DN. Source: The Journal of Burn Care & Rehabilitation. 1993 November-December; 14(6): 602-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8300695&dopt=Abstract

•

Free radical-induced biological damage and the critical roles of vitamin A, vitamin C, vitamin D and vitamin E and of copper, iron, selenium and zinc. Author(s): Willson RL. Source: J Nutr Sci Vitaminol (Tokyo). 1992; Spec No: 541-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1297807&dopt=Abstract

88

Vitamin E

•

Free radical-mediated chain oxidation of low density lipoprotein and its synergistic inhibition by vitamin E and vitamin C. Author(s): Sato K, Niki E, Shimasaki H. Source: Archives of Biochemistry and Biophysics. 1990 June; 279(2): 402-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2350187&dopt=Abstract

•

Friedreich's ataxia phenotype not linked to chromosome 9 and associated with selective autosomal recessive vitamin E deficiency in two inbred Tunisian families. Author(s): Ben Hamida M, Belal S, Sirugo G, Ben Hamida C, Panayides K, Ionannou P, Beckmann J, Mandel JL, Hentati F, Koenig M, et al. Source: Neurology. 1993 November; 43(11): 2179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8232925&dopt=Abstract

•

Friedreich's ataxia with isolated vitamin E deficiency: a neuropathological study of a Tunisian patient. Author(s): Larnaout A, Belal S, Zouari M, Fki M, Ben Hamida C, Goebel HH, Ben Hamida M, Hentati F. Source: Acta Neuropathologica. 1997 June; 93(6): 633-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9194904&dopt=Abstract

•

Friedreich's ataxia-vitamin E responsive type. The chromosome 8 locus. Author(s): Belal S, Hentati F, Ben Hamida C, Ben Hamida M. Source: Clin Neurosci. 1995; 3(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7614093&dopt=Abstract

•

Function of vitamin E and zinc in maintaining endothelial integrity. Implications in atherosclerosis. Author(s): Hennig B, McClain CJ, Diana JN. Source: Annals of the New York Academy of Sciences. 1993 May 28; 686: 99-109; Discussion 109-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8512265&dopt=Abstract

•

Function of vitamin E in physical exercise: a review. Author(s): Gerster H. Source: Zeitschrift Fur Ernahrungswissenschaft. 1991 June; 30(2): 89-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1897277&dopt=Abstract

•

Functional deterioration and selenium-vitamin E treatment in myotonic dystrophy. A placebo-controlled study. Author(s): Orndahl G, Grimby G, Grimby A, Johansson G, Wilhelmsen L. Source: Journal of Internal Medicine. 1994 March; 235(3): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8120515&dopt=Abstract

Studies

89

•

Future directions of vitamin E and its analogues in minimizing myocardial ischemiareperfusion injury. Author(s): Mickle DA, Weisel RD. Source: The Canadian Journal of Cardiology. 1993 January-February; 9(1): 89-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8439833&dopt=Abstract

•

gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Author(s): Jiang Q, Christen S, Shigenaga MK, Ames BN. Source: The American Journal of Clinical Nutrition. 2001 December; 74(6): 714-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722951&dopt=Abstract

•

Gamma-tocopherol, the new vitamin E? Author(s): Devaraj S, Traber MG. Source: The American Journal of Clinical Nutrition. 2003 March; 77(3): 530-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600839&dopt=Abstract

•

Generalized contact dermatitis from vitamin E. Author(s): Garcia-Bravo B, Mozo P. Source: Contact Dermatitis. 1992 April; 26(4): 280. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1395583&dopt=Abstract

•

Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy. Author(s): Goringe AP, Brown S, O'Callaghan U, Rees J, Jebb S, Elia M, Poynton CH. Source: Bone Marrow Transplantation. 1998 April; 21(8): 829-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9603409&dopt=Abstract

•

Glycosylated hemoglobin concentrations and vitamin E, vitamin C, and beta-carotene intake in diabetic and nondiabetic older adults. Author(s): Shoff SM, Mares-Perlman JA, Cruickshanks KJ, Klein R, Klein BE, Ritter LL. Source: The American Journal of Clinical Nutrition. 1993 September; 58(3): 412-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8237854&dopt=Abstract

•

Green tea catechins and vitamin E inhibit angiogenesis of human microvascular endothelial cells through suppression of IL-8 production. Author(s): Tang FY, Meydani M. Source: Nutrition and Cancer. 2001; 41(1-2): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094614&dopt=Abstract

90

Vitamin E

•

Growth inhibition and apoptosis of RL human B lymphoma cells by vitamin E succinate and retinoic acid: role for transforming growth factor beta. Author(s): Turley JM, Funakoshi S, Ruscetti FW, Kasper J, Murphy WJ, Longo DL, Birchenall-Roberts MC. Source: Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research. 1995 June; 6(6): 655-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7669719&dopt=Abstract

•

Growth inhibition of human hepatoma cells (HepG2) by polyunsaturated fatty acids. Protection by albumin and vitamin E. Author(s): Hostmark AT, Lystad E. Source: Acta Physiologica Scandinavica. 1992 January; 144(1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1317655&dopt=Abstract

•

Growth of human lung adenocarcinoma in nude mice is influenced by various types of dietary fat and vitamin E. Author(s): Maehle L, Lystad E, Eilertsen E, Einarsdottir E, Hostmark AT, Haugen A. Source: Anticancer Res. 1999 May-June; 19(3A): 1649-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10470096&dopt=Abstract

•

Haemolytic anaemia secondary to vitamin E deficiency in premature infants. Author(s): Kumar RK, Edwards KN, Bury G. Source: Indian J Pediatr. 2000 July; 67(7): 537-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10957841&dopt=Abstract

•

Haloperidol-induced extrapyramidal reaction: lack of protective effect by vitamin E. Author(s): Eranti VS, Gangadhar BN, Janakiramaiah N. Source: Psychopharmacology. 1998 December; 140(4): 418-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888616&dopt=Abstract

•

Health-related quality of life and long-term therapy with pravastatin and tocopherol (vitamin E) in older adults. Author(s): Carlsson CM, Papcke-Benson K, Carnes M, McBride PE, Stein JH. Source: Drugs & Aging. 2002; 19(10): 793-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390056&dopt=Abstract

•

Hemodialysis impairs endothelial function via oxidative stress: effects of vitamin Ecoated dialyzer. Author(s): Miyazaki H, Matsuoka H, Itabe H, Usui M, Ueda S, Okuda S, Imaizumi T. Source: Circulation. 2000 March 7; 101(9): 1002-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10704167&dopt=Abstract

Studies

91

•

Herbal drug curbicin and anticoagulant effect with and without warfarin: possibly related to the vitamin E component. Author(s): Yue QY, Jansson K. Source: Journal of the American Geriatrics Society. 2001 June; 49(6): 838. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454132&dopt=Abstract

•

High doses of vitamin E in the treatment of disorders of the central nervous system in the aged. Author(s): Vatassery GT, Bauer T, Dysken M. Source: The American Journal of Clinical Nutrition. 1999 November; 70(5): 793-801. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10539737&dopt=Abstract

•

High serum concentrations of vitamin E and cholesterol and low mortality from ischaemic heart disease in northern Finland. Author(s): Luoma P, Nayha S, Hassi J. Source: Arctic Med Res. 1995; 54 Suppl 2: 26-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8900828&dopt=Abstract

•

High vitamin E plasma levels and low low-density lipoprotein oxidation are associated with the absence of atherosclerosis in octogenarians. Author(s): Cherubini A, Zuliani G, Costantini F, Pierdomenico SD, Volpato S, Mezzetti A, Mecocci P, Pezzuto S, Bregnocchi M, Fellin R, Senin U; VASA Study Group. Source: Journal of the American Geriatrics Society. 2001 May; 49(5): 651-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380761&dopt=Abstract

•

High-dose vitamin E lowers urine porphyrin levels in patients affected by porphyria cutanea tarda. Author(s): Pinelli A, Trivulzio S, Tomasoni L, Bertolini B, Pinelli G. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2002 April; 45(4): 355-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030801&dopt=Abstract

•

High-dose vitamin E plus vitamin B6 treatment of risperidone-related neuroleptic malignant syndrome. Author(s): Dursun SM, Oluboka OJ, Devarajan S, Kutcher SP. Source: Journal of Psychopharmacology (Oxford, England). 1998; 12(2): 220-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9694035&dopt=Abstract

92

Vitamin E

•

High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes. Author(s): Bursell SE, Clermont AC, Aiello LP, Aiello LM, Schlossman DK, Feener EP, Laffel L, King GL. Source: Diabetes Care. 1999 August; 22(8): 1245-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480765&dopt=Abstract

•

Hollow-fiber dialyzer employing vitamin E-bonded membrane: a morphological analysis. Author(s): Ballestri M, Tonelli M, Inguaggiato P, Albertazzi A. Source: Contrib Nephrol. 1999; 127: 113-27. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629781&dopt=Abstract

•

Homocysteine and lipid peroxidation in haemodialysis: role of folinic acid and vitamin E. Author(s): Bayes B, Pastor MC, Bonal J, Junca J, Romero R. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 November; 16(11): 2172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682663&dopt=Abstract

•

Human alpha-tocopherol transfer protein: gene structure and mutations in familial vitamin E deficiency. Author(s): Hentati A, Deng HX, Hung WY, Nayer M, Ahmed MS, He X, Tim R, Stumpf DA, Siddique T, Ahmed. Source: Annals of Neurology. 1996 March; 39(3): 295-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8602747&dopt=Abstract

•

Human keratinocyte growth inhibition by ultraviolet B and the protective effect of vitamin E. Author(s): Du H, Ding ZH. Source: Di Yi June Yi Da Xue Xue Bao. 2003 April; 23(4): 326-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12697464&dopt=Abstract

•

Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with deuterated natural and synthetic vitamin E. Author(s): Burton GW, Traber MG, Acuff RV, Walters DN, Kayden H, Hughes L, Ingold KU. Source: The American Journal of Clinical Nutrition. 1998 April; 67(4): 669-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9537614&dopt=Abstract

Studies

93

•

Human plasma patterns during 14 days ingestion of vitamin E, beta-carotene, ascorbic acid, and their various combinations. Author(s): Baker H, DeAngelis B, Baker E, Khalil M, Frank O. Source: Journal of the American College of Nutrition. 1996 April; 15(2): 159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8778146&dopt=Abstract

•

Human plasma vitamin E kinetics demonstrate rapid recycling of plasma RRR-alphatocopherol. Author(s): Traber MG, Ramakrishnan R, Kayden HJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 1994 October 11; 91(21): 10005-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7937827&dopt=Abstract

•

Hydraulic and flow dynamic characteristics of vitamin E-bonded dialyzers. Author(s): Brendolan A, Ronco C, Ghezzi PM, La Greca G. Source: Contrib Nephrol. 1999; 127: 79-88. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629778&dopt=Abstract

•

Hypothesis: vitamin E complements polyunsaturated fatty acids in essential fatty acid deficiency in cystic fibrosis. Author(s): Wood LG, Fitzgerald DA, Garg ML. Source: Journal of the American College of Nutrition. 2003 August; 22(4): 253-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897038&dopt=Abstract

•

Immune dysfunction and cytokine production in hemodialysis. Could they be lessened by vitamin E-coated dialyzer membrane? Author(s): Senatore M, Cecere P, Colombo P, Costantini L, Filiberti O, Piccini G, Peona C, Buemi M, Nicoletti A, Rizzuto G. Source: Nephron. 2002 December; 92(4): 758-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399618&dopt=Abstract

•

Impaired discrimination between stereoisomers of alpha-tocopherol in patients with familial isolated vitamin E deficiency. Author(s): Traber MG, Sokol RJ, Kohlschutter A, Yokota T, Muller DP, Dufour R, Kayden HJ. Source: Journal of Lipid Research. 1993 February; 34(2): 201-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8429255&dopt=Abstract

94

Vitamin E

•

Impaired vitamin E status in patients with parenchymal liver cirrhosis: relationships with lipoprotein compositional alterations, nutritional factors, and oxidative susceptibility of plasma. Author(s): Ferre N, Camps J, Prats E, Girona J, Gomez F, Heras M, Simo JM, Ribalta J, Joven J. Source: Metabolism: Clinical and Experimental. 2002 May; 51(5): 609-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11979394&dopt=Abstract

•

Improved bioavailability of vitamin E with a self emulsifying formulation. Author(s): Julianto T, Yuen KH, Noor AM. Source: International Journal of Pharmaceutics. 2000 April 25; 200(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10845685&dopt=Abstract

•

Improvement of early functional atherosclerotic changes in males with hypercholesterolemia after vitamin E supplementation. Author(s): Borovnicar A, Keber I, Stavljenic Rukavina A, Yaletel Kragelj L. Source: Pflugers Archiv : European Journal of Physiology. 2000; 440(5 Suppl): R126-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005639&dopt=Abstract

•

In vitro antioxidant activity of 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6hydroxychroman (alpha-CEHC), a vitamin E metabolite. Author(s): Betancor-Fernandez A, Sies H, Stahl W, Polidori MC. Source: Free Radical Research. 2002 August; 36(8): 915-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420750&dopt=Abstract

•

Indication of vitamin E on microalbuminuria in patients with incipient diabetic nephropathy. Author(s): Yokoyama M, Torita M, Yoshizawa M, Usuda R. Source: Diabetes & Metabolism. 2001 November; 27(5 Pt 1): 611-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694862&dopt=Abstract

•

Induction of apoptosis by superoxide anion and the protective effects of selenium and Vitamin E. Author(s): Guo L, Xue AN, Wang SQ, Chen JY, Wu YD, Zhang B. Source: Biomed Environ Sci. 2001 September; 14(3): 241-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723725&dopt=Abstract

•

Infants discriminate between natural and synthetic vitamin E. Author(s): Stone WL, LeClair I, Ponder T, Baggs G, Reis BB. Source: The American Journal of Clinical Nutrition. 2003 April; 77(4): 899-906. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663289&dopt=Abstract

Studies

95

•

Influence of apolipoprotein E polymorphism on plasma vitamin A and vitamin E levels. Author(s): Gomez-Coronado D, Entrala A, Alvarez JJ, Ortega H, Olmos JM, Castro M, Sastre A, Herrera E, Lasuncion MA. Source: European Journal of Clinical Investigation. 2002 April; 32(4): 251-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952810&dopt=Abstract

•

Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. Author(s): Lassnigg A, Punz A, Barker R, Keznickl P, Manhart N, Roth E, Hiesmayr M. Source: British Journal of Anaesthesia. 2003 February; 90(2): 148-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538369&dopt=Abstract

•

Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer's disease. Author(s): Kontush A, Mann U, Arlt S, Ujeyl A, Luhrs C, Muller-Thomsen T, Beisiegel U. Source: Free Radical Biology & Medicine. 2001 August 1; 31(3): 345-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11461772&dopt=Abstract

•

Inhibitory activity of vitamin E and alpha-naphthoflavone on beta-carotene-enhanced transformation of BALB/c 3T3 cells by benzo(a)pyrene and cigarette-smoke condensate. Author(s): Perocco P, Mazzullo M, Broccoli M, Rocchi P, Ferreri AM, Paolini M. Source: Mutation Research. 2000 February 16; 465(1-2): 151-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10708981&dopt=Abstract

•

Inhibitory effects of vitamin E on endothelial-dependent adhesive interactions with leukocytes induced by oxidized low density lipoprotein. Author(s): Yoshida N, Manabe H, Terasawa Y, Nishimura H, Enjo F, Nishino H, Yoshikawa T. Source: Biofactors (Oxford, England). 2000; 13(1-4): 279-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11237194&dopt=Abstract

•

Intakes of carotenoids, vitamin C, and vitamin E and MS risk among two large cohorts of women. Author(s): Zhang SM, Hernan MA, Olek MJ, Spiegelman D, Willett WC, Ascherio A. Source: Neurology. 2001 July 10; 57(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445631&dopt=Abstract

96

Vitamin E

•

Inter- and intra-individual variation in plasma and red blood cell vitamin E after supplementation. Author(s): Roxborough HE, Burton GW, Kelly FJ. Source: Free Radical Research. 2000 October; 33(4): 437-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11022852&dopt=Abstract

•

Is the bioreactivity of vitamin-E-modified dialyzer an expression of increased plasmatic vitamin E concentration? Author(s): Senatore M, Nicoletti A, Rizzuto G. Source: Nephron. 2002 October; 92(2): 487-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218339&dopt=Abstract

•

Is the emperor wearing clothes? Clinical trials of vitamin E and the LDL oxidation hypothesis. Author(s): Heinecke JW. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 August; 21(8): 1261-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11498450&dopt=Abstract

•

Is the photoprotective effect of vitamin E based on its antioxidative capacity? Author(s): Podhaisky HP, Wohlrab W. Source: Journal of Dermatological Science. 2002 January; 28(1): 84-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916134&dopt=Abstract

•

Is vitamin E the magic bullet for the treatment of Alzheimer's disease (AD)? Author(s): Woo K. Source: Perspectives. 2000 Spring; 24(1): 7-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026332&dopt=Abstract

•

Lipid composition and vitamin E content in human colostrum and mature milk. Author(s): Barbas C, Herrera E. Source: J Physiol Biochem. 1998 September; 54(3): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217214&dopt=Abstract

•

Lipid peroxidase and erythrocyte redox system in systemic vasculitides treated with corticoids. Effect of vitamin E administration. Author(s): Serban MG, Balanescu E, Nita V. Source: Rom J Intern Med. 1994 October-December; 32(4): 283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7613501&dopt=Abstract

Studies

97

•

Lipid peroxidation and vitamin E in human coronary atherosclerotic lesions. Author(s): Jachec W, Tomasik A, Ceglarek W, Wos S, Wodniecki J, Wojciechowska C, Skrzep-Poloczek B, Walichiewicz P, Widenka K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 April; 330(1-2): 121-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636930&dopt=Abstract

•

Lipid peroxidation and vitamin E in ischemic heart disease. Author(s): Nand N, Budhiraja N, Singh GP, Sharma M, Aggarwal HK. Source: J Assoc Physicians India. 1997 November; 45(11): 839-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229180&dopt=Abstract

•

Lipid peroxidation and vitamin E levels in preeclampsia. Author(s): Kharb S, Gulati N, Singh V, Singh GP. Source: Gynecologic and Obstetric Investigation. 1998; 46(4): 238-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9813441&dopt=Abstract

•

Lipid peroxidation, leukocyte function and apoptosis in hemodialysis patients treated with vitamin E-modified filters. Author(s): Galli F, Rovidati S, Benedetti S, Canestrari F, Ferraro B, Floridi A, Buoncristiani U. Source: Contrib Nephrol. 1999; 127: 156-71. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629785&dopt=Abstract

•

Lipid peroxide, beta-carotene and alpha-tocopherol in ischaemic stroke and effect of exogenous vitamin E supplementation on outcome. Author(s): Daga MK, Madhuchhanda, Mishra TK, Mohan A. Source: J Assoc Physicians India. 1997 November; 45(11): 843-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229181&dopt=Abstract

•

Lipoprotein oxidation and plasma vitamin E in nondiabetic normotensive obese patients. Author(s): Myara I, Alamowitch C, Michel O, Heudes D, Bariety J, Guy-Grand B, Chevalier J. Source: Obesity Research. 2003 January; 11(1): 112-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529493&dopt=Abstract

•

Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders. Author(s): Copp RP, Wisniewski T, Hentati F, Larnaout A, Ben Hamida M, Kayden HJ. Source: Brain Research. 1999 March 20; 822(1-2): 80-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10082886&dopt=Abstract

98

Vitamin E

•

Localization of vitamin E in membranes. Author(s): Quinn PJ. Source: Subcell Biochem. 1998; 30: 319-43. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9932521&dopt=Abstract

•

Long-term effects of vitamin E, vitamin C, and combined supplementation on urinary 7-hydro-8-oxo-2'-deoxyguanosine, serum cholesterol oxidation products, and oxidation resistance of lipids in nondepleted men. Author(s): Porkkala-Sarataho E, Salonen JT, Nyyssonen K, Kaikkonen J, Salonen R, Ristonmaa U, Diczfalusy U, Brigelius-Flohe R, Loft S, Poulsen HE. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 September; 20(9): 208793. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10978253&dopt=Abstract

•

Long-term effects of vitamin E-bonded dialysis membrane on mononuclear cell activation, malondialdehyde generation and endothelial function in ESRD patients. Author(s): Schiecke G, Gwinner W, Radermacher J, Bahlmann J, Lonnemann G. Source: Contrib Nephrol. 1999; 127: 243-50. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629793&dopt=Abstract

•

Long-term pharmacologic doses of vitamin E only moderately affect the erythrocytes of patients with type 1 diabetes mellitus. Author(s): Manuel y Keenoy B, Shen H, Engelen W, Vertommen J, Van Dessel G, Lagrou A, De Leeuw I. Source: The Journal of Nutrition. 2001 June; 131(6): 1723-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11385059&dopt=Abstract

•

Long-term treatment effects of vitamin E for tardive dyskinesia. Author(s): Adler LA, Edson R, Lavori P, Peselow E, Duncan E, Rosenthal M, Rotrosen J. Source: Biological Psychiatry. 1998 June 15; 43(12): 868-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9627740&dopt=Abstract

•

Low concentrations of 17beta-estradiol reduce oxidative modification of low-density lipoproteins in the presence of vitamin C and vitamin E. Author(s): Huang M, Li J, Teoh H, Man RY. Source: Free Radical Biology & Medicine. 1999 August; 27(3-4): 438-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468219&dopt=Abstract

•

Low vitamin E status is a potential risk factor for insulin-dependent diabetes mellitus. Author(s): Knekt P, Reunanen A, Marniemi J, Leino A, Aromaa A. Source: Journal of Internal Medicine. 1999 January; 245(1): 99-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10095823&dopt=Abstract

Studies

99

•

Low-density lipoprotein level reduction by the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitor simvastatin is accompanied by a related reduction of F2isoprostane formation in hypercholesterolemic subjects: no further effect of vitamin E. Author(s): De Caterina R, Cipollone F, Filardo FP, Zimarino M, Bernini W, Lazzerini G, Bucciarelli T, Falco A, Marchesani P, Muraro R, Mezzetti A, Ciabattoni G. Source: Circulation. 2002 November 12; 106(20): 2543-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427649&dopt=Abstract

•

Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Author(s): de Gaetano G; Collaborative Group of the Primary Prevention Project. Source: Lancet. 2001 January 13; 357(9250): 89-95. Erratum In: Lancet 2001 April 7; 357(9262): 1134. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197445&dopt=Abstract

•

Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defenses in that illness. Author(s): Maes M, De Vos N, Pioli R, Demedts P, Wauters A, Neels H, Christophe A. Source: Journal of Affective Disorders. 2000 June; 58(3): 241-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10802134&dopt=Abstract

•

Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic acid, carnosic acid, or garlic. Author(s): Fuhrman B, Volkova N, Rosenblat M, Aviram M. Source: Antioxidants & Redox Signalling. 2000 Fall; 2(3): 491-506. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229363&dopt=Abstract

•

Malabsorption of vitamin E in cystic fibrosis improved after ursodeoxycholic acid. Author(s): Thomas PS, Bellamy M, Geddes D. Source: Lancet. 1995 November 4; 346(8984): 1230-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7475686&dopt=Abstract

•

Malformations in offspring of diabetic rats: morphometric analysis of neural crestderived organs and effects of maternal vitamin E treatment. Author(s): Siman CM, Gittenberger-De Groot AC, Wisse B, Eriksson UJ. Source: Teratology. 2000 May; 61(5): 355-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10777831&dopt=Abstract

•

Maternal and cord serum vitamin E levels in normal and abnormal pregnancy. Author(s): von Mandach U, Huch R, Huch A. Source: Int J Vitam Nutr Res. 1994; 64(1): 26-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8200744&dopt=Abstract

100

Vitamin E

•

Maternal levels of vitamin E in normal and preeclamptic pregnancy. Author(s): Akyol D, Mungan T, Gorkemli H, Nuhoglu G. Source: Archives of Gynecology and Obstetrics. 2000 April; 263(4): 151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834320&dopt=Abstract

•

Measurement of serum vitamin E isomers in fullterm and preterm infants. Author(s): Wu SC, Chou YH. Source: Chang Gung Med J. 2001 December; 24(12): 793-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858395&dopt=Abstract

•

Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of alpha-tocopherol. Author(s): Morinobu T, Yoshikawa S, Hamamura K, Tamai H. Source: European Journal of Clinical Nutrition. 2003 March; 57(3): 410-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627176&dopt=Abstract

•

Mechanisms of vitamin E regulation: research over the past decade and focus on the future. Author(s): Parks E, Traber MG. Source: Antioxidants & Redox Signalling. 2000 Fall; 2(3): 405-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11229354&dopt=Abstract

•

Methodology of the VECAT study: vitamin E intervention in cataract and age-related maculopathy. Author(s): Garrett SK, McNeil JJ, Silagy C, Sinclair M, Thomas AP, Robman LP, McCarty CA, Tikellis G, Taylor HR. Source: Ophthalmic Epidemiology. 1999 September; 6(3): 195-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487974&dopt=Abstract

•

Microcirculation, vitamin E and omega 3 fatty acids: an overview. Author(s): Bruckner G. Source: Advances in Experimental Medicine and Biology. 1997; 415: 195-208. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9131193&dopt=Abstract

•

Modulation of cell proliferation and cell cycle regulators by vitamin E in human prostate carcinoma cell lines. Author(s): Venkateswaran V, Fleshner NE, Klotz LH. Source: The Journal of Urology. 2002 October; 168(4 Pt 1): 1578-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352461&dopt=Abstract

Studies

101

•

Modulation of the endogenous leukotriene production by fish oil and vitamin E. Author(s): Denzlinger C, Kless T, Sagebiel-Kohler S, Lemmen C, Jacob K, Wilmanns W, Adam O. Source: Journal of Lipid Mediators and Cell Signalling. 1995 March; 11(2): 119-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7780681&dopt=Abstract

•

Molecular action of vitamin E in lipoprotein oxidation: implications for atherosclerosis. Author(s): Thomas SR, Stocker R. Source: Free Radical Biology & Medicine. 2000 June 15; 28(12): 1795-805. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946221&dopt=Abstract

•

Molecular epidemiologic studies within the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Author(s): Hoque A, Albanes D, Lippman SM, Spitz MR, Taylor PR, Klein EA, Thompson IM, Goodman P, Stanford JL, Crowley JJ, Coltman CA, Santella RM. Source: Cancer Causes & Control : Ccc. 2001 September; 12(7): 627-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11552710&dopt=Abstract

•

Molecular mechanisms of vitamin E transport. Author(s): Traber MG, Arai H. Source: Annual Review of Nutrition. 1999; 19: 343-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448528&dopt=Abstract

•

Mononuclear leukocyte apoptosis in haemodialysis patients: the role of cell thiols and vitamin E. Author(s): Galli F, Ghibelli L, Buoncristiani U, Bordoni V, D'Intini V, Benedetti S, Canestrari F, Ronco C, Floridi A. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 August; 18(8): 1592-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897100&dopt=Abstract

•

Monounsaturated diet lowers LDL oxidisability in type IIb and type IV dyslipidemia without affecting coenzyme Q10 and vitamin E contents. Author(s): Svegliati Baroni S, Amelio M, Fiorito A, Gaddi A, Littarru G, Battino M. Source: Biofactors (Oxford, England). 1999; 9(2-4): 325-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10416048&dopt=Abstract

•

Morphologic evaluation of red blood cells using vitamin E-modified dialysis filters. Author(s): Calzavara P, De Angeli S, Gatto C, Dugo M, Puggia R, Calconi G. Source: Contrib Nephrol. 1999; 127: 172-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10629786&dopt=Abstract

102

Vitamin E

•

Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Author(s): Sokol RJ, Butler-Simon N, Conner C, Heubi JE, Sinatra FR, Suchy FJ, Heyman MB, Perrault J, Rothbaum RJ, Levy J, et al. Source: Gastroenterology. 1993 June; 104(6): 1727-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8500733&dopt=Abstract

•

Myeloperoxidase-catalyzed phenoxyl radicals of vitamin E homologue, 2,2,5,7,8pentamethyl- 6-hydroxychromane, do not induce oxidative stress in live HL-60 cells. Author(s): Kagan VE, Kuzmenko AI, Shvedova AA, Kisin ER, Tyurina YY, Yalowich JC. Source: Biochemical and Biophysical Research Communications. 2000 April 21; 270(3): 1086-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772954&dopt=Abstract

•

Myoclonic dystonia as unique presentation of isolated vitamin E deficiency in a young patient. Author(s): Angelini L, Erba A, Mariotti C, Gellera C, Ciano C, Nardocci N. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002 May; 17(3): 612-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112220&dopt=Abstract

•

N-acetylcysteine and vitamin E: an in vitro study of their effect on homogentisic acid polymerization. Author(s): Chindamo D, Catenaccio M, Lorenzini S, Selvi E, Molinelli M, Cavallo G, Marcolongo R. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 269. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747292&dopt=Abstract

•

N-Acetylcysteine, vitamin C and vitamin E diminish homocysteine thiolactoneinduced apoptosis in human promyeloid HL-60 cells. Author(s): Huang RF, Huang SM, Lin BS, Hung CY, Lu HT. Source: The Journal of Nutrition. 2002 August; 132(8): 2151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163654&dopt=Abstract

•

Nephrotic origin hyperlipidemia, relative reduction of vitamin E level and subsequent oxidative stress may promote atherosclerosis. Author(s): Skrzep-Poloczek B, Tomasik A, Tarnawski R, Hyla-Klekot L, Dyduch A, Wojciechowska C, Wesolowski W, Kopieczna-Grzebieniak E, Zalejska-Fiolka J, Widera E. Source: Nephron. 2001 September; 89(1): 68-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528235&dopt=Abstract

Studies

103

•

Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Author(s): Pace A, Savarese A, Picardo M, Maresca V, Pacetti U, Del Monte G, Biroccio A, Leonetti C, Jandolo B, Cognetti F, Bove L. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 1; 21(5): 927-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610195&dopt=Abstract

•

Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17beta. Author(s): Kolsch H, Ludwig M, Lutjohann D, Rao ML. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2001; 108(4): 475-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475014&dopt=Abstract

•

New acrylic bone cements conjugated to vitamin E: curing parameters, properties, and biocompatibility. Author(s): Mendez JA, Aguilar MR, Abraham GA, Vazquez B, Dalby M, Di Silvio L, San Roman J. Source: Journal of Biomedical Materials Research. 2002 November; 62(2): 299-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209951&dopt=Abstract

•

New scope in angiogenesis: role of vascular endothelial growth factor (VEGF), NO, lipid peroxidation, and vitamin E in the pathophysiology of pre-eclampsia among Egyptian females. Author(s): El-Salahy EM, Ahmed MI, El-Gharieb A, Tawfik H. Source: Clinical Biochemistry. 2001 June; 34(4): 323-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440734&dopt=Abstract

•

New synthesis of (+/-)-alpha-CMBHC and its confirmation as a metabolite of alphatocopherol (vitamin E). Author(s): Pope SA, Burtin GE, Clayton PT, Madge DJ, Muller DP. Source: Bioorganic & Medicinal Chemistry. 2001 May; 9(5): 1337-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11377190&dopt=Abstract

•

Nonalcoholic fatty liver disease: relationship to insulin sensitivity and oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 August; 7(4): 276-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197781&dopt=Abstract

104

Vitamin E

•

Non-antioxidant molecular functions of alpha-tocopherol (vitamin E). Author(s): Azzi A, Ricciarelli R, Zingg JM. Source: Febs Letters. 2002 May 22; 519(1-3): 8-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023009&dopt=Abstract

•

Non-nutritive bioactive food constituents of plants: tocopherols (vitamin E). Author(s): Elmadfa I, Wagner KH. Source: Int J Vitam Nutr Res. 2003 March; 73(2): 89-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747215&dopt=Abstract

•

Nutritional approaches to radioprotection: vitamin E. Author(s): Kumar KS, Srinivasan V, Toles R, Jobe L, Seed TM. Source: Military Medicine. 2002 February; 167(2 Suppl): 57-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11873518&dopt=Abstract

•

Nutritional assessment of vitamin E in malnourished patients with AIDS. Author(s): Pontes Monteiro J, Ferreira da Cunha D, Freire Carvalho Cunha S, Modesto dos Santos V, Jordao AA, Correia D, Silva-Vergara ML, Vannucchi H, Junior VR, Pires Bianchi ML. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 May; 16(5): 339-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793300&dopt=Abstract

•

On the biological activity of vitamin E. Author(s): Kayden HJ, Wisniewski T. Source: The American Journal of Clinical Nutrition. 2000 July; 72(1): 201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10871582&dopt=Abstract

•

Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in beta-thalassemia intermedia patients. Author(s): Tesoriere L, D'Arpa D, Butera D, Allegra M, Renda D, Maggio A, Bongiorno A, Livrea MA. Source: Free Radical Research. 2001 May; 34(5): 529-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378535&dopt=Abstract

•

Oxidant and antioxidant systems in niddm patients: influence of vitamin E supplementation. Author(s): Gokkusu C, Palanduz S, Ademoglu E, Tamer S. Source: Endocrine Research. 2001 August; 27(3): 377-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678585&dopt=Abstract

Studies

105

•

Oxidative stability of low density lipoproteins and vitamin E levels increase in maternal blood during normal pregnancy. Author(s): De Vriese SR, Dhont M, Christophe AB. Source: Lipids. 2001 April; 36(4): 361-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11383686&dopt=Abstract

•

Oxidative stress and erythrocyte integrity in end-stage renal failure patients hemodialysed using a vitamin E-modified membrane. Author(s): Westhuyzen J, Saltissi D, Stanbury V. Source: Ann Clin Lab Sci. 2003 Winter; 33(1): 3-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661892&dopt=Abstract

•

Oxidative stress induced by phenylketonuria in the rat: Prevention by melatonin, vitamin E, and vitamin C. Author(s): Martinez-Cruz F, Pozo D, Osuna C, Espinar A, Marchante C, Guerrero JM. Source: Journal of Neuroscience Research. 2002 August 15; 69(4): 550-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210848&dopt=Abstract

•

Oxidative stress is reduced by the long-term use of vitamin E-coated dialysis filters. Author(s): Satoh M, Yamasaki Y, Nagake Y, Kasahara J, Hashimoto M, Nakanishi N, Makino H. Source: Kidney International. 2001 May; 59(5): 1943-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11318967&dopt=Abstract

•

Oxidative stress, vitamin A and vitamin E behaviour in patients submitted to conservative surgery for complicated Crohn's disease. Author(s): Sampietro GM, Cristaldi M, Cervato G, Maconi G, Danelli P, Cervellione R, Rovati M, Porro GB, Cestaro B, Taschieri AM. Source: Dig Liver Dis. 2002 October; 34(10): 696-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469796&dopt=Abstract

•

Oxidative stress, vitamin E and progestin breakthrough bleeding. Author(s): Subakir SB, Abdul Madjid O, Sabariah S, Affandi B. Source: Human Reproduction (Oxford, England). 2000 August; 15 Suppl 3: 18-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11041217&dopt=Abstract

•

Ozone potentiates vitamin E depletion by ultraviolet radiation in the murine stratum corneum. Author(s): Valacchi G, Weber SU, Luu C, Cross CE, Packer L. Source: Febs Letters. 2000 January 21; 466(1): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10648834&dopt=Abstract

106

Vitamin E

•

Phospholipid transfer protein deficiency protects circulating lipoproteins from oxidation due to the enhanced accumulation of vitamin E. Author(s): Jiang XC, Tall AR, Qin S, Lin M, Schneider M, Lalanne F, Deckert V, Desrumaux C, Athias A, Witztum JL, Lagrost L. Source: The Journal of Biological Chemistry. 2002 August 30; 277(35): 31850-6. Epub 2002 June 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12105225&dopt=Abstract

•

Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts. Author(s): Offord EA, Gautier JC, Avanti O, Scaletta C, Runge F, Kramer K, Applegate LA. Source: Free Radical Biology & Medicine. 2002 June 15; 32(12): 1293-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12057767&dopt=Abstract

•

Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: The Insulin Resistance and Atherosclerosis Study (IRAS). Author(s): Mayer-Davis EJ, Costacou T, King I, Zaccaro DJ, Bell RA; The Insulin Resistance and Atherosclerosis Study (IRAS). Source: Diabetes Care. 2002 December; 25(12): 2172-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453956&dopt=Abstract

•

Plasma carotenoid and vitamin E concentrations in women living in a rural west African (Gambian) community. Author(s): Bates CJ, Matthews N, West B, Morison L, Walraven G. Source: Int J Vitam Nutr Res. 2002 May; 72(3): 133-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098880&dopt=Abstract

•

Plasma levels of vitamin E in pregnant women prior to the development of preeclampsia and other hypertensive complications. Author(s): Ben-Haroush A, Harell D, Hod M, Bardin R, Kaplan B, Orvieto R, Bar J. Source: Gynecologic and Obstetric Investigation. 2002; 54(1): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297714&dopt=Abstract

•

Plasma vitamin E and A changes during cardiopulmonary bypass and in the postoperative course. Author(s): Schindler R, Berndt S, Schroeder P, Oster O, Rave G, Sievers HH. Source: Langenbeck's Archives of Surgery / Deutsche Gesellschaft Fur Chirurgie. 2003 January; 387(9-10): 372-8. Epub 2002 November 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12536333&dopt=Abstract

Studies

107

•

Plasma vitamin E, total antioxidant status and vascular function in young adults. Author(s): Leeson CP, Mann A, Kattenhorn M, Deanfield JE, Lucas A, Muller DP. Source: European Journal of Clinical Investigation. 2002 December; 32(12): 889-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534447&dopt=Abstract

•

PoleStriding exercise and vitamin E for management of peripheral vascular disease. Author(s): Collins EG, Edwin Langbein W, Orebaugh C, Bammert C, Hanson K, Reda D, Edwards LC, Littooy FN. Source: Medicine and Science in Sports and Exercise. 2003 March; 35(3): 384-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618567&dopt=Abstract

•

Profiling of human cytokines in healthy individuals with vitamin E supplementation by antibody array. Author(s): Lin Y, Huang R, Santanam N, Liu YG, Parthasarathy S, Huang RP. Source: Cancer Letters. 2002 December 10; 187(1-2): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359346&dopt=Abstract

•

Prospective study of serum vitamin E levels and esophageal and gastric cancers. Author(s): Taylor PR, Qiao YL, Abnet CC, Dawsey SM, Yang CS, Gunter EW, Wang W, Blot WJ, Dong ZW, Mark SD. Source: Journal of the National Cancer Institute. 2003 September 17; 95(18): 1414-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130117&dopt=Abstract

•

Quantitation of vitamin E and a carotenoid pigment in cataractous human lenses, and the effect of a dietary supplement. Author(s): Bates CJ, Chen SJ, Macdonald A, Holden R. Source: Int J Vitam Nutr Res. 1996; 66(4): 316-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8979159&dopt=Abstract

•

Quantitative analysis by liquid chromatography-tandem mass spectrometry of deuterium-labeled and unlabeled vitamin E in biological samples. Author(s): Lauridsen C, Leonard SW, Griffin DA, Liebler DC, McClure TD, Traber MG. Source: Analytical Biochemistry. 2001 February 1; 289(1): 89-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161299&dopt=Abstract

•

Quantitative analysis of vitamin E, cholesterol and phospholipid fatty acids in a single aliquot of human platelets and cultured endothelial cells. Author(s): Leray C, Andriamampandry M, Gutbier G, Cavadenti J, Klein-Soyer C, Gachet C, Cazenave JP. Source: J Chromatogr B Biomed Sci Appl. 1997 August 15; 696(1): 33-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9300906&dopt=Abstract

108

Vitamin E

•

Randomized trial of a combination of natural products (cernitin, saw palmetto, Bsitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH). Author(s): Preuss HG, Marcusen C, Regan J, Klimberg IW, Welebir TA, Jones WA. Source: International Urology and Nephrology. 2001; 33(2): 217-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092634&dopt=Abstract

•

Reduced vitamin E antioxidant capacity in sickle cell disease is related to transfusion status but not to sickle crisis. Author(s): Marwah SS, Blann AD, Rea C, Phillips JD, Wright J, Bareford D. Source: American Journal of Hematology. 2002 February; 69(2): 144-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835354&dopt=Abstract

•

Reduction of neutrophil activation by vitamin E modified dialyzer membranes. Author(s): Omata M, Higuchi C, Demura R, Sanaka T, Nihei H. Source: Nephron. 2000 July; 85(3): 221-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867537&dopt=Abstract

•

Regulation of cell signalling by vitamin E. Author(s): Rimbach G, Minihane AM, Majewicz J, Fischer A, Pallauf J, Virgli F, Weinberg PD. Source: The Proceedings of the Nutrition Society. 2002 November; 61(4): 415-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691170&dopt=Abstract

•

Regulation of heat shock protein synthesis in human skin fibroblasts in response to oxidative stress: role of vitamin E. Author(s): Calabrese V, Scapagnini G, Catalano C, Bates TE, Geraci D, Pennisi G, Giuffrida Stella AM. Source: Int J Tissue React. 2001; 23(4): 127-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771776&dopt=Abstract

•

Response of human oral epithelial cells to oxidative damage and the effect of vitamin E. Author(s): Royack GA, Nguyen MP, Tong DC, Poot M, Oda D. Source: Oral Oncology. 2000 January; 36(1): 37-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10889917&dopt=Abstract

•

Retinoic acid and vitamin E modulate expression and release of CD178 in carcinoma cells: consequences for induction of apoptosis in CD95-sensitive cells. Author(s): Salih HR, Starling GC, Knauff M, Llewellyn MB, Davis PM, Pitts WJ, Aruffo A, Kiener PA. Source: Experimental Cell Research. 2001 November 1; 270(2): 248-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11640888&dopt=Abstract

Studies

109

•

Role of vitamin E and oxidative stress in exercise. Author(s): Sacheck JM, Blumberg JB. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 October; 17(10): 809-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684385&dopt=Abstract

•

Role of vitamin E in rheumatic chorea. Author(s): Rawat MS, Patel AB, Thete AR, Bokde C. Source: Indian J Pediatr. 2000 August; 67(8): 563-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984995&dopt=Abstract

•

Roles of Fas signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells. Author(s): Wu K, Li Y, Zhao Y, Shan YJ, Xia W, Yu WP, Zhao L. Source: World Journal of Gastroenterology : Wjg. 2002 December; 8(6): 982-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439910&dopt=Abstract

•

SELECT: the selenium and vitamin E cancer prevention trial. Author(s): Klein EA, Thompson IM, Lippman SM, Goodman PJ, Albanes D, Taylor PR, Coltman C. Source: Urologic Oncology. 2003 January-February; 21(1): 59-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684129&dopt=Abstract

•

Selenium and Vitamin E Cancer Prevention Trial--this one's for us. Author(s): Cook ED. Source: Journal of the National Medical Association. 2002 September; 94(9): 856-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392050&dopt=Abstract

•

Serum and hepatic vitamin E assessment in cirrhotics before transplantation. Author(s): Ukleja A, Scolapio JS, McConnell JP, Dickson RC, Nguyen JH, O'Brien PC. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 January-February; 27(1): 71-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549602&dopt=Abstract

•

Serum ex vivo lipoprotein oxidizability in patients with ischemic heart disease supplemented with vitamin E. Author(s): Nagyova A, Mongiellova V, Krivosikova Z, Blazicek P, Spustova V, Gajdos M, Dzurik R. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2002; 51(5): 457-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470198&dopt=Abstract

110

Vitamin E

•

Severe tardive dyskinesia in affective disorders: treatment with vitamin E and C. Author(s): Michael N, Sourgens H, Arolt V, Erfurth A. Source: Neuropsychobiology. 2002; 46 Suppl 1: 28-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571430&dopt=Abstract

•

Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Author(s): Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z, Ghozzi H, Hammami S, Zghal K, Fki H, Damak J, Bahloul A. Source: Archives of Andrology. 2003 March-April; 49(2): 83-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623744&dopt=Abstract

•

Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults. Author(s): Upritchard JE, Schuurman CR, Wiersma A, Tijburg LB, Coolen SA, Rijken PJ, Wiseman SA. Source: The American Journal of Clinical Nutrition. 2003 November; 78(5): 985-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594786&dopt=Abstract

•

Supernatant protein factor and tocopherol-associated protein: an unexpected link between cholesterol synthesis and vitamin E (review). Author(s): Porter TD. Source: The Journal of Nutritional Biochemistry. 2003 January; 14(1): 3-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559471&dopt=Abstract

•

Supernatant protein factor in complex with RRR-alpha-tocopherylquinone: a link between oxidized Vitamin E and cholesterol biosynthesis. Author(s): Stocker A, Baumann U. Source: Journal of Molecular Biology. 2003 September 26; 332(4): 759-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972248&dopt=Abstract

•

Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. Author(s): Wluka AE, Stuckey S, Brand C, Cicuttini FM. Source: The Journal of Rheumatology. 2002 December; 29(12): 2585-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465157&dopt=Abstract

•

The antioxidants--vitamin C,vitamin E, selenium, and carotenoids. Author(s): Johnson LJ, Meacham SL, Kruskall LJ. Source: J Agromedicine. 2003; 9(1): 65-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563626&dopt=Abstract

Studies

111

•

The association between vitamin C and vitamin E supplement use before hematopoietic stem cell transplant and outcomes to two years. Author(s): Bruemmer B, Patterson RE, Cheney C, Aker SN, Witherspoon RP. Source: Journal of the American Dietetic Association. 2003 August; 103(8): 982-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891146&dopt=Abstract

•

The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes. Author(s): Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA. Source: The British Journal of Nutrition. 2000 August; 84(2): 195-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11029970&dopt=Abstract

•

The effects of endurance exercise and vitamin E on oxidative stress in the elderly. Author(s): Jessup JV, Horne C, Yarandi H, Quindry J. Source: Biological Research for Nursing. 2003 July; 5(1): 47-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886670&dopt=Abstract

•

The level of serum lipids, vitamin E and low density lipoprotein oxidation in Wilson's disease patients. Author(s): Rodo M, Czonkowska A, Pulawska M, Swiderska M, Tarnacka B, Wehr H. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2000 September; 7(5): 491-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054132&dopt=Abstract

•

The molecular basis of vitamin E retention: structure of human alpha-tocopherol transfer protein. Author(s): Meier R, Tomizaki T, Schulze-Briese C, Baumann U, Stocker A. Source: Journal of Molecular Biology. 2003 August 15; 331(3): 725-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899840&dopt=Abstract

•

The role of vitamin E in atherogenesis: linking the chemical, biological and clinical aspects of the disease. Author(s): Neuzil J, Weber C, Kontush A. Source: Atherosclerosis. 2001 August; 157(2): 257-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11472726&dopt=Abstract

•

The selenium and vitamin E cancer prevention trial. Author(s): Klein EA, Lippman SM, Thompson IM, Goodman PJ, Albanes D, Taylor PR, Coltman C. Source: World Journal of Urology. 2003 May; 21(1): 21-7. Epub 2003 March 08. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756490&dopt=Abstract

112

Vitamin E

•

Therapeutic potential of vitamin E in heart disease. Author(s): Bunout D. Source: Expert Opinion on Investigational Drugs. 2000 November; 9(11): 2629-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060825&dopt=Abstract

•

Treatment of atherosclerosis in the new millennium: is there a role for vitamin E? Author(s): Meagher EA. Source: Preventive Cardiology. 2003 Spring; 6(2): 85-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732794&dopt=Abstract

•

Ultraviolet-treated lipoproteins as a model system for the study of the biological effects of lipid peroxides on cultured cells. III. The protective effect of antioxidants (probucol, catechin, vitamin E) against the cytotoxicity of oxidized LDL occurs in two different ways. Author(s): Negre-Salvayre A, Alomar Y, Troly M, Salvayre R. Source: Biochimica Et Biophysica Acta. 1991 June 5; 1096(4): 291-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2065102&dopt=Abstract

•

Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E, and the carotenoids. Author(s): Rock CL, Jacob RA, Bowen PE. Source: Journal of the American Dietetic Association. 1996 July; 96(7): 693-702; Quiz 7034. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8675913&dopt=Abstract

•

Upper limit of vitamin E in infant formulas. Author(s): Bell EF. Source: The Journal of Nutrition. 1989 December; 119(12 Suppl): 1829-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2693643&dopt=Abstract

•

Urinary excretion and plasma vitamin E levels in patients with AIDS. Author(s): Jordao Junior AA, Silveira S, Figueiredo JF, Vannucchi H. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1998 May; 14(5): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9614305&dopt=Abstract

•

Use of vitamin E and glutamine in the successful treatment of severe veno-occlusive disease following bone marrow transplantation. Author(s): Nattakom TV, Charlton A, Wilmore DW. Source: Nutr Clin Pract. 1995 February; 10(1): 16-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7898412&dopt=Abstract

Studies

113

•

Use of water-soluble liquid vitamin E to enhance cyclosporine absorption in children after liver transplant. Author(s): Boudreaux JP, Hayes DH, Mizrahi S, Maggiore P, Blazek J, Dick D. Source: Transplantation Proceedings. 1993 April; 25(2): 1875. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8470210&dopt=Abstract

•

Utility of breath ethane as a noninvasive biomarker of vitamin E status in children. Author(s): Refat M, Moore TJ, Kazui M, Risby TH, Perman JA, Schwarz KB. Source: Pediatric Research. 1991 November; 30(5): 396-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1754293&dopt=Abstract

•

Utilization of vitamin E. Author(s): Traber MG. Source: Biofactors (Oxford, England). 1999; 10(2-3): 115-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10609871&dopt=Abstract

•

UVA-induced immune suppression in human skin: protective effect of vitamin E in human epidermal cells in vitro. Author(s): Clement-Lacroix P, Michel L, Moysan A, Morliere P, Dubertret L. Source: The British Journal of Dermatology. 1996 January; 134(1): 77-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8745890&dopt=Abstract

•

Vitamin E and beta carotene supplementation in high risk for stroke: a subgroup analysis of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Author(s): Leppala JM, Virtamo J, Fogelholm R, Albanes D, Taylor PR, Heinonen OP. Source: Archives of Neurology. 2000 October; 57(10): 1503-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11030804&dopt=Abstract

•

Vitamin E and its role in the prevention of atherosclerosis and carcinogenesis: a review. Author(s): Dutta A, Dutta SK. Source: Journal of the American College of Nutrition. 2003 August; 22(4): 258-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897039&dopt=Abstract

•

Vitamin E and prevention of heart disease in high-risk patients. Author(s): Meydani M. Source: Nutrition Reviews. 2000 September; 58(9): 278-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060998&dopt=Abstract

114

Vitamin E

•

Vitamin E for Alzheimer's disease. Author(s): Tabet N, Birks J, Grimley Evans J. Source: Cochrane Database Syst Rev. 2000; (4): Cd002854. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034775&dopt=Abstract

•

Vitamin E in fortified cow milk uniquely enriches human plasma lipoproteins. Author(s): Hayes K, Pronczuk A, Perlman D. Source: The American Journal of Clinical Nutrition. 2001 August; 74(2): 211-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470723&dopt=Abstract

•

Vitamin E inhibits cyclosporin A and H2O2 promoted Epstein-Barr virus (EBV) transformation of human B cells as assayed by EBV oncogene LMP1 expression. Author(s): Chen C, Reddy KS, Johnston TD, Khan TT, Ranjan D. Source: The Journal of Surgical Research. 2003 August; 113(2): 228-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957134&dopt=Abstract

•

Vitamin E levels during chemotherapy for ovarian carcinoma. Author(s): Ananth N, Shetty BV, Vasudevan DM. Source: Natl Med J India. 2003 July-August; 16(4): 231-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606777&dopt=Abstract

•

Vitamin E may slow kidney failure owing to oxidative stress. Author(s): Fryer MJ. Source: Redox Report : Communications in Free Radical Research. 1997 OctoberDecember; 3(5-6): 259-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754323&dopt=Abstract

•

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Author(s): Brion LP, Bell EF, Raghuveer TS. Source: Cochrane Database Syst Rev. 2003; (3): Cd003665. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917978&dopt=Abstract

•

Vitamin E-coated dialyzer reduces oxidative stress in hemodialysis patients. Author(s): Clermont G, Lecour S, Cabanne JF, Motte G, Guilland JC, Chevet D, Rochette L. Source: Free Radical Biology & Medicine. 2001 July 15; 31(2): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11440835&dopt=Abstract

Studies

115

•

Water-miscible tocopherol is not superior to fat-soluble preparation for vitamin E absorption in cystic fibrosis. Author(s): Soltani-Frisk S, Gronowitz E, Andersson H, Strandvik B. Source: Acta Paediatrica (Oslo, Norway : 1992). 2001 October; 90(10): 1112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697419&dopt=Abstract

•

What dose of vitamin E is required to reduce susceptibility of LDL to oxidation? Author(s): Simons LA, Von Konigsmark M, Balasubramaniam S. Source: Aust N Z J Med. 1996 August; 26(4): 496-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8873932&dopt=Abstract

•

Which studies of therapy merit credence? Vitamin E and estrogen therapy as cautionary examples. Author(s): Spector R, Vesell ES. Source: Journal of Clinical Pharmacology. 2002 September; 42(9): 955-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12211220&dopt=Abstract

•

Whither vitamin E and tardive dyskinesia? Author(s): Lohr JB, Lavori P. Source: Biological Psychiatry. 1998 June 15; 43(12): 861-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9627738&dopt=Abstract

•

Whole blood production of thromboxane, prostacyclin and leukotriene B4 after dietary fish oil supplementation in man: effect of vitamin E. Author(s): Engstrom K, Luostarinen R, Saldeen T. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1996 June; 54(6): 419-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8888353&dopt=Abstract

•

Why don't we use vitamin E in dermatology? Author(s): Pehr K, Forsey RR. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 1993 November 1; 149(9): 1247-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8221479&dopt=Abstract

•

Will the 'good fairies' please prove to us that vitamin E lessens human degenerative disease? Author(s): Diplock AT. Source: Free Radical Research. 1997 November; 27(5): 511-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9518068&dopt=Abstract

116

Vitamin E

•

Will the 'good fairies' please prove to us that vitamin E lessens human degenerative disease? Author(s): Diplock AT. Source: Free Radical Research. 1997 June; 26(6): 565-83. Review. Corrected and Republished In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9212350&dopt=Abstract

•

Xanthomatous reaction following contact dermatitis from vitamin E. Author(s): Parsad D, Saini R, Verma N. Source: Contact Dermatitis. 1997 December; 37(6): 294. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9455633&dopt=Abstract

117

CHAPTER 2. NUTRITION AND VITAMIN E Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and vitamin E.

Finding Nutrition Studies on Vitamin E The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “vitamin E” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

118

Vitamin E

The following is a typical result when searching for recently indexed consumer information on vitamin E: •

Nutrition and fitness: a conference report. Author(s): The Center for Genetics, Nutrition and Health Source: Simopoulos, A.P. Nutrition-today (USA). (December 1992). volume 27(6) page 24-29.

Additional consumer oriented references include: •

A supplement worth watching: vitamin E hasn't lost its glow. Source: Anonymous Consum-Repage 1997 March; 62(3): 70 0010-7174

•

Antioxidants. Vitamin E may cut prostate cancer risk. Source: Anonymous Harv-Health-Lett. 1998 May; 23(7): 7 1052-1577

•

Ask the doctor. In your article on Alzheimer's disease (March, 1999), you mention “high doses of vitamin E” as helpful in slowing the progression of the condition. Specifically, what dose is recommended? Source: Nicholson, C R Harv-Womens-Health-Watch. 1999 May; 6(9): 8 1070-910X

•

Ask the doctor. I've been taking vitamin E for years in hopes that it will prevent heart problems. Now the news is that it is of no help at all. Can you shed some light on this? Source: Lee, T H Harv-Heart-Lett. 2000 April; 10(8): 8 1051-5313

•

Effects of diets containing fish oil and vitamin E on rheumatoid arthritis. Author(s): Loyola University Medical Center, Maywood, IL 60153, USA. Source: Tidow Kebritchi, S Mobarhan, S Nutr-Revolume 2001 October; 59(10): 335-8 0029-6643

•

From starring role to bit part: Has the curtain come down on vitamin E. Source: Webb, D. Environ-nutr. New York : Environmental Nutrition, Inc.,. May 2002. volume 25 (5) page 1, 4. 0893-4452

•

Has the vitamin E bubble burst? EN evaluates whether to supplement. Source: Antinoro, L. Environ-nutr. New York : Environmental Nutrition, Inc.,. November 2000. volume 23 (11) page 1, 4. 0893-4452

•

Health beat. Vitamin E: E for exaggerated? Source: Anonymous Harv-Health-Lett. 2000 March; 25(5): 6 1052-1577

•

I am undergoing treatment for hypertension and have been taking 200 mg of vitamin E daily for the past few years. I read that even lower doses might raise my risk of having a hemorrhagic stroke. Is this true? Source: Goldfinger, S E Harv-Health-Lett. 1999 January; 24(3): 3 1052-1577

•

Inhibition of free radial chain oxidation by alpha-tocopherol and other plasma antioxidants. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. May 1988. volume 46 (5) page 206-207. 0029-6643

•

Megavitamin E supplementation and vitamin K-dependent carboxylation. Source: Himms Hagen, Jean. Nutr-Rev. Washington, D.C. : Nutrition Foundation. Sept 1983. volume 41 (9) page 268-270. 0029-6643

•

Nutrition. Should you take a vitamin E supplement? Source: Anonymous Harv-Health-Lett. 2001 September; 26(11): 1-3 1052-1577

Nutrition

119

•

Reversal of defective nerve conduction with vitamin E supplementation in type 2 diabetes: a preliminary study. Author(s): Department of Endocrinology, Internal Medicine, Hacettepe University Faculty of Medicine, Ankara, Turkey. [email protected] Source: Tutuncu, N B Bayraktar, M Varli, K Diabetes-Care. 1998 November; 21(11): 19158 0149-5992

•

The neurologic syndrome of vitamin E deficiency: Laboratory and electrophysiologic assessment. Source: Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. April 1990. volume 48 (4) page 169-177. charts. 0029-6643

•

The vitamin E debate. Source: Anonymous Harv-Health-Lett. 2002 September; 27(11): 6 1052-1577

•

Vitamin E and blood thinners. You advised readers not to take extra vitamin E if they were taking aspirin or Coumadin. Why? Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 1999 October; 11(8): 8 1042-1882

•

Vitamin E and coronary heart disease. Source: Arens, U. BNF-nutr-bull. London : The Foundation,. Sept 1993. volume 18 (69) page 157-159. 0141-9684

•

Vitamin E and the risk of coronary disease. Source: Nutrition-and-the-M.D (USA). (August 1993). volume 19(8) page 4-5. vitamin e heart diseases risk vitamins duration women men 0732-0167

•

Vitamin E deficiency in children with chronic cholestasis. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. August. 1984. volume 42 (8) page 284-286. 0029-6643

•

Vitamin E- Exploding some of the myths. Source: Tufts-Univ-Diet-Nutr-Lett. New York, N.Y. : Tufts University Diet and Nutrition Letter. February 1984. volume 1 (12) page 3-5. charts. 0747-4105

•

Vitamin E lives up to its image as protective nutrient. Source: Schepers, A. Environ-Nutr. New York, N.Y. : Environmental Nutrition, Inc. January 1989. volume 12 (1) page 1, 6-7. charts. 0893-4452

•

Vitamin E recommendations. Is there a difference between natural and synthetic vitamin E? Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 2000 March; 12(1): 8 1042-1882

•

Vitamin E reduction of protein glycosylation in diabetes. Source: Virtanen, S.M. Rasanen, L. Aro, A. Lindstrom, J. Sippola, H. Lounamaa, R. Toivanen, L. Tuomilehto, J. Akerblom, H.K. Diabetes-Care. Alexandria, Va. : American Diabetes Association. January 1991. volume 14 (1) page 68-72. 0149-5992

•

Vitamin E seen lowering heart disease risk. Source: Wash-Post. [Washington, D.C.] : The Washington Post Co. May 20, 1993. page A3. 0190-8286

•

Vitamin E shows no benefit in heart disease. Source: Anonymous Health-News. 2000 February; 6(2): 6 1081-5880

120

Vitamin E

The following information is typical of that found when using the “Full IBIDS Database” to search for “vitamin E” (or a synonym): •

A possible correlation between unscheduled DNA repair and cholesterolemia in Wistar rat, modulated by vitamin E. Author(s): Victor Babes Institute, Bucharest-Romania. Source: Mihalache, D Preoteasa, V Carloban, A Stanculescu, A Dragomir, C T RoumArch-Microbiol-Immunol. 2001 Oct-December; 60(4): 349-58 1222-3891

•

A relative high dose of vitamin E does not attenuate unweighting-induced oxidative stress and ubiquitination in rat skeletal muscle. Author(s): Department of Nutrition, School of Medicine, University of Tokushima. Source: Ikemoto, M Okamura, Y Kano, M Hirasaka, K Tanaka, R Yamamoto, T Sasa, T Ogawa, T Sairyo, K Kishi, K Nikawa, T J-Physiol-Anthropol-Appl-Human-Sci. 2002 September; 21(5): 257-63 1345-3475

•

Attenuation of amiodarone-induced pulmonary fibrosis by vitamin E is associated with suppression of transforming growth factor-beta1 gene expression but not prevention of mitochondrial dysfunction. Author(s): Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada. Source: Card, J W Racz, W J Brien, J F Massey, T E J-Pharmacol-Exp-Ther. 2003 January; 304(1): 277-83 0022-3565

•

Beneficial effects of Hippophae rhamnoides L. on nicotine induced oxidative stress in rat blood compared with vitamin E. Author(s): Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey. Source: Suleyman, H Gumustekin, K Taysi, S Keles, S Oztasan, N Aktas, O Altinkaynak, K Timur, H Akcay, F Akar, S Dane, S Gul, M Biol-Pharm-Bull. 2002 September; 25(9): 1133-6 0918-6158

•

By the way, doctor. I take vitamin E pills, but I've heard they can cause bleeding. Is this anything to worry about? Source: Bistrian, B Harv-Health-Lett. 2002 December; 28(2): 8 1052-1577

•

Calixarene-type macrocycles by oxidation of phenols related to vitamin E. Author(s): Institut fur Chemie, Universitat fur Bodenkultur, Vienna, Austria. Source: Rosenau, T Potthast, A Hofinger, A Kosma, P Angew-Chem-Int-Ed-Engl. 2002 April 2; 41(7): 1171-3 0570-0833

•

Concurrent administration of water-soluble vitamin E can increase the oral bioavailability of cyclosporine a in healthy dogs. Author(s): Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. Source: Fischer, J R Harkin, K R Freeman, L C Vet-Ther. 2002 Winter; 3(4): 465-73 15283593

•

Effect of oral vitamin E supplementation in children with cholestasis. Author(s): Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Source: Roongpraiwan, R Suthutvoravut, U Feungpean, B Phuapradit, P J-Med-AssocThai. 2002 November; 85 Suppl 4: S1199-205 0125-2208

Nutrition

121

•

Effects of a vitamin E-bonded membrane and of glutathione on anemia and erythropoietin requirements in hemodialysis patients. Author(s): Nephrology and Dialysis Service, Manerbio Hospital, Brescia, Italy. [email protected] Source: Usberti, M Gerardi, G Micheli, A Tira, P Bufano, G Gaggia, P Movilli, E Cancarini, G C De Marinis, S D'Avolio, G Broccoli, R Manganoni, A Albertin, A Di Lorenzo, D J-Nephrol. 2002 Sep-October; 15(5): 558-64 1120-3625

•

Effects of serum vitamin E levels on skin vitamin E levels in dogs and cats. Author(s): Hill's Science and Technology Center, 1035 NE 43rd Street, Topeka, KS 66617, USA. Source: Jewell, D E Yu, S Joshi, D K Vet-Ther. 2002 Fall; 3(3): 235-43 1528-3593

•

Effects of vitamin E deficiency on fatigue and muscle contractile properties. Author(s): School of Human Movement Studies, Rm 520, Connell Building, University of Queensland, St Lucia, QLD 4072, Australia. [email protected] Source: Coombes, J S Rowell, B Dodd, S L Demirel, H A Naito, H Shanely, R A Powers, S K Eur-J-Appl-Physiol. 2002 July; 87(3): 272-7 1439-6319

•

Influence of high levels of vitamin E on semen parameters of cocks. Author(s): Institute of Physiological Chemistry, School of Veterinary Medicine, Hannover, Germany. Source: Danikowski, S Sallmann, H P Halle, I Flachowsky, G J-Anim-Physiol-AnimNutr-(Berl). 2002 December; 86(11-12): 376-82 0931-2439

•

Inhibition of angiogenesis and promotion of melanoma dormancy by vitamin E succinate. Author(s): Department of Surgery, Southern Illinois University School of Medicine, Springfield, Illinois, USA. [email protected] Source: Malafa, M P Fokum, F D Smith, L Louis, A Ann-Surg-Oncol. 2002 December; 9(10): 1023-32 1068-9265

•

Mossbauer studies of the non-heme iron and cytochrome b559 in a Chlamydomonas reinhardtii PSI- mutant and their interactions with alpha-tocopherol quinone. Author(s): Institute of Nuclear Physics, ul. Radzikowskiego 152, 31-342 Cracow, Poland. Source: Burda, K Kruk, J Borgstadt, R Stanek, J Strzalka, K Schmid, G H Kruse, O FEBSLett. 2003 January 30; 535(1-3): 159-65 0014-5793

•

Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Author(s): Neuroscience Department, Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy. [email protected] Source: Pace, A Savarese, A Picardo, M Maresca, V Pacetti, U Del Monte, G Biroccio, A Leonetti, C Jandolo, B Cognetti, F Bove, L J-Clin-Oncol. 2003 Mar 1; 21(5): 927-31 0732183X

•

Protective role of melatonin and a combination of vitamin C and vitamin E on lung toxicity induced by chlorpyrifos-ethyl in rats. Author(s): Suleyman Demirel University, Faculty of Medicine, Department of Histology, Isparta, Turkey. Source: Karaoz, E Gultekin, F Akdogan, M Oncu, M Gokcimen, A Exp-Toxicol-Pathol. 2002 August; 54(2): 97-108 0940-2993

122

Vitamin E

•

Roles of Fas signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells. Author(s): Department of Nutrition and Food Hygiene, Public Health School, Harbin Medical University, Heilongjiang Province, China. [email protected] Source: Wu, K Li, Y Zhao, Y Shan, Y J Xia, W Yu, W P Zhao, L World-J-Gastroenterol. 2002 December; 8(6): 982-6 1007-9327

•

Stabilization and first direct spectroscopic evidence of the o-quinone methide derived from vitamin E. Author(s): University of Agricultural Sciences, Institute of Chemistry, Muthgasse 18, A1190 Vienna, Austria. [email protected] Source: Rosenau, T Potthast, A Elder, T Kosma, P Org-Lett. 2002 November 28; 4(24): 4285-8 1523-7060

•

The effects of vitamin E succinate on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells. Author(s): Department of Nutrition and Food Hygiene, Public Health School, Harbin Medical University, Harbin 150001, Heilongjiang Province, China. Source: Zhao, Y Wu, K Xia, W Shan, Y J Wu, L J Yu, W P World-J-Gastroenterol. 2002 October; 8(5): 782-6 1007-9327

•

The protective effects of melatonin, vitamin E and octreotide on retinal edema during ischemia-reperfusion in the guinea pig retina. Author(s): Department of Ophthalmology, School of Medicine, Firat University, Elazig, Turkey. [email protected] Source: Yilmaz, T Celebi, S Kukner, A S Eur-J-Ophthalmol. 2002 Nov-December; 12(6): 443-9 1120-6721

•

The results of the interference of nitrates and vitamin E in the metabolism in the connective tissue of rat's liver. Author(s): Department of General and Analytical Chemistry, Pharmacy Faculty, Silesian Academy of Medicine, Sosnowiec, Poland. [email protected] Source: Pawlowska Goral, K Kusz, E Wardas, M Adamek, E Wardas, P Exp-ToxicolPathol. 2002 August; 54(2): 147-50 0940-2993

•

Vitamin E and neurodegenerative disorders associated with oxidative stress. Author(s): Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington 40506, USA. [email protected] Source: Butterfield, D A Castegna, A Drake, J Scapagnini, G Calabrese, V Nutr-Neurosci. 2002 September; 5(4): 229-39 1028-415X

•

Vitamin E and thetreatment and prevention of diabetes: a case for a controlled clinical trial. Author(s): Department of Biochemistry, Faculty of Medicine, National University of Singapore, MD 7 #03-15, 8 Medical Drive, Singapore 117597. [email protected] Source: Halliwell, B Singapore-Med-J. 2002 September; 43(9): 479-84 0037-5675

•

Vitamin E as an antioxidant agent in CAPD patients. Author(s): Nephrological Clinic, University Hospital, Kosice, Slovak Republic. Source: Mydlik, M Derzsiova, K Racz, O Sipulova, A Boldizsar, J Lovasova, E Hribikova, M Int-J-Artif-Organs. 2002 May; 25(5): 373-8 0391-3988

•

Vitamin E attenuates myocardial ischemia-reperfusion injury in murine AIDS. Author(s): Divison of Health Prevention Science, College of Public Health and Cardiovascular and Thoracic Surgery and The Sarver Heart Center, School of Medicine, University of Arizona, Tucson, AZ 85724, USA.

Nutrition

123

Source: Chen, Y Davis Gorman, G Watson, R R McDonagh, P F Cardiovasc-Toxicol. 2002; 2(2): 119-27 1530-7905 •

Vitamin E binding protein afamin protects neuronal cells in vitro. Author(s): JSW Research GmbH, Graz, Austria. Source: Heiser, M Hutter Paier, B Jerkovic, L Pfragner, R Windisch, M Becker Andre, M Dieplinger, H J-Neural-Transm-Suppl. 2002; (62): 337-45 0303-6995

•

Vitamin E biosynthesis: biochemistry meets cell biology. Author(s): Institut fur Pflanzengenetik und Kulturpflanzenforschung (IPK), Corrensstrasse 3, D-06466 Gatersleben, Germany. Source: Hofius, D Sonnewald, U Trends-Plant-Sci. 2003 January; 8(1): 6-8 1360-1385

•

Vitamin E protection from/potentiation of the cytogenetic toxicity of cisplatin in Swiss mice. Author(s): Department of Zoology, Berhampur University, Orissa, India. [email protected] Source: Choudhury, R C Jagdale, M B J-Chemother. 2002 August; 14(4): 397-405 1120009X

•

Vitamin E reduces transendothelial migration of neutrophils and prevents lung injury in endotoxin-induced airway inflammation. Author(s): Department of Medical Countermeasures, Divison of NBC Defence, Swedish Defence Research Agency, Umea, Sweden. [email protected] Source: Rocksen, D Ekstrand Hammarstrom, B Johansson, L Bucht, A Am-J-Respir-CellMol-Biol. 2003 February; 28(2): 199-207 1044-1549

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

124

Vitamin E

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMDHealth: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to vitamin E; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Ascorbic Acid Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Multiple Vitamin-Mineral Supplements Source: Healthnotes, Inc.; www.healthnotes.com Provitamin A Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: Healthnotes, Inc.; www.healthnotes.com Vitamin A Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html

Nutrition

125

Vitamin B1 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B2 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin C (Ascorbic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin E Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html Vitamin K Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin K Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10068,00.html •

Minerals Alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com

126

Vitamin E

Beta-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com D-alpha-tocopherol Alternative names: Vitamin E Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Isotretinoin Source: Healthnotes, Inc.; www.healthnotes.com Lovastatin Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Selenium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html Simvastatin Source: Healthnotes, Inc.; www.healthnotes.com Sodium Fluoride Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Vinpocetine Source: Prima Communications, Inc.www.personalhealthzone.com •

Food and Diet Abalone Source: Healthnotes, Inc.; www.healthnotes.com Almonds Source: Healthnotes, Inc.; www.healthnotes.com Almonds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,113,00.html Avocados Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,46,00.html Brazil Nuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,115,00.html Bulgur Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,305,00.html Carp Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Fat Alternatives and Fat Replacers Source: Healthnotes, Inc.; www.healthnotes.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Hazelnuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,307,00.html High-Fiber Diet Source: Healthnotes, Inc.; www.healthnotes.com

127

128

Vitamin E

Kale Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,127,00.html Mangoes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,56,00.html Monounsaturated Fats Source: Healthnotes, Inc.; www.healthnotes.com Natural Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com Nuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,84,00.html Oats Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,73,00.html Peanuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,110,00.html Polyunsaturated Fats Source: Healthnotes, Inc.; www.healthnotes.com Sprains and Strains Source: Healthnotes, Inc.; www.healthnotes.com Sunflower Seeds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,158,00.html Wheat Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,78,00.html

129

CHAPTER 3. ALTERNATIVE MEDICINE AND VITAMIN E Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to vitamin E. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to vitamin E and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “vitamin E” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to vitamin E: •

A comparative study of antioxidants S-allyl cysteine sulfoxide and vitamin E on the damages induced by nicotine in rats. Author(s): Helen A, Krishnakumar K, Vijayammal PL, Augusti KT. Source: Pharmacology. 2003 March; 67(3): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571405&dopt=Abstract

•

A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS. Author(s): Mu L, Feng SS. Source: Journal of Controlled Release : Official Journal of the Controlled Release Society. 2003 January 9; 86(1): 33-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490371&dopt=Abstract

•

A prospective study on supplemental vitamin e intake and risk of colon cancer in women and men.

130

Vitamin E

Author(s): Wu K, Willett WC, Chan JM, Fuchs CS, Colditz GA, Rimm EB, Giovannucci EL. Source: Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2002 November; 11(11): 1298-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433706&dopt=Abstract •

A relative high dose of vitamin E does not attenuate unweighting-induced oxidative stress and ubiquitination in rat skeletal muscle. Author(s): Ikemoto M, Okamura Y, Kano M, Hirasaka K, Tanaka R, Yamamoto T, Sasa T, Ogawa T, Sairyo K, Kishi K, Nikawa T. Source: Journal of Physiological Anthropology and Applied Human Science. 2002 September; 21(5): 257-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491823&dopt=Abstract

•

A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Author(s): Malmberg KJ, Lenkei R, Petersson M, Ohlum T, Ichihara F, Glimelius B, Frodin JE, Masucci G, Kiessling R. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2002 June; 8(6): 1772-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12060616&dopt=Abstract

•

A2E-epoxides damage DNA in retinal pigment epithelial cells. Vitamin E and other antioxidants inhibit A2E-epoxide formation. Author(s): Sparrow JR, Vollmer-Snarr HR, Zhou J, Jang YP, Jockusch S, Itagaki Y, Nakanishi K. Source: The Journal of Biological Chemistry. 2003 May 16; 278(20): 18207-13. Epub 2003 March 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12646558&dopt=Abstract

•

Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Author(s): Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu CR, Liu CH, Hwang J, Selzer RH, Azen SP; VEAPS Research Group. Source: Circulation. 2002 September 17; 106(12): 1453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234947&dopt=Abstract

•

Alpha-tocopheryl succinate, the most effective form of vitamin E for adjuvant cancer treatment: a review. Author(s): Prasad KN, Kumar B, Yan XD, Hanson AJ, Cole WC. Source: Journal of the American College of Nutrition. 2003 April; 22(2): 108-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672706&dopt=Abstract

Alternative Medicine 131

•

Altered RNA structural constituents in aging and vitamin E deficiency. Author(s): Malatesta M, Bertoni-Freddari C, Fattoretti P, Caporaloni C, Fakan S, Gazzanelli G. Source: Mechanisms of Ageing and Development. 2003 February; 124(2): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633937&dopt=Abstract

•

Aluminium administration is associated with enhanced hepatic oxidant stress that may be offset by dietary vitamin E in the rat. Author(s): Abubakar MG, Taylor A, Ferns GA. Source: International Journal of Experimental Pathology. 2003 February; 84(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694486&dopt=Abstract

•

An argument for Vitamin E supplementation in the management of systemic inflammatory response syndrome. Author(s): Bulger EM, Maier RV. Source: Shock (Augusta, Ga.). 2003 February; 19(2): 99-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578114&dopt=Abstract

•

An update: vitamin E supplementation and heart disease. Author(s): Blumberg JB. Source: Nutrition in Clinical Care : an Official Publication of Tufts University. 2002 March-April; 5(2): 50-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134710&dopt=Abstract

•

Anemia, myopathy, and pansteatitis in vitamin E-deficient captive marmosets (Callithrix spp.). Author(s): Juan-Salles C, Prats N, Resendes A, Domingo M, Hilton D, Ruiz JM, Garner MM, Valls X, Marco AJ. Source: Veterinary Pathology. 2003 September; 40(5): 540-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949411&dopt=Abstract

•

Assessment of DNA strand breakage by the alkaline COMET assay in dialysis patients and the role of Vitamin E supplementation. Author(s): Kan E, Undeger U, Bali M, Basaran N. Source: Mutation Research. 2002 September 26; 520(1-2): 151-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297155&dopt=Abstract

•

Chronic administration of EGb 761 modulates synaptic and mitochondrial plasticity in adult vitamin E-deficient rats. Author(s): Bertoni-Freddari C, Fattoretti P, Caselli U, Paoloni R, Solazzi M. Source: Cell Mol Biol (Noisy-Le-Grand). 2002 September; 48(6): 709-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396083&dopt=Abstract

132

Vitamin E

•

Combined vitamin E and vitamin C supplement use and risk of cardiovascular disease mortality. Author(s): Simon JA. Source: Archives of Internal Medicine. 2002 December 9-23; 162(22): 2630; Author Reply 2630. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456238&dopt=Abstract

•

Consequences of exposure to serum, with or without vitamin E supplementation, in terms of the fatty acid content and viability of bovine blastocysts produced in vitro. Author(s): Reis A, Rooke JA, McCallum GJ, Staines ME, Ewen M, Lomax MA, McEvoy TG. Source: Reproduction, Fertility, and Development. 2003; 15(5): 275-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14588185&dopt=Abstract

•

Dietary supplementation with vitamin E modulates avian intestinal immunity. Author(s): Muir WI, Husband AJ, Bryden WL. Source: The British Journal of Nutrition. 2002 June; 87(6): 579-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067428&dopt=Abstract

•

Dietary vitamin E and C supplementation prevents fructose induced hypertension in rats. Author(s): Vasdev S, Gill V, Parai S, Longerich L, Gadag V. Source: Molecular and Cellular Biochemistry. 2002 December; 241(1-2): 107-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482032&dopt=Abstract

•

Dietary vitamin E supplementation affects tissue lipid peroxidation of hybrid tilapia, Oreochromis niloticus x O. aureus. Author(s): Huang CH, Chang RJ, Huang SL, Chen W. Source: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. 2003 February; 134(2): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568804&dopt=Abstract

•

Dietary vitamin E supplementation lowers blood pressure in spontaneously hypertensive rats. Author(s): Vasdev S, Gill V, Parai S, Longerich L, Gadag V. Source: Molecular and Cellular Biochemistry. 2002 September; 238(1-2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12349898&dopt=Abstract

•

Differential indicators of diabetes-induced oxidative stress in New Zealand White rabbits: role of dietary vitamin E supplementation. Author(s): Davis RL, Lavine CL, Arredondo MA, McMahon P, Tenner TE Jr.

Alternative Medicine 133

Source: International Journal of Experimental Diabetes Research. 2002 July-September; 3(3): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458660&dopt=Abstract •

Does vitamin E supplementation prevent cardiovascular events? Author(s): Manson JE, Bassuk SS, Stampfer MJ. Source: Journal of Women's Health (2002). 2003 March; 12(2): 123-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12741415&dopt=Abstract

•

Early Vitamin E supplementation in young but not aged mice reduces Abeta levels and amyloid deposition in a transgenic model of Alzheimer's disease. Author(s): Sung S, Yao Y, Uryu K, Yang H, Lee VM, Trojanowski JQ, Pratico D. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 December 4 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14656990&dopt=Abstract

•

Effect of ascorbic acid and Vitamin E supplementation on semen quality and biochemical parameters of male rabbits. Author(s): Yousef MI, Abdallah GA, Kamel KI. Source: Animal Reproduction Science. 2003 March 20; 76(1-2): 99-111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559724&dopt=Abstract

•

Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. Author(s): Graat JM, Schouten EG, Kok FJ. Source: Jama : the Journal of the American Medical Association. 2002 August 14; 288(6): 715-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169075&dopt=Abstract

•

Effect of oral vitamin E supplementation in children with cholestasis. Author(s): Roongpraiwan R, Suthutvoravut U, Feungpean B, Phuapradit P. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549795&dopt=Abstract

•

Effect of various doses of palm vitamin E and tocopherol on aspirin-induced gastric lesions in rats. Author(s): Jaarin K, Gapor MT, Nafeeza MI, Fauzee AM. Source: International Journal of Experimental Pathology. 2002 December; 83(6): 295-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657138&dopt=Abstract

•

Effect of vitamin E supplementation and partial substitution of poly- with monounsaturated fatty acids in pig diets on muscle, and microsome extract alpha-

134

Vitamin E

tocopherol concentration and lipid oxidation. Author(s): Lopez-Bote CJ, Isabel B, Ruiz J, Daza A. Source: Archiv Fur Tierernahrung. 2003 February; 57(1): 11-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801076&dopt=Abstract •

Effect of vitamin E supplementation on antioxidant defense systems and humoral immune responses in young, middle-aged and elderly Korean women. Author(s): Park OJ, Kim HY, Kim WK, Kim YJ, Kim SH. Source: J Nutr Sci Vitaminol (Tokyo). 2003 April; 49(2): 94-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12887154&dopt=Abstract

•

Effects of dietary n-6 and n-3 fatty acids and vitamin E on the immune response of healthy geriatric dogs. Author(s): Hall JA, Tooley KA, Gradin JL, Jewell DE, Wander RC. Source: Am J Vet Res. 2003 June; 64(6): 762-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828263&dopt=Abstract

•

Effects of dietary vitamin E and selenium on antioxidative defense mechanisms in the liver of rats treated with high doses of glucocorticoid. Author(s): Beytut E, Aksakal M. Source: Biological Trace Element Research. 2003 March; 91(3): 231-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663947&dopt=Abstract

•

Effects of exogenous vitamin E supplementation on the levels of oxidants and antioxidants in chronic obstructive pulmonary disease. Author(s): Daga MK, Chhabra R, Sharma B, Mishra TK. Source: Journal of Biosciences. 2003 February; 28(1): 7-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682418&dopt=Abstract

•

Effects of feeding aspirin and supplemental vitamin E on plasma concentrations of 3methylindole, 3-methyleneindolenine-adduct concentrations in blood and pulmonary tissues, lung lesions, and growth performance in feedlot cattle. Author(s): Loneragan GH, Morley PS, Wagner JJ, Mason GL, Yost GS, Thoren MA, Wittum TE, Bray TM. Source: Am J Vet Res. 2002 December; 63(12): 1641-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492277&dopt=Abstract

•

Effects of gossypol from cottonseed meal and dietary vitamin E on the reproductive characteristics of superovulated beef heifers. Author(s): Velasquez-Pereira J, Arechiga CF, McDowell LR, Hansen PJ, Chenoweth PJ, Calhoun MC, Risco CA, Batra TR, Williams SN, Wilkinson NS.

Alternative Medicine 135

Source: Journal of Animal Science. 2002 September; 80(9): 2485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12350026&dopt=Abstract •

Effects of megadoses of dietary vitamin E on the antioxidant status of rats fed lard or salmon oil. Author(s): Flader D, Brandsch C, Hirche F, Eder K. Source: Int J Vitam Nutr Res. 2003 July; 73(4): 275-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12951900&dopt=Abstract

•

Effects of modified tall oil and vitamin E on growth performance, carcass characteristics, and meat quality of growing-finishing pigs. Author(s): Waylan AT, O'Quinn PR, Unruh JA, Nelssen JL, Goodband RD, Woodworth JC, Tokach MD, Koo SI. Source: Journal of Animal Science. 2002 June; 80(6): 1575-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078739&dopt=Abstract

•

Effects of vitamin E and C supplementation either alone or in combination on exercise-induced lipid peroxidation in trained cyclists. Author(s): Bryant RJ, Ryder J, Martino P, Kim J, Craig BW. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2003 November; 17(4): 792-800. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14666945&dopt=Abstract

•

Effects of vitamin E and carotenoid status on oxidative stress in health and disease. Evidence obtained from human intervention studies. Author(s): Winklhofer-Roob BM, Rock E, Ribalta J, Shmerling DH, Roob JM. Source: Molecular Aspects of Medicine. 2003 December; 24(6): 391-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585310&dopt=Abstract

•

Effects of vitamin E supplementation during erythropoietin treatment of the anaemia of prematurity. Author(s): Pathak A, Roth P, Piscitelli J, Johnson L. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 July; 88(4): F324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819167&dopt=Abstract

•

Effects of vitamin E supplementation on blood antioxidants levels in patients with Behcet's disease. Author(s): Kokcam I, Naziroglu M. Source: Clinical Biochemistry. 2002 November; 35(8): 633-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12498998&dopt=Abstract

136

Vitamin E

•

Effects of vitamin E supplementation on recovery from repeated bouts of resistance exercise. Author(s): Avery NG, Kaiser JL, Sharman MJ, Scheett TP, Barnes DM, Gomez AL, Kraemer WJ, Volek JS. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2003 November; 17(4): 801-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636105&dopt=Abstract

•

Exercise and vitamin E intake are independently associated with metabolic abnormalities in human immunodeficiency virus-positive subjects: a cross-sectional study. Author(s): Gavrila A, Tsiodras S, Doweiko J, Nagy GS, Brodovicz K, Hsu W, Karchmer AW, Mantzoros CS. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1593-601. Epub 2003 Jun 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802761&dopt=Abstract

•

Folic acid and Vitamin E supplementation effects on homocysteinemia, endothelial function and plasma antioxidant capacity in young myocardial-infarction patients. Author(s): Assanelli D, Bonanome A, Pezzini A, Albertini F, Maccalli P, Grassi M, Archetti S, Negrini R, Visioli F. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2004 January; 49(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597156&dopt=Abstract

•

Green tea catechins and vitamin E inhibit angiogenesis of human microvascular endothelial cells through suppression of IL-8 production. Author(s): Tang FY, Meydani M. Source: Nutrition and Cancer. 2001; 41(1-2): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12094614&dopt=Abstract

•

HDL-holoparticle uptake by alveolar type II cells: effect of vitamin E status. Author(s): Kolleck I, Wissel H, Guthmann F, Schlame M, Sinha P, Rustow B. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 July; 27(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091246&dopt=Abstract

•

High-dose vitamin E lowers urine porphyrin levels in patients affected by porphyria cutanea tarda. Author(s): Pinelli A, Trivulzio S, Tomasoni L, Bertolini B, Pinelli G. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2002 April; 45(4): 355-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030801&dopt=Abstract

Alternative Medicine 137

•

In vivo antioxidant properties of vitamin E and chromium in cold-stressed Japanese quails. Author(s): Sahin N, Sahin K, Onderci M, Ozcelik M, Smith MO. Source: Archiv Fur Tierernahrung. 2003 June; 57(3): 207-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903865&dopt=Abstract

•

Increased antioxidant potential of combined topical vitamin E and C against lipid peroxidation of eicosapentaenoic acid in pig skin induced by simulated solar radiation. Author(s): Moison RM, Doerga R, M J Beijersbergen Van Henegouwen G. Source: International Journal of Radiation Biology. 2002 December; 78(12): 1185-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556345&dopt=Abstract

•

Influence of intravenous vitamin E supplementation in cardiac surgery on oxidative stress: a double-blinded, randomized, controlled study. Author(s): Lassnigg A, Punz A, Barker R, Keznickl P, Manhart N, Roth E, Hiesmayr M. Source: British Journal of Anaesthesia. 2003 February; 90(2): 148-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538369&dopt=Abstract

•

Inhibition of immunoglobulin E production in allergic model mice by supplementation with vitamin E and beta-carotene. Author(s): Bando N, Yamanishi R, Terao J. Source: Bioscience, Biotechnology, and Biochemistry. 2003 October; 67(10): 2176-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586106&dopt=Abstract

•

Interactions of dietary polyunsaturated fatty acids and vitamin E with regard to vitamin E status, fat composition and antibody responsiveness in layer hens. Author(s): Sijben JW, Schrama JW, Nieuwland MG, Hovenier R, Beynen AC, Verstegen MW, Parmentier HK. Source: British Poultry Science. 2002 May; 43(2): 297-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047096&dopt=Abstract

•

Iron supplementation increases disease activity and vitamin E ameliorates the effect in rats with dextran sulfate sodium-induced colitis. Author(s): Carrier J, Aghdassi E, Cullen J, Allard JP. Source: The Journal of Nutrition. 2002 October; 132(10): 3146-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368409&dopt=Abstract

•

Is vitamin E the magic bullet for the treatment of Alzheimer's disease (AD)? Author(s): Woo K. Source: Perspectives. 2000 Spring; 24(1): 7-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026332&dopt=Abstract

138

Vitamin E

•

Measurement of vitamin E metabolites by high-performance liquid chromatography during high-dose administration of alpha-tocopherol. Author(s): Morinobu T, Yoshikawa S, Hamamura K, Tamai H. Source: European Journal of Clinical Nutrition. 2003 March; 57(3): 410-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627176&dopt=Abstract

•

Metal working fluids: sub-chronic effects on pulmonary functions in B6C3F1 mice given vitamin E deficient and sufficient diets. Author(s): Shvedova AA, Kisin E, Murray A, Goldsmith T, Reynolds JS, Castranova V, Frazer DG, Kommineni C. Source: Toxicology. 2002 August 15; 177(2-3): 285-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135630&dopt=Abstract

•

Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Author(s): Pace A, Savarese A, Picardo M, Maresca V, Pacetti U, Del Monte G, Biroccio A, Leonetti C, Jandolo B, Cognetti F, Bove L. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 March 1; 21(5): 927-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610195&dopt=Abstract

•

Nonalcoholic fatty liver disease: relationship to insulin sensitivity and oxidative stress. Treatment approaches using vitamin E, magnesium, and betaine. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 August; 7(4): 276-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197781&dopt=Abstract

•

Oxidative status and semen characteristics of rabbit buck as affected by dietary vitamin E, C and n-3 fatty acids. Author(s): Castellini C, Lattaioli P, Dal Bosco A, Minelli A, Mugnai C. Source: Reproduction, Nutrition, Development. 2003 January-February; 43(1): 91-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785452&dopt=Abstract

•

Pharmacokinetics and antitumor effects of vincristine carried by microemulsions composed of PEG-lipid, oleic acid, vitamin E and cholesterol. Author(s): Junping W, Takayama K, Nagai T, Maitani Y. Source: International Journal of Pharmaceutics. 2003 January 30; 251(1-2): 13-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12527171&dopt=Abstract

•

Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: The Insulin Resistance and Atherosclerosis Study (IRAS). Author(s): Mayer-Davis EJ, Costacou T, King I, Zaccaro DJ, Bell RA; The Insulin Resistance and Atherosclerosis Study (IRAS).

Alternative Medicine 139

Source: Diabetes Care. 2002 December; 25(12): 2172-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453956&dopt=Abstract •

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations. Author(s): Di Leo MA, Ghirlanda G, Gentiloni Silveri N, Giardina B, Franconi F, Santini SA. Source: Free Radical Research. 2003 March; 37(3): 323-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688428&dopt=Abstract

•

Profiling of human cytokines in healthy individuals with vitamin E supplementation by antibody array. Author(s): Lin Y, Huang R, Santanam N, Liu YG, Parthasarathy S, Huang RP. Source: Cancer Letters. 2002 December 10; 187(1-2): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359346&dopt=Abstract

•

Prospective study of serum vitamin E levels and esophageal and gastric cancers. Author(s): Taylor PR, Qiao YL, Abnet CC, Dawsey SM, Yang CS, Gunter EW, Wang W, Blot WJ, Dong ZW, Mark SD. Source: Journal of the National Cancer Institute. 2003 September 17; 95(18): 1414-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130117&dopt=Abstract

•

Protective role of antioxidant vitamin E and catechin on idarubicin-induced cardiotoxicity in rats. Author(s): Kalender S, Kalender Y, Ates A, Yel M, Olcay E, Candan S. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2002 November; 35(11): 1379-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426639&dopt=Abstract

•

Randomized trial of a combination of natural products (cernitin, saw palmetto, Bsitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH). Author(s): Preuss HG, Marcusen C, Regan J, Klimberg IW, Welebir TA, Jones WA. Source: International Urology and Nephrology. 2001; 33(2): 217-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092634&dopt=Abstract

•

Relationship of vitamin E supplementation and antimicrobial treatment with acutephase protein responses in cattle affected by naturally acquired respiratory tract disease. Author(s): Carter JN, Meredith GL, Montelongo M, Gill DR, Krehbiel CR, Payton ME, Confer AW.

140

Vitamin E

Source: Am J Vet Res. 2002 August; 63(8): 1111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171163&dopt=Abstract •

Response of Cervical Intra-epithelial Lesions to Vitamin E Supplementation - A Preliminary Report. Author(s): Ganguly C, Dutta K, Sanyal U, Roy C, Basu PS, Das S. Source: Asian Pac J Cancer Prev. 2001; 2(4): 305-308. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718623&dopt=Abstract

•

Rumen-protected choline administration to transition cows: effects on milk production and vitamin E status. Author(s): Pinotti L, Baldi A, Politis I, Rebucci R, Sangalli L, Dell'Orto V. Source: Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine. 2003 February; 50(1): 18-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12650504&dopt=Abstract

•

Silymarin and vitamin E reduce amiodarone-induced lysosomal phospholipidosis in rats. Author(s): Agoston M, Orsi F, Feher E, Hagymasi K, Orosz Z, Blazovics A, Feher J, Vereckei A. Source: Toxicology. 2003 August 28; 190(3): 231-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927377&dopt=Abstract

•

Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Author(s): Keskes-Ammar L, Feki-Chakroun N, Rebai T, Sahnoun Z, Ghozzi H, Hammami S, Zghal K, Fki H, Damak J, Bahloul A. Source: Archives of Andrology. 2003 March-April; 49(2): 83-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623744&dopt=Abstract

•

Spread supplemented with moderate doses of vitamin E and carotenoids reduces lipid peroxidation in healthy, nonsmoking adults. Author(s): Upritchard JE, Schuurman CR, Wiersma A, Tijburg LB, Coolen SA, Rijken PJ, Wiseman SA. Source: The American Journal of Clinical Nutrition. 2003 November; 78(5): 985-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594786&dopt=Abstract

•

Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study. Author(s): Wluka AE, Stuckey S, Brand C, Cicuttini FM. Source: The Journal of Rheumatology. 2002 December; 29(12): 2585-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465157&dopt=Abstract

Alternative Medicine 141

•

Supplementation of vitamin E and selenium prevents hyperoxaluria in experimental urolithic rats. Author(s): Santhosh Kumar M, Selvam R. Source: The Journal of Nutritional Biochemistry. 2003 June; 14(6): 306-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873711&dopt=Abstract

•

Supplementation with vitamin E fails to attenuate oxidative damage in aged mice. Author(s): Sumien N, Forster MJ, Sohal RS. Source: Experimental Gerontology. 2003 June; 38(6): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814806&dopt=Abstract

•

Supplementing bovine milk immunoglobulin G prevents rats fed on a vitamin Edeficient diet from developing peroxidation stress. Author(s): Zommara MA, Toubo H, Imaizumi K. Source: Annals of Nutrition & Metabolism. 2002; 46(3-4): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169851&dopt=Abstract

•

The antioxidants--vitamin C,vitamin E, selenium, and carotenoids. Author(s): Johnson LJ, Meacham SL, Kruskall LJ. Source: J Agromedicine. 2003; 9(1): 65-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563626&dopt=Abstract

•

The association between vitamin C and vitamin E supplement use before hematopoietic stem cell transplant and outcomes to two years. Author(s): Bruemmer B, Patterson RE, Cheney C, Aker SN, Witherspoon RP. Source: Journal of the American Dietetic Association. 2003 August; 103(8): 982-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891146&dopt=Abstract

•

The effect of vitamin E supplementation on antioxidant enzyme activities and lipid peroxidation levels in hemodialysis patients. Author(s): Giray B, Kan E, Bali M, Hincal F, Basaran N. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 December; 338(1-2): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14637272&dopt=Abstract

•

The effect of vitamin E supplementation on discoloration of injection-site lesions in retail cuts and the greening reaction observed in injection-site lesions in muscles of the chuck. Author(s): Roeber DL, Belk KE, Engle TE, Field TG, Koontz SR, Scanga JA, Tatum JD, Mason GL, Van Metre D, Garry FB, Smith GC. Source: Journal of Animal Science. 2003 August; 81(8): 1885-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926769&dopt=Abstract

142

Vitamin E

•

The effect of warmth or/and vitamin E supplementation on forearm blood flow and forearm vascular resistance in sickle cell and non sickle cell anaemia subjects. Author(s): Jaja SI, Gbadamosi TA, Kehinde MO, Gbenebitse S. Source: Niger Postgrad Med J. 2003 March; 10(1): 6-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717457&dopt=Abstract

•

The effects of vitamin E and selenium intake on oxidative stress and plasma lipids in hamsters fed fish oil. Author(s): Poirier J, Cockell K, Hidiroglou N, Madere R, Trick K, Kubow S. Source: Lipids. 2002 December; 37(12): 1125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617464&dopt=Abstract

•

The influences of dietary intakes and supplementation with selenium and vitamin E on reproduction diseases and reproductive efficiency in cattle and sheep. Author(s): Hemingway RG. Source: Veterinary Research Communications. 2003 February; 27(2): 159-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12718509&dopt=Abstract

•

The safety of high-dose vitamin E supplementation in healthy Japanese male adults. Author(s): Morinobu T, Ban R, Yoshikawa S, Murata T, Tamai H. Source: J Nutr Sci Vitaminol (Tokyo). 2002 February; 48(1): 6-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026191&dopt=Abstract

•

Thermally oxidized dietary fats increase plasma thyroxine concentrations in rats irrespective of the vitamin E and selenium supply. Author(s): Eder K, Skufca P, Brandsch C. Source: The Journal of Nutrition. 2002 June; 132(6): 1275-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042446&dopt=Abstract

•

Trace element determination in vitamin E using ICP-MS. Author(s): Ponce De Leon CA, Montes Bayon M, Caruso JA. Source: Analytical and Bioanalytical Chemistry. 2002 September; 374(2): 230-4. Epub 2002 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324842&dopt=Abstract

•

Use of gamma-inulin/liposomes/Vitamin E adjuvant combination in contraceptive vaccines. Author(s): Fuentes P, Cooper PD, Barnadas R, Sabes M, Osterhoff C, Martinez P. Source: International Journal of Pharmaceutics. 2003 May 12; 257(1-2): 85-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12711164&dopt=Abstract

Alternative Medicine 143

•

Vascular endothelial dysfunction associated with elevated serum homocysteine levels in rat adjuvant arthritis: effect of vitamin E administration. Author(s): Can C, Cinar MG, Kosay S, Evinc A. Source: Life Sciences. 2002 June 14; 71(4): 401-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044840&dopt=Abstract

•

Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women. Author(s): Jacobs EJ, Henion AK, Briggs PJ, Connell CJ, McCullough ML, Jonas CR, Rodriguez C, Calle EE, Thun MJ. Source: American Journal of Epidemiology. 2002 December 1; 156(11): 1002-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446256&dopt=Abstract

•

Vitamin C and vitamin E supplementation reduce oxidative stress-induced embryo toxicity and improve the blastocyst development rate. Author(s): Wang X, Falcone T, Attaran M, Goldberg JM, Agarwal A, Sharma RK. Source: Fertility and Sterility. 2002 December; 78(6): 1272-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477524&dopt=Abstract

•

Vitamin E and C supplements and risk of dementia. Author(s): Laurin D, Foley DJ, Masaki KH, White LR, Launer LJ. Source: Jama : the Journal of the American Medical Association. 2002 November 13; 288(18): 2266-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12425703&dopt=Abstract

•

Vitamin E and drug metabolism. Author(s): Brigelius-Flohe R. Source: Biochemical and Biophysical Research Communications. 2003 June 6; 305(3): 737-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763054&dopt=Abstract

•

Vitamin E and thetreatment and prevention of diabetes: a case for a controlled clinical trial. Author(s): Halliwell B. Source: Singapore Med J. 2002 September; 43(9): 479-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568428&dopt=Abstract

•

Vitamin E deficiency and metabolic deficits in neuronal ceroid lipofuscinosis described by bioinformatics. Author(s): Griffin JL, Muller D, Woograsingh R, Jowatt V, Hindmarsh A, Nicholson JK, Martin JE.

144

Vitamin E

Source: Physiological Genomics. 2002 December 3; 11(3): 195-203. Epub 2002 October 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12388797&dopt=Abstract •

Vitamin E levels during chemotherapy for ovarian carcinoma. Author(s): Ananth N, Shetty BV, Vasudevan DM. Source: Natl Med J India. 2003 July-August; 16(4): 231-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14606777&dopt=Abstract

•

Vitamin E may worsen acute respiratory tract infections in the elderly. Author(s): Miller SM. Source: The Journal of Family Practice. 2002 November; 51(11): 925. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12485543&dopt=Abstract

•

Vitamin E ointment at high dose levels suppresses contact dermatitis in rats by stabilizing keratinocytes. Author(s): Kuriyama K, Shimizu T, Horiguchi T, Watabe M, Abe Y. Source: Inflammation Research : Official Journal of the European Histamine Research Society. [et Al.]. 2002 October; 51(10): 483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477076&dopt=Abstract

•

Vitamin E reduces progression of atherosclerosis in low-density lipoprotein receptordeficient mice with established vascular lesions. Author(s): Cyrus T, Yao Y, Rokach J, Tang LX, Pratico D. Source: Circulation. 2003 February 4; 107(4): 521-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566360&dopt=Abstract

•

Vitamin E requirement of adult cats increases slightly with high dietary intake of polyunsaturated fatty acids. Author(s): Hendriks WH, Wu YB, Shields RG, Newcomb M, Rutherfurd KJ, Belay T, Wilson J. Source: The Journal of Nutrition. 2002 June; 132(6 Suppl 2): 1613S-5S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042472&dopt=Abstract

•

Vitamin E supplementation and macular degeneration: randomised controlled trial. Author(s): Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ. Source: Bmj (Clinical Research Ed.). 2002 July 6; 325(7354): 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098721&dopt=Abstract

•

Vitamin E supplementation can alleviate negative effects of heat stress on egg production, egg quality, digestibility of nutrients and egg yolk mineral concentrations of Japanese quails. Author(s): Sahin K, Sahin N, Onderci M.

Alternative Medicine 145

Source: Research in Veterinary Science. 2002 December; 73(3): 307-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443690&dopt=Abstract •

Vitamin E supplementation does not alter azoxymethane-induced colonic aberrant crypt foci formation in young or old mice. Author(s): Chung H, Wu D, Han SN, Gay R, Goldin B, Bronson RE, Mason JB, Smith DE, Meydani SN. Source: The Journal of Nutrition. 2003 February; 133(2): 528-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566495&dopt=Abstract

•

Vitamin E supplementation does not increase the vitamin C radical concentration at rest and after exhaustive exercise in healthy male subjects. Author(s): Schneider M, Niess AM, Rozario F, Angres C, Tschositsch K, Battenfeld N, Schaffer M, Northoff H, Dickhuth HH, Fehrenbach E, Trommer WE, Biesalski HK. Source: European Journal of Nutrition. 2003 August; 42(4): 195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923650&dopt=Abstract

•

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Author(s): Brion L, Bell E, Raghuveer T. Source: Cochrane Database Syst Rev. 2003; 4: Cd003665. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583988&dopt=Abstract

•

Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Author(s): Brion LP, Bell EF, Raghuveer TS. Source: Cochrane Database Syst Rev. 2003; (3): Cd003665. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917978&dopt=Abstract

•

Vitamin E Supplementation in Patients With Carotid Atherosclerosis. Reversal of Altered Oxidative Stress Status in Plasma But Not in Plaque. Author(s): Micheletta F, Natoli S, Misuraca M, Sbarigia E, Diczfalusy U, Iuliano L. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 October 30 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592846&dopt=Abstract

•

Vitamin E supplementation in the mitigation of carbon tetrachloride induced oxidative stress in rats. Author(s): MacDonald-Wicks LK, Garg ML. Source: The Journal of Nutritional Biochemistry. 2003 April; 14(4): 211-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770645&dopt=Abstract

146

Vitamin E

•

Vitamin E supplementation increases circulating vitamin E metabolites tenfold in end-stage renal disease patients. Author(s): Smith KS, Lee CL, Ridlington JW, Leonard SW, Devaraj S, Traber MG. Source: Lipids. 2003 August; 38(8): 813-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14577659&dopt=Abstract

•

Vitamin E supplementation increases LDL resistance to ex vivo oxidation in hemodialysis patients. Author(s): Badiou S, Cristol JP, Morena M, Bosc JY, Carbonneau MA, Dupuy AM, Descomps B, Canaud B. Source: Int J Vitam Nutr Res. 2003 July; 73(4): 290-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12951902&dopt=Abstract

•

Vitamin E supplementation reduces plasma vascular cell adhesion molecule-1 and von Willebrand factor levels and increases nitric oxide concentrations in hypercholesterolemic patients. Author(s): Desideri G, Marinucci MC, Tomassoni G, Masci PG, Santucci A, Ferri C. Source: The Journal of Clinical Endocrinology and Metabolism. 2002 June; 87(6): 2940-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050277&dopt=Abstract

•

Vitamin E therapy in Parkinson's disease. Author(s): Fariss MW, Zhang JG. Source: Toxicology. 2003 July 15; 189(1-2): 129-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821288&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

•

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

•

Chinese Medicine: http://www.newcenturynutrition.com/

•

drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

•

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

•

Google: http://directory.google.com/Top/Health/Alternative/

•

Healthnotes: http://www.healthnotes.com/

•

MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

•

Open Directory Project: http://dmoz.org/Health/Alternative/

•

HealthGate: http://www.tnp.com/

Alternative Medicine 147

•

WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to vitamin E; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com Abnormal Pap Smear Source: Healthnotes, Inc.; www.healthnotes.com Acne Source: Integrative Medicine Communications; www.drkoop.com Acne Source: Prima Communications, Inc.www.personalhealthzone.com Age-Related Cognitive Decline Source: Healthnotes, Inc.; www.healthnotes.com Aging Source: Integrative Medicine Communications; www.drkoop.com AIDS and HIV Source: Integrative Medicine Communications; www.drkoop.com Alcohol Withdrawal Source: Healthnotes, Inc.; www.healthnotes.com Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Allergic Rhinitis Source: Integrative Medicine Communications; www.drkoop.com Alopecia Source: Integrative Medicine Communications; www.drkoop.com Alzheimer's Disease Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com

148

Vitamin E

Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Anemia Source: Integrative Medicine Communications; www.drkoop.com Angina Source: Healthnotes, Inc.; www.healthnotes.com Angina Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Arteriosclerosis Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Prima Communications, Inc.www.personalhealthzone.com Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Atherosclerosis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Autoimmune Conditions Source: Integrative Medicine Communications; www.drkoop.com Benign Prostatic Hyperplasia Source: Healthnotes, Inc.; www.healthnotes.com Bone Cancer Source: Integrative Medicine Communications; www.drkoop.com Bone Infection Source: Integrative Medicine Communications; www.drkoop.com Brain Cancer Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 149

Breast Cancer Source: Integrative Medicine Communications; www.drkoop.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Burns Source: Healthnotes, Inc.; www.healthnotes.com Burns Source: Integrative Medicine Communications; www.drkoop.com Cancer Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (Reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Candidiasis Source: Integrative Medicine Communications; www.drkoop.com Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Cataracts Source: Healthnotes, Inc.; www.healthnotes.com Cataracts Source: Integrative Medicine Communications; www.drkoop.com Cataracts (Prevention) Source: Prima Communications, Inc.www.personalhealthzone.com Cervical Dysplasia Source: Integrative Medicine Communications; www.drkoop.com Chickenpox and Shingles Source: Integrative Medicine Communications; www.drkoop.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Integrative Medicine Communications; www.drkoop.com Cirrhosis Source: Integrative Medicine Communications; www.drkoop.com Cold Sores Source: Healthnotes, Inc.; www.healthnotes.com

150

Vitamin E

Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Congestive Heart Failure Source: Integrative Medicine Communications; www.drkoop.com Connective Tissue Diseases Source: Integrative Medicine Communications; www.drkoop.com Coronary Artery Disease Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Cutaneous Drug Reactions Source: Integrative Medicine Communications; www.drkoop.com Cyclic Mastalgia Alternative names: Cyclic Mastitis, Fibrocystic Breast Disease Source: Prima Communications, Inc.www.personalhealthzone.com Cystic Fibrosis Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Integrative Medicine Communications; www.drkoop.com Dementia Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Source: Integrative Medicine Communications; www.drkoop.com Dermatitis Herpetiformis Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 151

Dupuytren's Contracture Source: Healthnotes, Inc.; www.healthnotes.com Dysmenorrhea Source: Integrative Medicine Communications; www.drkoop.com Eating Disorders Source: Healthnotes, Inc.; www.healthnotes.com Eczema Source: Healthnotes, Inc.; www.healthnotes.com Eczema Source: Integrative Medicine Communications; www.drkoop.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Endometriosis Source: Integrative Medicine Communications; www.drkoop.com Epilepsy Source: Healthnotes, Inc.; www.healthnotes.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Eye Disorders Source: Integrative Medicine Communications; www.drkoop.com Female Infertility Source: Healthnotes, Inc.; www.healthnotes.com Fibrocystic Breast Disease Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Frostbite Source: Integrative Medicine Communications; www.drkoop.com Gallbladder Disease Source: Integrative Medicine Communications; www.drkoop.com Gestational Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Glaucoma Source: Integrative Medicine Communications; www.drkoop.com

152

Vitamin E

Gout Source: Prima Communications, Inc.www.personalhealthzone.com Hair Disorders Source: Integrative Medicine Communications; www.drkoop.com Hair Loss Source: Integrative Medicine Communications; www.drkoop.com Hay Fever Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com Hemophilia Source: Integrative Medicine Communications; www.drkoop.com Hemorrhoids Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Herpes Zoster and Varicella Viruses Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com High Triglycerides Source: Healthnotes, Inc.; www.healthnotes.com HIV and AIDS Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 153

Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypertension Alternative names: High Blood Pressure Source: Prima Communications, Inc.www.personalhealthzone.com Hyperthyroidism Source: Integrative Medicine Communications; www.drkoop.com Hypoglycemia Source: Healthnotes, Inc.; www.healthnotes.com Hypoglycemia Source: Integrative Medicine Communications; www.drkoop.com Hypothyroidism Source: Integrative Medicine Communications; www.drkoop.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Immune System Disorders Source: Integrative Medicine Communications; www.drkoop.com Infection Source: Healthnotes, Inc.; www.healthnotes.com Insulin Resistance Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Intermittent Claudication Source: Healthnotes, Inc.; www.healthnotes.com Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Leukemia Source: Integrative Medicine Communications; www.drkoop.com Leukoplakia Source: Healthnotes, Inc.; www.healthnotes.com Liver Cirrhosis Source: Healthnotes, Inc.; www.healthnotes.com Liver Disease Source: Integrative Medicine Communications; www.drkoop.com

154

Vitamin E

Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Low Blood Sugar Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Lymphoma Source: Integrative Medicine Communications; www.drkoop.com Macular Degeneration Source: Healthnotes, Inc.; www.healthnotes.com Macular Degeneration Source: Integrative Medicine Communications; www.drkoop.com Macular Degeneration Source: Prima Communications, Inc.www.personalhealthzone.com Male Infertility Source: Healthnotes, Inc.; www.healthnotes.com Male Infertility Source: Prima Communications, Inc.www.personalhealthzone.com Memory Loss Source: Integrative Medicine Communications; www.drkoop.com Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Menorrhagia Source: Healthnotes, Inc.; www.healthnotes.com Menstrual Pain Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 155

Migraine Headache Source: Integrative Medicine Communications; www.drkoop.com Miscarriage Source: Integrative Medicine Communications; www.drkoop.com Multiple Sclerosis Source: Healthnotes, Inc.; www.healthnotes.com Multiple Sclerosis Source: Integrative Medicine Communications; www.drkoop.com Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Osgood-schlatter Disease Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.com Osteomyelitis Source: Integrative Medicine Communications; www.drkoop.com Pancreatic Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Parkinson's Disease Source: Integrative Medicine Communications; www.drkoop.com Pelvic Inflammatory Disease Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com

156

Vitamin E

Peripheral Vascular Disease Source: Healthnotes, Inc.; www.healthnotes.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Photosensitivity Source: Healthnotes, Inc.; www.healthnotes.com PMS Source: Integrative Medicine Communications; www.drkoop.com PMS Alternative names: Premenstrual Stress Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Preeclampsia Source: Healthnotes, Inc.; www.healthnotes.com Premenstrual Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Integrative Medicine Communications; www.drkoop.com Psoriasis Source: Prima Communications, Inc.www.personalhealthzone.com Pulmonary Edema Source: Integrative Medicine Communications; www.drkoop.com Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.com Radiation Damage Source: Integrative Medicine Communications; www.drkoop.com Raynaud's Phenomenon Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 157

Raynaud's Phenomenon Source: Prima Communications, Inc.www.personalhealthzone.com Reiter's Syndrome Source: Integrative Medicine Communications; www.drkoop.com Restless Legs Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Retinopathy Source: Healthnotes, Inc.; www.healthnotes.com Rheumatoid Arthritis Source: Healthnotes, Inc.; www.healthnotes.com Rheumatoid Arthritis Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Schizophrenia Source: Healthnotes, Inc.; www.healthnotes.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com Sexual Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Shingles and Chickenpox Source: Integrative Medicine Communications; www.drkoop.com Shingles and Postherpetic Neuralgia Source: Healthnotes, Inc.; www.healthnotes.com Sickle Cell Anemia Source: Healthnotes, Inc.; www.healthnotes.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Skin Conditions Source: Integrative Medicine Communications; www.drkoop.com Spontaneous Abortion Source: Integrative Medicine Communications; www.drkoop.com

158

Vitamin E

Sprains and Strains Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Tardive Dyskinesia Source: Healthnotes, Inc.; www.healthnotes.com Tendinitis Source: Integrative Medicine Communications; www.drkoop.com Tension Headache Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com Vaginal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Vaginitis Source: Healthnotes, Inc.; www.healthnotes.com Vaginitis Source: Integrative Medicine Communications; www.drkoop.com Varicella and Herpes Zoster Viruses Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Integrative Medicine Communications; www.drkoop.com Warts Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 159

Wound Healing Source: Healthnotes, Inc.; www.healthnotes.com Wounds Source: Integrative Medicine Communications; www.drkoop.com Yeast Infection Source: Integrative Medicine Communications; www.drkoop.com Yellow Nail Syndrome Source: Healthnotes, Inc.; www.healthnotes.com •

Alternative Therapy Nutrition Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Alfalfa Alternative names: Medicago sativa Source: Healthnotes, Inc.; www.healthnotes.com Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aloe Alternative names: Aloe vera, Aloe barbadensis Source: Healthnotes, Inc.; www.healthnotes.com Alpha Lipoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Alpha-Lipoic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10002,00.html Amiodarone Source: Healthnotes, Inc.; www.healthnotes.com Amiodarone Alternative names: Cordarone, Pacerone Source: Prima Communications, Inc.www.personalhealthzone.com Anthralin Source: Healthnotes, Inc.; www.healthnotes.com Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com

160

Vitamin E

Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html Antioxidants and Free Radicals Source: Healthnotes, Inc.; www.healthnotes.com Antituberculosis Agents Source: Integrative Medicine Communications; www.drkoop.com Arnica Alternative names: Arnica montana L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aspirin Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com AZT Source: Healthnotes, Inc.; www.healthnotes.com B-carotene Source: Integrative Medicine Communications; www.drkoop.com Benzamycin Source: Healthnotes, Inc.; www.healthnotes.com Beta-carotene Source: Healthnotes, Inc.; www.healthnotes.com Beta-carotene Alternative names: b-carotene, Trans-beta Carotene; Provitamin A, Betacarotenum Source: Integrative Medicine Communications; www.drkoop.com Beta-carotene Source: Prima Communications, Inc.www.personalhealthzone.com Betacarotenum Source: Integrative Medicine Communications; www.drkoop.com Bilberry Alternative names: Vaccinium myrtillus Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 161

Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com Bilberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10007,00.html Bile Acid Sequestrant Drugs Source: Prima Communications, Inc.www.personalhealthzone.com Bile Acid Sequestrants Source: Healthnotes, Inc.; www.healthnotes.com Calendula Alternative names: Calendula officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Carnosine Source: Healthnotes, Inc.; www.healthnotes.com Carotenoids Source: Healthnotes, Inc.; www.healthnotes.com Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html Catechins Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1023,00.html Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Colestipol Source: Healthnotes, Inc.; www.healthnotes.com CoQ10 Source: Integrative Medicine Communications; www.drkoop.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

162

Vitamin E

Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Cyclosporine Source: Healthnotes, Inc.; www.healthnotes.com Dapsone Source: Healthnotes, Inc.; www.healthnotes.com Dha Source: Integrative Medicine Communications; www.drkoop.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.drkoop.com Doxorubicin Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Source: Prima Communications, Inc.www.personalhealthzone.com Eicosapentaenoic Acid (EPA) Source: Integrative Medicine Communications; www.drkoop.com Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Fenofibrate Source: Healthnotes, Inc.; www.healthnotes.com Fibric Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Gemfibrozil Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

Alternative Medicine 163

Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Glyburide Source: Healthnotes, Inc.; www.healthnotes.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Grape Seed Alternative names: Vitis vinifera Source: Integrative Medicine Communications; www.drkoop.com Grape Seed Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,793,00.html Griseofulvin Source: Healthnotes, Inc.; www.healthnotes.com Haloperidol Source: Healthnotes, Inc.; www.healthnotes.com Heparin Alternative names: Hep-Lock Source: Prima Communications, Inc.www.personalhealthzone.com Insulin Source: Healthnotes, Inc.; www.healthnotes.com Isoniazid Source: Healthnotes, Inc.; www.healthnotes.com Lindane Source: Healthnotes, Inc.; www.healthnotes.com Lipoic Acid Source: Prima Communications, Inc.www.personalhealthzone.com Lutein Source: Healthnotes, Inc.; www.healthnotes.com Lycopene Source: Healthnotes, Inc.; www.healthnotes.com Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com

164

Vitamin E

Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Nonsteroidal Anti-inflammatory Drugs Source: Prima Communications, Inc.www.personalhealthzone.com OPCS (Oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com Origanum Alternative names: Oregano; Origanum vulgare Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Orlistat Source: Healthnotes, Inc.; www.healthnotes.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pentoxifylline Source: Healthnotes, Inc.; www.healthnotes.com Pentoxifylline Alternative names: Trental Source: Prima Communications, Inc.www.personalhealthzone.com Phenobarbital Source: Healthnotes, Inc.; www.healthnotes.com Phenothiazines Source: Prima Communications, Inc.www.personalhealthzone.com Pimpinella Alternative names: Anise; Pimpinella anisum (L) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Proanthocyanidins Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 165

Red Clover Source: Integrative Medicine Communications; www.drkoop.com Risperidone Source: Healthnotes, Inc.; www.healthnotes.com Rosmarinus Alternative names: Rosemary; Rosmarinus officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tamoxifen Source: Healthnotes, Inc.; www.healthnotes.com Thymus Alternative names: Thyme; Thymus vulgaris Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tocotrienols Source: Healthnotes, Inc.; www.healthnotes.com Trans-Beta-Carotene Source: Integrative Medicine Communications; www.drkoop.com Tribulus Puncture Alternative names: Puncture Vine, Goathead; Tribulus terrestris L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vitis Vinifera Source: Integrative Medicine Communications; www.drkoop.com Warfarin Source: Healthnotes, Inc.; www.healthnotes.com Warfarin Alternative names: Coumadin Source: Prima Communications, Inc.www.personalhealthzone.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html.

166

Vitamin E

This Web site provides a general overview of various topics and can lead to a number of general sources.

167

CHAPTER 4. DISSERTATIONS ON VITAMIN E Overview In this chapter, we will give you a bibliography on recent dissertations relating to vitamin E. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “vitamin E” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on vitamin E, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Vitamin E ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to vitamin E. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

An Esr Spin Trapping Study on the Role of Free Radicals, Glutathione and Vitamin E in 3-methylindole-induced Lung Disease by Kubow, Stanley Jan; PhD from University of Guelph (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK65604

•

Aspects of Vitamin E Deprivation in the Harp Seal, Pagophilus Groenlandicus by Engelhardt, F. Rainer; PhD from University of Guelph (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK20113

•

Dietary L-carnitine Alters the Metabolism and Body Status of Vitamin E in Rats by Zou, Wei; PhD from Kansas State University, 2002, 498 pages http://wwwlib.umi.com/dissertations/fullcit/3090393

•

Dietary Selenium, Vitamin E and Ultraviolet Light on the Skin of Chicks and Hairless Mice by Bernstein, Gisele Gruber; PhD from Cornell University, 2002, 228 pages http://wwwlib.umi.com/dissertations/fullcit/3050411

168

Vitamin E

•

Effect of Oxidized Fish Oil on the Vitamin E, Vitamin C and Essential Fatty Acid Status of Rainbow Trout, Salmo Gairdneri by Hung, Silas S. O; PhD from University of Guelph (Canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK48741

•

Effect of Vitamin E and Porcine Stress Syndrome (pss) Genotype on Antioxidant Status and Carcass Characteristics of Pigs by Mccully, Gerry Ann; Ms from Michigan State University, 2002, 79 pages http://wwwlib.umi.com/dissertations/fullcit/1411953

•

Effect of Vitamin E, Irradiation, and Display Time on the Quality and Sensory Characteristics of Pork by Ohene-adjei, Samuel; PhD from University of Illinois at Urbana-champaign, 2002, 90 pages http://wwwlib.umi.com/dissertations/fullcit/3070036

•

Effects of Methylmercury on Reproduction and Offspring Development and Potential Benefits of Supplemental Selenium and Vitamin E Intake in Rats by Beyrouty, Peter C.; Msc from Mcgill University (Canada), 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/MQ78834

•

Effects of Sel-plex (organic Selenium) and Vitamin E on Performance, Immune Response, and Beef Cut Shelf Life of Feedlot Steers by Clyburn, Bradley Scott; PhD from Texas Tech University, 2002, 101 pages http://wwwlib.umi.com/dissertations/fullcit/3056065

•

Effects of Vitamin E Intake on Oxidized Low-density Lipoprotein by Kirk, Shelley; PhD from University of Cincinnati, 2003, 169 pages http://wwwlib.umi.com/dissertations/fullcit/3081863

•

Effects of Vitamin E on Health, Performance, and Immune Responses of Feeder Cattle by Rivera, J. Daniel; PhD from New Mexico State University, 2002, 65 pages http://wwwlib.umi.com/dissertations/fullcit/3063787

•

Effects of Vitamin E Supplementation on Muscle Soreness, Plasma Creatine Kinase, and Plasma Malondialdehyde Following an Endurance-ergometer Ride by Lewis, Cynthia Lynn, PhD from The University of North Carolina at Greensboro, 1992, 200 pages http://wwwlib.umi.com/dissertations/fullcit/9303939

•

Evidence That Vitamin E and T Helper Cells May Have a Role in the Epidemiology of Asthma and Allergy by Anderson, Wendy Jane Anne; Md from Queen's University of Belfast (united Kingdom), 2002, 239 pages http://wwwlib.umi.com/dissertations/fullcit/f840545

•

Identification and Functional Analyses of Homogentisate Phytyltransferase; a Key Enzyme Involved in Tocopherol Synthesis in Photosynthetic Organisms by Collakova, Eva; PhD from Michigan State University, 2003, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3092126

•

Mating Type, Vitamin E and Morphogenesis in Ustilago Violacea and Other Smut Fungi by Castle, Alan James; PhD from The University of Western Ontario (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK61750

•

Modulation of Immune System Development and Function in Broilers by Dietary Vitamin E by Konjufca, Vjollca Hajdin; PhD from University of Arkansas, 2002, 195 pages http://wwwlib.umi.com/dissertations/fullcit/3055333

Dissertations 169

•

The Dose Response Effect of Almonds on Serum Vitamin E, Plasma Lipid Fractions and Erythrocyte Phospholipids by Jambazian, Pera R.; Drph from Loma Linda University, 2003, 150 pages http://wwwlib.umi.com/dissertations/fullcit/3094849

•

The Effect of Vitamin E on Muscular Strength, Cardiovascular and Pulmonary Function, Blood Chemistry and Anthropometric Measures by Jolley, Woodrow Wilson, Jr., Edd from University of Arkansas, 1980, 129 pages http://wwwlib.umi.com/dissertations/fullcit/8026084

•

The Effects of Alpha-tocopherol on Ethanol-induced Fetal Resorption in Pregnant Rats (tocopherol-alpha, Vitamin E) by Barao, Elvin Datingaling; Ms from Baylor University, 2002, 107 pages http://wwwlib.umi.com/dissertations/fullcit/1408509

•

The Kinetics of Erythropoiesis and Coagulation in Vitamin E and Selenium Deficient Swine by Fontaine, Michel; PhD from University of Guelph (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK22694

•

The Relationship of Vitamin E to Cognition, White Matter Hyperintensities and Vascular Risk Factors in Elderly Latinos by Zrelak, Patricia Ann; PhD from University of California, Davis, 2003, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3082581

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

171

CHAPTER 5. CLINICAL TRIALS AND VITAMIN E Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning vitamin E.

Recent Trials on Vitamin E The following is a list of recent trials dedicated to vitamin E.8 Further information on a trial is available at the Web site indicated. •

Double-blind, placebo-controlled trial of vitamin E as add-on therapy for children with epilepsy Condition(s): Epilepsy Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR) Purpose - Excerpt: This is a study to see if vitamin E helps children with epilepsy have fewer seizures. About 20-30% of children with epilepsy do not have adequate seizure control with established antiepileptic drugs (AEDs). Other options for patients with uncontrolled epilepsy are newer antiepileptic medications, ketogenic diet and surgery. However, a small percentage of patients are candidates for these options. Therefore, additional treatments are needed to improve seizure control in patients with uncontrolled epilepsy. Animal studies have shown an association between vitamin E supplementation and seizure reduction. A study in children also showed that vitamin E helped reduce seizures. However, a similar study in adults did not show a reduction in seizures with vitamin E supplementation. Therefore, this research study is being done to help define vitamin E's usefulness and safety as a treatment for epilepsy. Fifty patients will be recruited from the Children's Epilepsy Program at The Children's Hospital in Denver, Colorado. Qualifying patients will have a confirmed diagnosis of epilepsy that is currently uncontrolled with standard AEDs. The study period is 6 months and includes the following: Baseline period (1 month), Arm I (2 months), Wash-out period (1 month), and Arm II (2 months). Patients must have been on the same AEDs for 2 months

8

These are listed at www.ClinicalTrials.gov.

172

Vitamin E

before enrollment. All medications and complementary therapies must remain constant throughout the study. If at any point the physician feels it is not best for the patient to continue the study they will be discontinued. Before the study starts, study participants will be asked about seizure activity, what they eat and about any complementary and/or alternative medicine they may use. The study is two phases. Study participants will be given either vitamin E or placebo (fake pill/liquid) in each phase of the study. They will receive both vitamin E and placebo during the study. Which phase they receive vitamin E and placebo will be decided by chance (similar to rolling dice). Study participants will take liquid vitamin E or placebo two times per day. The study participants and study doctors will not know who is taking vitamin E and who is taking placebo. Study participants will come to the hospital for 3 outpatient and 2 inpatient visits. Health-related quality of life questionnaires will be filled out and blood will be drawn at three of the visits. Seizure diaries will be maintained throughout the study. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004637 •

Effect of High Dose Vitamin E on Carotid Atherosclerosis Condition(s): Cardiovascular Diseases Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The primary aim of the present study is to test the effect of alphatocopherol supplementation on the progression of carotid atherosclerosis in patients with coronary artery disease Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010699

•

Isotretinoin With or Without Vitamin E for Prevention of Lung Cancer Condition(s): Non-small cell lung cancer; Small Cell Lung Cancer; Drug Toxicity Study Status: This study is currently recruiting patients. Sponsor(s): University of Colorado Cancer Center Purpose - Excerpt: RATIONALE: Isotretinoin may prevent the development of cancer cells. PURPOSE: Randomized double-blinded phase II trial to study the effectiveness of isotretinoin with or without vitamin E for chemoprevention of cancer in persons at high risk of developing lung cancer. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002586

Clinical Trials 173

•

Isotretinoin, Interferon alfa, and Vitamin E in Treating Patients With Stage III or Stage IV Head and Neck Cancer Condition(s): Hypopharyngeal Cancer; Laryngeal Cancer; lip and oral cavity cancer; Oropharyngeal Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Eastern Cooperative Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy such as isotretinoin use different ways to stop tumor cells from dividing so they stop growing or die. Interferon alfa may interfere with the growth of tumor cells. Vitamin E may be able to decrease side effects caused by isotretinoin. It is not yet known whether combining isotretinoin and interferon alfa with vitamin E is more effective than observation in preventing recurrence of head and neck cancer after surgery and/or radiation therapy. PURPOSE: Randomized phase III trial to compare the effectiveness of isotretinoin and interferon alfa combined with vitamin E with that of observation in treating patients who have undergone surgery and/or radiation therapy for stage III or stage IV head and neck cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054561

•

Oxidative Stress and Vitamin E Requirements Condition(s): Smoking Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: The purpose of this study is to determine if oxidative stress derived from cigarette smoking increases vitamin E requirements. The study will also assess the role of vitamin C in modulating vitamin E requirements. Vitamin E requirements will be assessed by measuring vitamin E in plasma as well as by measuring the excreted metabolite in the urine. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00067899

•

Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE) Condition(s): Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA); National Cancer Institute (NCI) Purpose - Excerpt: The Prevention of Alzheimer's Disease by Vitamin E and Selenium (PREADVISE) prevention trial is an important addition to the Selenium and Vitamin E Cancer Prevention Trial (SELECT). As a prevention trial, PREADVISE is trying to find out if taking selenium and/or Vitamin E supplements can help to prevent memory loss and dementia such as Alzheimer's disease.

174

Vitamin E

Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00040378 •

Selenium and Vitamin E in Preventing Prostate Cancer Condition(s): Prostate Cancer Study Status: This study is currently recruiting patients. Sponsor(s): Southwest Oncology Group; National Cancer Institute (NCI); National Center for Complementary and Alternative Medicine (NCCAM); Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. It is not yet known which regimen of selenium and/or vitamin E may be more effective in preventing prostate cancer. PURPOSE: Randomized phase III trial to determine the effectiveness of selenium and vitamin E, either alone or together, in preventing prostate cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006392

•

Vitamin E in Aging Persons With Down Syndrome Condition(s): Down Syndrome; Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA); National Institute of Child Health and Human Development (NICHD); National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The goal of this study is to determine the safety and efficacy of the administration of vitamin E, which has been shown to delay the progression of Alzheimer's disease, in slowing the rate of cognitive/functional decline in older persons with Down syndrome. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056329

•

Vitamin E to Treat Uveitis-Associated Macular Edema Condition(s): Cystoid Macular Edema; Uveitis Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will evaluate whether vitamin E can help treat swelling of the macular area of the retina (the back part of the eye) associated with uveitis

Clinical Trials 175

(inflammatory eye disease). The macula is responsible for sharp vision; swelling in this area is one cause of vision loss in uveitis patients. Macular swelling is also associated with eye problems related to diabetes. In these patients, the swelling is thought to be caused by a substance called vascular endothelial growth factor, or VEGF. High doses of vitamin E have been used to treat these eye problems in diabetics. This study is a first step to find out if vitamin E will help reduce the retinal swelling in uveitis, which may also be caused by VEGF. Patients 9 years of age and older with macular edema associated with uveitis may be eligible for this study. Candidates will be screened with the following tests and procedures: - Medical history and physical examination. This includes measurement of vital signs (blood pressure, pulse, temperature and breathing rate) and examination of the head and neck, heart, lungs, abdomen, arms and legs. - Eye examination. This includes measurement of visual acuity using a vision chart, measurement of eye pressure and examination of the pupils and eye movements. The pupils will be dilated with drops to permit examination of the back of the eye. Fluorescein angiography. This test uses a yellow dye (fluorescein) to take photos of the retina. The fluorescein is injected into an arm vein and travels to the blood vessels in the eye. The camera flashes a blue light into the eye and takes pictures of the retina. The pictures show if the dye has leaked from the blood vessels into the retina. - Stereoscopic color fundus photography. These are photographs of the back of the eye, taken after the pupils have been dilated with drops. - Optical coherence tomography. This test measures the macular swelling. It is used to determine if the swelling is getting worse, better or staying the same. - Blood tests. About a tablespoon of blood is drawn to measure inflammation and cell counts and side effects of treatment. - Pregnancy test. All women of child-bearing potential are tested for pregnancy. Participants will be randomly assigned to daily treatment with oral high-dose vitamin E (1600 units) or placebo (a pill with no active ingredient) for 4 months. They will be examined at 2 months and 4 months with the same tests performed for screening and will return for a final clinic visit 1 month after treatment has ended. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021645 •

Vitamin E, Selenium, and Soy Protein in Preventing Cancer in Patients With HighGrade Prostate Neoplasia Condition(s): Prostate Cancer Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute of Canada Purpose - Excerpt: RATIONALE: Chemoprevention therapy is the use of certain substances to try to prevent the development or recurrence of cancer. Vitamin E, selenium, and soy protein may be effective in preventing the development of prostate cancer. PURPOSE: Randomized phase II trial to study the effectiveness of combining vitamin E, selenium, and soy protein in preventing prostate cancer in patients who have high-grade prostate neoplasia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

176

Vitamin E

Web Site: http://clinicaltrials.gov/ct/show/NCT00064194 •

Donepezil and Vitamin E to Prevent Side Effects Caused By Radiation Therapy to the Head in Patients Receiving Treatment for Small Cell Lung Cancer Condition(s): extensive stage small cell lung cancer; limited stage small cell lung cancer; Depression; Delirium; Recurrent Small Cell Lung Cancer; radiation toxicity; psychosocial effects/treatment; Quality of Life Study Status: This study is no longer recruiting patients. Sponsor(s): National Cancer Institute (NCI); North Central Cancer Treatment Group Purpose - Excerpt: RATIONALE: Donepezil and vitamin E may be able to decrease side effects caused by radiation therapy given to prevent brain metastases in patients with small cell lung cancer. It is not yet known if donepezil and vitamin E are effective in preventing side effects caused by radiation therapy to the head. PURPOSE: Randomized phase III trial to determine the effectiveness of donepezil and vitamin E in preventing side effects caused by radiation therapy given to prevent brain metastases in patients who have small cell lung cancer. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006349

•

Supplemental Selenium and Vitamin E and Pulmonary Function Condition(s): Chronic Obstructive Pulmonary Disease; Lung Diseases; Lung Diseases, Obstructive Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test whether anti-oxidant supplementation with selenium and/or vitamin E affects pulmonary function. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00063453

•

Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa Condition(s): Retinitis Pigmentosa Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether supplements of vitamin A or vitamin E alone or in combination affect the course of retinitis pigmentosa. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000114

Clinical Trials 177

•

Trial of Aspirin and Vitamin E in Women (Women's Health Study - WHS) Condition(s): Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Heart Diseases; Myocardial Infarction; Myocardial Ischemia; Vascular Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the effects of vitamin E and low-dose aspirin in primary prevention of cardiovascular disease and cancer in apparently healthy women. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000479

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “vitamin E” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

•

For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

•

For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

•

For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

•

For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

178

Vitamin E

•

For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

•

For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

•

For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

•

For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

•

For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

179

CHAPTER 6. PATENTS ON VITAMIN E Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “vitamin E” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on vitamin E, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Vitamin E By performing a patent search focusing on vitamin E, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

180

Vitamin E

will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on vitamin E: •

Anti-corrosive coating including a filler with a hollow cellular structure Inventor(s): Schmidt; Christina (Althengstett, DE) Assignee(s): DaimlerChrysler AG (Stuttgart, DE) Patent Number: 6,383,271 Date filed: January 27, 2000 Abstract: An anti-corrosive coating composition suitable for providing corrosion protection for a sheet metal substrate includes from 20 to 97 wt. % of a filler dispersed in a polymeric base or matrix material. The filler includes at least one filler material having a hollow cellular structure, of which the hollow cells are loaded with organic and/or inorganic inhibitors and/or antioxidants. The hollow cellular structure material may be diatomaceous earth, zeolite, or carbon. The inhibitors and/or antioxidants may be selected from carbonic acids, amines, ketones, aldehydes, heterocyclic compounds, phosphates, benzoates, silicates, vanadates, tungstates, zirconates, borates, molybdates, benzaldehyde, vitamin C, vitamin E, or the like. A long term durable corrosion protection is achieved because the inhibitors and/or antioxidants are released from the hollow cells of the filler material in a dosed time-release manner over the operating lifetime of the anti-corrosive coating. Excerpt(s): This application is based on and claims the priority under 35 U.S.C.sctn.119 of German Patent Application 199 03 400.1, filed on Jan. 29, 1999, the entire disclosure of which is incorporated herein by reference. The invention relates to an anti-corrosive coating that is based on an organic polymer coating matrix material with filler materials dispersed therein, and that is suitable for coating and protecting a metal substrate against corrosion. In the present state of the art, high demands are placed on the coating of metallic substrate surfaces with regard to the corrosion protection that is to be provided by such coatings. This is especially true with regard to the long term durability of the corrosion protection effect that is provided by such coatings, especially when they are subjected to strongly varying environmental conditions, for example as typically arise in connection with vehicles of all types. Namely, during the operating lifetime of conventional vehicles, such as automobiles and trucks for example, the various metal components and especially the sheet metal body panels of such vehicles are subjected to various harsh environmental influences, such as water, salt, chemicals, alternating hot and cold temperatures, and the like, which tend to accelerate the corrosion of the metal material. Web site: http://www.delphion.com/details?pn=US06383271__

•

Antimicrobial biocidic fiber-plastic composite and method of making same Inventor(s): George; Richard (407 Rockland Ave., Manchester, NH 03102), Saide; Joseph G. (3756 Cypress Lake Dr., Lakewood, FL 33467), Saide; Mildred A. (407 Rockland Ave., Manchester, NH 03102) Assignee(s): none reported Patent Number: 6,627,676 Date filed: August 25, 2000

Patents 181

Abstract: An antimicrobial biocidic fiber-plastic composite is capable of killing bacteria on contact. The composite can be produced from a cellulose fiber material obtained from agricultural waste, a plastic material obtained from industrial waste, and one or more biocides that kill bacteria without being harmful to humans. Lignin is removed from the fiber material through a delignification process to allow the biocides to bind directly with the cellulose fibers. In one example, the biocides include Sodium Hypochlorite, Nchloro-p-toluenesulfonamide sodium salt-trihydrate, Vitamin E and Citric Acid. After adding the biocides, lignin is added back to the mixture to allow the cellulose fibers to bind with the plastic material. The fiber-plastic composition can then be extruded, pelletized, and molded into any shape or size. Excerpt(s): The present invention relates to biocidic materials and to fiber-plastic composite materials and more particularly, to the production of an antimicrobial biocidic fiber-plastic composite. Plastic composites, such as fiber-plastic composites, have become increasingly popular because of their variety of applications. In particular, plastic composites made from recycled materials have become popular as a result of environmental concerns. A plastic composite capable of killing bacteria on contact is also desirable to eliminate health concerns. In some applications, such as food applications, contamination by microorganisms must be avoided. Microbial contamination-of food during packaging and transportation is a serious concern among health professionals. If contamination by the packaging or transportation agents occurs, the effort spent to eliminate pathogenic organisms during processing is wasted. Annually, there are literally thousands of reports of food poisoning that are directly the result of the transportation of the food. Ingestion of these contaminants may cause considerable illness, and in some cases death to the infected person. Web site: http://www.delphion.com/details?pn=US06627676__ •

Coenzyme Q10 formulation and process methodology for soft gel capsules manufacturing Inventor(s): Udel; Ronald G. (Beverly Hills, CA) Assignee(s): Soft Gel Technologies, Inc. (Los Angeles, CA) Patent Number: 6,616,942 Date filed: March 28, 2000 Abstract: A formulation of Coenzyme Q.sub.10, beta-carotenes, Vitamin E, and medium chain triglycerides in rice bran oil and an optional thickener, such as bee's wax, is provided in a soft gel capsule so that a maximum of the Coenzyme Q.sub.10 is absorbed by the human body. Generally, about 60 mg of Coenzyme Q.sub.10 is the normal amount provided daily to a healthy sedentary adult. Excerpt(s): This invention relates to an improved formulation and process methodology of Coenzyme Q.sub.10 in producing soft gel capsules of this formulation. Coenzyme Q.sub.10 (CoQ.sub.10 or Ubiquinone) is a large molecular weight (863.63 grams) lipid compound that is produced in the liver and perhaps other body organs. The total body content is estimated to be 1.4 to 1.8 grams, depending on the age and the physical fitness of the individual. Although CoQ.sub.10 is found in the mitochondria and other organelles of every living cell, it appears to be most abundant in tissues with a high number of mitochondria and a high level of metabolic activity. For example, in the metabolically inactive blood there is approximately 4 mg, in the heart, and in the skeletal muscle 1000 mg. The blood acts as a CoQ.sub.10 reservoir and transport media

182

Vitamin E

between endogenous CoQ.sub.10 synthesis in the liver, exogenous CoQ.sub.10 absorption from digested food substances in the intestinal tract, and the body cells. Endogenous synthesis appears to be responsible for 56 percent and exogenous sources for 44 percent of the body's CoQ.sub.10 requirements. These numbers are currently being studied and endogenous CoQ.sub.10 synthesis may be significantly deficient in the elderly. These deficiencies are not related to the total caloric intake, but rather to the vitamin content of ingested foods. The body requires multiple vitamins for the synthesis of CoQ.sub.10. CoQ.sub.10 requirements of the body are also variable between individuals and are dependent on age, physical activity, and disease. It is estimated that the body CoQ.sub.10 utilization is between 5 and 9 mg per day. Intercellular CoQ.sub.10 is required for the synthesis of energy and therefore essential for life. Energy synthesis occurs in the mitochondria, where CoQ.sub.10 provides an electron for the electron transport chain in the cytochrome system, in which adenosine tripohosphate (ATP) is synthesized. As CoQ.sub.10 gives up an electron for ATP synthesis, it gets oxidized. If CoQ.sub.10 is used as an antioxidant, it gets oxidized and is no longer available to provide electrons and function in the synthesis of ATP. Under conditions of high metabolic stress, endogenous sources may become inadequate to meet the body's CoQ.sub.10 requirement for ATP synthesis. Under such conditions, dietary CoQ.sub.10 supplementation has been shown to be an effective source. An improved soft gel formulation and process of CoQ.sub.10 soft gel capsule manufacturing has uses to treat heart failure, chronic fatigue and patients with psoriasis and planter warts. In all cases, it has been found that the improved soft gel formulation at ingestion rates of 30-100 mg/day of CoQ.sub.10 have been proven to be superior to commercially available 60 mg dry powder capsules, and existing 100 mg/day CoQ.sub.10 soft gel formulations. An appropriate CoQ.sub.10 dosage for a normal individual compared to the dosage necessary for a diseased individual has been difficult to ascertain. Recommended doses of 10 to 30 mg/day were found to be ineffective for patients with significant CoQ.sub.10 deficiencies. In the past 15 years, it has become generally accepted that poor intestinal absorption of certain CoQ.sub.10 formulations limits their effective use. For this reason, 50 and 150 mg CoQ.sub.10 containing tablets or capsules are commercially available to the consumer, at a considerably higher cost. Web site: http://www.delphion.com/details?pn=US06616942__ •

Combination of a GABAA alpha 5 inverse agonist and COX-2 inhibitor, NSAID, estrogen or vitamin E Inventor(s): Block; Gilbert A. (Ardmore, PA), Lines; Christopher R. (Philadelphia, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,440,967 Date filed: November 10, 1999 Abstract: Combinations of a GABA.sub.A alpha 5 inverse agonist and a COX-2 inhibitor, NSAID, estrogen or vitamin E are disclosed for treating neurodegenerative conditions such as Alzheimer's Disease. Excerpt(s): The present invention relates to a combination of a COX-2 inhibitor, NSAID, estrogen or vitamin E and an inverse agonist of the GABA.sub.A.alpha.5 receptor subtype, and the use of the combination in treating neurodegenerative conditions such as Alzheimer's Disease. Alzheimer's Disease is a poorly understood neurodegenerative condition mainly affecting the elderly but also younger people who are generally genetically predispositioned to it. In a first embodiment the present invention provides a

Patents 183

new and surprisingly effective synergistic combination of a COX-2 inhibitor and an inverse agonist of the GABA.sub.A.alpha.5 receptor subtype for separate, sequential or simultaneous administration. Web site: http://www.delphion.com/details?pn=US06440967__ •

Composition for growth hormone production and release, appetite suppression, and methods related thereto Inventor(s): Mann; Morris A. (21669 N. 57th Ave., Glendale, AZ 85308) Assignee(s): none reported Patent Number: 6,521,266 Date filed: September 23, 2000 Abstract: A method for enhancing growth hormone production and release, for appetite suppression, or both, in a subject in need thereof. The method comprises administering to the subject an effective amount of a first composition, wherein the first composition increases cholinergic tone and growth hormone synthesis, and the second composition inhibits somatostatin. The first composition may be a combination of an acetylcholinesterase inhibitor and Vitamin E D-.alpha.-succinate, whereas the second composition may be a salt of cysteamine and an alkali buffer, or may be pantothenic acid and an alkali metal salt. A two-part composition comprising the first and second compositions as also disclosed. Excerpt(s): The present invention is generally directed to methods and compositions that enhance growth hormone production and release, and which have been found to suppresses appetite, in human subjects. Growth hormone plays an important role in the physiology of warm-blooded animals, including humans. To date, there have been several methods developed to increase growth hormone levels within the body to influence a disease state such as, for example, pituitary dwarfism, or to facilitate healing after trauma associated with burns, surgery, etc. Relatedly, it has been noted that growth hormone levels within the body markedly decrease after puberty, and gradually decline thereafter throughout life. It has also been noted that growth hormone supplementation in elderly individuals cause physiological changes consistent with rejuvenation. Accordingly, growth hormone supplementation is considered by many to be highly advantageous. Additionally, there are several known compounds which are considered to be growth hormone secretogogues, but these compounds do not necessarily promote growth hormone synthesis. There are also several known compounds which promote growth hormone synthesis, but these compounds do not necessarily induce the release or secretion of the growth hormone. Moreover, due to the large size and fragility associated with growth hormone molecules (191 peptide residues), growth hormone (and similar agents) is generally administered into the body via an injection. There are, however, several shortcomings associated with systemic delivery by injection, shortcomings such as increased risk of infection at the site of delivery. Web site: http://www.delphion.com/details?pn=US06521266__

184

•

Vitamin E

Compositions and methods for prophylactic and therapeutic supplementation of nutrition in subjects Inventor(s): Balzer; Charles (Lavalette, NJ), Giordano; John A. (West Orange, NJ) Assignee(s): Everett Laboratories, Inc. (West Orange, NJ) Patent Number: 6,660,293 Date filed: October 19, 2001 Abstract: The present invention relates to compositions without added iron and methods for prophylactic nutritional supplementation and therapeutic nutritional supplementation. Specifically, the method involves administering to an individual a composition comprising carotenoids, vitamin E, vitamin D, vitamin C, thiamine, riboflavin, niacin, folic acid, pyridoxine, biotin, pantothenic acid, cobalamin, magnesium, manganese, zinc, selenium, chromium, copper, alpha lipoic acid, and lutein, wherein the composition is free of added iron. Excerpt(s): The present invention relates to compositions comprising various vitamins and minerals, and without added iron, and methods for using these compositions for prophylactic nutritional supplementation and therapeutic nutritional supplementation in, for example, physiologically stressful conditions and to minimize the effect of exogenous iron supplementation. Nutrition plays a critical role in maintaining good health. Proper nutrition prevents dietary deficiencies, and also protects against the development of disease. Proper nutrition plays an increasingly important role as the body faces physiological stress. For example, as the body ages it suffers significant physiological stresses. Specifically, as the body metabolism shifts to accumulating larger fat stores and decreasing lean body mass, this increase in body weight may lead to obesity and associated conditions such as diabetes, cardiovascular disease, hypertension, osteoarthritis, and cancer. Other conditions, such as anorexia, malnutrition, gastrointestinal disorders, chronic alcoholism, chronic infections, acute infections, congestive heart failure, hyperthyroidism, poorly controlled diabetes, cheilosis, gingivitis, stomatitis and dietary restrictions, often result in physiological stresses that may be exacerbated by poor nutrition. In particular, these disease states may result in increased oxidative stress or elevated homocysteine levels that further compromise health. Thus, nutritional supplementation serves a vital role in protecting against poor nutrition and disease. More specifically, nutritional supplementation may provide the necessary vitamins, minerals, and other nutrients that might otherwise be lacking in the diet, and provide the nutritional defense against disease development. The invention herein provides for compositions and methods, specifically using an ironfree multi-vitamin/mineral/antioxidant formulation, designed to optimize health and wellness, minimize oxidative stress, and normalize homocysteine levels. Web site: http://www.delphion.com/details?pn=US06660293__

•

Conditioner that provides skin like an angel Inventor(s): Malmgren; Janice K. (8815 Woodbrook Dr., Dallas, TX 75243), Moreno; Sonya K. (304 Wedgewood Ln., Cedar Hill, TX 75104) Assignee(s): none reported Patent Number: 6,544,534 Date filed: August 21, 2001

Patents 185

Abstract: A skin conditioner made of all natural ingredients that eliminates body dandruff leaving the skin able to breathe and feeling soft and supple; "skin like an angel". The conditioner can be heated prior to application in order to provide a more relaxing feel to the user and is massaged into the skin of all or part of the body. Thereafter, the conditioner is rinsed or showered off. The conditioner can also be massaged into the scalp to eliminate dandruff and condition the scalp and hair. Ingredients of the conditioner include sea salt, Epsom salt, almond oil, apricot kernel oil, avocado oil, jojoba oil, aloe vera gel, castor oil, vitamin E, vegetable glycerin and soap. Essential oils may optionally be included in the conditioner to add fragrance. The preferred soap is castile however other soaps such as antibacterial soap can be used. If the product is heated prior to use, it should not be heated above 100.degree. F. in order to prevent a change in the molecular structure of some of the ingredients. Excerpt(s): The present invention relates generally to skin conditioners and more particularly to a skin conditioner made of all natural ingredients that eliminates body dandruff and provides the user with skin like an angel. The skin is the largest organ in the human body. It is a protective organ covering the external surface of the body. The skin forms a protective barrier against the action of physical, chemical, and bacterial agents on the deeper tissues and contains the special sensitive end organs for the sense of touch. Through the activity of its sweat glands and blood vessels, it also plays an important role in maintaining body temperature. One square inch of skin contains up to 15 feet of blood vessels, which have as one of their functions the regulation of body temperature. Each square inch of skin also contains hundreds of sweat glands that are controlled by a heat regulation center in the brain. These glands secrete moisture, which evaporates, cools the body surface, and helps maintain normal body temperature. In this capacity the skin acts as an excretory organ. The skin is elastic, and except for a few areas such as the palms, soles, and ears, is loosely attached to the underlying tissues. The skin varies in thickness from 0.02 inches (in.) on the eyelids to 0.17 in. or more on the palms and soles. In structure the skin is composed of two distinct layers. The outer layer, called the epidermis is several cells thick and has an external, horny layer of dead cells that are constantly shedding from the surface. The dead cells, sometimes referred to as body dandruff, are replaced by new cells from a lower basal layer of cells called the stratum germinativum. The inner layer, called the dermis, is composed of a network of collagen and elastic fibers, blood vessels, nerves, fat lobules, and the bases of hair follicles and sweat glands. Web site: http://www.delphion.com/details?pn=US06544534__ •

Cytokine-free culture of dendritic cells Inventor(s): Alzona; Mortimer T. (Vernon Hills, IL), Aono; Frederick M. (Arlington Hills, IL), Vachula; Mona (Lake Villa, IL), Van Epps; Dennis E. (Coto de Caza, CA) Assignee(s): Nexell Therapeutics Inc. (Irvine, CA) Patent Number: 6,458,585 Date filed: July 31, 1997 Abstract: A method for producing human dendritic cells for therapeutic purposes which allows culture-deriving dendritic cells using no cytokines, or reduced cytokines. The method involves culturing mononuclear cells from blood or bone marrow in a medium containing at least one agent such as a calcium ionophore, e.g. A23187, theophylline, protaglandin E1, dibutyryl cyclic AMP, Vitamin D3, Vitamin E, retinoic acid, or a fatty acid. The culture is maintained for a sufficient time, typically 4-14 days, to produce a

186

Vitamin E

culture enriched for dendritic cells, as evidenced by at least about 2.5% of total cells exhibiting dendritic cell processes, or a dendritic dell antigen such as CD80, CD86, or CD1a. Also provided is a method to produce antigen-specific human T-cells by pulsing the dendritic cells obtained by the method of the invention with an antigen such as a viral, tumor, bacterial, or cell surface antigen, and then co-culturing T-cells with the antigen-pulsed dendritic cells. Useful for treatment of viral or bacterial infections, useful as a cancer vaccine, useful to induce tolerance of allo- or xeno- graft. Excerpt(s): This invention is in the field of ex vivo culture of hematopoietic cells, more specifically in the culture of human dendritic cells and T-cells for therapeutic purposes. Dendritic cells play an important role in immune responses. They provide the immune system with an effective means of antigen presentation, unlike that of any other cell. Dendritic cells are the most potent antigen presenting cells in the immune system. They have been characterized to have a unique morphology and cell surface phenotype that may contribute to their potency in initiating cellular immune responses, specifically T cell dependent responses. Therefore, dendritic cells have been proposed as a valuable component in cellular based therapies that require presentation of antigen to effector cells. Dendritic effector cells can be primed ex vivo to create activated cells to be reintroduced into the body in order to combat disease. However, dendritic cells comprise less than 1% of leukocytes circulating in peripheral blood, which makes it difficult to obtain an amount sufficient to use in therapy. Dendritic Cells (DC) along with monocytes/macrophages and B lymphocytes are considered professional antigenpresenting cells (APC); (reviews by Caux et al., Immunology Today 16: 2-4, 1995; Steinman, Annu. Rev. Immunol9: 271-296, 1991; Young, J W, et al., Stem Cells 14:376387, 1996; Steinman, R M, Exptl Hematol 24:859-882, 1996). Even though antigenpresenting cells take in, process, and present antigen to T lymphocytes, they serve different immune functions. DC are the most potent initiators of the immune response and are the APCs responsible for the induction of primary antigen-specific immune reactions (Bhardwaj et al., J. Exp. Med. 175: 267-273, 1992; Bhardwaj et al., J. Exp. Med. 178: 633-642, 1993). The DC, as are all hematopoietic cells, are derived from CD34+ stem cells. These hematopoietic cells arise in the bone marrow and as they mature traffic to the peripheral blood where they circulate (T cells make a detour to the thymus) and then may enter tissues. The differentiation pathway from a CD34+ cell to a DC is not completely understood (Santiago-Schwarz et al., J. Leukoc. Biol. 52: 274-281, 1992; Galy et al., Immunity 3: 459-473, 1995; Rosenzwajg et al., Blood 87: 535-544, 1996). DC are found in very low levels in peripheral blood (<1%) compared to other white blood cells (WBC) or leukocytes (neutrophils about 60%, lymphocytes about 35%, monocytes about 5%, eosinophils about 2%, basophils <1%); (Laboratory Medicine Hematology, editor: J. Miale, publisher: C.V. Mosby Co., 1982). Thus, in order to use DC therapeutically, it would be most practical to expand them ex vivo. To date, the culture of DC cells has been performed in serum-containing media and semi-closed tissue culture plates or flasks. To expand DC under these conditions, GM-CSF appears to be important for DC differentiation, and addition of TNF-.alpha. appears to be inhibitory to other CD34+ progenitors as greater DC are seen in those cultures (Santiago-Schwarz et al., Blood 82: 3019-3028, 1993). Addition of IL-4 causes the down regulation of CD14+ monocytes (Sallusto et al., J. Exp. Med. 179: 1109-1118, 1994; Romani et al., J. Exp. Med. 180: 83-93, 1994). Thus cultures that included those cytokines have shown preferential outgrowth of DC. Web site: http://www.delphion.com/details?pn=US06458585__

Patents 187

•

Food supplement formulation Inventor(s): Green; Lonny S. (10825 Cherry Hill Dr., Glen Allen, VA 23059) Assignee(s): none reported Patent Number: 6,555,142 Date filed: July 1, 2002 Abstract: A food supplement formulation comprises yi zhi ren, shan zhu yu, wu wei zi, ginseng, valerian root, passiflora incarnate, L-methionine, L-arginine, and a genderspecific complex selected from the group consisting of a mixture comprising betasitosteroi, saw palmetto, pollen extract, selenium, zinc, vitamin E, and lycopene, and a mixture comprising black cohosh, genistein, vitamin E, and cramp bark. Excerpt(s): The present invention relates generally to a food supplement formulation. More particularly, the invention is directed to a food supplement formulation which may additionally aid bladder control. Herbal and mineral formulations have been used as dietary supplements and natural medicaments for many years. In addition to providing compounds necessary to the human body for good nutrition, such formulations additionally may aid the body in dealing with a number of urinary tract maladies. In addition to desiring a supplement to the daily diet, many persons suffer from a condition known as "overactive bladder," wherein the patient has difficulty controlling urinary flow. Web site: http://www.delphion.com/details?pn=US06555142__

•

Fortified rice bran food product and method for promoting cardiovascular health Inventor(s): Hoffpauer; Diane Wright (P.O. Box 393, Crowley, LA 70526), Wright, lll; Salmon L. (POB 1425, Crowley, LA 70527) Assignee(s): none reported Patent Number: 6,436,431 Date filed: July 2, 2001 Abstract: A fortified rice bran food product for preventing and/or treating cardiovascular disease in animals, contains in admixture:(a) rice bran as a carrier;(b) at least about 12.5 milligrams of vitamin B.sub.1 per 30 grams of the rice bran;(c) at least about 250 milligrams of vitamin C per 30 grams of the rice bran;(d) at least about 12.5 milligrams of vitamin B.sub.6 per 30 grams of the rice bran;(e) at least about 75 micrograms of vitamin B.sub.12 per 30 grams of the rice bran;(f) at least about 100 International Units of vitamin E per 30 grams of the rice bran;(g) at least about 0.25 milligrams of folic acid per 30 grams of the rice bran; and(h) at least about 250 milligrams of omega-3-fatty acids per 30 grams of the rice bran.A method for preventing and/or treating cardiovascular disease in an animal involves orally administering a therapeutically effective amount of the fortified rice bran food product to the animal for a therapeutically effective period of time. Excerpt(s): This invention relates to a fortified food product which can be used as a dietary supplement or as an added ingredient for fortifying various food components. More particularly, this invention relates to a fortified rice bran food product that is capable of preventing and/or treating cardiovascular disease including, e.g., hypertension. In addition, this invention relates to a method of preventing and/or treating cardiovascular disease involving oral ingestion of the food product of this

188

Vitamin E

invention. Cardiovascular disease is a major health issue in the United States. Several compositions and methods have been developed over the years in an attempt to prevent or treat this disease. U.S. Pat. No. 6,126,943 (Cheruvanky et al.) discloses a method for reducing mammalian serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels, by ingesting a stabilized rice bran derivative selected from the group consisting of an enzyme treated stabilized rice bran, an insolubilized fraction and mixtures thereof. The patent teaches that the rice bran used therein is rich in B-complex vitamins, vitamin E and its isomers, minerals like potassium, magnesium, and phosphorous, and several potent antioxidants. Web site: http://www.delphion.com/details?pn=US06436431__ •

Herbal hair treatments and method of making the same Inventor(s): Fluker; Annette (30 Summit St., East Orange, NJ 07018) Assignee(s): none reported Patent Number: 6,475,476 Date filed: November 22, 2000 Abstract: A herbal hair treatments and method of making the same for protecting and strengthening hair. The herbal hair treatments and method of making the same includes mixing sage, horsetail, kelp, nettle leaf, horsetail, rosemary and mineral water to form a mixture. Heating the mixture to a full boil. Straining the mixture to form an herb liquid. Mixing into the herb liquid rosemary oil, vitamin E, castor oil and a soap to form a shampoo. Excerpt(s): The present invention relates to hair treatments and more particularly pertains to a new herbal hair treatments and method of making the same for protecting and strengthening hair. The use of hair treatments is known in the prior art. More specifically, hair treatments heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements. Known prior art includes U.S. Pat. No. 4,477,438; U.S. Pat. No. 5,482,644; U.S. Pat. No. 5,468,492; U.S. Pat. No. 5,405,609; U.S. Pat. No. 4,511,555; and U.S. Pat. No. 4,658,839. Web site: http://www.delphion.com/details?pn=US06475476__

•

Hyper-absorption of vitamin E combined with milk protein Inventor(s): Hayes; Kenneth C. (Wellesley, MA), Perlman; Daniel (Arlington, MA) Assignee(s): Brandeis University (Waltham, MA) Patent Number: 6,503,545 Date filed: September 28, 2000 Abstract: A milk product providing an individual at least 31 IU (International Units) of vitamin E per serving, or an ingestible blend of at least one mammalian milk protein or fragment thereof, and vitamin E or other fat-soluble micronutrient or pharmacological agent is described. The vitamin E is uniformly microdispersed throughout the milk product, and ingestion of at least 100 IU of vitamin E per day in the product is sufficient to cause the fasting plasma vitamin E/cholesterol ratio in human subjects to be elevated

Patents 189

at least 50% above the basal fasting level of vitamin E measured in the same subjects consuming no vitamin E dietary supplements. A method for elevating the plasma vitamin E level at least 50% in human subjects is also described. The method includes ingesting a milk product as described. A method for increasing the bioavailability of an orally administered fat-soluble micronutrient or pharmaceutical agent is also described. The method includes providing a microdispersed mixture of at least one fat-soluble micronutrient or pharmaceutical agent, and at least one mammalian milk protein or fragment thereof, in which the weight ratio of the milk protein to the micronutrient or pharmaceutical agent is between 1:1 and 1000:1. Excerpt(s): This invention relates to milk-based food products, and in particular to the microdispersal of vitamin E in milks (milkfat-based milk, skim milk, vegetable oil-filled milk, and blends thereof) at a level providing at least 31 IU (International Units) per serving. The invention also relates to a substantially lactose-free and milkfat-free composition for oral administration to a human or other mammal, including a microdispersed mixture of at least one mammalian milk protein or fragment thereof, and at least one fat-soluble micronutrient or pharmaceutical agent, where the weight ratio of said mammalian milk protein to said fat-soluble micronutrient or pharmaceutical agent is between 1:1 and 1000:1. The information provided herein is solely to assist the understanding of the reader; none of that information or cited references is admitted to be prior art to the present invention. In the past five years several major prospective health studies have been published demonstrating that vitamin E supplement ingestion is associated with a reduced risk of coronary heart disease (CHD) in both women and men (e.g., Stampfer et al., NEJM, 328, 1444-1449, 1993 Rimm et al., NEJM, 328, 1450-1456, 1993). In a four year study of nearly 40,000 males, Rimm et al., showed that the risk of CHD diminished significantly as the daily supplemental level of vitamin E increased. This study indicates that the current Recommended Daily Allowance (RDA) of 30 international units (IU) of vitamin E is insufficient for obtaining the full protective benefits of vitamin E. In fact, the study data suggest that for most adult males, a daily supplement of at least 100 IU of vitamin E is appropriate for helping to protect against CHD. In another prospective study, long-term ingestion of vitamin E was tested for its ability to reduce the incidence of myocardial infarction in patients having a documented condition of coronary atherosclerosis (Stephens et al., Lancet, 347, 781-786, 1996). In this study, it was shown that sustained supplementation of the patients' diets with 400 IU of RRR-.alpha.-tocopherol ingested once per day in capsules was sufficient to reduce the risk of non-fatal heart attacks by 77%. This protective effect became apparent after about 200 days of treatment with the vitamin. In still another study (Losonczy et al., Am. J. Clin. Nutr. 64, 190-196, 1996), individuals in an elderly population (n=11,178) aged 67-105, were each followed for 6 years, and their uses of vitamin E and/or vitamin C supplements were correlated with their risk of developing cancer and CHD. While vitamin C supplements could not be shown to have a significant protective effect over the 6 year period, vitamin E supplements (greater than 100 IU per day) were shown to reduce all-cause mortality 2734%, CHD mortality 41-47%, and cancer mortality 22-23% (in these ranges, the first number is the age and sex-adjusted risk, and the second is a multi-covariable adjusted risk). Web site: http://www.delphion.com/details?pn=US06503545__

190

•

Vitamin E

Immune stimulating dietary supplement and method of use thereof Inventor(s): Meydani; Mohsen (Newton, MA), Meydani; Simin Nikbin (Newton, MA) Assignee(s): Trustees of Tufts College (Medford, MA) Patent Number: 6,642,259 Date filed: March 25, 2002 Abstract: The immune system of middle aged and elderly individuals is stimulated with a dietary supplement. The dietary supplement includes Vitamin E, Vitamin B6 and conjugated linoleic acid. The dietary supplement can further include glutathione alone or in combination with Vitamin C, folic acid, zinc, selenium, Vitamin D, copper and Vitamin B12. The dietary supplement is administered to middle aged and elderly individuals in a suitable form for consumption by the individual. Suitable forms of consumption can include a snack bar, tablet, capsule, powder, drink, or dairy products. Excerpt(s): Immune responses gradually decline with increasing age. Coincident with a decline in immune responses is a concomitant increase in the incidence of tumor development, infection and inflammatory diseases in middle aged and elderly populations of individuals. ("Fundamental Immunology" ed. W.E. Paul, Raven Press, NY (1989); Miller, R. A., Exp. Gerontol. 29:21-35 (1994). Compromised nutritional status can contribute to the impaired immunological state and, hence, declining health of aging individuals. Thus, there is a need to develop convenient and effective methods that augment the nutritional requirements of middle aged and elderly individuals, thereby stimulating the immune system to combat disease. The present invention relates to a dietary supplement. It also is directed to a method to stimulate the immune system of middle aged and elderly individuals or to stimulate proliferation of a lymphocyte by administration of the dietary supplement. In one embodiment, the dietary supplement comprises Vitamin E, Vitamin B6 and conjugated linoleic acid. In a specific embodiment, the dietary supplement includes Vitamin E in an amount in a range of between about 10 milligrams and about 267 milligrams per milligram of Vitamin B6, and conjugated linoleic acid in an amount in a range of between about 17 milligrams and about 100 milligrams per milligram of Vitamin B6. In another specific embodiment, the dietary supplement further includes glutathione Vitamin C, folic acid, zinc, selenium, Vitamin D, copper, Vitamin B12 and glutathione. Preferably, the dietary supplement includes Vitamin C in an amount in a range of between about 17 milligrams and about 200 milligrams per milligram of Vitamin B6; folic acid in an amount in a range of between about 0.05 milligrams and about 0.2 milligrams per milligram of Vitamin B6; zinc in an amount in a range of between about 1.67 milligrams and about 10 milligrams per milligram of Vitamin B6; selenium in an amount in a range of between about 0.005 milligrams and about 0.02 milligrams per milligram of Vitamin B6; Vitamin D in an amount in a range of between about 0.0008 milligrams and about 0.005 milligrams per milligram of Vitamin B6; copper in an amount in a range of between about 0.00008 milligrams and about 0.0007 milligrams per milligram of Vitamin B6; Vitamin B12 in an amount in a range of between about 0.0002 milligrams and about 0.001 milligrams per milligram of Vitamin B6; and glutathione in an amount in a range of between about 4 milligrams and about 33 milligrams per milligram of Vitamin B6. Web site: http://www.delphion.com/details?pn=US06642259__

Patents 191

•

Mesoporous compositions and method of preparation Inventor(s): Balkus, Jr.; Kenneth J. (The Colony, TX), Coutinho; Decio H. (Dallas, TX) Assignee(s): Board of Regents The University of Texas System (Austin, TX) Patent Number: 6,630,170 Date filed: April 26, 2001 Abstract: The present invention encompasses novel mesoporous compositions comprising vitamin E, and methods for their synthesis. The mesoporous compositions are synthesized in a range of conditions to produce varied morphologies including, but not limited, to gyroids, hexagons, hexagonal rods, discs, and spheres. Excerpt(s): The present invention relates to a mesoporous composition and a method for its synthesis. The invention provides a mesoporous composition of a new category in that the templating molecule used in the synthesis comprises vitamin E. The invention further relates to the synthesis of mesoporous compositions showing controlled morphology. The invention also relates to mesoporous compositions comprising vitamin E for use in drug delivery systems, catalysis and other bioanalytical applications. Porous substances are generally divided by pore size. For example, those having pore sizes smaller than 2 nm are classified as microporous substances, between 2 and 50 nm are classified as mesoporous substances and larger than 50 nm are classified as macroporous substances. Because of the range of their pore sizes, mesoporous materials are compatible with applications such as separation or sensing of relatively large organic molecules. Typical of the mesoporous materials are amorphous or polycrystalline solids such as pillared clays and silicates. Unfortunately, the pores in these materials are often irregularly spaced and broadly distributed in size. There is growing interest in the use of inorganic materials as host matrices for bioactive molecules. The principal advantages of such host/guest type materials include the stability and relative inertness of the materials as well as their easy transportation as free flowing powders. Considerable synthetic effort has therefore been devoted to developing molecular sieve frameworks with pore diameters within the mesoporous range, and the development of a series of molecular sieves having a hexagonal array of uniform mesopores has been reported. A group of researchers at Mobil Oil Corporation have reported a series of mesoporous molecular sieves, named MCM-41, in U.S. Pat. Nos. 5,057,296 and 5,102,643, which are fully incorporated by reference. According to these patents, MCM-41 has a structure exhibiting hexagonal arrangement of straight channels, such as a honeycomb, on a silica plate. MCM-41 is synthesized using the cationic type surfactant, quaternary alkyltrimethylammonium salts [C.sub.n H.sub.2n+1 (CH.sub.3).sub.3 N.sup.+ X.sup.- ] and various silica sources, like sodium silicates, tetraethyl orthosilicate, or silica gel, under hydrothermal conditions. On the other hand, the mesoporous materials in the SBA series, another group of synthetic mesoporous materials, are synthesized using neutral templates. Web site: http://www.delphion.com/details?pn=US06630170__

192

•

Vitamin E

Method and composition for improving fertility health in female and male animals and humans Inventor(s): Trant; Aileen Sontag (Mountain View, CA) Assignee(s): The Daily Wellness Company (Sunnyvale, CA) Patent Number: 6,497,885 Date filed: December 22, 2000 Abstract: In a new supplemental combination, the herb, Vitex agnus-castus (chasteberry), enhances hormone balance by increasing luteinizing hormone (LH) and progesterone release and, therefore, ovulation frequency. The antioxidants, green tea, vitamin E, and selenium, improve overall reproductive health. L-arginine, an amino acid, stimulates the reproductive organs by improving circulation. Folic acid, vitamins B6 and B12, iron, zinc and magnesium help promote women's fertility. Excerpt(s): Because of delayed child bearing, unhealthy diets and use of tobacco, caffeine, alcohol, drugs and environmental contaminants, difficulties in conceiving have been experienced. Needs exist for pharmaceutical compounds that improve fertility in both women and men. This invention provides combinations of bioeffecting compounds for promoting fertility in men and women. The combinations include nutritional components that benefit fertility health. All the components have been studied separately, to determine their individual efficacy. The invention provides the first products to put these components together synergistically in women's and men's formulations. Web site: http://www.delphion.com/details?pn=US06497885__

•

Method for preparing vitamin e Inventor(s): Dhainaut; Jildaz (Lyons, FR), Durand; Thierry (Antony, FR) Assignee(s): Aventis Animal Nutrition, S.A. (Antony, FR) Patent Number: 6,518,439 Date filed: May 14, 2001 Abstract: The invention concerns a novel method for preparing vitamin E. More particularly, it concerns a novel method for the condensation of Arimethylhydroquinone and isophytol. Excerpt(s): This application is a 371 of PCT/FR99/02196 filed on Sep. 15, 1999. The present invention relates to a novel process for the preparation of vitamin E. It relates more particularly to a novel process for the condensation of trimethylhydroquinone and isophytol. It is known, for example according to Japanese Patents No. 60064977, No. 53144574 and No. 53015381, to condense isophytol with trimethylhydroquinone in the presence of a Lewis acid, restricted to zinc chloride, in the presence of an inorganic acid chosen from halogenated acids and polyphosphoric acid in a solvent composed of methylene chloride and acetic acid. Web site: http://www.delphion.com/details?pn=US06518439__

Patents 193

•

Method for retarding and preventing sunburn by UV light Inventor(s): Lorenz; R. Todd (Kailua-Kona, HI) Assignee(s): Cyanotech Corporation (Kailu-Kona, HI) Patent Number: 6,433,025 Date filed: April 13, 2000 Abstract: Astaxanthin is a potent antioxidant, over 500 times more powerful than Vitamin E and 10 times stronger than other carotenoids such as zeaxanthin, lutein, canthaxanthin and beta-carotene. Astaxanthin has also been shown to enhance and modulate the immune system. Disclosed is a method and treatment for retarding and preventing sunburns. The method comprises administering a source of astaxanthin in a therapeutically effective amount to prevent and retard sunburns. Excerpt(s): This invention relates to the treatment and prevention of sunburns by UV light exposure. More particularly the invention relates to a method for prevention of sunburns using, as a basis, the protective properties of astaxanthin. Most particularly, the invention relates to prevention of sunburns using orally administered astaxanthin. Tanning is pigmentation of the skin due to the synthesis and dispersion of melanin in the epidermis. It is of great cosmetic and societal significance and a key physiological defense against sun-induced injuries such as sunburn, photocarcinogenesis and photoaging. However, during recent decades, there has been a dramatic increase in skin cancers, including melanoma, due to habitual sun exposure. At present, in the United States, about one in 75 individuals are projected to develop malignant melanoma during their lifetime. Unfortunately, progress in preventing sun-related injuries has been slow, in part due to lack of understanding of the molecular mechanisms involved in pigmentation. There have been increasing incidence and mortality rates due to melanoma in most countries where they are being recorded. The highest incidences occur in areas with the highest flux of solar radiation such as the southern US, regions near the equator or at higher elevations. Ultraviolet radiation (UVR) increases about 4% for every 1000 feet in elevation. Lighter-skinned individuals are affected more frequently and severely. Significant transmission of UVR may occur through some types of clothing resulting in sunburned skin. The initial approach in many countries has been to develop some form of early detection program in an attempt to diagnose and treat at a curable stage the melanomas that are occurring now. The long-term morbidity and mortality associated with chronic sun exposure is related primarily to the development of cutaneous neoplasms, including basal cell carcinoma and malignant carcinoma. Web site: http://www.delphion.com/details?pn=US06433025__

•

Method for the chromatographic isolation of vitamin E isomers Inventor(s): Basiron; Yusof (Kajang, MY), May; Choo Yuen (Kajang, MY), Ngan; Ma Ah (Kajang, MY) Assignee(s): Malaysian Palm Oil Board (Kajang, MY) Patent Number: 6,656,358 Date filed: February 2, 2001 Abstract: A method for the chromatographic separation of vitamin E isomers such as.alpha.-tocopherol,.beta.-tocopherol,.gamma.-tocopherol,.delta.-tocopherol,.alpha.tocotrienol,.beta.-tocotrienol,.gamma.-tocotrienol and.delta.-tocotrienol from a vitamin

194

Vitamin E

E containing mixture by combining the vitamin E mixture with an adsorbent to effect adsorption of the vitamin E isomers on the adsorbent; and then selectively desorbing the vitamin E isomers from the adsorbent with a solvent under supercritical conditions. Excerpt(s): The invention relates to methods for the chromatographic isolation of vitamin E isomers. In particular to methods of isolating individual vitamin E isomers such as.alpha.-tocopherol,.beta.-tocopherol,.gamma.-tocopherol,.delta.tocopherol,.alpha.-tocotrienol,.alpha.-tocotrienol,.gamma.-tocotrienol,.delta.-tocotrienol and the like from vitamin E containing mixtures such as crude palm oil, palm oil products, palm oil by-products, vegetable oils, and the like. Tocols are vitamin E compounds that include tocopherols (T) and tocotrienols (T.sub.3) that are found in vegetable oils in varying quantities (See, e.g., Table A). The tocols present in most vegetable oils are typically in the form of tocopherols (.alpha.-,.beta.-,.gamma.-, and.delta.-tocopherols). Palm oil, however, is unique since the tocols are present mainly in the form of tocotrienols (.alpha.-T.sub.3,.gamma.-T.sub.3, and.delta.-T.sub.3). Each of the tocols exhibits interesting physiological properties. Both tocopherols and tocotrienols act as powerful nutritional antioxidants and help to reduce cellular damage due to free radicals arising from the body's normal oxidative energy metabolism or from the action of toxic chemicals and pollutants in our environment. Free radicals have been implicated in aging, chronic degenerative diseases, and cancer. Web site: http://www.delphion.com/details?pn=US06656358__ •

Method for the preparation of UHMWPE doped with an antioxidant and an implant made thereof Inventor(s): Bengtsson; Peter (Goteborg, SE), Lidgren; Lars (Lund, SE), Sjovall; Peter (Sandby, SE), Wesslen; Bengt (Staffanstorp, SE) Assignee(s): Bone Support AB (Tollarp, SE) Patent Number: 6,448,315 Date filed: December 27, 2001 Abstract: The invention relates to a method for the preparation in a reactor of a UHMWPE material doped with an antioxidant, preferably vitamin E. Excerpt(s): The present invention relates to a method for the preparation of UHMWPE doped with an antioxidant, preferably vitamin E. The invention also relates to an implant comprising UHMWPE doped with an antioxidant by using said method. The majority of endoprosthetic joint replacements currently implanted in patients comprises a highly polished metal or ceramic component articulating on ultra high molecular weight polyethylene (UHMWPE) material. Although such combination of materials has been used over the last 30 years, the present clinical practice of using said prostheses in an increasing number of younger patients and older patients with longer life expectancy has generated renewed concern about the wear and durability of UHMWPE. Web site: http://www.delphion.com/details?pn=US06448315__

Patents 195

•

Method for the prevention and treatment of cachexia and anorexia Inventor(s): Abbruzzese; Bonnie Chandler (Dublin, OH), Cope; Frederick Oliver (Worthington, OH), DeMichele; Stephen Joseph (Dublin, OH), McCamish; Mark Anthony (Worthington, OH) Assignee(s): Abbott Laboratories (Abbott Park, IL) Patent Number: 6,387,883 Date filed: August 18, 2000 Abstract: The present invention relates to methods and nutritional compositions for the prevention and treatment of cachexia and anorexia. The methods of the invention comprise administering a composition comprising effective amounts of.omega.-3 fatty acids such as alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid or mixtures thereof; of branched-chain amino acids valine, leucine, isoleucine or mixtures thereof; with or without reduced levels of tryptophan and 5-hydroxytryptophan; and of antioxidant system selected from the group comprising beta-carotene, vitamin C, vitamin E, selenium, or mixtures thereof. Excerpt(s): The present invention relates to methods and nutritional compositions for the prevention and treatment of cancer cachexia and anorexia. In the practice of the present invention patients are enterally administered.omega.-3 fatty acids including, but not limited to alpha-linolenic (18:3.omega.-3), stearidonic (18:4.omega.-3), eicosapentaenoic (20:5.omega.-3) docosapentaenoic: (22:5.omega.-3), and docosahexaenoic (22:6.omega.-3), in combination with antioxidants including, but not limited to, beta-carotene, vitamin C, vitamin E, selenium, or mixtures thereof; a source of amino-nitrogen with high levels of branched-chain amino acids including valine, leucine, isoleucine, and with or without reduced levels of tryptophan and 5hydroxytryptophan. Cancer cachexia is a syndrome characterized by anorexia, weight loss, premature satiety, asthenia, loss of lean body mass, and multiple organ dysfunction. The majority of patients with cancer whose disease progresses to metastatic disease develop cachexia during their treatment program and the cachexia contributes to their deaths. The frequency of weight loss in cancer patients ranges from 40% for patients with breast cancer, acute myelocytic leukemia, and sarcoma to more than 80% in patients with carcinoma of the pancreas and stomach. About 60% of patients with carcinomas of the lung, colon or prostate have experienced weight loss prior to beginning chemotherapy. Although the relationship between pretreatment malnutrition (weightless) and adverse outcome is established, no consistent relationship has been demonstrated between the development of cachexia and tumor size, disease stage, and type or duration of the malignancy. Development of cachexia in the cancer patient is not caused simply by increased energy expenditure by the host or by the tumor. The malignant cachexia is partially related to reduced caloric intake. Cancer cachexia is not simply a local effect of the tumor. Alterations in protein, fat, and carbohyrate metabolism occur commonly. For example, abnormalities in carbohydrate metabolism include increased rates of total glucose turnover, increased hepatic gluconeogenesis, glucose intolerance and elevated glucose levels. Increased lipolysis, increased free fatty acid and glycerol turnover, hyperlipidemia, and reduced lipoprotein lipase activity pre frequently noted. The weight loss associated with cancer cachexia is caused not only by a reduction in body fat stores but also by a reduction in total body protein mass, with extensive skeletal muscle wasting. Increased protein turnover and poorly regulated amino acid oxidation may also be important. Presence of host-derived factors produced in response to the cancer have been implicated as causative agents of cachexia, e.g.,

196

Vitamin E

tumor necrosis factor-.alpha. (TNF) or cachectin, interleukin-1 (IL-1), IL-6, gammainterferon (IFN), and prostaglandins (PGs) (e.g., PGE.sub.2). Web site: http://www.delphion.com/details?pn=US06387883__ •

Method for the treatment of symptoms related to normal hormonal variations in women Inventor(s): Hedman; Christer (Molnlycke, SE), Karnerud; Lars (Tenhult, SE), Winther; Kaj (Copenhagen, DK) Assignee(s): Natumin Pharma AB (Huskvarna, SE) Patent Number: 6,569,471 Date filed: August 31, 2001 Abstract: A method for the treatment of symptoms related to normal hormonal variations in women during fertile, peri- and post-menopausal age, by the administering of a composition comprising, as active ingredients, a water and/or fat-soluble cytosolic extract of pollen, optionally combined with Royal Jelly and Vitamin E. Excerpt(s): The invention relates in a first aspect to a method for the treatment of symptoms related to normal hormonal variations in women during fertile as well as, peri- and post-menopausal age, by the administering of a composition comprising, as active ingredients, a water and/or fat soluble cytosolic extract of pollen, optionally combined with Royal Jelly and Vitamin E. The invention, in another aspect, relates to the use of a composition comprising, as active ingredients, a water and/or fat soluble extract of pollen optionally combined with Royal Jelly and Vitamin E for the manufacturing of a medicament for the treatment of symptoms relating to normal hormonal variations in women during fertile, as well as peri- and post-menopausal age. An extract of combined pollen and pistils combined with a pollen grain extract, Royal Jelly and Vitamin E has been sold by Interhealth AB, Kungsangsvagen 27, 561 56 Huskvarna, Sweden, for the treatment of Pre-Menstrual Syndrome (PMS). Web site: http://www.delphion.com/details?pn=US06569471__

•

Method for treating, controlling, and preventing Diabetes Mellitus Inventor(s): Farouqi; Hafez Taji (Amman, JO), Murad; Osama Mansour (Amman, JO), Seir; Husni Abu (Amman, JO) Assignee(s): Diabex, Inc. (Wake Forest, NC) Patent Number: 6,555,126 Date filed: January 2, 2001 Abstract: This invention pertains to a method that can control, treat, and prevent Diabetes Mellitus. The method includes means of administering a potent product, including mainly the active ingredient Linalool, in any one of several forms, alone or with other additives and catalysts, such as vitamin E to enable the body to handle and control, then correct the complications of Diabetes Mellitus. A modest percentage of users suffering from this disease can be cured completely while the majority of others improve remarkably and experience lower blood glucose and reduce the glycated hemoglobin HbAlc readings to what are medically acceptable and healthy levels. Others, who are vulnerable to the disease due to hereditary factors, or other reasons, can

Patents 197

help prevent it. The method works in several ways, including activation of the pancreas and re-establishing the ability of body cells to utilize and handle better and well, the glucose in the blood, and regulate the level of natural insulin in the body. The method employs Linalool in any one of its forms that can be found naturally or synthetically. Excerpt(s): This invention relates to a method that can be used to treat, control, cure, and prevent Diabetes Mellitus, of all types, through the administration of Linalool, alone, in any form, and possibly with other hypoglycemic additives in several forms, and by various means. The method does not cause any harmful or unpleasant side effects. Diabetes Mellitus is a feared and complex disorder. It has been a most distressing disease that can develop to a seriously life threatening condition. For ages, society was resigned to accepting various methods and medications that became a standard with no real hope for a cure, or drastic eradication of the disease. In fact, many of the drugs used cause serious side effects. A most important indicator of the ability of the body to deal with the complications of diabetes is the glycated hemoglobin HbAlc, that gives an integrated reading of the level of blood glucose. While all other known methods and medications help lower the glucose level at limited periods of the day or night time, the HbAlC remains higher than the normal 4.3 to 6.7 range regardless of the insulin dosage and other medicines. No full cure is expected or hoped for by the present regimens. The described method herein is new and unique, and actually reduces the HbAlc reading to the normal levels and for all patients. This method has actually cured some patients of both types I and II diabetes to such a degree that they stopped taking any medication while leading normal lives. Web site: http://www.delphion.com/details?pn=US06555126__ •

Method of chromatographic isolation for non-glyceride components Inventor(s): Basiron; Yusof (6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, MY 43000), May; Choo Yuen (6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, MY 43000), Ngan; Ma Ah (6, Persiaran Institusi, Bandar Baru Bangi, Kajang, Selangor, MY 43000) Assignee(s): none reported Patent Number: 6,586,201 Date filed: November 2, 2000 Abstract: A method of chromatographic isolation for non-glyceride components (squalenes, carotenes, vitamin E, sterols and/or the like) from a non-glyceride components-comprising compound by the steps ofa. introducing the non-glyceride components-comprising compound onto a selective adsorbent to allow an adsorption of the non-glyceride components, and subsequentlyb. desorbing the non-glyceride components from the adsorbent, whereinthe adsorption and/or desorption of the nonglyceride components is carried out under a supercritical fluid environment. Excerpt(s): The invention relates to a method of chromatographic isolation for nonglyceride components particularly squalenes, carotenes, vitamin E (sometimes abbreviated as Vit. E) sterols and/or the like, from crude palm oil, palm oils products and/or by-products, vegetable oils and/or the like non-glyceride componentscomprising compounds. Crude palm oil contains about 5% of "non-glyceride components" which include carotenoids, tocols (tocopherols and tocotrienols), sterols and squalene. The carotenoids, present at 500-700 ppm and comprising mainly.alpha. and.beta. carotenes, are important constituents with pro-vitamin A activity, possible

198

Vitamin E

antitumor formation properties, and other physiological activities. The tocols which are Vitamin E and also natural anti-oxidants, are present at approximately 600 to 1000 ppm in crude palm oil; the major component being the gamma-tocotrienol which has recently been found to have anti-cancer properties besides its known anti-oxidant activity. Tocotrienol has been found to lower blood cholesterol. The sterols consisting mainly of.beta.-sitosterol, stigmasterol and campesterol, provide raw materials for steroid intermediates and drugs.beta.-Sitosterol also possesses hypocholesterolemic effect. Squalene is an important ingredient for cosmetics. It also shows beneficial physiological properties. (i) Extraction by saponification e.g. British Patent 567,682; U.S. Pat. Nos. 2,460,796; 2,440,029; 2,572,467; 2,652,433. Web site: http://www.delphion.com/details?pn=US06586201__ •

Nutritional composition made from conventional foods for mixing onsite in a blender and treating patients with hepatic disorders Inventor(s): Muszynska; Julia (108 Center St., Staten Island, NY 10306) Assignee(s): none reported Patent Number: 6,524,610 Date filed: February 26, 2001 Abstract: A nutritional composition made from conventional food mixed on-site in a blender and treating patients with hepatic disorders. The composition includes a vitamin A enriched conventional food, a vitamin D enriched conventional food, a vitamin E enriched conventional food, a vitamin K enriched conventional food, a vitamin C enriched conventional food, a thiamine enriched conventional food, a riboflavin enriched conventional food, a niacin enriched conventional food; a pyridoxine enriched conventional food, a folic acid enriched conventional food, a pantothenic acid enriched conventional food, a vitamin B12 enriched conventional food, a biotin enriched conventional food, a chloine enriched conventional food, a sodium enriched conventional food, a potassium enriched conventional food, a chlorine enriched conventional food, a calcium enriched conventional food, a phosphorus enriched conventional food, a magnesium enriched conventional food, a copper enriched conventional food, an Iodine enriched conventional food, a manganese enriched conventional food, and a zinc enriched conventional food. Excerpt(s): The present invention relates to a nutritional composition. More particularly, the present invention relates to a nutritional composition made from conventional foods for mixing on site in a blender and treating patients with hepatic disorders. The liver, and its proper functioning, is of utmost importance to the survival of a patient. Because it is responsible for the metabolism of nearly all nutrients, and is the primary site for the inactivation of numerous toxins, the liver is one of the most important organs of the body. For example, the liver accounts for approximately 20% of the body's basal metabolism. The liver extracts a majority of the amino acids, carbohydrates, lipids, vitamins, and minerals from portal circulation. These nutrients, extracted by the liver, are used as substrates or cofactors in all metabolic processes carried out in the liver. Synthesis of plasma proteins and bile secretion are additionally important processes carried out by the liver. Web site: http://www.delphion.com/details?pn=US06524610__

Patents 199

•

Nutritive composition for cardiovascular health containing fish oil, garlic, rutin, capsaicin, selenium, vitamins and juice concentrates Inventor(s): Fan; David (Mission Veijo, CA), Hsia; Houn Simon (Foothill Ranch, CA) Assignee(s): Viva Life Science (Costa Mesa, CA) Patent Number: 6,440,464 Date filed: April 21, 1997 Abstract: The present invention relates to the use of nutritional supplement compositions to overcome nutritional deficiencies typically associated with the normal mammalian diet. The compositions of the present invention are obtained by combining fish oil, garlic powder, rutin, capsaicin, vitamin A, vitamin C, vitamin E, selenium, and one or more juice concentrates. Excerpt(s): The present invention provides a novel nutritive compositions, and more specifically to nutritive compositions containing fish oil, garlic, rutin, capsaicin, vitamin A (beta carotene) , vitamin E, vitamin C, selenium and selected juice concentrates, for reducing the levels of triglycerides, cholesterol, and low density lipoprotein (LDL) in human blood serum, and for lowering the blood pressure, and for increasing the levels of high density lipoprotein (HDL) in human blood serum. In the last few years, scientific literature has provided strong evidence for a bona fide link between micronutrient compositions (such as vitamins, minerals, fish oils, and plant extracts) and cardiovascular disease. For humans of high risk for cardiovascular diseases, realizing an appreciable reduction in the levels of high cholesterol, triglycerides, low density lipoprotein (LDL) in their blood serum is known to be important for reducing the risk of cardiac diseases. It is also known that effecting an increase in the levels of high density lipoprotein (HDL) also provides a significant decrease to the risk of cardiac diseases. Cardiovascular disease resulting from the buildup of arterial plaque is known to be a leading cause of illness and death in humans. Arterial plaque is caused by precipitous material formed chiefly of oxidized low density lipoprotein (O-LDL). The buildup of plaque in the form of O-LDL in the arteries is understood to be a factor in ischemic heart disease. Free radical oxidants, many of which come from naturally occurring sources such as sun exposure, metabolism of certain nutrients, exercise, or are otherwise often observed in persons suffering from diabetes and high blood pressure, act to oxidize LDL into its deleterious form, O-LDL. Free radical "scavengers" such as vitamins A, E, C, and selenium are believed to react with these oxidants and render them incapable of oxidation. The inhibitory action of these antioxidants thus inhibits the formation of OLDL, thereby lowering the levels of arterial plaque deposits in blood vessels. In contrast, the presence of high density lipoprotein (HDL) in the body is understood to have beneficial health effects. Specifically, HDL is known to be a more soluble form of lipoprotein, hence its presence does not significantly contribute to the formation of arterial plaque. In addition, it is known that HDL is able to absorb plaque material and may thus directly reduce the amount of arterial plaque. Web site: http://www.delphion.com/details?pn=US06440464__

200

•

Vitamin E

Plastic compositions including vitamin E for medical containers and methods for providing such compositions and containers Inventor(s): Shang; Shaye-Wen (Vernon Hills, IL) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 6,468,258 Date filed: July 18, 1997 Abstract: Plastic compositions, medical containers and methods for providing such compositions and containers are disclosed. The plastic compositions and the medical containers made thereof include a plastic resin, Vitamin E and a plasticizer. The plastic resin may be polymeric material such as polyvinyl chloride or polyolefin. Excerpt(s): The present invention relates, in general, to plastic compositions and, in particular, to plastic compositions that may be used for medical containers, such as containers for the storage of blood and/or blood cells. The present invention also relates to methods for storing blood and/or blood cells in containers made from such compositions. Whole blood is typically described as being made up of various cellular components such as red blood cells (RBCs), white blood cells (WBCs) and platelets, suspended in a liquid component, plasma. Each component plays a specific and important role in the human body. For example, platelets (together with clotting factors and other substances in the blood) are responsible for blood clotting. WBCs are primarily responsible for fighting disease. RBCs transport oxygen (O.sub.2) and carbon dioxide (CO.sub.2) to and from body tissues. The O.sub.2 and CO.sub.2 are carried by a protein called hemoglobin, which is found inside the RBC. Blood and blood components are collected in a variety of ways. One of the most common blood collection techniques, and perhaps the most well known, is the manual collection of whole blood from healthy donors. This is usually performed at a local hospital, blood collection center or even a community center such as a local school or church as part of a blood collection drive. In the manual technique, a needle is inserted into the donor's arm and blood is withdrawn from the donor through the needle and associated tubing. The withdrawn whole blood is collected in a sterile plastic collection container or pouch attached to the other end of the tubing. The collected "unit" of whole blood may then be transfused into a patient. Web site: http://www.delphion.com/details?pn=US06468258__

•

Preparation of d,1-.alpha.-tocopherol Inventor(s): Bonrath; Werner (Freiburg, DE), Wang; Shaoning (Basel, CH) Assignee(s): Roche Vitamins Inc. (Parsippany, NJ) Patent Number: 6,423,851 Date filed: August 17, 2001 Abstract: The present invention provides a process for preparing of d,l-.alpha.tocopherol by the catalyzed condensation of trimethylhydroquinone with isophytol. This process includes carrying out the condensation in the presence of bis(trifluoromethylsulphonyl)amine [HN(SO.sub.2 CF.sub.3).sub.2 ] or a metal salt thereof of the formula Met (N(SO.sub.2 CF.sub.3).sub.2).sub.n (I) as the catalyst and supercritical carbon dioxide or nitrous oxide as the solvent, wherein Met is a metal atom such as for example boron, magnesium, aluminum, silicon, scandium, titanium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, yttrium, zirconium, rhodium,

Patents 201

palladium, silver, tin, lanthanum, cerium, neodymium, praseodymium, europium, dysprosium, ytterbium, hafnium, platinum and gold, and n is the corresponding valency (1, 2, 3, or 4) of the metal atom Met. A cosolvent may also be used, which is a lower aliphatic alkanol, ketone or hydrocarbon. The product of the process is the most active member of the vitamin E group. Excerpt(s): The present invention is concerned with a novel process for the manufacture of d,l-.alpha.-tocopherol by the catalyzed condensation of trimethylhydroquinone with isophytol in a solvent. As is known, d,l-.alpha.-tocopherol is a diastereomer mixture of 2,5,7,8-tetramethyl-2-(4',8',12'-trimethyl-tridecyl)-6-chromanol (.alpha.-tocopherol), which is the most active and industrially most important member of the vitamin E group. Many processes for the manufacture of d,l-.alpha.-tocopherol by the condensation of trimethylhydroquinone (TMHQ) with isophytol (IP) in the presence of various catalysts or catalyst systems and in various solvents are described in the literature. These processes go back to the work of Karrer et al., Bergel et al. as well as Smith et al. (see Helv. Chim. Acta 21, 520-525 (1938), Nature 142, 36 (1938) and, respectively, Science 88, 37-38 (1938) and J. Am. Chem. Soc. 61, 2615-2618 (1939)). While Karrer et al. carried out the synthesis of d,l-.alpha.-tocopherol from TMHQ and phytyl bromide in the presence of anhydrous zinc chloride (ZnCl.sub.2; a Lewis acid), not only Bergel et al., but also Smith et al used TMHQ and phytol as starting materials. In the following years modifications, such as alternative solvents and Lewis acids, were developed. From the work of Karrer et al. a process was developed in 1941 for the manufacture of d,l-.alpha.-tocopherol which was based on the condensation of TMHQ with IP in the presence of the catalyst system ZnCl.sub.2 /hydrochloric acid (HCl) (Karrer et al., U.S. Pat. No. 2,411,969). Later publications, e.g. Japanese Patent Publications (Kokai) 54380/1985, 64977/1985 and 226979/1987 (Chemical Abstracts (C.A.) 103, 123731s (1985), C.A. 103, 104799d (1985) and, respectively, C.A. 110, 39217r (1989)), disclose this condensation in the presence of zinc and ZnCl.sub.2 and a Bronsted (protonic) acid, such as a hydrohalic acid, e.g. HCl, trichloroacetic acid, acetic acid and the like, especially ZnCl.sub.2 /HCl, as the catalyst system. Disadvantages of these and further published processes featuring ZnCl.sub.2 in combination with a Bronsted acid are the corrosive properties of the acids and the contamination of the waste water with zinc ions as a result of the relatively large amount of ZnCl.sub.2 required for the catalysis. Web site: http://www.delphion.com/details?pn=US06423851__ •

Process for preparing d,l-.alpha.-tocopherol Inventor(s): Aquino; Fabrice (Reiningue, FR), Bonrath; Werner (Freiburg, DE) Assignee(s): Roche Vitamins Inc. (Parsippany, NJ) Patent Number: 6,452,023 Date filed: June 29, 1999 Abstract: A process for the manufacture of d,l-.alpha.-tocopherol by the acid-catalyzed condensation of trimethylhydroquinone with isophytol or phytol in ethylene or propylene carbonate or a mixture of both carbonates, or in a mixture of one or both of the carbonates and a non-polar solvent, comprises carrying out the condensation in the presence of at most 0.4 weight percent based on the weight of isophytol or phytol of 12tungstophosphoric acid, 12-molybdophosphoric acid or 12-tungstosilicic acid. The product of the process is the most active and industrially important member of the vitamin E group.

202

Vitamin E

Excerpt(s): The present invention is concerned with a novel process for the manufacture of d,1-.alpha.-tocopherol by the acid-catalyzed condensation of trimethylhydroquinone (TMHQ) with isophytol (IP) or phytol (PH) in a solvent. As is known, d,1-.alpha.tocopherol is a diastereoisomeric mixture of 2,5,7,8-tetramethyl-2-(4',8',12'-trimethyltridecyl)-6-chromanol (.alpha.-tocopherol), which is the most active and industrially most important member of the vitamin E group. Many processes for the manufacture of d,1-.alpha.-tocopherol by the condensation of TMHQ with IP or PH in the presence of a catalyst or catalyst system and in a solvent or solvent system are described in the literature. These processes go back to the work of Karrer et al., Bergel et al., as well as, Smith et al. [see Helv. Chim. Acta 21, 520 et seq. (1938), Nature 142, 36 et seq. (1938) and, respectively, Science 88, 37 et seq. (1938) and J. Am. Chem. Soc. 61, 2615 et seq. (1939)]. While Karrer et al., carried out the synthesis of d,1-.alpha.-tocopherol from TMHQ and phytyl bromide in the presence of anhydrous zinc chloride (ZnCl.sub.2; a Lewis acid), Bergel et al. and Smith et al. used TMHQ and PH as starting materials. In the following years many modifications, e.g., alternative solvents and Lewis acids, were developed. From the work of Karrer et al., a technically interesting process for the manufacture of d,1-.alpha.-tocopherol was developed in 1941 that was based on the condensation of TMHQ with IP in the presence of the catalyst system ZnCl.sub.2 /hydrochloric acid (HCl). See, U.S. Pat. No. 2,411,969. Later publications, e.g., Japanese Patent Publications (Kokai) 54380/1985, 64977/1985 and 226979/1987 [Chemical Abstracts (C.A.) 103, 123731s (1985), C.A. 103, 104799d (1985) and, respectively, C.A. 110, 39217r (1989)], describe this condensation in the presence of zinc and/or ZnCl.sub.2 and a Bronsted (protonic) acid, such as a hydrohalic acid, e.g., HCl, trichloroacetic acid, acetic acid and the like, especially ZnCl.sub.2 /HCl, as the catalyst system. Disadvantages of these and further published processes featuring ZnCl.sub.2 in combination with a Bronsted acid are the corrosive properties of the acids and the contamination of the waste water with zinc ions as a result of the large amount of ZnCl.sub.2 required for the catalysis. The manufacture of d,1-.alpha.-tocopherol by the reaction of TMHQ with phytyl chloride, PH or IP in the presence of boron trifluoride (BF.sub.3) or its etherate (BF.sub.3.Et.sub.2 O) is described in German Patents 960720 and 1015446 as well as in U.S. Pat. No. 3,444,213. However BF.sub.3 also has corrosive properties. Web site: http://www.delphion.com/details?pn=US06452023__ •

Process for the production of 2,3,5-trimethylhydroquinone diesters Inventor(s): Huthmacher; Klaus (Geinhausen, DE), Krill; Steffen (Speyer, DE) Assignee(s): Degussa-Huls AG (Frankfurt am Main, DE) Patent Number: 6,417,409 Date filed: February 11, 2000 Abstract: The invention relates to an improved process for the production of 2,3,5trimethylhydroquinone diesters by rearrangement of 2,6,6-trimethyl-2-cyclohexene-1,4dione (4-oxoisophorone, ketoisophorone) in the presence of a dissolved, acidic catalyst and an acylating agent, such as for example carboxylic anhydrides or carboxylic acid halides. The 2,3,5-trimethylhydroquinone diester can optionally then be saponified to give free 2,3,5-trimethylhydroquinone (TMHQ), which is a valuable building block in the synthesis of vitamin E. Excerpt(s): This application is based on German Application DE 199 05 685.4, filed Feb. 11, 1999, the disclosure of which is incorporated in its entirety herein by reference. 2,3,5Trimethylhydroquinone diesters and the corresponding TMHQ are important

Patents 203

intermediates which are used in the production of vitamin E and vitamin E acetate. In addition to the known production process based on aromatic starting materials, 2,3,5trimethylhydroquinone can be produced from a non-aromatic compound, 2,6,6trimethyl-2-cyclohexene-1,4-dione, by rearrangement under acylating conditions and subsequent hydrolysis. In patent specification DE 26 46 172 C2, a process is described in which 2,6,6-trimethyl-2-cyclohexene-1,4-dione is rearranged directly to trimethylhydroquinone in the vapor phase at a high temperature in contact with an acidic catalyst. However, the yield in this process is only low (50% with 30% conversion). If the aromatization of 2,6,6-trimethyl-2-cyclohexene-1,4-dione is carried out in the presence of an acylating agent, trimethylhydroquinone diesters are obtained which lead to trimethylhydroquinone by subsequent hydrolysis. Web site: http://www.delphion.com/details?pn=US06417409__ •

Process to modulate disease risk with doses of a nutraceutical Inventor(s): Block; Jerome Bernard (Rancho Palos Verdes, CA), Evans; Steven (Omaha, NE) Assignee(s): Genetic Services Management, Inc. (Omaha, NE) Patent Number: 6,630,160 Date filed: September 5, 2000 Abstract: A dietary supplement is created, comprised of material from the following nutrients, vitamins, herbs, minerals, and food and plant substances and food and plant derivatives: lycopene, vitamin E, selenium, green tea, coenzyme Q10, garlic, folic acid, vitamin C, curcumin, seaweed, Cordyceps sinsensis mushroom, Lentinus edodes (shiitake) mushroom, and Ganoderma lucidum (reishi) mushroom. The composition is administered orally for individuals who wish to reduce their risk of disease, particularly cancer-risk. Excerpt(s): Cancer care is reported to have cost Americans more than $110 billion in 1992, more than 11% of all expenditures spent on diseases in America. Researchers have indicated that from 50-90% of all cancers could be prevented through proper nutrition. There has evolved a new professional descriptive term "nutraceuticals" which combines the term "nutrient" and the term "pharmaceuticals" to describe this genre of medicinal agents that may be comprised of one or more complex combinations of ingredients made from nutrients, vitamins, minerals, herbs, and food and plant derivatives. We shall employ this term "nutraceutical" to refer to such a composition of one or more ingredients. This invention addresses the need for a dietary supplement that can reduce risk of disease, particularly cancer risk, that will be efficacious for a significant segment of the population. There have been tests and clinical trials on numerous individual agents for their role as cancer preventatives, such as coenzyme Q10 or selenium, but the daunting task of intelligently combining complex compositions has precluded exploration of complex compositions of nutraceuticals for cancer risk reduction. Thus in the past, one single ingredient would be selected and tested for its role as a cancer preventative for some specific cancer, usually in individuals who already had cancer. For example, selenium was tested for cancer prevention in patients who had had carcinoma of the skin [Clark, L. C., Combs; G. F., Jr., Turnbull, B. W., Slate, E. H., Chalker, D. K., Chow, J., Davis, L. S., Glover, R. A., Graham, G. F., Gross, E. G., Krongrad, A., Lesher, J. L., Park, H. K., Sanders, B. B., Jr., Smith, C. L., Taylor, J. R. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. JAMA. 276 (24): 1957-1963, Dec. 1996]. Similarly

204

Vitamin E

the effects of coenzyme Q10 suggested possible efficacious results in limited case studies with individuals with breast cancer [Lockwood, K., Moesgaard, S., Folkers, K. Partial and complete regression of breast cancer in patients in relation to dosage of coenzyme Q10. Biochem Biophys Res Comm. 199: 1504-1508, 1994]. However researchers as noted have been preoccupied with traditional experimental design methodology whereby these investigators wish to determine whether one specific ingredient is effective or not, usually for one specific cancer, and even then, as a treatment rather than a preventative. Another reason single individual ingredients were selected is because researchers have focused on just one of the following biologic, cancer-fighting, etiologically-oriented domains of interest: (1) anti-tumor activity, or (2) immune stimulating activity, or (3) anti-viral activity, or (4) anti-inflammatory activity, or (5) antimutagenic activity, or (6) antiproliferative activity, or (7) anti-free-radical development. This micro-focus has precluded the realization that by combining all those ingredients which work for one subset or another of the population, for one type of cancer or another, for one etiological reason or another, a powerful net effect can be achieved, along with the synergy of the ingredients working together. The present invention provides a complex composition (a "nutraceutical") comprising material from known nutrients, vitamins, herbs, minerals, and food and plant substances and food and plant derivatives which are useful to reduce risk of disease, particularly cancer risk, for one or more of all the known etiological factors that affect cancer development and hence yields cancer prevention for the consumer of this nutraceutical. This nutraceutical profoundly reduces risk of cancers through the multiple actions of all the etiological factors addressing cancer-causing conditions, such as providing (1) anti-tumor activity, and (2) immune stimulating activity, and (3) anti-viral activity, and (4) anti-inflammatory activity, and (5) antimutagenic activity, and (6) antiproliferative activity, and (7) anti-free-radical development. The nutraceutical is comprised of lycopene, vitamin E, selenium, green tea polyphenols, Coenzyme Q-10, garlic, folic acid, vitamin C, curcumin, seaweed, Cordyceps sinsensis mushroom, Lentinus edodes (shiitake) mushroom, and Ganoderma lucidum (reishi) mushroom. Preferably the material from each of such entries is in dried powder form. Web site: http://www.delphion.com/details?pn=US06630160__ •

Proenergetic food supplement based on NADH, octocosanol and vitamin E Inventor(s): Adams; Peter (London, GB) Assignee(s): World Pharma Tech Ltd. (London, GB) Patent Number: 6,500,451 Date filed: January 22, 2001 Abstract: The object of this invention is a food supplement based on NADH, Octocosanol and Vitamin E, which stimulates the generation of energy by the organism. Excerpt(s): As the most powerful antioxidant present in the body, NADH is capable of rigenerating other important antoxidants meant to protect the body at against the attack of free radicals. A few molecules of NADH can have a powerful effect on the body's anti-oxidizing defenses against free radicals causing disease. The lack of NADH translates to an energy deficiency on a cellular level, and its relative symptom is tiredness. Unfortunately, the NADH level found in the human body drops with age, and the same happens to the enzymes depending on NADH, in particular to those destined for producing energy.

Patents 205

Web site: http://www.delphion.com/details?pn=US06500451__ •

Reduced pigment gene of carrot and its use Inventor(s): Breitbach; D. Nicholas (Middleton, WI), Goldman; Irwin L. (Madison, WI) Assignee(s): Wisconsin Alumni Research Foundation (Madison, WI) Patent Number: 6,437,222 Date filed: August 20, 1998 Abstract: This invention relates to a carrot plant having Vitamin E biosynthesis, a recessive gene for reduced pigment designated rp, a carrot inbred line with Vitamin E biosynthesis. The carrot plant contains at least 0.01 mg.alpha.-tocopherol per 100 grams of fresh weight of the carrot root. The present invention also relates to a method for producing F.sub.1 hybrid carrot root. The method includes crossing a first parent carrot plant with a second parent carrot plant and harvesting the resultant F.sub.1 hybrid carrot root. Excerpt(s): The present invention relates to a Daucus carota reduced pigment gene, a carrot seed, a carrot plant, a carrot inbred and a method of producing carrot hybrids. The reduced pigment gene of the present invention can be incorporated into various Daucus genetic backgrounds. The present invention also relates to a carrot root having an increased level of.alpha.-tocopherol. Carrot (Daucus carota L.) is a biennial plant that belongs to the parsley family. Carrot roots are commonly-known as a good source of Vitamin A. In particular, it has been estimated that carrots contribute approximately 14% of the total Vitamin A to the human diet in the United States (Senti, F. R., and R. L. Rizek, 1975, Nutrient Levels in Horticultural Crops. Hort.Science. 10:243-246). Vitamin A content is related to the pigmentation in the carrot roots. In particular, carrot roots contain.beta.-carotene which animals convert into provitamin A. Beta carotene is also responsible for the orange color of carrot roots. Carrot pigmentation is present in carrots in many different forms. Carrot roots can exhibit several colors including white, yellow, orange, red and purple (Banga, 0., 1964, Origin and Distribution of the Western Cultivated Carrot. Genetica Agrafia. 17:357-370). Of these colors, purple pigmentation is due to the presence of anthocyanins whereas yellow, orange and red pigmentation are due to carotenoids. The primary carotenoids in orange carrot tissue are.alpha. and.beta.carotene (Laferriere, L., and W. H. Gabelman, 1968, Inheritance of Color, Total Carotenoids, Alpha-carotene, and Beta-carotene in Carrots, Daucus carota L., Proc. Amer. Soc. Hort. Sci. 93:408-418). Carrot cultivars are often separated into several categories for market use. These include 1) fresh market, 2) cut and peel, and 3) processing. Fresh market carrots are typically known as Imperator types and have long, straight, thin roots. They are also known as cello or bunching carrots because they are sold bunched in cello bags in the market. Cut and peel carrots refer to the "baby" carrot now seen in markets throughout the world. These carrots have roots that are similar in type to the fresh market carrot, however, they have been cut into small sections for market. Processing carrots are large, often tapered, bulky roots used for canning, freezing, and other processed carrot products. Cultivars of processed carrot and fresh market carrot are developed and maintained in separate breeding programs. Web site: http://www.delphion.com/details?pn=US06437222__

206

•

Vitamin E

Sheet for whitening cosmetics and method for using the same Inventor(s): Kawasaki; Takashi (Osaka, JP), Konno; Masayuki (Osaka, JP) Assignee(s): Nitto Denko Corporation (Osaka, JP) Patent Number: 6,458,379 Date filed: October 15, 1999 Abstract: A sheet for whitening cosmetics comprises a sheet-like substrate and an adhesive layer which comprises a wet pressure-sensitive adhesive composition formed on the substrate. The whitening component includes vitamin C or its derivatives such as magnesium L-ascorbyl-2-phosphate, vitamin E nicotinate, kojic acid, hydroquinone, ellagic acid, albumin, galenical extracts, and rice bran extracts. Kojic acid and magnesium L-ascorbyl-2-phosphate are preferred. By contacting the adhesive layer with water and/or a hydrophilic medium such as alcohols, e.g., methanol, ethanol, etc., the wet pressure-sensitive adhesive composition exhibits excellent stickiness and excellent applicability to skin as well as excellent whitening effect with alleviating or eliminating stains, freckles, non-transparency, etc. on the skin. Excerpt(s): The present invention relates to a sheet for whitening cosmetics and to a method for using the same. More particularly, it relates to a sheet for whitening cosmetics for alleviating or eliminating stains, freckles, non-transparency, etc. due to deposition of pigments or pigmentation on the surface of a skin and to a method for using such a sheet for whitening cosmetics. Cosmetics which exhibit various effects are commercially available. Among them, attention has been being increasingly paid to those cosmetics which exhibit an effect of causing a skin to look whiter, i.e., a so-called whitening effect. Stains, freckles, non-transparency, etc. once occurred on the skin, in particular, the skin of a face, are difficult to be eliminated. Many companies have developed preparations for preventing these symptoms and put them on the market. It is generally believed that exposure of a skin to ultraviolet rays generates melanine pigment in the skin, which causes such a pigmentation. Therefore, whitening cosmetics which inhibit the generation of or remove the melanine pigments in the skin to prevent various symptoms attributable to the deposition of pigments have been developed and there have been various commercial products. Most of them are liquid or cream-like products. Web site: http://www.delphion.com/details?pn=US06458379__

•

Solid composition comprising vitamin E acetate Inventor(s): Nabi; Zeenat (Cranbury, NJ), Riesgraf; Diane (Hillsborough, NJ), Soliman; Nadia (East Brunswick, NJ) Assignee(s): Colgate-Palmolive Company (New York, NY) Patent Number: 6,500,792 Date filed: January 25, 2001 Abstract: A solid cleansing composition comprisinga. About 1 to about 90 wt. % soap,b. About 0.02 to about 2.0 wt. % of a Vitamin E precursor or mixture thereof,c. A Vitamin E precursor deposition effective amount of a cationic deposition polymer or mixture thereof, andd. From zero to the essential absence of Vitamin E. Excerpt(s): Antioxidants are known to be useful in combating various conditions of the body associated with the activity of free radicals. Antioxidants quench free radicals so

Patents 207

they can not interact with the body's systems. Among the most well known antioxidants are the vitamins, particularly Vitamin E and its precursors. When used in topical compositions, particularly cleansing compositions, the Vitamin E and its precursors can have difficulty with deposition on skin. We have now discovered a soap bar, which can deposit significant levels of Vitamin E precursor as well as other vitamins and their precursor(s). Web site: http://www.delphion.com/details?pn=US06500792__ •

Super absorption coenzyme Q10 Inventor(s): Hari; Siva P. (Riverside, CA), Udell; Ronald G. (Beverly Hills, CA) Assignee(s): Soft Gel Technologies, Inc. (Los Angeles, CA) Patent Number: 6,623,734 Date filed: June 22, 2001 Abstract: A new soft gelatine formulation and process methodology is disclosed herein that increases single Coenzyme Q10 molecules presented to the absorption channels of the small intestines by providing medium chain triglycerides, Vitamin E, and natural beta carotene to Coenzyme Q10 in a soft gel capsule to increase the absorption thereof. Excerpt(s): This invention relates to a new soft gelatine formulation and process methodology that increases single Coenzyme Q10 molecules presented to the absorption channel of the small intestines. Coenzyme Q.sub.10 (CoQ.sub.10) is a large molecular weight lipid compound that is produced in the liver and other organs. The total human body content is 1.4 to 1.8 grams depending on the individual's age and fitness level. CoQ.sub.10 is found in all tissues of the body. It is mostly concentrated in the mitochondria and other organelles that help the body metabolize nutrients into energy. These include organs with high levels of metabolic activity. Organs, whose primary purpose is energy production, tend to store and use CoQ.sub.10 in large amounts. Such organs include the heart, liver, and skeletal muscle tissue. The heart and skeletal muscle of an aaverage human contain about 1000 mg of CoQ.sub.10. This is in contrast to metabolically inactive body components such as the blood, which only contains about 4 mg of CoQ.sub.10. However, blood plays an important role in as a CoQ.sub.10 reservoir. Blood helps to transport CoQ.sub.10 from endogenous CoQ.sub.10 made in the liver and exogenous CoQ.sub.10 absorbed from digested food in the intestinal tract. Endogenous CoQ.sub.10 accounts for approximately 56 percent of the body's supply. The remaining 44 percent must be provided through diet and supplementation. These numbers are currently being studied but the latest studies indicate lower endogenous production of CoQ.sub.10, which indicates a significant deficiency, in correlation with increased age. Furthermore, certain disease states such as cardio myopathy and high cholesterol levels, which are treated with Statin drugs, seem to deplete endogenous CoQ.sub.10 production thereby indicating a need for supplementation. These deficiencies in the nutrient have no relation to daily caloric intake but are indicative of poor vitamin absorption from ingested foods. The body requires the addition of vitamins to aid in the endogenous production of CoQ.sub.10; in particular, the B Vitamins play a crucial role in this synthesis. The human body's need for CoQ.sub.10 varies between individuals. Factors that affect this are age, physical activity, and health. The body uses an estimated 5 to 9 mg per day of CoQ.sub.10. This nutrient is essential for life because it is important in the synthesis of energy. The vast majority of energy synthesis occurs in the mitochondria of cells. Here CoQ.sub.10 primarily functions as an electron carrier in the Electron Transport Chain where Adenosine Triphosphate (ATP) is

208

Vitamin E

synthesized. CoQ.sub.10 donates an electron during ATP synthesis and is subsequently oxidized. CoQ.sub.10 also can function as an antioxidant during synthesis where oxidation removes its electron making it non-functional for use in ATP synthesis. Web site: http://www.delphion.com/details?pn=US06623734__ •

Synergistic compositions for lycopene and Vitamin E for the prevention of LDL oxidation Inventor(s): Aviram; Michael (Kiryat Haim, IL), Fuhrman; Bianca (Haifa, IL), Nir; Zohar (Meitar, IL), Zelkha; Morris (Omer, IL) Assignee(s): Lycored Natural Products Industries Ltd. (Beer Sheva, IL) Patent Number: 6,515,018 Date filed: April 3, 2000 Abstract: A synergistic mixture containing lycopene and Vitamin E and its use in the prevention of LDL oxidation. Lycopene is either synthetic or from natural sources. Furthermore the preparation of a pharmaceutical and a dietary composition for arresting the progression of atheroclerosis is described. Excerpt(s): The present invention concerns a composition containing lycopene and Vitamin E. This present invention more particularly relates to a synergistic mixture of lycopene and vitamin E and its use in the prevention of LDL oxidation, and preparing pharmaceutical and dietary compositions for arresting the progression of atheroclerosis. Atherosclerosis is the major single cause of mortality in western society. It is assumed to reach up to 50% of all mortality (Davies M J, and Woolf N. Atherosclerosis: what is it and why does it occur? Br Heart J 69:S3, 1993). In addition, it results in significant cardiac morbidity, such as anginal syndromes, myocardial infarctions, ischemic cardiomyopathy, sudden cardiac death, cerebrovascular accidents, and peripheral vascular disease. Indisputable evidence for an association between coronary heart disease (CHD) and risk factors, such as arterial hypertension, cigarette smoking and hyperlipidemia, has been derived from a variety of epidemiological studies. Of all the risk factors established thus far, lipid disorders play a key role in the pathogenesis of atherosclerotic vascular disease, especially of CHD. Many epidemiological and clinical trials have demonstrated the powerful association between hyperlipidemia and the widespread incidence of CHD. The Framingham Heart Study (Castelli W P, Anderson K, Wilson P W., Levy D. Lipids and risk of coronary heart disease. The Framingham Study. Ann Epidemiol 2(1-2): 23-28, 1992), which has been continuous since 1984, showed that hypercholesterolemia is a major contributor to the development of CHD. The link between atherosclerosis and cholesterol has been confirmed by a number of clinical trials. Web site: http://www.delphion.com/details?pn=US06515018__

Patents 209

•

Therapeutic nutrient regimen for alleviating mucositis, stomatitis and cachexia in oncology patients Inventor(s): Sherratt; J. Dale (Sherborn, MA), Somerville; Joann (Reading, MA) Assignee(s): Baxter International Inc. (Deerfield, IL) Patent Number: 6,479,068 Date filed: June 30, 2000 Abstract: The present invention relates to a daily regimen for oncology patient suffering from mucositis, stomatis, and cachexia wherein the daily regimen involves administering to the patient at least one dose of an oral composition in unit dosage form which comprises L-glutamine, vitamin A, vitamin C, vitamin E, and selenium; and at least four glutamine lozenges throughout the day which comprises about 2 grams of glutamine each, beginning 4-7 days prior to said treatment and continuing through said treatment. Excerpt(s): The present invention relates to the use of the amino acid glutamine in combination with additional nutrients in a composition for alleviating side effects of oncology treatment in a cancer patient comprising administering to the patient a daily regimen which comprises administering (a) at least one dose of an oral composition in unit dosage form which comprises L-glutamine, vitamin A, vitamin C, vitamin E, and selenium twice daily; and (b) at least four glutamine lozenges throughout the day which comprise about 2 grams of glutamine each, beginning 4-7 days prior to said treatment and continuing through said treatment. The daily regimen allows for physical contact of mucosal membranes with glutamine as well as systemic administration for alleviating the side effects of oncology therapy. Skubitz et al. in U.S. Pat. Nos. 5,438,075 and 5,545,668 disclose an oral glutamine composition which is used to treat oropharyngeal mucositis in patients undergoing chemotherapy or radiotherapy. The patents disclose a method of alleviating stomatitis or esophagitis originating from treatment with chemotherapy and/or radiotherapy by administering the glutamine composition described in the patent. Anderson et al. disclose a patient study involving administration of a glutamine suspension to swish and swallow on days of chemotherapy administration and for at least 14 additional days. Anderson et al. conclude that low dose oral glutamine supplementation during and after chemotherapy significantly reduced both the duration and severity of chemotherapy-associated stomatitis and decreased the chance of patients developing mouth sores as a consequence of intensive cancer chemotherapy. See Anderson et al., Cancer, vol. 83 pages 1433-9 (1998). Web site: http://www.delphion.com/details?pn=US06479068__

•

Tobacco products with stabilized additives having vitamin E activity Inventor(s): Russo; Joseph D. (Palo Alto, CA) Assignee(s): Rousseau Research, Institute (Palo Alto, CA) Patent Number: 6,584,980 Date filed: May 26, 2000 Abstract: A substantially pure stabilized compound having Vitamin E activity is added to smokable or smokeless tobacco or non-tobacco products to achieve less irritation and antioxidant benefits. In a preferred embodiment, a substantially pure "dry" powdered

210

Vitamin E

ester analog of Vitamin E, such as Vitamin E acid succinate, Vitamin E acetate or dalpha-tocopheryl polyethylene glycol 1000 succinate is mixed directly with the tobacco during the curing or manufacturing process. For cigarette applications, these Vitamin E compounds can also be inserted into a cigarette filter, holder and/or paper, either in powdered form or in microencapsulated form. Although not preferred, a common oily form of Vitamin E can be used in the present invention so long as it is stabilized and does not ruin the appearance and function of the tobacco or non-tobacco products. Excerpt(s): The present invention relates to smoking tobacco products, such as cigarettes, cigars, pipe tobacco (bulk), roll your own tobacco and smokeless tobacco products, also known as "snuff" or "chewing tobacco" and non-tobacco smokable or mouthable products. More particularly, a novel form of smokable cigarette, cigar and bulk tobacco, including cured and uncured leaves, non-tobacco smokables or mouthables and smokeless tobacco is disclosed which includes as additives one or more stabilized health enhancing compounds that exhibit Vitamin E activity. Health problems associated with cigarette smoking, cigar smoking, pipe smoking and smokeless tobacco have been well publicized. In various scientific studies, cigarette smoking, cigar smoking, pipe smoking and use of smokeless tobacco have been causally linked to diseases such as lung, throat, mouth and other cancers as well as emphysema, smoker's cough and heart disease. Various attempts have been made to address cigarette health problems through reformulation of cigarettes. For example, special blends of tobacco have been formulated for cigarettes with reduced levels of tar and nicotine. Unfortunately, each reduction of the tar and nicotine level has been accompanied by a corresponding reduced level of smoker satisfaction requiring unhealthy longer, stronger puffs to increase smoker's satisfaction. As such, sales of lowered tar and nicotine cigarettes, particularly those commercially classified as "ultra low tar and nicotine", have not lived up to expectations. More recently, efforts have been made to altogether remove additives from cigarettes. While such "additive free" cigarettes may provide a purer tobacco smoke, it is unclear whether they provide any corresponding health benefits. In fact, in some cases, they have been shown to be stronger in tar and nicotine since they contain relatively more tobacco than non-additive containing cigarettes. Web site: http://www.delphion.com/details?pn=US06584980__ •

Treatment and prevention of hepatic disorders Inventor(s): Buck; Martina (San Diego, CA), Chojkier; Mario (San Diego, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,420,428 Date filed: November 28, 2000 Abstract: The present invention provides new methods for the treatment of viral hepatitis C involving the administration of vitamin E and other compounds with antioxidant properties. Treatment with high doses of vitamin E is effective in treating chronic hepatitis C in patients refractory to interferon. In addition, new methods are described for the treatment of hepatic fibrosis and hepatic conditions manifesting hepatic fibrosis involving the administration of butylated hydroxytoluene and a metabolite of pentoxifylline, 1-[3-carboxypropyl]-3,7-dimethylxanthine. Furthermore, new methods are described for the treatment and prevention of hepatic disorders involving the use of 2,6-di-tert-butylphenol derivatives.

Patents 211

Excerpt(s): The present invention relates generally to the treatment and prevention of hepatic fibrosis, and more particularly to the administration of pharmacologically active compounds for the treatment and prevention of viral hepatitis C. The majority of patients suffering from chronic hepatitis are infected with either chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV) or autoimmune disease. While each type is associated with certain distinct characteristics, generally speaking, chronic hepatitis can progress to cirrhosis and hepatic failure. Unfortunately, there are few effective treatments for hepatitis. For example, treatment of autoimmune chronic hepatitis is generally limited to immunosuppressive treatment with corticosteroids. For the treatment of hepatitis B and C, the FDA has approved administration of recombinant interferon alpha. However, interferon alpha is associated with a number of dosedependent adverse effects, including thrombocytopenia, leukopenia, bacterial infections, and influenza-like symptoms. Indeed, normal interferon alpha dosing parameters for the treatment of chronic hepatitis B require discontinuance or dosing adjustment in approximately 20-50% of patients. Other agents used to treat chronic hepatitis B or C include the nucleoside analog ribovirin and ursodeoxycholic acid; however, neither has been shown to be very effective. [See Medicine, (D. C. Dale and D. D. Federman, eds.) (Scientific American, Inc., New York), 4:VIII:1-8 (1995)]. Indeed, current therapies do not effectively prevent or cure hepatitis C or the hepatic fibrosis associated with the disease. Clearly, new alternative treatment methods and agents are needed and would be welcomed by those plagued by hepatitis C who either cannot tolerate available treatment regimens or who are refractory to those regimens. Web site: http://www.delphion.com/details?pn=US06420428__ •

Vitamin E and derivatives thereof prevent potassium ion leakage and other types of damage in red cells that are virus sterilized by phthalocyanines and light Inventor(s): Ben-Hur; Ehud (New York, NY), Horowitz; Bernard (New Rochelle, NY), Rywkin; Shanti (Brooklyn, NY) Assignee(s): New York Blood Center, Inc. (New York, NY) Patent Number: 6,541,229 Date filed: October 15, 1999 Abstract: Disclosed is an improved process for irradiating cell-containing compositions, especially, red cell-containing compositions, wherein vitamin E or a derivative thereof is added to the cell-containing composition prior to, during or after such irradiation. Addition of vitamin E or a derivative thereof is protective of cells in such compositions, but not of virus. Cells irradiated using the inventive process show a reduced leakage of K.sup.+ from cells and also a reduced loss of negative charges from the cell membrane compared to cells subjected to the similar process wherein vitamin E or a derivative thereof are not used. In addition, red blood cells sterilized by this process are better preserved during storage and their life-time in the circulation in vivo is greatly enhanced. Excerpt(s): The present invention concerns an improved process for rendering a cellcontaining composition substantially free of enveloped and non-enveloped viruses contained therein without substantial disruption or inactivation of cells contained therein and without significant loss of labile proteins or other valuable biological components also contained therein. Viral inactivation of cell-containing composition by treatment with irradiation, e.g., UV or visible light, a photosensitizer compound and, optionally, one or more quencher compounds has been described in the applications

212

Vitamin E

and patents mentioned above, the entire disclosures of which are hereby incorporated by reference. Such treatments are known to cause K.sup.+ leakage from red cells. See, e.g., J. van Steveninck et al., 1985, "The influence of cupric ions on porphyrin-induced photodynamic membrane damage in human red blood cells", Biochim. Biophys. Acta., 821: 1-7. Irradiation is used in other contexts involving cell-containing compositions for example, ionizing radiation, e.g.,.gamma.-irradiation or X-irradiation, to prevent graftversus host disease in immunodeficient patients. For this particular purpose, collected red cells increasingly are being stored for variable periods in transfusion service inventories following irradiation. Other reports of elevated K.sup.+ in irradiated, stored RBC, have recently surfaced. See, for example, Elaine K. Jeter et al., 1991, "Effects of irradiation on red cells stored in CPDA-1 and CPD-ADSOL (AS-1)", Ann. Clin. Lab. Sci., 21: 177-186; and A. M. Ramirez et al., 1987, "High potassium levels in stored irradiated blood", Transfusion, 27: 444-445. For blood centers offering red cell irradiation, prolonged storage following irradiation may expose selected patient populations to a significant K.sup.+ load following transfusion. Web site: http://www.delphion.com/details?pn=US06541229__ •

Wildlife nutritional supplement Inventor(s): Fuhr; David R. (Winigan, MO), Hauser; David (Winigan, MO) Assignee(s): 4 Seasons Wildlife Nutrition, LLC (Winigan, MO) Patent Number: 6,572,903 Date filed: May 8, 2002 Abstract: The present invention is a wildlife nutritional supplement for free ranging ruminants including about 7.5-8.5% calcium, about 3.5% phosphorus, about 32-37% salt, at least one "B" series vitamin is selected from a group consisting of pantothenic acid, folic acid, riboflavin, niacin, thiamine, cobalamin, and pyridoxine hydrocholoride, about 16-19% sodium, about 0.15% magnesium, about 0.15% potassium, about 2.5% sulfur, about 1,200 PPM iron, about 20 PPM copper, about 105 PPM manganese, about 45 PPM zinc, about 5 PPM cobalt, about 1 PPM selenium, about 1 PPM iodine, about 50,000 IU/LB Vitamin A, about 20,000 IU/LB Vitamin D, about 50 IU/LB Vitamin E, about 134 MG/LB biotin, about 60 MG/LB ascorbic acid, oxytetracycline and fenbendazole. Excerpt(s): This invention relates to wildlife nutritional supplements, and more particularly to a ruminant feed supplement having enhanced palatability and immunesystem bolstering effects. The reduction of habitat due to human development has left a noticeable impact on the health and vitality of wild ruminant animals. Ruminant animals such as deer, elk and the like, suffer diminished reproduction, decreased weight, smaller antlers, and susceptibility to disease and parasites. There are seven major minerals that have an important effect on wildlife: (1) calcium aids in the growth of bones, teeth and antlers and is important in the function of muscles and nerves; (2) phosphorus aids in the growth of bones, teeth and antlers, enhances energy metabolism and enzymation as well as proper protein utilization; (3) potassium is integral in the function of nerves, enzyme processes, as well as mineral and water balance; (4) sulfur is an essential component of some proteins; (5) sodium is vital to the function of muscles and nerves and also maintains water balance; (6) chloride of sodium forms hydrochloric acid in the abomasums which aids in protein breakdown; and (7) magnesium is an important component is almost all body processes. Web site: http://www.delphion.com/details?pn=US06572903__

Patents 213

Patent Applications on Vitamin E As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to vitamin E: •

2:1 Complex of beta- or gamma-cyclodextrin and alpha-tocopherol Inventor(s): Kupka, Michaela; (Burghausen, DE), Regiert, Marlies; (Munchen, DE) Correspondence: Collard & Roe, P.C.; 1077 Northern Boulevard; Roslyn; NY; 11576; US Patent Application Number: 20030130231 Date filed: December 19, 2002 Abstract: A complex of.beta.-cyclodextrin or.gamma.-cyclodextrin and.alpha.-tocopherol is based upon.beta.-cyclodextrin or.gamma.-cyclodextrin and.alpha.-tocopherol in a molar ratio of 2:1. Excerpt(s): The present invention relates to a 2:1 complex of.beta.- or.gamma.cyclodextrin and.alpha.-tocopherol, to its preparation and use. Cyclodextrins are cyclic oligosaccharides made up of 6, 7 or 8.alpha.(1-4)-linked anhydroglucose units. The.alpha.-,.beta.- or.gamma.-cyclodextrins prepared by enzymatic starch conversion differ in the diameter of their hydrophobic cavity and are generally suitable for the inclusion of numerous lipophilic substances.alpha.-Tocopherols are chroman-6-ols (3,4dihydro-2H-1-benzopyran-- 6-ols) substituted in the 2-position by a 4,8,12trimethyltridecyl radical. They occur in nature in the D-form, for example in relatively large amounts in, inter alia, wheatgerm and cottonseed oil.alpha.-Tocopherols are slightly yellowish-reddish, oily liquids. They are insoluble in water, soluble in fats and oils, and the usual solvents for fats. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Anti-inflammatory complex containing flaxseed oil Inventor(s): Maffetone, Philip B.; (St. Augustine, FL) Correspondence: Steptoe & Johnson Llp; 1330 Connecticut Avenue, N.W.; Washington; DC; 20036; US Patent Application Number: 20030077336 Date filed: November 6, 2002 Abstract: A nutritional supplement includes flaxseed oil, ginger, sesame, citrus, garlic, tumeric, vitamins and minerals. The nutritional supplement preferably includes about 400 to 800 mg of flaxseed oil, about 50 to 100 mg of ginger, about 50 to 100 mg of sesame, about 50 to 100 mg of citrus, about 50 to 100 of garlic, about 10 to 30 mg of tumeric, about 6 to 10 mg of Vitamin C, about 1 to 5 IU of Vitamin E, about 0.25 to 1 mg of Vitamin B6, about 0.25 to 1 mg of niacin, about 3 to 6 mg of magnesium, and about 0.25 to 1 mg of zinc. The nutritional supplement may be used in a method of treating inflammation by administering to a patient in need thereof an effective dose of the nutritional supplement.

10

This has been a common practice outside the United States prior to December 2000.

214

Vitamin E

Excerpt(s): The present invention relates to a nutritional supplement containing a variety of naturally occurring substances useful for treating inflammatory conditions. Flaxseed oil contains significant amounts of alpha linolenic acid (ALA), an essential fatty acid. ALA is an omega-3 fatty acid. The body turns ALA to a limited extent into eicosapentaenoic acid (EPA), which requires a variety of vitamins and minerals. EPA and DHA are omega-3 fatty acids also found in fish oil. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antioxidant combination composition and use thereof Inventor(s): De Simone, Claudio; (Ardea RM, IT) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe RD.; Arlington; VA; 22201-4714; US Patent Application Number: 20030068309 Date filed: October 3, 2001 Abstract: An orally or parenterally administrable composition which comprises the following components:(a) L-carnitine inner salt or a pharmacologically acceptable salt thereof;(b) acetyl L-carnitine inner salt or a pharmacologically acceptable salt thereof;(c).alpha.-lipoic acid;(d) coenzyme Q.sub.10;(e) Vitamin E; and(f) selenomethionine,suitable for counteracting oxidative stress and use thereof are disclosed. Excerpt(s): The present invention relates to a combination composition for the prevention and/or treatment of disorders or diseases brought about by oxidative stress, untimely early physiological apoptotic phenomena following oxidative stress and/or environmental agent-induced apoptosis. Accordingly, the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in. Diseases which can effectively be prevented or treated with the composition of the present invention include atherosclerosis, ischaemia-reperfusion injuries, rheumatoid arthritis, cancer, stroke, cataract and other eye diseases, thyroid diseases, liver diseases, sexual impotence, Parkinson's disease, Alzheimer's disease and degenerative disorders affecting virus-infected patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Antioxidant compositions and methods for companion animals Inventor(s): Harper, E. Jean; (Leicester, GB), Heaton, Paul R.; (Leicestershire, GB) Correspondence: Fulbright & Jaworski, Llp; 1301 Mckinney; Suite 5100; Houston; TX; 77010-3095; US Patent Application Number: 20030198661 Date filed: October 29, 2002 Abstract: The present invention provides, amongst others, a means to overcome the problem of oxidative stress in the domestic cat and dog. There is provided a method for increasing the plasma vitamin E level in a cat or dog, the method comprising the step of administering to said cat or dog, an amount of Vitamin E sufficient to increase the

Patents 215

plasma vitamin E level. There is also provided use of vitamin C in the manufacture of a dog or cat foodstuff for the prevention or treatment of a disorder which has a component of oxidative stress. The present invention utilizes an antioxidant cocktail to overcome the problem of oxidative stress in a cat or dog. Such cocktail can be used to prevent or treat a disorder which has a component of oxidate stress or to maintain, optimise or boost immunological response. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/890,289, which is a continuation-in-part of PCT/GB00/00270 filed Jan. 31, 2000, claiming priority to GB0018769.0 filed Jul. 31, 2000, GB9902051.3 filed Jan. 29, 1999 and GB9928549.6 filed Dec. 2, 1999. The present invention provides, among others, a means to overcome the problem of oxidative stress in the domestic cat and dog and more particularly an antioxidant cocktail to overcome the problem of oxidative stress in the domestic cat or dog. Such cocktail can be used to prevent or treat a disorder which has a component of oxidate stress or to maintain, optimise or boost immunological response. Free radicals are inherent in the aerobic metabolism of living organisms and are generated by both physiological and pathological processes. They are sometimes generated intentionally to serve biological functions, such as microbicides in phagocyte cells, or may be accidents of chemistry following which they exhibit destructive behaviours. Whatever their mechanism of generation, if free radical production and removal is not controlled, then their effects on an organism can be damaging. To combat excessive and inappropriate damage, an elaborate system of antioxidant defences has evolved. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Artificial nail remover Inventor(s): Lee, Cheon Sook; (Seoul, KR) Correspondence: Raymond Sun; 12420 Woodhall Way; Tustin; CA; 92782; US Patent Application Number: 20030054964 Date filed: September 20, 2001 Abstract: An artificial nail remover includes the following ingredients: acetone, methyl ethyl ketone, ethanol, dimethyl esters, Glycerine, water, vitamin E, and a perfume. Excerpt(s): The present invention relates to a nail remover that is used to remove artificial nails. Artificial nails are currently very popular. Unfortunately, all artifical nails eventually need to be removed. Most conventional artificial nails are made primarily of Acrylonitride Butadiene Styrene (ABS), which is a type of plastic material. Cyanoacrylate (which is the primary ingredient of glue) is typically used to attach the artificial nail to the user's real nail. At this time, acetone is most commonly used to remove artificial nails, and functions to decompose cyanoacrylate. The removal process typically involves soaking the artificial nail in a container that contains acetone for a period of time. Unfortunately, the use of acetone as an artificial nail remover has created problems of chlorosis, the removal of fat, and the creation of a strong and unpleasant odor. Chlorosis is the condition where the acetone dries and the remaining material reacts with air and remains on the surface of the white, which becomes white. Thus, there remains a need for an improved artificial nail remover that can effectively remove artificial nails while overcoming the drawbacks mentioned above. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

216

•

Vitamin E

BONE GRAFT MATERIAL INCORPORATING DEMINERALIZED BONE MATRIX AND LIPIDS Inventor(s): Nimni, Marcel E.; (Santa Monica, CA) Correspondence: Att: Michael B. Farber, ESQ.; Oppenheimer Wolff & Donnelly Llp; Suite 3800; 2029 Century Park East; Los Angeles; CA; 90067; US Patent Application Number: 20030049326 Date filed: September 10, 2001 Abstract: A demineralized bone putty composition comprises: (1) demineralized bone matrix (DBM); and (2) a lipid fraction selected from the group consisting of lecithin and a mixture of lecithin and triglycerides containing unsaturated fatty acids. The putty composition is moldable, biocompatible, slowly resorbable, and soluble in tissue fluids, and non-extrudable. The composition delivers a biologically active product to animals and humans that will enhance bone formation at sites where bone is lost, deficient, or present in suboptimal amounts. The composition can further comprise calcium, an antioxidant such as Vitamin E or Vitamin C, or a hydrophilic polymer such as methylcellulose or hydroxypropyl methylcellulose. Excerpt(s): This invention is directed to a bone graft material incorporating demineralized bone matrix and lipids for particular use in enhancing bone formation. One of the few tissues that regenerates in mammals is bone. To a great extent, this is due to the ability of specific growth factors to stimulate stem cells along the chondrogenic and osteogenic pathways and the role of mechanical forces that encourage bone remodeling. Significant efforts have been made to enhance bone healing using decalcified bone matrix as an inducer. Decalcified bone matrix, which is mostly collagen with small amounts of growth- and differentiation-inducin- g molecules, is able to stimulate bone formation, even after implantation (subcutaneously or intramuscularly) at ectopic sites where there is no bone. The chondro-osteogenic response induced by implants of demineralized rabbit (M. R. Urist & T. A. Dowell, "The Inductive Substratum for Osteogenesis in Pellets of Particulate Bone Matrix," Clin. Orthoped. Rel. Res. 61:61-68 (1969); M. R. Urist & B. S. Strates, "Bone Morphogenetic Protein," J. Dent. Res. 50:1392-1406 (1971)) and rat bone matrix (C. B. Huggins et al., "Transformation of Fibroblasts by Allogeneic and Xenogeneic Transplants of Demineralized Tooth and Bone," J. Exp. Med. 132:1250-1258 (1970); A. H. Reddi & C. B. Huggins, "Influence of Transplanted Tooth and Bone on Transformation of Fibroblasts," Proc. Soc. Exp. Biol. Med. 143:634-637 (1973); G. D. Syftestad & M. R. Urist, "Degradation of Bone Matrix Morphogenetic Activity by Pulverization," Clin. Orthoped. Rel. Res. 141:281-286 (1979)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Clear micellized formulations of beta-carotene and method of treating leukoplakia Inventor(s): Alosio, Edward; (Coto De Caza, CA), Dema-Ala, Bricini Faith; (Aliso Viejo, CA), Li, Wenjie; (Aliso Viejo, CA), Rutolo, David A. JR.; (Dove Canyon, CA) Correspondence: Gabor L. Szekeres; Klein & Szekeres, Llp; 4199 Campus DR., STE. 700; Irvine; CA; 92612; US Patent Application Number: 20030149098 Date filed: February 1, 2002

Patents 217

Abstract: A clear aqueous formulation for topical application in the oral cavity of humans to treat leukoplakia contains water,.beta.-carotene, a water miscible polyol, an unsaturated fatty acid ester, and a surfactant, preferably polyethoxylated castor oil. The formulation preferably also contains a pharmaceutically acceptable anti-oxidant, preferably d-alpha-tocopherol (vitamin E), and is in the form of an oral rinse or as a gel well suited for spreading on gums or other parts of the oral cavity. The formulation is applied in a gel form on a substantially regular daily basis to areas in the oral cavity where leukoplakia lesions are present. Persistent application of the gel results in substantial diminution or total elimination of the leukoplakia lesions. Excerpt(s): The present invention is in the field of formulations of.beta.-carotene, and methods of using such formulations. More particularly, the present invention relates to clear micellized formulations of.beta.-carotene adapted for treating leukoplakia in human patients, and to the process of such treatment.beta.-carotene is a well known naturally occurring substance and has been used in the prior art in nutritional supplements, vitamin or vitamin related formulations, as well as in other formulations applied to the human skin. U.S. Pat. No. 4,572,915 describes clear, micellized aqueous formulations of several fat soluble vitamins, essential nutrients, herb oils and other fat soluble pharmaceutical agents, including a formulation of.beta.-carotene. The formulations of U.S. Pat. No. 4,572,915 are to be ingested by humans as nutritional and/or vitamin supplements. Leukoplakia is a disease characterized by formation of white or off-white colored lesions in the mouth which have the potential of developing into oral cancer. It follows that partial or total elimination of the pre-malignant leukoplakia lesions is medically desirable, and may well serve as a life-saving measure by preventing the development of potentially disfiguring or fatal oral cancer. The present invention provides a.beta.-carotene formulation which is specifically adapted for treating leukoplakia lesions with highly favorable results. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Combination of antioxidant substances for the treatment of alzheimer's disease Inventor(s): Bassili, Joseph; (Montreal, CA), Elfarrah, Khassam; (Dollard-des-Ormeaux, CA), Saragovi, Uri; (Montreal, CA) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20030158237 Date filed: September 4, 2002 Abstract: Disclosed is a pharmaceutical composition for the treatment of cognitive symptoms caused by Alzheimer's disease in a mammal. This composition comprising vitamin E, quercitin, caffeic acid, nicotinic acid or derivatives and/or analog thereof, and a pharmaceutically acceptable excipient. Excerpt(s): The present invention relates to the use of a combination of antioxidant substances for the treatment of cognitive disorders such as Alzheimer's disease (AD). Alzheimer's disease (AD) is the most common of dementias. Its frequency, in later years, has dramatically increased due to the rise of life expectancy. This disease represents, according to different statistical data, from 50 to 75% of all dementias. Etiological hypotheses of AD such as those based on amyloid hypothesis, cholinergic hypothesis, oxidative hypothesis, genetic hypothesis and immunologic hypothesis are numerous and complex. It is considered that the trigger of the disease is a combination of them,

218

Vitamin E

and particularly of genetic and neurobiologic processes that take place simultaneously. The patient's brain with Alzheimer's disease is invaded by a protein known as betaamyloid peptide (beta A4). Beta A4 is part of the senile plaques that together with the neurofibrillary degeneration constitute the histopathology of AD, of other dementias and of the aging process depending on the density of the injury. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition Inventor(s): Bielli, Cristina; (Hillsborough, NJ) Correspondence: Colgate-palmolive Company; 909 River Road; P.O. Box 1343; Piscataway; NJ; 08855-1343; US Patent Application Number: 20030108576 Date filed: October 25, 2001 Abstract: An aqueous liquid composition which comprises:a. a surfactant or mixture of surfactants in quantities effective to cleanse skin, andb. an amount of Vitamin E in quantities sufficient to protect skin, andc. a Vitamin E stabilizing effective amount of 2tertiary butyl hydroquinone, andd. the balance water. Excerpt(s): Vitamin E itself provides immediate benefit to human skin, for example protection from the deleterious effects of sun, air pollutants such as ozone, and the like. However, this form of the vitamin is very unstable in aqueous compositions and is generally not used in personal care products. Various derivatives of the vitamin are more stable, particularly the esters such as Vitamin E acetate. However, these derivatives are not active until the enzymes found naturally in the skin convert the derivative, particularly esters such as Vitamin E acetate, into active Vitamin E. An antioxidant has now been discovered which brings about significantly more stabilization of Vitamin E than brought about by the usage of other known antioxidants. d. the balance water. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Composition and method for reducing the risk or progression of cardiovascular, glaucoma and tardive dyskinesia diseases Inventor(s): Lang, Philip C.; (Toms River, NJ), Sosnowski, Robert E.; (Manasquan, NJ) Correspondence: Gerald T. Bodner; Bodner & O'rourke, Llp; 425 Broadhollow Road, Suite 108; Melville; NY; 11747; US Patent Application Number: 20030220225 Date filed: June 23, 2003 Abstract: Elevated levels of homocysteine have been implicated as an important risk factor for cardiovascular and other diseases. A composition for decreasing levels of plasma homocysteine and a method for administering the composition are provided the composition containing dextromethorphan (DM), folic acid and vitamins B.sub.6 and B.sub.12. The composition provides a synergistic therapeutic effect so that lower amounts of the above ingredients may be employed to minimize any undesirable side effects caused by the use of high levels of a component such as DM. Preferred compositions for cardiovascular diseases further include lecithin, vitamin E, beta-

Patents 219

carotene, procyanidins/flavonoids, trimethylglycine, garlic oil and minerals. Other compositions for treating glaucoma include bilberry, bioflavonoids and beta-carotene and for treating tardive dyskinesia include an antioxidant such as grape seed extract and pine bark extract, lecithin and oligomeric proanthocyanidins. The compositions may be administered using any suitable means such as orally or intravenous. Excerpt(s): This application is a division of co-pending U.S. Application Ser. No. 09/845,141, filed on Apr. 30, 2001, and entitled, "Composition and Method for Reducing the Risk or Progression of Cardiovascular, Glaucoma and Tardive Dyskinesia Diseases", the disclosure of which is incorporated herein by reference. The present invention relates to a composition and method for reducing the risk or progression of cardiovascular, glaucoma and tardive dyskinesia diseases and, more particularly, to a composition containing a number of ingredients which are present in amounts lower than amounts considered harmful to the body but which act synergistically to provide enhanced disease inhibition. Cardiovascular disease is the most frequent cause of death in industrialized countries. Atherosclerosis (AS) is the principal cause of cardiovascular disease. AS is a disease of the intima of the arteries that leads to fatty lesions called artheromatous plaques on the inside surface of the arteries. This deposit of fat and cholesterol narrows the arteries, and often becomes calcified, providing sites for abnormal blood clots to form, leading to high blood pressure, heart attacks and strokes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition for topically delivering vitamin c Inventor(s): Fitzpatrick, Richard E; (Sante Fe, CA), Garruto, John A; (Encinitas, CA) Correspondence: David A Farah; Sheldon & Mak; 9th Floor; 225 South Lake Avenue; Pasadena; CA; 91101; US Patent Application Number: 20030211126 Date filed: January 10, 2003 Abstract: A composition for the topical application of vitamin C consisting essentially of one or more lipid-soluble forms of vitamin C, one or more water-soluble forms of vitamin C and one or more alpha hydroxylated acids. The composition can also include an anhydrous gel, ethoxydiglycol, a lipid-soluble analog of pro-vitamin B-5, alphaBisabolol, and one or more forms of vitamin E. A composition for the topical application of vitamin C consisting of one or more lipid-soluble forms of vitamin C, one or more water-soluble forms of vitamin C and one or more alpha hydroxylated acids. The composition can also include an anhydrous gel, ethoxydiglycol, a lipid-soluble analog of pro-vitamin B-5, alpha-Bisabolol, and one or more forms of vitamin E. Excerpt(s): This application is a national phase filing under 35 U.S.C.sctn.371 of PCT Application PCT/US01/21949, filed Jul. 12, 2001 and titled "Composition for the Topical Delivery of Vitamin C"; which claims priority from U.S. patent application Ser. No. 09/614,691, filed Jul. 13, 2000 and titled "Composition for the Topical Delivery of Vitamin C," the contents of which are incorporated herein by reference in their entirety. L-ascorbic acid, generally known as vitamin C, is an essential requirement in the diets of primates, including humans. Vitamin C is necessary for the normal synthesis of collagen. Deficiencies in vitamin C leads to impairment of peptidyl hydroxylation of procollagen and a reduction in collagen formation and collagen secretion by connective tissue. The manifestations of vitamin C deficiency include fragile capillaries leading to hemorrhages and poor wound healing. Additionally, vitamin C deficiency leads to

220

Vitamin E

atrophy of the dermis layer of the skin which causes wrinkles and wounds. Vitamin C can be taken orally. However, it is advantageous in some conditions to apply vitamin C topically to a site where connective tissue formation is needed. These conditions include evidential signs of aging such as wrinkling caused by environmental exposure such as actinic aging caused by exposure to ultraviolet radiation from the sun. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition including essential oils Inventor(s): Thrash, W. E.; (Tyler, TX) Correspondence: Ronald B. Sefrna; Sefrna & Associates; 505 South Bois D'arc; P.O. Box 567; Tyler; TX; 75710-0567; US Patent Application Number: 20030039709 Date filed: August 20, 2002 Abstract: A composition for application to the skin includes a combination of essential oils consisting essentially of sweet almond essential oil, sweet orange essential oil, and lemon essential oil, and provides unexpectedly beneficial and effective treatment results. The proportion of each essential oil within the combination of essential oils ranges between about ten percent and about ninety percent. The essential oils are preferably suspended with moisturizing agents in water by an emulsifying agent to form a lotion or gel base to facilitate application to the skin. Aloe Vera extract and vitamin E may also be added. Excerpt(s): The present invention generally relates to compositions of matter, and more specifically relates to compositions including essential oils, principally for cosmetic uses as shaving gels and lotions and skin lotions. Essential oils are natural components of plants that are well known to mankind, and have been extracted and used for centuries to provide fragrance to a wide variety of preparations and formulations, including perfumes, cosmetics, and foods. Several essential oils, specifically menthol, eucalyptus oil, camphor, peppermint oil, and wintergreen oil, are used in topical preparations for pain relief. Essential oils are used in these preparations in high concentrations, up to about 30% of the preparation. Vapors from some essential oils are believed to be beneficial when inhaled, as in "aroma therapy", for the relief of various conditions. The use of essential oils known in the prior art for cosmetic products have been primarily for the purpose of fragrance or flavor to the products, rather than for any direct effect or benefit derived from the essential oils themselves. The properties of, and attributed to, specific essential oils and various combinations of essential oils have been studied and cataloged for many years, but the vast number of possible combinations has not been fully explored. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 221

•

Cosmetic method Inventor(s): O'Prey, Conor James; (Belfast, GB), Trani, Marina; (Ascot, GB), Weisgerber, David John; (Cincinnati, OH) Correspondence: The Procter & Gamble Company; Intellectual Property Division; Winton Hill Technical Center - Box 161; 6110 Center Hill Avenue; Cincinnati; OH; 45224; US Patent Application Number: 20030211068 Date filed: March 12, 2003 Abstract: A cosmetic method for providing improved skin hydration is provided comprising the steps of topically applying to the skin a protease enzyme, and simultaneously or sequentially, topically applying to the skin a skin care active selected from a vitamin B.sub.3 component, vitamin E acetate, panthenol and mixtures thereof.Also provided is a cosmetic method for providing improved skin hydration comprising the steps of topically applying to the skin a skin care active selected from a vitamin B.sub.3 component, vitamin E acetate, panthenol and mixtures thereof, and simultaneously or sequentially, topically applying to the skin a protease enzyme. Excerpt(s): This application is a continuation of International Application No. PCT/US00/25026, filed Sep. 13, 2000. The present invention relates to the use of cosmetic compositions comprising a protease enzyme and a selected skin care active for improving skin hydration, skin softness and skin smoothness. Skin is made up of several layers of cells which coat and protect the keratin and collagen fibrous proteins that form the skeleton of its structure. The outermost of these layers, referred to as the stratum corneum, is known to be composed of 25 nm protein bundles surrounded by 8 nm thick layers. Anionic surfactants and organic solvents typically penetrate the stratum corneum membrane and, by delipidization (i.e. removal of the lipids from the stratum corneum), destroy its integrity. This destruction of the skin surface topography leads to a rough feel and may eventually permit the surfactant or solvent to interact with the keratin, creating irritation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Cover sheet for personal care products Inventor(s): Hwang, EoYeon; (Seoul, KR), Kang, EunJung; (Seoul, KR), Kim, HyungByum; (TaeJon-city, KR), Park, HyungWoo; (Kyung Ki-Do, KR) Correspondence: Kimberly-clark Worldwide, INC.; 401 North Lake Street; Neenah; WI; 54956 Patent Application Number: 20030093046 Date filed: November 14, 2001 Abstract: There is provided a liner for personal care products having a hydrophilic first apertured nonwoven layer laminated with a hydrophobic second apertured nonwoven layer. The apertures may be aligned. The first layer may, further, be made of durably hydrophilic fibers and the second of non-durably hydrophilic fibers. The liner may be made by a spunlace process. The liner may further have a treatment applied to the hydrophilic layer, where the treatment is aloe, vitamin E, mineral oil, baking soda and combinations thereof. Also provided is a pantiliner having a liquid permeable liner, a liquid impervious baffle, and an absorbent core positioned therebetween. The liner has a

222

Vitamin E

hydrophilic first apertured nonwoven layer laminated according to a spunlace process with a hydrophobic second apertured nonwoven layer. The apertures of the first layer and the second layer may be aligned. Excerpt(s): The present invention concerns liners, top sheets or cover sheets for personal care products like feminine hygiene products, diapers, training pants and the like. Liners are designed to be permeable to liquid and to be non-irritating to the skin since they are the outermost layer of a personal care product and so in contact with the wearer. Liners feel soft to the skin and allow urine and menses to penetrate quite easily. Liners have been made from various materials including nonwoven webs, apertured films, foams and combinations thereof. The nonwovens and films may be made from synthetic polymers, including polyolefins like polyethylene and polypropylene. The nonwovens may also be made from natural fibers or combinations of natural and synthetic fibers. Liners may also be made from creped materials such as creped nonwoven webs. Liners have advanced significantly over the years, though rewet of the wearer's skin and leakage, especially in the case of feminine hygiene products, remains an important issue. There remains a need, therefore, for a liner that will rapidly take in fluids like urine and menses and retard or prevent it from moving upwardly towards the wearer again. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Diclofenac pharmaceutical hyaluronidase

composition

based

on

vitamin-e,

papain

and

Inventor(s): De Nucci, Gilberto; (Sao Paulo, BR), Falci, Marcio; (Sao Paulo, BR), Santana, Cristiano A.R.; (Sao Paulo, BR) Correspondence: Larson & Taylor, Plc; 1199 North Fairfax Street; Suite 900; Alexandria; VA; 22314; US Patent Application Number: 20030103955 Date filed: November 14, 2002 Abstract: The present application refers to a new pharmaceutical composition of diclofenac comprising the following formulation: PAPAIN. 0.1 to 15%, HYALURONIDASE. 50 to 900 utr/mg, VITAMIN E. 10 to 2000 mg. Excerpt(s): The present invention relates to a new DICLOFENAC PHARMACEUTICAL COMPOSITION BASED ON VITAMIN-E, PAPAIN AND HYALURONIDASE. A Said composition is preferably of topical application, non-toxic and features a high rate of penetration through the skin. The skin permeability varies according to the region of the body, being the skin folds and the face those that present the highest absorption rate. A product applied over the skin will present a longer period of contact and percutanial absorption. According to the classic book "Histologia dos epitlios", by Walter A. Hadler and Sineli R. Silveira, Editora Campus, Campinas, 1993, it is considered that: "bearing in mind the general morphological characteristics and the specialized functions that they perform, the epitelium cells are predominantly classified into two categories, which correspond to two epitelium classes: coating epitelium cells and secreting epitelium cells. The cells of these two classes mix with each other to constitute, respectively, the coating epiteliums and the secreting epiteliums, each one of them performing specific functions that are inherent to them. Such division is also fundamented in the distribution of these two classes of epitelium in the organism, which altough wide is is distinctive for both. With the purpose of forming the coating epiteliums the epitelium

Patents 223

cells associate side-by-side, so as to originate "membranes" or layers superimposed over the base membrane, which function is to coat surfaces. On the contrary, the secreting cells unite to form organized functional units, better suited for performing their specialized function, related to the secretion products synthesys; thus are constituted the secreting units. The coating epiteliums are defined as living membranes, usually featuring a discontinuity, that isolate the organism from the environment, separating the internal media from the external one. Furthermore, these epiteliums isolate from each other the various internal media compartments, among which are the intravascular compartment, the serum compartment and several others. Among the various functions performed by the coating epiteliums some are performed by specialized variants that are specifically adapted to perform one or more functions. Others are incorporated as general functions presented without distinction by every coating epitelium cell. The coating epitelium cell, in the same way as most of the living cells, passively absorbs water and electrolytes and eliminates them actively; this function is well developed in the epitelium cells. On that account it is very important to observe that generally it is understood as absorption the penetration of solutions through the cells plasmatic membrane. However two different specific forms of absorption must be distinguished from one another: the passive absorption, that occurs according to the osmotic laws, and the active absorption, that entails the effective participation of the epitelium cell and that does not follow such physic laws. On the other hand it must be considered that every single substance that penetrates the interior of a multi-cellular organism, or else is excreted or elliminated, must cross at least one coating epitelium, because every superior organism is penetrated internally and externally by epiteliums. It must also be observed that the coating epiteliums, altough continuously covering and protecting those surfaces it coats, are not impervious at all; that is why they do not behave as inert "membranes". On the contrary, they allow for the exchange of gases, water, several kinds of electrolytes and certain other solutes between the internal and the external media, or between the various internal compartments, which characterizes its permeability. The coating epitelium cells limit in a controlled and selective way the permeability of the respective epiteliums, with the purpose of protecting the organism and still participate of the control of its homeostasis. In order to perform such function the epiteliums are organized and arrange their cells in a special form, in order to build up coatings which cells abbut the base membrane and are united with each other by means of intracellular junctions; in turn the cells are coated by the plasmatic membrane, which features special characteristics, and by the glicochalice, both able to express well defined functional properties. The functional characteristics expressed by the plasmatic membrane portion that coats the cells apical surface are different from those expressed by the portion situated in its basal or basolateral face; such differences, which occur mainly on the funsctional aspect, contribute for the remarkable degree of polarization expressed by the coating epitelium cells. The prime function performed by the coating epiteliums correspond essentialy to the protection rendered to the surface that they coat, characterizing their protective coating function. Such function features a special characteristic, being a coating that, besides offering mechanical, physical and chemical protection to the coated surface, is not inert. The coating epiteliums are pervious, which allows for the controlled and selective passage of several products through its wall. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

224

•

Vitamin E

Emulsion vehicle for poorly soluble drugs Inventor(s): Constantinides, Panayiotis P.; (Bothell, WA), Lambert, Karel J.; (Woodinville, WA), Quay, Steven C.; (Edmonds, WA) Correspondence: Christensen, O'connor, Johnson, Kindness, Pllc; 1420 Fifth Avenue; Suite 2800; Seattle; WA; 98101-2347; US Patent Application Number: 20030104015 Date filed: May 17, 2002 Abstract: An emulsion of.alpha.-tocopherol, stabilized by biocompatible surfactants, as a vehicle or carrier for therapeutic drugs, which is substantially ethanol free and which can be administered to animals or humans various routes is disclosed. Also included in the emulsion is PEGylated vitamin E. PEGylated.alpha.-tocopherol includes polyethylene glycol subunits attached by a succinic acid diester at the ring hydroxyl of vitamin E and serves as a primary surfactant, stabilizer and a secondary solvent in emulsions of.alpha.-tocopherol. Excerpt(s): This application is a non-provisional application based on U.S. Provisional Application No. 60/034,188 filed Jan. 7, 1997 and U.S. Provisional Application No. 60/048,840 filed Jun. 6, 1997. Hundreds of medically useful compounds are discovered each year, but clinical use of these drugs is possible only if a drug delivery vehicle is developed to transport them to their therapeutic target in the human body. This problem is particularly critical for drugs requiring intravenous injection in order to reach their therapeutic target or dosage but which are water insoluble or poorly water soluble. For such hydrophobic compounds, direct injection may be impossible or highly dangerous, and can result in hemolysis, phlebitis, hypersensitivity, organ failure and/or death. Such compounds are termed by pharmacists "lipophilic", "hydrophobic", or in their most difficult form, "amphiphobic". A few examples of therapeutic substances in these categories are ibuprofen, diazepam, griseofulvin, cyclosporin, cortisone, proleukin, etoposide and paclitaxel. Kagkadis, KA et al. (1996) PDA J Pharm Sci Tech 50(5):317-323; Dardel, O 1976. Anaesth Scand 20:221-24. Sweetana, S and MJU Akers. (1996) PDA J Pharm Sci Tech 50(5):330-342. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Emulsion vehicle for poorly soluble drugs Inventor(s): Lambert, Karel J.; (Woodinville, WA), Quay, Steven C.; (Edmonds, WA), Tustian, Alexander K.; (Bothell, WA) Correspondence: Christensen, O'connor, Johnson, Kindness, Pllc; 1420 Fifth Avenue; Suite 2800; Seattle; WA; 98101-2347; US Patent Application Number: 20030109575 Date filed: June 28, 2002 Abstract: An emulsion of tocopherol incorporating a co-solvent and, stabilized by biocompatible surfactants, as a vehicle or carrier for therapeutic drugs, which is substantially ethanol free and which can be administered to animals or humans by various routes is disclosed. Also included in the emulsion is PEGylated vitamin E. PEGylated.alpha.-tocopherol includes polyethylene glycol subunits attached by a succinic acid diester at the ring hydroxyl of vitamin E and serves as a primary surfactant, stabilizer and a secondary solvent in emulsions of.alpha.-tocopherol.

Patents 225

Excerpt(s): This application is a continuation-in-part application of U.S. application Ser. No. 09/003,173 filed Jan. 5, 1998 which claims the benefit under 35 U.S.C.sctn.119(e) of U.S. provisional application No. 60/048,840 filed Jun. 6, 1997 and U.S. provisional application No. 60/034,188, filed Jan. 7, 1997. This invention is in the field of pharmaceutical agents. In particular, this invention relates to pharmaceutical agents wherein tocopherol is used as a primary solvent. Hundreds of medically useful compounds are discovered each year, but clinical use of these drugs is possible only if a drug delivery vehicle is developed to transport them to their therapeutic target in the human body. This problem is particularly critical for drugs requiring intravenous injection in order to reach their therapeutic target or dosage but which are water insoluble or poorly water soluble. For such hydrophobic compounds, direct injection may be impossible or highly dangerous, and can result in hemolysis, phlebitis, hypersensitivity, organ failure and/or death. Such compounds are termed by pharmacists "lipophilic", "hydrophobic", or in their most difficult form, "amphiphobic". Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Fenofibrate galenic formulations and method for obtaining same Inventor(s): Blouquin, Pascale; (Talant, FR), Lemut, Josiane; (Dijon, FR), Reginault, Philippe; (Fontaine-Les-Dijon, FR) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20030082215 Date filed: June 19, 2002 Abstract: The present invention relates to a pharmaceutical composition for the oral administration of fenofibrate in the form of a preconcentrate capable of forming an oilin-water microemulsion spontaneously on contact with an aqueous medium, of the type comprising:a lipophilic phase preferably comprising an oil based on glycerol or propylene glycol esters; andan emulsifying system comprising:a lipophilic surfactant; anda hydrophilic co-surfactant.According to the invention, this composition is characterized in that it also comprises vitamin E acetate in a sufficient amount to stabilize said preconcentrate without the incorporation of an additional hydrophilic component, and makes it possible to prepare novel drugs in the form of sealed gelatin capsules or soft capsules. Excerpt(s): The present invention relates to novel galenical fenofibrate formulations for oral administration, to the process for their preparation and to the drugs manufactured from these formulations. Fenofibrate (INN) is a medicinal active principle which has been known for many years for its efficacy in lowering blood triglyceride and cholesterol levels. Thus fenofibrate is widely prescribed in numerous countries when it is necessary to reduce the risk of atherogenesis. It is also known that, to obtain a satisfactory hypocholesterolemic effect, it is desirable to maintain a blood level of fenofibric acid (which is the active metabolite of fenofibrate) in the order of 6 to 10 mg/l. Such a level is obtained particularly with a unit dose of 300 mg of fenofibrate in gelatin capsule form (cf. Drugs 40 (2) pp. 260-290 (1990)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

226

•

Vitamin E

Fortified drinking water Inventor(s): Marcano, Adrian Monsalve; (Caracas, VE), Mehansho, Haile; (Fairfield, OH), Mellican, Renee Irvine; (Bradenton, FL), Nunes, Raul Victorino; (Loveland, OH) Correspondence: The Procter & Gamble Company; Intellectual Property Division; Winton Hill Technical Center - Box 161; 6110 Center Hill Avenue; Cincinnati; OH; 45224; US Patent Application Number: 20030049352 Date filed: May 16, 2002 Abstract: A drinking water composition fortified with minerals and/or vitamins, including iron and zinc, having clarity, color and flavor improvements. The drinking water contains at least 5 ppm of a bioavailable iron compound which is stable to oxidation in the drinking water composition, without the need for excessive amounts of reducing agents or for fruit and/or botanical flavors and colorants to mask the metal taste or after-taste of the iron. Vitamins such as the B vitamins, vitamin A, vitamin C, and vitamin E can optionally be added to the drinking water. A method is disclosed for fortifying the drinking water with certain bioavailable zinc and iron compounds without producing undesirable clarity, color or metal taste or after-taste. Excerpt(s): This application claims priority to Provisional Application Serial No. 60/294,760, filed May 31, 2001. The present invention relates to drinking water compositions supplemented with iron or zinc compounds, or mixtures of iron and zinc compounds that have excellent bioavailability. The drinking water containing the iron and zinc compounds does not have an off-flavor/aftertaste, is stable, and overcomes the problem of discoloration caused by the addition of these minerals to water. The compositions can also include optionally other minerals, vitamins, and other nutrients. The present invention further relates to packaged drinking water, preferably made from oxygen-barrier materials to ensure the stability of the mineral-fortified drinking water. The present invention further relates to a method of making the drinking water fortified with iron and zinc that avoids objectionable color, taste, and precipitates in the water. In many countries, the average diet does not contain sufficient levels of iron, zinc, iodine, vitamin A or the B vitamins. Iron deficiency is well documented. Although iron deficiency is one of the few nutritional deficiencies in the U.S., it is common in most developing countries. Recent evidence suggests that nutritional zinc deficiency may be common among the people of many developing countries where they subsist on diets of plant origin (e.g. cereal and legume). Marginal zinc deficiency may be widespread even in the U.S. because of self-imposed dietary restrictions, use of alcohol and cereal proteins, and the increasing use of refined foods that decrease the intake of trace minerals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Improved method for the biosynthesis of vitamin e Inventor(s): Ebneth, Marcus; (Berlin, DE), Geiger, Michael; (Quedlinburg, DE), Kunze, Irene; (Gatersleben, DE) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20030182679 Date filed: March 11, 2003

Patents 227

Abstract: The invention relates to improved processes for the biosynthesis of vitamin E. These processes comprise inhibiting the breakdown of homogentisate via maleyl acetoacetate and fumaryl acetoacetate to give fumarate and acetoacetate. Also in accordance with the invention is the combination of this inhibition with processes which increase the supply of homogentisate, or which promote the conversion of homogentisate into vitamin E.According to the invention are nucleic acid constructs and vectors with which the processes according to the invention can be carried out, and transgenic plant organisms generated on the basis of this. Excerpt(s): The invention relates to improved processes for the biosynthesis of vitamine E. These processes are characterized by inhibiting homogentisate (HG) breakdown via maleyl acetoacetate (MAA), fumaryl acetoacetate (FAA) to give fumarate and acetoacetate. Also in accordance with the invention is the combination of this inhibition with processes which further increase the supply of homogentisate, or which promote the conversion of homogentisate into vitamin E. Homogentisate is an important metabolite. It is a degradation product of the amino acids tyrosine and phenylalanine. In humans and animals, homogentisate is broken down further to maleyl acetoacetate, subsequently to fumaryl acetoacetate and then into fumarate and acetoacetate. Plants and other photosynthesizing microorganism furthermore utilize homogentisate as starting material for the synthesis of tocopherols and tocotrienols. For the purposes of the present invention, vitamin E is to be understood as meaning all of the eight abovementioned tocopherols and tocotrienols with vitamin E activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Insect repellent comprising essential volatile oils and use thereof Inventor(s): Willis, Mark T.; (Goetzville, MI) Correspondence: Mark T. Willis; 12941 E. Townline Road; Goetzville; MI; 49736; US Patent Application Number: 20030108582 Date filed: December 10, 2001 Abstract: A composition that has insect repellent properties is made from essential volatile oils. The inventive composition includes a combination of menthol, eucalyptus oil, citronella oil and/or tea tree oil, alcohol, water and skin moisturizing components. Menthol in crystal or liquid form. Essential oil of eucalyptus. Essential oil of citronella and/or tea tree oil. Isopropyl alcohol, grain alcohol or any other type of distilled alcohol. Deionized, distilled or any other type of sterile water. Skin conditioning oils including but not limited to mineral oil, jojoba oil, glycerin, Vitamin E. The topical composition can be formulated as a solution, suspension, cream, ointment, gel, film or spray. Excerpt(s): The present invention relates generally to a composition for use in repelling insects and more specifically it relates to a non-toxic insect repellent composition using only naturally occurring insect repellent components. Insect repellents have been used for centuries to prevent insect pests from bothering and annoying humans and animals. Some examples of known repellents include citronella candles made from the essential oil of citronella. In the past century, synthetic chemicals have been designed and developed that more effectively repel insects. Included in these newer synthetic compounds are 2-ethyl-3-hexanediol, (DDT) and N,N-diethyl toluamide, (DEET). However, most synthetic chemical compound repellents, when absorbed through the skin or somehow ingested are toxic as in the ban of the insecticide DDT which was shown to be harmful to the environment by poisoning wildlife, and DEET is suspected

228

Vitamin E

to be a carcinogen, teratogen and or mutagen. Therefore, some states and federal regulations limit the percentage of DEET to 10% to 30%, which may be used in compositions for children, adults and animals use. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Intermediates for use in the preparation of vitamin e Inventor(s): Ancel, Jean-Erick; (Saint Genis Laval, FR), Meilland, Pierre; (Chaponost, FR) Correspondence: Oliff & Berridge; PO Box 19928; Alexandria; VA; 22320; US Patent Application Number: 20030166950 Date filed: March 18, 2003 Abstract: Novel intermediate compounds which can be used in the preparation of phytone and Vitamin E and a process for the preparation thereof. A process for the preparation of phytone and Vitamin E from these compounds is also claimed. Excerpt(s): The present invention relates to a process for the preparation of intermediate compounds useful in the preparation of phytone and/or Vitamin E. Vitamin E has been prepared chemically for a long time using many various processes. In general, this vitamin is prepared from an intermediate compound. European Patent 0544588 discloses a process for the production of Vitamin E through the condensation of a polyunsaturated allyl alcohol derivative. U.S. Pat. No. 3,867,408 discloses the preparation of novel ketal compounds which may be used in the preparation of phytone which in turn is an intermediate in the production of Vitamin E. We have now found a new process for the preparation of certain beta olefinic compounds which can be used to synthesise phytone and in some cases which can be used to synthesise vitamin E directly from this intermediate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Method of treatment Inventor(s): Hedman, Christer; (Molnlycke, SE), Karnerud, Lars; (Tenhult, SE), Winter, Kaj; (Copenhage, DK) Correspondence: Browdy And Neimark, P.L.L.C.; 624 Ninth Street, N.W.; Washington; DC; 20001; US Patent Application Number: 20030161890 Date filed: June 28, 2002 Abstract: A method for the treatment of disorders related to normal hormonal variations in women during fertile, peri- and post-menopausal age, by the administering of a composition comprising, as active ingredients, a water and/or fat-soluble cytosolic extract of pollen and optionally pistils, optionally combined with Royal Jelly and vitamin E. Excerpt(s): The invention relates in a first aspect to a method for the treatment of disorders related to normal hormonal variations in women during fertile as well as, peri- and post-menopausal age, by the administering of a composition comprising, as active ingredients, a water- and/or fat-soluble cytosolic extract of pollen and optionally pistils. The invention, in another aspect, relates to a composition comprising, as active

Patents 229

ingredients, a water- and/or fat-soluble cytosolic extract of pollen and optionally pistils for the treatment of disorders relating to normal hormonal variations in women during fertile, as well as peri- and post-menopausal age. Disorders relating to normal variation of the sex hormone cycle of women of fertile age are tension, irritability, dysphoria, abdominal distension or bloatedness, severe breast tension, headache or migraine, edema, weight changes, sleep disturbances etc. The overall well being as well as the social and professional life may be influenced. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for administration of paclitaxel Inventor(s): Joshi-Hangal, Rajashree; (Union City, CA), Rubinfeld, Joseph; (Danville, CA), Sands, Howard; (Wilmington, DE) Correspondence: Wilson Sonsini Goodrich & Rosati; 650 Page Mill Road; Palo Alto; CA; 943041050 Patent Application Number: 20030191179 Date filed: January 23, 2003 Abstract: Methods are provided for using paclitaxel for treating diseases associated with abnormal cell proliferation and angiogenesis. In particular, methods are provided for administration of paclitaxel formulated with vitamin E derivatives such as d-.alpha.tocopherol polyethylene glycol succinate to a cancer patient. By administering to a patient paclitaxel in a vehicle containing a solubilizer other than Cremophor, acute hypersensitivity caused by Cremophor can be avoided and therapeutic index of paclitaxel may also be increased through potentiation of anti-neoplastic effects by the vitamin E derivatives. Excerpt(s): This is a continuation-in-part of U.S. Application entitled "Paclitaxel Formulation", Ser. No. 09/948,133, filed Sep. 5, 2001, which is a continuation of U.S. Application entitled "Oral Formulation For Paclitaxel", Ser. No. 09/665,890, filed Sep. 20, 2000, now U.S. Pat. No. 6,319,943, which is a continuation of U.S. Application entitled "Formulation For Paclitaxel", Ser. No. 09/427,153, filed Oct. 25, 1999, now U.S. Pat. No. 6,136,846. Theses applications are hereby incorporated by reference. This invention relates to compositions that may be used as pharmaceutical compositions, methods and kits, more particularly to improved pharmaceutical formulations for paclitaxel that include vitamin-E derivatives. Paclitaxel is a unique diterpene anticancer compound derived from the bark of the Taxus brevifolia (Pacific yew) tree. A crude extract of the bark demonstrated antineoplastic activity in preclinical tumor screening 30 years ago as part of the National Cancer Institute's (NCI's) large-scale screening program. The active component of the extract, paclitaxel, was isolated and described by M. C. Wani et al, Plant antitumor agents, VI: The isolation and structure of Paclitaxel, a novel antileukemic and antitumor agent from Taxus brevifolia, J. Am. Chem. Soc. 93:2325-2327 (1971). This document, and all others referred to herein, are incorporated by reference as if reproduced fully below. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

230

•

Vitamin E

Methods for improving conifer embryogenesis Inventor(s): Pullman, Gerald S.; (Alpharetta, GA) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030153080 Date filed: January 27, 2003 Abstract: The present invention provides methods for initiating, capturing, maintaining and multiplying embryogenic cultures of coniferous plants. Methods include the use of novel media compositions containing Vitamin B.sub.12, Vitamin E, or organic acids including.alpha.-ketoglutaric acid, pyruvic acid, or p-aminobenzoic acid to improve the frequency of embryogenic tissue initiation, capture, maintenance and multiplication. The methods are well suited for initiating embryogenic cultures in recalcitrant conifer varieties. The method is also well suited for producing somatic embryos that can be further cultured to produce large numbers of plants. Further, the invention provides novel methods that may be used to enhance somatic embryogenesis in a broad range of species. Excerpt(s): This patent application claims benefit of priority of provisional application U.S. Ser. No. 60/350,944, filed Jan. 25, 2002. The present invention is directed to methods for improved somatic embryogenesis in conifers and, particularly, in loblolly pine. Methods and compositions of media are provided for promoting initiation of conifer explants, improving maintenance and increasing the yield of conifer embryo multiplication. The methods comprise providing culture medium supplemented with vitamin B.sub.12, vitamin E, the K&M vitamin mixture, organic acids, such as, for example, TCA cycle acids and p-aminobenzoic acids, or a combination of these vitamins and acids. The methods are also useful for more efficient capture of previously initiated embryogenic tissue. Implementation of clonal tree production is a major step that will be taken by the forest products industry in coming years. Clonal deployment of advance generation selections is expected to increase forest productivity by some 10% to 20% and increase uniformity of the fiber output (Libby et al., For. Chron. 60:145-149 (1984)). Significant economic and biological barriers exist to large-scale clonal propagation and plantation of softwood trees (Stelzer et al., Can. J. For. Res. 27:442-446 (1997)). For many softwood trees including loblolly pine, somatic embryogenesis is the most promising method to overcome these barriers (Cheliak et al., Can. J. For. Res. 20:452-463 (1990)). Somatic embryogenesis is widely used in a variety of plant species to produce multiple copies of genetically identical organisms. Somatic embryogenesis is becoming the method of choice for clonal propagation of spruce. However, for loblolly pine, the most important species in the United States, somatic embryogenesis has lagged behind. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Multiple antioxidant micronutrients Inventor(s): Haase, Gerald M.; (Greenwood Village, CO), Prasad, Kedar N.; (Denver, CO) Correspondence: Ostrolenk, Faber, Gerb & Soffen, Llp; 1180 Avenue OF The Americas; New York; NY; 10036-8403; US Patent Application Number: 20030147996 Date filed: August 28, 2002

Patents 231

Abstract: A method for optimizing the health of humans according to their age and sex is disclosed wherein the method comprises administering to said humans a daily dose of a multiple antioxidant micronutrient composition comprising vitamin A (palmitate), beta-carotene (from natural d. salina), vitamin C (calcium ascorbate), vitamin D-3 (cholecalciferol), natural source vitamin E including both d-alpha tocopherol and dalpha tocopheryl acid succinate, thiamine mononitrate, riboflavin, niacinamide ascorbate, d-calcium pantothenate, pyridoxine hydrochloride, cyanocobalamin, folic acid (folacin), d-biotin, selenium (l-seleno methionine), chromium picolinate, zinc glycinate, calcium citrate, and magnesium citrate.For persons over the age of about 51, the composition preferably further comprises one or more of co-enzyme Q.sub.10, Nacetyl cysteine, and alpha lipoic acid. Preferably, also, vitamin D is added for women over the age of about 36. Excerpt(s): We claim the benefit under Title 35, United States Code,.sctn.120 of U.S. Provisional Application No. 60/315,523, filed Aug. 29, 2001, entitled MULTIPLE ANTIOXIDANT MICRONUTRIENTS FOR OPTIMAL HEALTH. In the beginning, the earth's atmosphere had no oxygen. Anaerobic organisms, which can live without oxygen, were thriving. About 2.5 billion years ago, blue-green algae in the ocean acquired the ability to split water into hydrogen and oxygen and this chemical reaction initiated the release of oxygen into the atmosphere. The increased levels of atmospheric oxygen caused extinction of many anaerobic organisms owing to oxygen's toxicity. This important biological event also led to the evolution of multicellular organisms, including humans, who utilize oxygen for survival. The content of oxygen in the air gradually increased to the current amounts of about 21 percent in dry air and about 34 percent in water. The use of oxygen by any organism generates free radicals that are toxic. Therefore, during this period of atmospheric oxygenation, organisms must have struggled to survive the sudden exposure to oxygen toxicity. There must have been enormous rearranging of nucleotides in genes to produce specific proteins that could protect organisms against the damage produced by free radicals. This process eventually led to the production of three antioxidant enzymes. Superoxide dismutase (SOD) requires manganese, copper, or zinc for its biological activity. Mn-SOD is present in mitochondria, whereas Cu-SOD and Zn-SOD are present in the cytoplasm and nucleus of the cell. All three can destroy free radicals and hydrogen peroxide. Another enzyme, catalase, requires iron for its biological activity and it destroys H.sub.2O.sub.2 in cells. Human tissue also contains glutathione peroxidase which requires selenium for its biological activity. It is also responsible for removing hydrogen peroxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Multi-vitamin and hormone replacement supplement Inventor(s): Fox, Dorothy Jean; (Chesapeake, VA), Schloss, Caroline Maxine; (Knotts Island, NC) Correspondence: Kimberly A Chasteen; Williams Mullen Clark & Dobbins; One Iod Oyster Point Road; Suite 210; Newport News; VA; 23602 Patent Application Number: 20030096018 Date filed: September 23, 2002 Abstract: A supplement is disclosed for use by naturally or surgically menopausal women. The supplement includes: Estrogen, Selenium, Zinc, Chromium, Calcium, Copper, Phosphorus, Magnesium, Molybdenum, Iodine, Beta Carotene, Ascorbic Acid, Vitamin D, Vitamin E, Vitamin K, Thiamin, Riboflavin, Vitamin B6, Vitamin B12, Folic

232

Vitamin E

Acid, Iron, Pantothenic Acid, and Biotin. The supplement provides hormone replacement therapy along with nutritional supplements. Excerpt(s): The present invention relates generally to a pharmaceutical supplement for menopausal women and more specifically to a pharmaceutical supplement which combines the hormone estrogen with daily supplemental vitamins to treat menopausal women and women who have undergone complete hysterectomies as more fully set forth in the below specifications, drawings and claims. It is well known that estrogen is critical to a woman's health in that it helps to protect the cardiovascular system, helps protect against bone loss and aids mental sharpness. At menopause or subsequent to a complete hysterectomy, the estrogen levels decline significantly thus, the protective aspects of estrogen are significantly reduced for these women. Because heart disease is a major cause of death in women, this creates an increased risk for menopausal and posthysterectomy women. Further, loss of the protection against bone loss can lead to osteoporosis, another major problem for these women. The impairment of cognitive abilities can be another side effect of the significant estrogen loss suffered in menopause or post-hysterectomy. Additional side effects have been linked to reduced estrogen levels such as urinary incontinence and weight gain. Many women are treated with hormone replacement therapy to help reduce these symptoms. The treatment generally consists of supplemental estrogen. This reduces the problems noted above, heart disease, bone loss, loss of cognitive ability, urinary incontinence, weight gain, as well as other well-known symptoms such as hot flashes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Natural therapeutic composition for the treatment of wounds and sores Inventor(s): Harrison, Dorothy; (Strathmore, CA), Harrison, Ernest; (Strathmore, CA) Correspondence: Thomas E. Malyszko; Suite 1500; 250 - 6 Avenue, S.W.; Calgary; T2p 3h7; CA Patent Application Number: 20030072828 Date filed: July 5, 2002 Abstract: A therapeutic composition comprised of natural ingredients, namley quantities of Vitamin A, Vitamin E, Evening Primrose Oil and Mineral Oil, utilized with or without a suitable carrier, to safely and effectively sooth inflammation, ease pain, and promote the natural healing process of wounds and sores, particularly bed sores, and in the treatment of diseases, particularly psoriasis and ezcema.More specifically, the invention, in one of its preferred embodiments, is a composition comprised of a combination of Vitamin A, Vitamin E, Evening Primrose Oil and Mineral Oil is specific quantities, to be applied topically or orally, particularly to bed sores, to reduce inflamation, ease pain, and assist the healing process of such wounds, sores and diseases. A quantity of Vitamin C and other natural ingredients may also be added to the composition with complimentary effects and with or without a carrier such as Petroleum Jelly in topical applications. Excerpt(s): This invention relates to a therapeutic composition for the treatment of wounds, sores, and diseases. Studies have shown that Vitamin A plays a role in the maintenance of skin; that Vitamin C helps fight infections, promotes the healing of cuts, abrasions and wounds and is required to maintain structural and functional integrity of cell walls and small blood vessels; that Vitamin E helps preened oxidation of fatty acids present in the membrane of all cells; that Evening Primrose Oil has anti-inflammatory

Patents 233

and pain relieving effects; that Mineral Oil may be used to cleanse the skin; and that petroleum jelly may be used as a carrier for topical compositions. The prior art relevant to this invention consists of various wound healing and anti-inflammatory compositions comprised of one or a few of the above ingredients and other herbal, vitamin and chemical mixtures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Natural vegetable oil concentrated in unsaponifiable matters as food ingredient Inventor(s): Kohler, Carole; (Paris, FR), Msika, Philippe; (Paris, FR), Piccirilli, Antoine; (Versailles, FR) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030108650 Date filed: December 18, 2002 Abstract: The invention concerns a natural vegetable oil selected among palm oil, corn germ oil, sunflower oil and canola oil, concentrated in unsaponifiable matters, such that said oil unsaponifiable matter content is 3 to 15 % m/m. Said concentrated natural vegetable oil constitutes a novel food ingredient enriched in particular in vitamin E and phytosterol, useful as favoured food source in vitamin E and phytosterol, meeting recommended daily intake. Excerpt(s): The present invention relates to a natural plant oil concentrated in its unsaponifiable fraction, as a food ingredient, to a food composition or a food supplement comprising said concentrated plant oil, and to a process for preparing this oil. Plant oils and food compositions or food supplements comprising these concentrated plant oils are used, for the purposes of the present invention, for dietary, nutritional and cosmetic purposes. The present invention also relates to an oral cosmetic treatment method, in particular for improving the appearance of the skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

NON-SURGICAL METHOD FOR BREAST AUGMENTATION Inventor(s): GIAKOUMAKIS, MARIANTHI; (MONTREAL, CA) Correspondence: Douglas R Hanscom; Jones Tullar & Cooper; P O Box 2266 Eads Station; Arlington; VA; 22202 Patent Application Number: 20030177089 Date filed: June 16, 1997 Abstract: Breast augmentation usually involves a surgical procedure. A non-surgical method for breast augmentation involves the use of cocoa butter and Vitamin E, either subsequently to each other or in combination. Excerpt(s): The present invention relates to a method for breast augmentation, and in particular to a non-surgical method for breast augmentation. Breast augmentation is a growing industry. In the United States alone, it is estimated that each year over one million women undergo surgery for breast enlargement. The most commonly used procedure for breast augmentation is mammaplastry, which is, surgical augmentation of

234

Vitamin E

the breasts. This procedure generally involves making a surgical incision to create a pocket in the breast followed by insertion of a mammary prosthesis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nucleic acid sequences to proteins involved in tocopherol synthesis Inventor(s): Lassner, Michael W.; (Davis, CA), Mitsky, Timothy; (Maryland Heights, MO), Post-Beittenmiller, Martha Ann; (Manchester, MO), Savidge, Beth; (Davis, CA), Weiss, James D.; (Kirkwood, MO) Correspondence: Renessen Llc; IP Legal Department; Suite 300 South; 3000 Lakeside Drive; Bannockburn; IL; 60015; US Patent Application Number: 20030170833 Date filed: January 23, 2003 Abstract: Nucleic acid sequences and methods are provided for producing plants and seeds having altered tocopherol content and compositions. The methods find particular use in increasing the tocopherol levels in plants, and in providing desirable tocopherol compositions in a host plant cell. Excerpt(s): This application claims the benefit of the filing date of the provisional Application U.S. Serial No. 60/129,899, filed Apr. 15, 1999, and the provisional Application, U.S. Serial No. 60/146,461, filed Jul. 30, 1999. The present invention is directed to nucleic acid and amino acid sequences and constructs, and methods related thereto. Isoprenoids are ubiquitous compounds found in all living organisms. Plants synthesize a diverse array of greater than 22,000 isoprenoids (Connolly and Hill (1992) Dictionary of Terpenoids, Chapman and Hall, New York, N.Y.). In plants, isoprenoids play essential roles in particular cell functions such as production of sterols, contributing to eukaryotic membrane architecture, acyclic polyprenoids found in the side chain of ubiquinone and plastoquinone, growth regulators like abscisic acid, gibberellins, brassinosteroids or the photosynthetic pigments chlorophylls and carotenoids. Although the physiological role of other plant isoprenoids is less evident, like that of the vast array of secondary metabolites, some are known to play key roles mediating the adaptative responses to different environmental challenges. In spite of the remarkable diversity of structure and function, all isoprenoids originate from a single metabolic precursor, isopentenyl diphosphate (IPP) (Wright, (1961) Annu. Rev. Biochem. 20:525-548; and Spurgeon and Porter, (1981) in Biosynthesis of Isoprenoid Compounds., Porter and Spurgeon eds (John Wiley, New York) Vol. 1, pp 1-46). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

NUTRACEUTICAL COMPOSITION Inventor(s): Cartwright, Rudolph; (Odessa, TX), Hendricks, Leo Edward; (Washington, DC) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030091552 Date filed: November 13, 2001 Abstract: Provided is a nutraceutical composition including a tripeptoid component, a flavonoid component, guanidine hydrochloride,.alpha.-lipoic acid, an amino acid

Patents 235

component, a brazilin component, catalase, and, optionally, vitamin E ans selenium. The composition is effective to maintain normal blood sugar levels and normal levels of nonenzymatic protein glycosylation in a human. Excerpt(s): The present invention relates to a nutraceutical composition and a method for maintaining normal levels of blood sugar and normal levels of non-enzymatic protein glycosylation. U.S. Pat. No. 5,156,852 teaches that a composition containing both selenium and vitamin E is useful in treating macular degeneration. U.S. Pat. No. 5,405,613 teaches vitamin and mineral compositions that include bioflavonoids for restoring energetic balance or intensity. Administration of glutathione in combination with vitamin E and selenium has been taught to reduce hematological toxicities in patients undergoing radiation therapy. See U.S. Pat. No. 5,639,482. U.S. Pat. No. 5,976,568 teaches that the bioflavonoid quercetin can inhibit the enzyme cyclooxygenase and U.S. Pat. No. 6,190,678 teaches a personal care product (skin cleaner) containing, inter alia, brazilin, rutin, glutathione, and.alpha.-lipoic acid. Vitamin E and.alpha.-lipoic acid are taught as components of a multicomponent supplement, that also includes aspirin and magnesium salts, for the treatment and control of diabetes. See U.S. Pat. No. 5,976,568. Applicant is the first to recognize that a bioflavonoid such as quercetin or rutin can be combined with brazilin,.alpha.-lipoic acid, and other substances to produce a composition that, when administered to a mammal, is effective to promote normal levels of non-enzymatic protein glycosylation in that mammal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nutritional composition Inventor(s): Anantharaman, Helen Gillian; (Bridgewater, CT), Fuchs, Eileen C.; (Gaylordsville, CT), Garcia-Rodenas, Clara L.; (Forel, CH), Guigoz, Yves; (Epalinges, CH), Leathwood, Peter; (Blonay, CH), Mallangi, Chandrasekhara R.; (New Milford, CT), Reiffers-Magnani, Kristel; (La Tour-de-Peilz, CH), Turini, Marco; (Epalinges, CH) Correspondence: Robert M. Barrett, ESQ.; Bell, Boyd & Lloyd; P.O. Box 1135; Chicago; IL; 60690-1135; US Patent Application Number: 20030202992 Date filed: May 13, 2003 Abstract: A composition for a nutritional supplement for convalescing patients recovering from illness or surgery, those with limited appetite such as the elderly, children or anorexic patients, or those who have impaired ability to digest other sources of protein such as persons having chronic gastritis who have a reduced gastric pepsin digestion. The supplement comprises: (i) a protein source which provides at least about 8% total calories of the composition and which includes at least about 50% by weight whey protein; (ii) a lipid source having an omega 3:6 fatty acid ratio of about 5:1 to about 10:1 and which provides at least about 18% total calories of the composition; (iii) a carbohydrate source; and (iv) a balanced macronutrient profile comprising at least vitamin E and vitamin C. The supplement has reduced capacity to induce satiety. Also disclosed are a method of production of the composition; use of the composition in the manufacture of a functional food or medicament; and a method of treatment which comprises administering an effective amount of the composition. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/227,117 filed on Aug. 22, 2000. The present invention relates to a composition for a nutritional supplement; a method of production of the composition; use of the

236

Vitamin E

composition in the manufacture of a functional food or medicament for the nutrition, prevention or treatment of convalescing patients recovering from illness or surgery, those with limited appetite such as the elderly, or anorexic patients, or those who have impaired ability to digest other sources of protein such as persons having chronic gastritis who have a reduced gastric pepsin digestion; and a method of providing nutrition or treatment which comprises administering an effective amount of the composition. Many people do not take in sufficient nutrients for a nutritionally complete diet. In order to assist these people, nutritional supplements have been developed. Nutritional supplements are usually not intended to provide all the nutrients necessary for a nutritionally complete diet; instead they are generally intended to supplement the diet such that it becomes more nutritionally complete. However, in some instances they may provide complete nutrition. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for the preparation of vitamin E Inventor(s): Dhainaut, Jildaz; (Lyon, FR), Durand, Thierry; (Ecully, FR) Correspondence: Connolly Bove Lodge & Hutz Llp; 1220 Market Street; P.O. Box 2207; Wilmington; DE; 19899; US Patent Application Number: 20030153772 Date filed: December 19, 2002 Abstract: The invention concerns a novel method for preparing vitamin E. More particularly, it concerns a novel method for the condensation of Arimethylhydroquinone and isophytol. Excerpt(s): The present invention relates to a novel process for the preparation of vitamin E. It relates more particularly to a novel process for the condensation of trimethylhydroquinone and isophytol. It is known, for example according to Japanese Patents No. 60064977, No. 53144574 and No. 53015381, to condense isophytol with trimethylhydroquinone in the presence of a Lewis acid, restricted to zinc chloride, in the presence of an inorganic acid chosen from halogenated acids and polyphosphoric acid in a solvent composed of methylene chloride and acetic acid. It is also known, from Japanese Patents No. 59190987 and No. 48072168, to condense trimethylhydroquinone with isophytol in the presence of a catalyst based on zinc chloride and of an acid chosen from hydrochloric acid or trichloroacetic acid; the reaction being carried out in a solvent composed of an acetyl ester and in particular of isopropyl acetate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Riluzole and alpha-tocopherol combination Inventor(s): Dib, Michel; (Paris, FR) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206; Mail Code: D303a; Bridgewater; NJ; 08807; US Patent Application Number: 20030125363 Date filed: February 18, 2003

Patents 237

Abstract: The invention concerns a combination of alpha-tocopherol and riluzole or a pharmaceutically acceptable salt thereof and the use of said combination for treating amyotrophic lateral sclerosis. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/854,318, filed May 11, 2001, now allowed, which is a continuation of International application No. PCT/FR99/02,753, filed Nov. 9, 1999; which claims the benefit of priority of French Patent Application No. 98/14,250, filed Nov. 13, 1998. The present invention relates to the combination of.alpha.-tocopherol and of riluzole or of a pharmaceutically acceptable salt of this compound and the use of this combination for the treatment of amyotrophic lateral sclerosis (ALS). Amyotrophic lateral sclerosis, also known by the name of CHARCOT's disease and LOU GEHRIG's disease, was described for the first time by CHARCOT in 1865. ALS is a fatal disease resulting from degeneration of the motoneurons. The disease is accompanied by progressive paralysis, leading to the loss of motor and respiratory functions and then to death within a period of two to eight years after the appearance of the first symptoms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Sports drink composition for enhancing glucose uptake into the muscle and extending endurance during physical exercise Inventor(s): Portman, Robert; (Woodbridge, NJ) Correspondence: Ezra Sutton, P.A.; Plaza 9, 900 Route 9; Woodbridge; NJ; 07095; US Patent Application Number: 20030064135 Date filed: October 29, 2002 Abstract: The present invention provides for a nutritional composition in a dry powder form or a liquid drink form for optimizing muscle performance during exercise. The dry nutritional composition includes carbohydrate and protein in a ratio, in the range of 2.54.2 parts of the carbohydrate to 1.0 part of the protein. One or more carbohydrates are sugars in the range of 70.65% to 78.24% by weight of the dry composition wherein the carbohydrates are a mixture of high and low glycemic sugars. One or more proteins are in the range of 15.80% to 21.90% by weight of the dry composition. The dry nutritional composition further includes a first vitamin being Vitamin C in the range of 0.28% to 0.42% of the dry composition for use as an antioxidant for preventing free radical formation during exercise and includes a second vitamin being Vitamin E in the range of 0.28% to 0.42% of the dry composition for use as an antioxidant for preventing free radical formation during exercise. The dry nutritional composition also includes electrolytes for replenishing electrolytes lost during exercise and for facilitating intestinal reabsorption of fluid. Additionally, the dry nutritional composition includes the amino acid arginine in the range of 0.24% to 0.35% by weight of the dry composition for further stimulating insulin during exercise. Excerpt(s): This is a continuation application of patent application Ser. No. 09/824,357, filed on Apr. 2, 2001. The present invention relates to a nutritional composition for optimizing muscle performance and extending endurance during exercise and preventing free radical buildup and muscle damage after exercise. More particularly, the nutritional composition includes carbohydrates and protein in a 4-1 ratio to stimulate insulin and glucose uptake during exercise, arginine for stimulating the release of insulin, Vitamins C and E for reducing free radical buildup and electrolytes for replenishing electrolytes and water lost during exercise. Over the past thirty years,

238

Vitamin E

there has been extensive research conducted on the role hydration and carbohydrate supplementation play in improving exercise performance. This research led to the development of sports drinks that contain carbohydrate in the range of 6-8%, as well as essential electrolytes such as sodium, potassium, magnesium and chloride. Numerous studies have shown that consumption of a sports drink during exercise containing carbohydrate and electrolytes enables athletes to extend their endurance capacity to a greater extent than by the consumption of water alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Synthetic glove and process for making Inventor(s): Sumarta, Gentho; (Jakarta, ID) Correspondence: Goodwin Procter L.L.P.; 7 Becker Farm Road; Roseland; NJ; 07068; US Patent Application Number: 20030216701 Date filed: December 17, 2002 Abstract: A process for preparing a synthetic, individual latex glove including mixing step the base material of glove comprising PVC resin, or latex, plasticizer, stabilizer and then added with vitamin E. The preparation including dipping of glove mold into the dipping tank, heating, cooling, forming, applying powder or liquid in glove and removing the glove. Excerpt(s): The present invention relates to synthetic gloves made with added vitamin E (alpha-tocopherol). The conventional synthetic clove (including in this term gloves from synthetic resins, such as PVC, as well as of latex) is composed of the thin latex or synthetic film or rubber designed fit tightly around the hand, thereby will give comfort sensitivity to the hand. The glove functions as a protector for preventing contamination from foreign materials of the skin of the hand of the wearer. Therefore the skin of the hand that will be in direct contact with the glove should be protected form adverse effects, and to minimize such effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Tissue products containing softness Inventor(s): Buder, Philip; (Mississauga, CA), Desaulniers, Marc Joseph Gilles; (Repentigny, CA), Gendron, Richard Hector; (Gatineau, CA), Perez, Jose Enrique Castell; (Carabobo, VE), Stewart, Charles William Alexander; (Burnaby, CA) Correspondence: Miller Thompson, Llp; 20 Queen Street West, Suite 2500; Toronto; ON; M5h 3s1; CA Patent Application Number: 20030188841 Date filed: May 21, 2003 Abstract: A composition for cellulostic fibers containing amino silicone to impart improved hand feel. The composition may be included in a lotion applied to tissue paper and may include a hydrophilic softener. A carrier for trace substances, fragrances, vitamin E, aloes and colouring agents may also be used. Such carrier may comprise microcapsules.

Patents 239

Excerpt(s): This invention relates generally to tissue paper, and more specifically to tissue paper having a soft tactile feel, a process for the production of tissue paper having softeners and particular compositions of said tissues. Tissues are widely used for a variety of uses including nose care, removal of cosmetics, eye glass cleaning and wipe ups around the home. Such tissues have gained widespread use for a variety of reasons including the relative inexpensiveness of the product and thus disposability of the tissues. Such tissue papers require a variety of characteristics depending on their usage. For example softness is a major benefit when the tissue papers are used for nose care or removal of cosmetics. Tissues used for wipe ups, however, generally require absorbency while non-smearing is a preferred benefit when using tissue papers for eyeglass cleaning. Generally speaking most individuals prefer strength of the product for most applications. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Tocopherol derivatives Inventor(s): Zhang, Yuehua; (Mill Creek, WA), Lal, Manjari; (Bellevue, WA), Palepu, Nagesh; (Mill Creek, WA) Correspondence: Christensen, O'connor, Johnson, Kindness, Pllc; 1420 Fifth Avenue; Suite 2800; Seattle; WA; 98101-2347; US Patent Application Number: 20030149099 Date filed: February 5, 2002 Abstract: Tocopherol derivatives are provided. In one embodiment, the tocopherol derivative includes a tocopherol moiety covalently coupled to branched hydrophilic moiety. In another embodiment, the tocopherol derivative includes a first tocopherol moiety covalently coupled to a second tocopherol moiety through a hydrophilic moiety. In other embodiments, the derivative includes three or more tocopherol moieties. Excerpt(s): The present invention relates to tocoperol derivatives and, more particularly, to tocopherol derivatives in which a tocopherol moiety is covalently coupled to a branched hydrophilic moiety. Surfactants are molecules that are composed of groups of opposing solubility properties. The presence of two structurally dissimilar groups within a single molecule is a defining characteristic of surfactants. Surfactants typically include hydrophobic and hydrophilic groups. In contrast to cationic and anionic surfactants, nonionc surfactants are electronically neutral molecules that do not have a discrete charge when dissolved in aqueous media. The hydrophilicity of nonionic surfactants is provided by hydrogen bonding of the surfactant's hydrophilic group with water molecules. The hydrophilic groups of the surfactant often include oxygen atoms. Common nonionic surfactants include polyoxyethylene surfactants. In addition to the hydrophilic portion, the hydrophobic portion of a surfactant can be chosen to achieve the desired surfactant properties. While hydrocarbon chains are a common hydrophobic group, a surfactant's hydrophobic group can include a variety of organic groups that are relatively hydrophobic. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

240

•

Vitamin E

Tocopherol enriched compositions and amelioration of inflammatory symptoms Inventor(s): Beinlich, Peggy; (San Mateo, CA), Boddupalli, Sekhar; (San Jose, CA), Brown, Lesley A.; (East Palo Alto, CA), Dreon, Darlene M.; (Menlo Park, CA), Flaim, Stephen; (San Diego, CA), Miller, Guy; (San Jose, CA), Phinney, Stephen D.; (Elk Grove, CA) Correspondence: Gladys H. Monroy; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030100603 Date filed: August 21, 2002 Abstract: The present invention provides non-alpha-tocopherol enriched tocopherol compositions and non-alpha-tocopherol metabolite enriched compositions for use in the reduction of inflammatory markers associated with inflammation and for use in the treatment and/or amelioration of symptoms of inflammation associated with for example, cardiovascular diseases or disorders, infectious diseases, diabetes, SIRS, asthma, neurodegenerative disorders, PMS; muscle fatigue or inflammation; and dermal conditions. Excerpt(s): This application claims benefit of U.S. Provisional Patent Application Serial No. 60/314,257, filed Aug. 21, 2001, U.S. Provisional Patent Application Serial No. 60/314,223, filed Aug. 21, 2001, and U.S. Provisional Patent Application Serial No. 60/314,256, filed Aug. 21, 2001, all of which are incorporated by reference herein in their entirety. This invention generally relates to non-alpha-tocopherol compositions such as gamma-tocopherol, beta-tocopherol or delta-tocopherol, and/or metabolite(s) thereof, and methods for treating and/or ameliorating the symptoms of inflammation in a mammalian subject. The invention also relates to methods of making such compositions. Inflammation is an important component of host protection, and is a composite response including successive events in response to an injury which may be infectious or non-infectious. Inflammation involves a variety of events on the cellular, molecular and physiologic levels. These events include vasodilatation; increased vascular permeability; extravasation of plasma leading to interstitial edema; chemotaxis of neutrophils, macrophages and lymphocytes; cytokine production; acute phase reactants; leukocytosis; fever; increased metabolic rate; impaired albumin production and hypoalbuminemia; activation of complement; and stimulation of antibodies. Inflammation is associated with diseases or disorders such as, for example, neurodegenerative diseases, SIRS, asthma, diabetes associated nephropathy and retinopathy, protein wasting, muscle fatigue or inflammation and PMS, infectious diseases, as well as various cardiovascular disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Topical urea composition Inventor(s): Perlmutter, Alan Lorne; (London, CA), Singh, Parashu Ram; (North York, CA) Correspondence: Blake, Cassels & Graydon Llp; Box 25, Commerce Court West; 199 Bay Street; Toronto; ON; M5l 1a9; CA Patent Application Number: 20030104080 Date filed: March 5, 2002

Patents 241

Abstract: Topical composition that contains about 10 to about 50% by weight urea with respect to the total composition weight of the composition; and a topically effective amount of an anti-oxidant compatible with skin. Compositions containing vitamin E, vitamin C, vitamin D and green tea are described. Also described is a method of enhancing delivery of an anti-oxidant to the viable epidermis, including topically applying a composition of the invention to a skin surface of a mammal. Excerpt(s): This application is a continuation-in-part application of PCT/CA 00/01031 filed Sep. 7, 2000 designating the United States, which application claims priority from U.S. Provisional Patent Application Serial No. 60/152,637 filed Sep. 7, 1999. Both of these prior applications are incorporated herein by reference. International patent application No. PCT/CA 00/01031 was published in English under Article 21 of the Patent Cooperation Treaty under No. WO 01/17484 on Mar. 15, 2001. This invention relates to a topical skin composition containing an active ingredient and urea for enhancing delivery of the ingredient. The active ingredient can be, alone, or in combination with another active ingredient, one or more of an antioxidant, vitamin, a.beta.-glucan, or other active ingredient. Particularly useful is a composition containing vitamin E and urea, or a composition containing urea, vitamins A, C and E, and green tea extract. Topical compositions are widely used in the cosmetics and pharmaceutical industries. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

VACCINE FOR PROTECTION OF POULTRY AGAINST SALMONELLOSIS AND A PROCESS FOR PREPARING THE SAME Inventor(s): Barman, Tarani Kanta; (Kaithalkuchi, IN), Garg, Shri Krishna; (Pantnagar, IN), Kumar, Subodh; (Pantnagar, IN), Mishra, Ram Sagar; (Khuthan, IN), Sharma, Vishwashwar Dutt; (Pantnagar, IN) Correspondence: Sidney Austin Brown & Wood Llp; 1501 K Street NW; Washington; DC; 20005; US Patent Application Number: 20030124709 Date filed: March 19, 2001 Abstract: This invention relates to a process for the preparation of Salmonella vaccine by treating entrotoxin and cytotoxins with formalin and adding immuno-potentiator selected from Freund's complete adjuvant (FCA) or Vitamin E or Saponin to said concentrated toxoids to get the desired vaccine.The present invention also provides a Salmonella vaccine for protection against Salmonellosis in poultry. Excerpt(s): This invention relates to a vaccine for protection of poultry against salmonellosis and a process for preparing the same. Salmonellosis remains an important human and animal problem worldwide. In spite of intensive research efforts, many of the details of its pathogenesis are not known. Despite a lack of precise knowledge on the virulence mechanisms of Salmonella, vaccines of varying efficacy have been used for many years (Wray, 1995). Lax, et al (1995) have reviewed the efficiency of different vaccines against salmonellosis. According to them, the efficacy of both live attenuated and dead vaccines remains unclear. Since vaccines developed so far have not been targeted against the virulence factor(s) playing a key role in the pathogenesis of the disease, they may not have for this reason been optimally effective. Moreover, their efficacy have been limited to homologous or antigenically related serovars as Salmonella serovars differ significantly in their flagellar and somatic antigens. U.S. Pat. No.

242

Vitamin E

4,053,036 also describes a bacterial vaccine against Salmonella fevers, typhoid and paratyphoid fevers. The said vaccine is obtained by fermentation, extraction and purification, vaccinating membrane antigens being extracted by putting the bacterial residue obtained by centrifuging, in contact with a solvent of the tris(hydroxyalkyl) aminoalkane class, with stirring at lower temperature, pH adjusted between 8.4 and 8.6 for a period of at least 60 hours, then separated by decanting, followed by purifying the antigens and fractionating by ultra-filtration and then freeze drying the vaccinating antigen fraction. This patent does not disclose the nature of antigen and whether it has got any role in the pathogenesis of salmonellosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Zeaxanthin formulations for human ingestion Inventor(s): Garnett, Kevin M.; (Morristown, NJ), Gierhart, Dennis L.; (Chesterfield, MO), Guerra-Santos, Luis H.; (Ballwin, MO) Correspondence: Patrick D. Kelly; 11939 Manchester #403; ST. Louis; MO; 63131; US Patent Application Number: 20030108598 Date filed: December 17, 2002 Abstract: Preparations are disclosed containing the 3R-3'R stereoisomer of zeaxanthin, packaged for oral ingestion by humans as a therapeutic drug or nutritional supplement. Zeaxanthin is a yellow carotenoid pigment found in the macula (in the center of the human retina), which helps protect retinal cells against phototoxic damage. The R-R stereoisomer can be prepared by fermenting cells, such as Flavobacterium multivorum (ATCC 55238), which do not create any detectable quantity of the undesired and potentially toxic S-S or S-R isomers, and which do not synthesize any other carotenoids. The R-R isomer can be concentrated, in large quantities and at low cost, into a viscous oily fluid containing about 5 to 20% zeaxanthin, by means of a simple solvent extraction process. This oily fluid can be mixed with a carrier such as vegetable oil and enclosed within a digestible capsule, comparable to a conventional capsule containing Vitamin E. It can also be prepared in a microencapsulated granular formulation, and/or in a tablet form with an enteric coating. Alternately, a zeaxanthin fluid can be added to various types of foods, such as margarine, dairy products, syrup, cookie dough, and meat preparations that are not subjected to harsh cooking. Such processing can be used to create formulations such as ingestible tablets, and particulate formulations that can be added to soups, salads, drinks, or other foods. Preferred stabilizers and anti-oxidants are also disclosed. When consumed by humans in any of these modes, the R-R isomer of zeaxanthin can help treat and prevent macular degeneration, one of the leading causes of blindness and vision loss, especially among the elderly. Excerpt(s): This is a continuation of U.S. patent application Ser. No. 09/699,985, filed on Oct. 27, 2000, which requested reissuance of U.S. Pat. No. 5,827,652, which arose from application Ser. No. 08/551,153, filed on Oct. 31, 1995. This invention is in the field of pharmacology, and relates to human use of a yellow pigment called zeaxanthin (ZX) in preventing or treating macular degeneration, a disease which damages retinal tissue and causes blindness. A related U.S. Pat. No. 5,854,015 ("Method of Making Pure 3R-3'R Stereoisomer of Zeaxanthin for Human Ingestion", assigned to the same assignee herein) contains a fairly extensive discussion of retinal physiology and carotenoid chemistry. The contents of that patent are incorporated herein by reference. Although that Background information will not be repeated herein in its entirety, a brief overview is provided in the next paragraphs, to help introduce and explain this invention.

Patents 243

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with vitamin E, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “vitamin E” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on vitamin E. You can also use this procedure to view pending patent applications concerning vitamin E. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

245

CHAPTER 7. BOOKS ON VITAMIN E Overview This chapter provides bibliographic book references relating to vitamin E. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on vitamin E include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “vitamin E” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on vitamin E: •

Low-Fat Living for Real People. 2nd ed Source: New York, NY: Lake Isle Press, Inc. 1998. 252 p. Contact: Available from Lake Isle Press, Inc. 2095 Broadway, Suite 404, New York, NY 10023. (800)462-6420 or (212) 769-2361. PRICE: $14.95. ISBN: 096274039X. Summary: This book, written by a humorist and a registered dietitian, is designed to help readers adjust to eating foods that are lower in fat. Nine chapters provide practical information about fat intake, carbohydrates, protein, snacks, exercise, eating out, and coping with family rebellion. Chapter 10 addresses phytochemicals, folic acid, fiber, soybeans, garlic, nuts, vitamin E, and LDL cholesterol. Chapters 11 and 12 provide answers to frequently asked questions and information about using food labels to select foods low in fat. The last chapter includes easy to prepare recipes in seven categories: rice, pasta, potatoes, barley, and beans; vegetables; soups and salads; appetizers, dressings, and sauces; chicken and turkey; fish; and desserts. All recipes include serving

246

Vitamin E

sizes and nutritional analyses noting calories, fat, carbohydrate, protein, and sodium. Pen and ink illustrations appear throughout the book. A subject index and a list of resources to consult for further information conclude the book. 43 endnotes. (AA-M).

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “vitamin E” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “vitamin E” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “vitamin E” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

All About Vitamin E (Frequently Asked Questions) by Jack Challem (Editor), Melissa Diane Smith; ISBN: 0895299410; http://www.amazon.com/exec/obidos/ASIN/0895299410/icongroupinterna

•

Basic Health Publications User's Guide to Vitamin E: Don't Be a Dummy: Become an Expert on What Vitamin E Can Do for Your Health by Jack Challem, et al; ISBN: 1591200032; http://www.amazon.com/exec/obidos/ASIN/1591200032/icongroupinterna

•

Biology of Vitamin E (Ciba Foundation Symposium, No 101) by Ciba Foundation Symposium; ISBN: 0471910708; http://www.amazon.com/exec/obidos/ASIN/0471910708/icongroupinterna

•

Chromans and Tocopherols by Ellis; ISBN: 0471030384; http://www.amazon.com/exec/obidos/ASIN/0471030384/icongroupinterna

•

Clinical and Nutritional Aspects of Vitamin E: Proceedings of the International Symposium on Vitamin E Held in Kyoto, Japan, 4-6 December 1986 by O. Hayaishi, M. Mino (Editor); ISBN: 0444808981; http://www.amazon.com/exec/obidos/ASIN/0444808981/icongroupinterna

•

Common Questions on Vitamin E and Their Answers by Shute Institute for Clinical and Laboratory Medicine; ISBN: 087983191X; http://www.amazon.com/exec/obidos/ASIN/087983191X/icongroupinterna

•

Determination of Vitamin E: Tocopherols and Tocotrienols by Claude Bourgeois; ISBN: 1851667547; http://www.amazon.com/exec/obidos/ASIN/1851667547/icongroupinterna

•

Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids: A Report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation Anduses by Institute Of Medicine; ISBN: 0309069351; http://www.amazon.com/exec/obidos/ASIN/0309069351/icongroupinterna

•

DK Pocket Healers: Vitamin E: Anti-ageing Antioxidant - Safe and Effective Self-care for Younger Skin and Healthier Hair (DK Pocket Healers Healers) by Stephanie Pederson; ISBN: 0751331023; http://www.amazon.com/exec/obidos/ASIN/0751331023/icongroupinterna

Books

247

•

Doctor Wilfrid E. Shute's Complete Updated Vitamin E Book by Wilfrid E. Shute; ISBN: 0879830883; http://www.amazon.com/exec/obidos/ASIN/0879830883/icongroupinterna

•

Dr. Wilfrid E. Shute's Complete.Updates Vitamin E Book by Willard Shute, Wilfrid E. Shute; ISBN: 0879831510; http://www.amazon.com/exec/obidos/ASIN/0879831510/icongroupinterna

•

Health Preserver : Defining the Versatility of Vitamin E by Wilfrid E., M.D. Shute; ISBN: 0878571892; http://www.amazon.com/exec/obidos/ASIN/0878571892/icongroupinterna

•

Heart and Vitamin E by Evan V.and Shute Institute Staff Shute, et al; ISBN: 0879831650; http://www.amazon.com/exec/obidos/ASIN/0879831650/icongroupinterna

•

Improving Your Health With Vitamin E by Ruth Adams (1978); ISBN: 0915962225; http://www.amazon.com/exec/obidos/ASIN/0915962225/icongroupinterna

•

Kesan perlindungan vitamin E kelapa sawit ke atas kanser hepar by Zurinah Wan Ngah; ISBN: 9679423867; http://www.amazon.com/exec/obidos/ASIN/9679423867/icongroupinterna

•

Mega Vitamin E: Is It Safe by H. J. Roberts; ISBN: 0963326090; http://www.amazon.com/exec/obidos/ASIN/0963326090/icongroupinterna

•

Natural Care Library Vitamin E: Safe and Effective Self-Care for Younger Skin and Healthy Hair by Stephanie Pedersen; ISBN: 0789451980; http://www.amazon.com/exec/obidos/ASIN/0789451980/icongroupinterna

•

No Ordinary Vitamin: Vitamin E and Health by Laura Pawlak (Editor), Michelle Albers (Editor) (1998); ISBN: 1893549003; http://www.amazon.com/exec/obidos/ASIN/1893549003/icongroupinterna

•

SELECT, selenium and vitamin E cancer prevention trial (SuDoc HE 20.3152:SE 4/2) by U.S. Dept of Health and Human Services; ISBN: B000115FGM; http://www.amazon.com/exec/obidos/ASIN/B000115FGM/icongroupinterna

•

The Vitamin E Factor : The Miraculous Antioxidant for the Prevention and Treatment of Heart Disease, Cancer, and Aging by Andreas Papas (1999); ISBN: 0060984430; http://www.amazon.com/exec/obidos/ASIN/0060984430/icongroupinterna

•

The World Market for Unmixed Vitamin E and Derivatives: A 2004 Global Trade Perspective [DOWNLOAD: PDF]; ISBN: B000134BPQ; http://www.amazon.com/exec/obidos/ASIN/B000134BPQ/icongroupinterna

•

Tocopherol, Oxygen, and Biomembranes: Proceedings of the International Symposium on Tocopherol, Oxygen, and Biomembranes, Held at Lake Yamanaka, japa by Oxygen, and Biomembranes, yaman International Symposium on Tocopherol; ISBN: 0444800433; http://www.amazon.com/exec/obidos/ASIN/0444800433/icongroupinterna

•

Tocotrienols and Vitamin E (Good Health Guides) by Stephen T., Md. Sinatra, et al; ISBN: 0658004115; http://www.amazon.com/exec/obidos/ASIN/0658004115/icongroupinterna

•

Vitamin E by Remi Cooper (1998); ISBN: 1580540015; http://www.amazon.com/exec/obidos/ASIN/1580540015/icongroupinterna

•

Vitamin E; ISBN: 0668015144; http://www.amazon.com/exec/obidos/ASIN/0668015144/icongroupinterna

248

Vitamin E

•

Vitamin E & Disease Prevention Including Cancer: Index of New Information With Authors, Subjects & References by Gus J. Torelli (1997); ISBN: 0788313428; http://www.amazon.com/exec/obidos/ASIN/0788313428/icongroupinterna

•

Vitamin E : The Rejuvenation Vitamin by Carlson Wade (Author); ISBN: 0441712312; http://www.amazon.com/exec/obidos/ASIN/0441712312/icongroupinterna

•

Vitamin E : Your Protection Against Exercise Fatigue, Weakened Immunity, Heart Disease, Cancer, Aging, Diabetic Damage, Environmental T by Ruth Winter (Author); ISBN: 0609801325; http://www.amazon.com/exec/obidos/ASIN/0609801325/icongroupinterna

•

Vitamin E and aging by Erwin Di Cyan; ISBN: 0515027618; http://www.amazon.com/exec/obidos/ASIN/0515027618/icongroupinterna

•

Vitamin E and Cancer (Evaluation of Publicly Available Scientific Evidence Regarding Certain nutrIent Series) by Ching K. Chow (1991); ISBN: 9992239921; http://www.amazon.com/exec/obidos/ASIN/9992239921/icongroupinterna

•

Vitamin E for ailing and healthy hearts by Wilfrid E. Shute (Author), Harald J. Taub (Author); ISBN: B00005X3S2; http://www.amazon.com/exec/obidos/ASIN/B00005X3S2/icongroupinterna

•

Vitamin E in Health and Disease by Lester Packer (Editor), Jurgen Fuchs (Editor) (1993); ISBN: 0824786920; http://www.amazon.com/exec/obidos/ASIN/0824786920/icongroupinterna

•

Vitamin E manufacture, 1969 by T. Rubel; ISBN: 0815502753; http://www.amazon.com/exec/obidos/ASIN/0815502753/icongroupinterna

•

Vitamin E Updated by Len Mervyn, et al; ISBN: 0879832746; http://www.amazon.com/exec/obidos/ASIN/0879832746/icongroupinterna

•

Vitamin E Wonder Worker of the 70's by Ruth and Frank Murray Adams; ISBN: 0532152069; http://www.amazon.com/exec/obidos/ASIN/0532152069/icongroupinterna

•

Vitamin E, Biochemical, Hematological, and Clinical Aspects by Bertram H. Lubin (1982); ISBN: 0897661761; http://www.amazon.com/exec/obidos/ASIN/0897661761/icongroupinterna

•

Vitamin E, biochemical, hematological, and clinical aspects; ISBN: 089766177X; http://www.amazon.com/exec/obidos/ASIN/089766177X/icongroupinterna

•

Vitamin E, Key to Youthful Longevity by Raymond F. Bock; ISBN: 0682482048; http://www.amazon.com/exec/obidos/ASIN/0682482048/icongroupinterna

•

Vitamin E: A Comprehensive Treatise by MacHlin; ISBN: 0824768426; http://www.amazon.com/exec/obidos/ASIN/0824768426/icongroupinterna

•

Vitamin E: Biochemistry and Health Implications (Annals of the New York Academy of Sciences 570) by Anthony T. Diplock, et al (1989); ISBN: 0897665368; http://www.amazon.com/exec/obidos/ASIN/0897665368/icongroupinterna

•

Vitamin E: Everything You Need to Know by Jennifer Hay (1998); ISBN: 188260637X; http://www.amazon.com/exec/obidos/ASIN/188260637X/icongroupinterna

•

Vitamin E: Food Chemistry, Composition, and Analysis (Food Science and Technology) by R. Lee, Jr Eitenmiller, Junsoo Lee (2003); ISBN: 0824706889; http://www.amazon.com/exec/obidos/ASIN/0824706889/icongroupinterna

Books

249

•

Vitamin E: For a Healthy Heart and a Longer Life by Herbert Bailey, Herb Bailey; ISBN: 078670053X; http://www.amazon.com/exec/obidos/ASIN/078670053X/icongroupinterna

•

Vitamin E: Is It Safe by H. J. Roberts (1994); ISBN: 0963326082; http://www.amazon.com/exec/obidos/ASIN/0963326082/icongroupinterna

•

Vitamin E: Its Usefulness in Health and Curing Diseases by Makoto Mini, et al (1993); ISBN: 3805557531; http://www.amazon.com/exec/obidos/ASIN/3805557531/icongroupinterna

•

Vitamin E: key to sexual satisfaction by Gary Brandner; ISBN: 0840280009; http://www.amazon.com/exec/obidos/ASIN/0840280009/icongroupinterna

•

Vitamin E: the miracle worker by Ruth Winter; ISBN: 0668026642; http://www.amazon.com/exec/obidos/ASIN/0668026642/icongroupinterna

•

Vitamin E: The Vitality Vitamin by Leonard Mervyn; ISBN: 0722505337; http://www.amazon.com/exec/obidos/ASIN/0722505337/icongroupinterna

•

Vitamin E-Bounded Membrane: A Further Step in Dialysis Optimization (Contributions to Nephrology) by C. Ronco (Editor), G. LA Greca (Editor) (1999); ISBN: 3805569068; http://www.amazon.com/exec/obidos/ASIN/3805569068/icongroupinterna

•

Your Child and Vitamin E by Wilfrid E. Shute; ISBN: 0879832029; http://www.amazon.com/exec/obidos/ASIN/0879832029/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “vitamin E” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Common questions on vitamin E, and their answers. Author: Shute Institute for Clinical and Laboratory Medicine, London, Ont.; Year: 1977; Detroit, Cardiac Society [c1959]

•

Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids: a report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Author:

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

250

Vitamin E

Institute of Medicine (U.S.). Panel on Dietary Antioxidants and Related Compounds.; Year: 1984; Washington, D.C.: National Academy Press, c2000; ISBN: 0309069491 http://www.amazon.com/exec/obidos/ASIN/0309069491/icongroupinterna •

FDA's regulation of the marketing of unapproved new drugs: the case of E-Ferol vitamin E aqueous solution: hearing before a subcommittee of the Committee on Government Operations, House of Representatives, Ninety-eighth Congress, second session, May 4, 1984. Author: United States. Congress. House. Committee on Government Operations. Intergovernmental Relations and Human Resources Subcommittee.; Year: 1975; Washington: U.S. G.P.O., 1984

•

International Symposium on Vitamin E; recent advance in physiology and clinical use. Edited by N. Shimazono and Y. Takagi. Author: Shimazono, Norio.; Year: 1976; Tokyo, Kyoritsu Shuppan, 1972

•

Studies on the tolerance to iron in piglets and mice: with special reference to vitamin E, synthetic antioxidants, and sodium-selenite Author: Tollerz, Gunnar.; Year: 1974; Stockholm: [s.n.], 1965

•

The vitamin E story: the medical memoirs of Evan Shute Author: Shute, Evan.; Year: 1983; Burlington, Ont.: Welch Pub. Co., c1985; ISBN: 0920413048

•

Vitamin E: its usefulness in health and in curing diseases Author: Mino, Makoto.; Year: 1985; Tokyo: Japan Scientific Societies Press, Basel: New York: Karger, c1993; ISBN: 4762267279

•

Vitamin E and its role in cellular metabolism. Editors: Padmanabhan P. Nair [and] Herbert J. Kayden. Author: Kayden, Herbert J.; Year: 1971; [New York, 1972]

•

Vitamin E and retinopathy of prematurity: report of a study by a committee of the Institute of Medicine, Division of Health Sciences Policy. Author: Institute of Medicine (U.S.). Division of Health Sciences Policy.; Year: 1977; Washington, D.C. (2101 Constitution Ave., N.W., Washington 20418): National Academy Press, [1986]

•

Vitamin E content of foods and feeds for human and animal consumption. Author: Dicks, Martha W.; Year: 1970; Laramie, 1965

•

Vitamin E fact book. Author: Vitamin E Research; Information Service.; Year: 1984; LaGrange, Ill.: VERIS Research Information Service, c1999

•

Vitamin E for ailing and healthy hearts, by Wilfrid E. Shute with Harald J. Taub. Author: Shute, Wilfrid E. (Wilfrid Eugene),; Year: 1971; New York, Pyramid House [c1969]

•

Vitamin E manufacture. Author: Rubel, T.; Year: 1970; Park Ridge, N. J., Noyes Development Corp., 1969

•

Vitamin E: key to youthful longevity Author: Bock, Raymond F.,; Year: 1962; New York: ARCO Pub. Co., 1977; ISBN: 0668040785 http://www.amazon.com/exec/obidos/ASIN/0668040785/icongroupinterna

Chapters on Vitamin E In order to find chapters that specifically relate to vitamin E, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and vitamin E using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “vitamin E” (or

Books

251

synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on vitamin E: •

Chemoprevention Source: in Ord, R.A. and Blanchaert, R.H., eds. Oral Cancer: The Dentist's Role in Diagnosis, Management, Rehabilitation, and Prevention. Chicago, IL: Quintessence Publishing Co, Inc. 1999. p. 231-237. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $79.00 plus shipping and handling. ISBN: 0867153571. Summary: Carcinogenesis (the development of cancer) is postulated to be a multistep process. Initiation events, which result in DNA damage, are followed by a reversible promotion phase, and finally by progression to full malignant cancer. This chapter on chemoprevention is from a book on oral cancer written specifically for dental health care providers, including dental students, general dentists, dental specialists, and hygienists. The author hypothesizes that premalignant intraepithelial neoplasia (dysplasia, or changes in cell structure) defined as a localized abnormal proliferation of cells that precedes malignant invasion, may represent a stage of carcinogenesis that is reversible. Chemoprevention refers to the administration of an agent to prevent a cancer from occurring. The agent can be a drug or a natural product, should be easy to administer, cause little or no toxicity, cause no long term adverse sequelae, be affordable, and, ideally, need to be administered only for a short time, relative to a lifetime. The author reviews the current status of clinical trials for prevention of the initial head and neck tumor in patients at high risk for developing the disease, as well as trials for prevention of second primary tumors after an initial tumor has received curative treatment. Agents discussed include retinoids, beta carotene, N acetylcysteine, nonsteroidal antiinflammatory agents (NSAIDs), vitamin E, interferons, curcumin, and green tea. 31 references.

•

Vitamins and Minerals Source: in Warshaw, H.S. and Webb, R. Diabetes Food and Nutrition Bible: A Complete Guide to Planning, Shopping, Cooking, and Eating. Alexandria, VA: American Diabetes Association. 2001. p. 7-14. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $18.95 plus shipping and handling. ISBN: 158040037. Summary: This chapter on vitamins and minerals is from a book that offers a complete food and nutrition resource for people with diabetes. The book brings readers up to date on meal planning, carbohydrate counting, vitamins, minerals, and the best ways to prepare healthy delicious meals. In this chapter, the authors emphasize that vitamins are essential to the proper functioning of the body and they must be eaten in sufficient quantities to maintain health. The authors describe Recommended Dietary Allowances (RDAs) and several new categories of recommendations being developed under the heading of Dietary Reference Intakes (DRIs): Recommended Dietary Allowance, Adequate Intake (AI), Estimated Average Requirement (EAR), and Tolerable Upper Intake Level (UL). The authors then discuss water soluble vitamins, including vitamin B1 (thiamin), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid),

252

Vitamin E

vitamin B6 (pyridoxine), folate or folic acid, vitamin B12 (cobalamin), vitamin C, and biotin. The chapter then addresses the fat-soluble vitamins, including vitamin A, vitamin D, vitamin E, and vitamin K; and minerals, including calcium, iron, phosphorus, iodine, magnesium, zinc, selenium, copper, fluoride, and chromium. For each vitamin or mineral, the authors note good food sources for obtaining that nutrient. •

Chapter 99: Granuloma Annulare Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 1. New York, NY: McGraw-Hill. 1999. p. 1152-1157. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail: [email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on the epidemiology, etiology, pathogenesis, clinical manifestations, laboratory findings, pathology, differential diagnosis, treatment, course, and prognosis of granuloma annulare. This benign, usually self-limited dermatosis of unknown cause is characterized by necrobiotic dermal papules that often assume an annular configuration. The disease occurs most frequently in children and young adults. Although the cause of granuloma annulare is unknown, it evokes a peculiar sort of immunologically mediated inflammation reaction in which inflammation surrounds blood vessels and the collagen and elastic tissues are altered. Granuloma annulare can be divided into various types, including localized lesions, generalized lesions, subcutaneous lesions, perforating lesions, arcate dermal erythema, and actinic granuloma. Granuloma annulare may be associated with various other diseases, including necrobiosis lioidica, rheumatoid arthritis, and ankylosis of a joint. Laboratory tests are usually normal, so they are not often recommended. The main laboratory aid in the diagnosis of granuloma annulare is biopsy because single or multiple foci of granulomatous inflammation can be observed at the level of the subpapillary plexus of blood vessels. Immunofluorescence examination of biopsies of granuloma annulare often reveals C3, immunoglobulin M, and fibrinogen in some dermal blood vessels. Granuloma annulare is a cosmetic disease that usually has no medical consequence, so treatment options include topical vitamin E and x-ray therapy, cryotherapy, laser destruction, or intralesional injection of triamcinolone. Other treatment options include glucocorticoids and psoralen plus ultraviolet A therapy. Although the disease tends to spontaneously resolve, resolution is believed to be less likely in middle-aged patients who have widespread, generalized granuloma annulare. 5 figures and 55 references.

•

Trace Elements and Vitamins in Renal Disease Source: in Mitch, W.E., and Klahr, S., eds. Nutrition and the Kidney. 2nd ed. Boston, MA: Little, Brown and Company. 1993. p. 114-131. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail: [email protected]. Website: http://www.lrpub.com. PRICE: $94.95. ISBN: 0316575003. Summary: This chapter, from a medical textbook on nutrition and the kidney, reviews the metabolism, concentrations, and requirements of trace elements and vitamins in patients with chronic renal failure (CRF) prior to the onset of dialysis and during treatment with either hemodialysis (HD) or continuous ambulatory peritoneal dialysis

Books

253

(CAPD). Topics include the alteration of trace element metabolism in kidney failure, including aluminum, iron, zinc, copper, selenium, and ultra trace elements; and vitamins, including thiamine (B1), riboflavin (B2), pyridoxine (B6), cobalamin (B12), folic acid, biotin, niacin, pantothenic acid, ascorbic acid (vitamin C), retinol (vitamin A), and tocopherol (vitamin E). The authors briefly discuss recommendations for supplementation. 4 tables. 101 references. •

Inborn Errors of Metabolism Source: in Thoene, J.G., ed. Physicians' Guide to Rare Diseases. 2nd ed. Montvale, NJ: Dowden Publishing Company. 1995. p. 167-248. Contact: Available from Dowden Publishing Company, Inc. 110 Summit Avenue, Montvale, NJ 07645. (201) 391-9100. Fax (201) 391-2778. PRICE: $97.50 plus shipping and handling. ISBN: 0962871613. Summary: This chapter, from a physicians' guidebook to rare diseases, discusses inborn errors of metabolism. The book's intent is to help doctors and their patients identify rare disorders and find treatments and support groups. After an introductory section, this chapter covers more than ninety disorders, including the following, which relate to the digestive system: Andersen disease; Fabry disease; Forbes disease; fructose intolerance; galactosemia; Gaucher disease; Menkes disease; phenylketonuria; porphyria; Refsum syndrome; Sandhoff disease; Tangier disease; vitamin E deficiency; von Gierke disease; Wilson disease; and Zellwinger syndrome. For each disorder, the author includes a description, synonyms, and information about signs and symptoms, etiology, epidemiology, related disorders, standard and investigational treatments, and support groups and additional resources. A brief reference list for each disorder is also included.

Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to vitamin E have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •

1998-1999 Complete Directory for People with Rare Disorders Source: Lakeville, CT: Grey House Publishing, Inc. 1998. 726 p. Contact: Available from Grey House Publishing, Inc. Pocket Knife Square, Lakeville, CT 06039. (860) 435-0868. Fax (860) 435-0867. PRICE: $190.00. ISBN: 0939300982. Summary: This directory, from the National Organization for Rare Disorders (NORD) provides a wealth of information on diseases and organizations. The directory offers four sections: disease descriptions, disease specific organizations, umbrella organizations, and government agencies. In the first section, the directory includes descriptions of 1,102 rare diseases in alphabetical order. Each entry defines the disorder, then refers readers to the organizations that might be of interest. Diseases related to

12

You will need to limit your search to “Directory” and “vitamin e” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “vitamin e” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.

254

Vitamin E

digestive diseases include achalasia, Addison's disease, Alagille syndrome, Barrett's esophagus, Budd Chiari syndrome, Caroli disease, celiac sprue, cholangitis, cholecystitis, cirrhosis, colitis, Crohn's disease, Cushing syndrome, cystic fibrosis, diverticulitis, Dubin Johnson syndrome, fructose intolerance, galactosemia, gastritis, gastroesophageal reflux, hepatitis, Hirschprung's disease, Hurler syndrome, imperforate anus, irritable bowel syndrome, jejunal atresia, Korsakoff's syndrome, lipodystrophy, maple syrup urine disease, Morquio syndrome, polyposis, porphyria, proctitis, prune belly syndrome, sarcoidosis, Stevens Johnson syndrome, Tropical sprue, tyrosinemia, valinemia, vitamin E deficiency, Whipple's disease, Wilson's disease, and Zollinger Ellison syndrome. Each of the 445 organizations listed in the second section is associated with a specific disease or group of diseases. In addition to contact information, there is a descriptive paragraph about the organization and its primary goals and program activities. Entries include materials published by the organization as well as the diseases the organizations cover, which refer readers to Section I. The third section lists 444 organizations that are more general in nature, serving a wide range of diseases (for example, the American Liver Foundation). The final section describes 74 agencies that are important federal government contacts that serve the diverse needs of individuals with rare disorders. A name and key word index concludes the volume.

255

CHAPTER 8. MULTIMEDIA ON VITAMIN E Overview In this chapter, we show you how to keep current on multimedia sources of information on vitamin E. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on vitamin E is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “vitamin E” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “vitamin E” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on vitamin E: •

Exploring Your Brain: Memory Source: New York, NY: Dana Foundation. 1998. Contact: Available from Films for the Humanities and Sciences. PO Box 2053, Princeton, NJ 08543-2053. (800) 257-5126, (609) 275-1400; FAX: (609) 275-3767. Internet: http://www.films.com. PRICE: $89.95. Item number: BVL8644. Summary: This video is one in a series about the brain, broadcast by the Public Broadcasting System. This show discussed the biology of memory and memory loss. The first segment of the program discussed types of memory such as explicit and implicit, and short and long term memory. The panelists then discussed the aging brain and the prospect of losing memory. Factors which can prevent or slow memory loss may include education, physical and mental activity, and a feeling of control over one's life. Current research into treating memory loss includes cholinesterase inhibitors, Vitamin E, and hormone replacement therapy. The next section of the show discussed memory distortion and recovered memory. Following a question and answer time with

256

Vitamin E

the audience, the panelists expressed their thoughts on future research into memory and the brain. •

How to Stay Dry: Seven Activities You Can Do to Stay or Become Dry Source: Milwaukee, WI: University of Wisconsin-Milwaukee School of Nursing. 1995. (videocassette). Contact: Available from Health Sciences Consortium. Distribution Department, 201 Silver Cedar Court, Chapel Hill, NC 27514-1517. (919) 942-8731. Fax (919) 942-3689. Email: [email protected]. PRICE: $195.00 (nonmembers) or $146.25 (members). HSC catalog number N951-VI-072. Summary: This videotape program is designed to help adults with urinary incontinence reduce or eliminate the possibility of a wetting accident. The viewer is introduced to seven activities that have been proven to help incontinence, none of which involve the use of instruments or medical procedures. The suggestions are to make environmental feature adjustments, such as using a raised toilet seat and wearing easy-to-remove clothing; drinking adequate liquids; making dietary changes for constipation, such as adding bran or prunes to the diet; emptying the bladder five to eight times daily; exercising the pelvic floor muscles as described in the program; stopping smoking, as coughing can cause wetting accidents; and taking vitamin E and vitamin B complex. (AA-M).

Bibliography: Multimedia on Vitamin E The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in vitamin E (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on vitamin E: •

Some new aspects of vitamin E in cellular metabolism [videorecording] Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; Year: 1973; Format: Videorecording; Houston: The Center, 1973

•

Vitamin E [slide] Source: A. L. Tappel; Year: 1973; Format: Slide; Annapolis, Md.: Nutrition Today, c1973

257

CHAPTER 9. PERIODICALS AND NEWS ON VITAMIN E Overview In this chapter, we suggest a number of news sources and present various periodicals that cover vitamin E.

News Services and Press Releases One of the simplest ways of tracking press releases on vitamin E is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “vitamin E” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to vitamin E. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “vitamin E” (or synonyms). The following was recently listed in this archive for vitamin E: •

High vitamin E levels reduce gut cancer risk Source: Reuters Health eLine Date: September 25, 2003

•

High serum alpha-tocopherol associated with reduced risk of upper GI cancers Source: Reuters Medical News Date: September 25, 2003

258

Vitamin E

•

Carotene, vitamin E don't prevent heart attacks Source: Reuters Health eLine Date: August 22, 2003

•

Exercise and vitamin E may protect against HIV-associated metabolic syndrome Source: Reuters Medical News Date: July 18, 2003

•

Vitamin E may protect against cisplatin-induced neurotoxicity Source: Reuters Medical News Date: April 03, 2003

•

Vitamin E use tied to reduced risk of bladder cancer mortality Source: Reuters Industry Breifing Date: December 13, 2002

•

Vitamin E, bladder cancer risk studied Source: Reuters Health eLine Date: December 09, 2002

•

Vitamin E unlikely to reduce microvascular complications in diabetics Source: Reuters Medical News Date: November 28, 2002

•

Foods rich in vitamin E may reduce Parkinson's disease risk Source: Reuters Medical News Date: November 06, 2002

•

Vitamin E may help keep arteries clear in women Source: Reuters Health eLine Date: September 09, 2002

•

Low vitamin E linked to early artery disease Source: Reuters Health eLine Date: August 27, 2002

•

Vitamin E use may adversely affect infection outcome in elderly Source: Reuters Medical News Date: August 14, 2002

•

Vitamin E may worsen elders' respiratory infections Source: Reuters Health eLine Date: August 13, 2002

•

Vitamin E may help keep people sharp in old age Source: Reuters Health eLine Date: July 17, 2002

•

Vitamin E intake may slow age-related decline in cognitive function Source: Reuters Medical News Date: July 17, 2002

•

Pentoxifylline plus vitamin E may reverse radiotherapy-induced uterine damage Source: Reuters Medical News Date: July 03, 2002

•

Clues on vitamin E's anti-prostate cancer effects Source: Reuters Health eLine Date: May 29, 2002

Periodicals and News

•

Vitamin E suppresses androgen receptor, PSA expression in prostate cancer Source: Reuters Medical News Date: May 28, 2002

•

Vitamin E may lessen post-workout muscle soreness Source: Reuters Health eLine Date: April 23, 2002

•

Vitamin E fights arthritis-like damage in mice Source: Reuters Health eLine Date: March 29, 2002

•

Vitamin E may help treat menstrual pain: study Source: Reuters Health eLine Date: January 24, 2002

•

Vitamin E hemodialyzer improves neutrophil function in renal failure patients Source: Reuters Industry Breifing Date: January 24, 2002

•

Vitamin E supplementation prevents ataxia in mouse model Source: Reuters Medical News Date: December 17, 2001

•

Vitamin E doesn't prevent osteoarthritis pain Source: Reuters Health eLine Date: October 26, 2001

•

Vitamin E is a pro-oxidant in smokers on a high-fat diet Source: Reuters Medical News Date: June 15, 2001

•

Hot flash: vitamin E may help Source: Reuters Health eLine Date: April 06, 2001

•

Oats, vitamin E open arteries after fatty meal Source: Reuters Health eLine Date: March 22, 2001

•

Vitamin E pills may not benefit the healthy Source: Reuters Health eLine Date: March 06, 2001

•

Value of supplemental vitamin E for healthy individuals questioned Source: Reuters Medical News Date: March 06, 2001

•

High-dose vitamin E seems to slow atherosclerosis Source: Reuters Medical News Date: March 05, 2001

•

High-dose vitamin E may protect arteries Source: Reuters Health eLine Date: March 05, 2001

•

Vitamin E does not benefit heart failure patients Source: Reuters Medical News Date: February 07, 2001

259

260

Vitamin E

•

Vitamin E may offer little help to heart patients Source: Reuters Health eLine Date: February 05, 2001

•

Aspirin, not vitamin E, prevents heart attack Source: Reuters Health eLine Date: January 12, 2001

•

Gamma-tocopherol levels associated with lower risk of prostate cancer Source: Reuters Industry Breifing Date: December 28, 2000

•

Concomitant vitamin E does not ameliorate side effects of isotretinoin Source: Reuters Medical News Date: December 28, 2000

•

Vitamin E may protect against prostate cancer Source: Reuters Health eLine Date: December 19, 2000

•

Bionutrics gets US patent for therapeutic niacin/vitamin E mix Source: Reuters Industry Breifing Date: November 30, 2000

•

Vitamin E may help ward off Alzheimer's Source: Reuters Health eLine Date: November 21, 2000

•

Vitamin E may help prevent Alzheimer's in certain patients Source: Reuters Medical News Date: November 21, 2000

•

Vitamin E may help heart in type 1 diabetics Source: Reuters Health eLine Date: November 14, 2000

•

Vitamin E may lower risk of allergies, asthma Source: Reuters Health eLine Date: November 07, 2000

•

High-dose vitamin E reduces serum levels of C-reactive protein in diabetes Source: Reuters Medical News Date: November 02, 2000

•

Vitamin E may reduce heart attack risk Source: Reuters Health eLine Date: October 26, 2000

•

Vitamin E may reduce stroke risk in hypertensive me Source: Reuters Health eLine Date: October 18, 2000

•

Vitamin E may reduce cardiac events in patients with end-stage renal disease Source: Reuters Medical News Date: October 11, 2000

•

Alcohol, vitamin E intakes affect survival in patients with gastric carcinoma Source: Reuters Medical News Date: September 27, 2000

Periodicals and News

•

261

Vitamin E protects muscles during weight lifting Source: Reuters Health eLine Date: September 25, 2000 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “vitamin E” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “vitamin E” (or synonyms). If you know the name of a company that is relevant to vitamin E, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “vitamin E” (or synonyms).

262

Vitamin E

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “vitamin E” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on vitamin E: •

Tufts Nutrition Research: From the Lab to Your Plate. Vitamin E for Easing Rheumatoid Arthritis Pain Source: Tufts University Health and Nutrition Letter. 18(12). Special Supplement. February 2001. Contact: 10 High Street, Suite 706, Boston, MA 02110. [email protected] www.healthletter.tufts.edu. Summary: This article reviews research suggesting that large doses of vitamin E may help reduce pain and inflammation in people who suffer from rheumatoid arthritis. Two German studies have found that those who take vitamin E daily experience a decrease in morning stiffness, joint tenderness, and joint pain. A Danish study suggests that high enough blood levels of vitamin E may help to prevent rheumatoid arthritis. Danish researchers have found that those who start with low blood levels of vitamin E are eight times more likely than those with higher levels to end up with the disease. This may occur because people with rheumatoid arthritis use up more antioxidants (such as vitamin E) to destroy free radicals (toxic oxygen molecules involved in causing inflammation). Jeffrey Blumberg, head of the Antioxidants Research Laboratory at Tufts University, states that although vitamin E is not the new arthritis treatment, it may be an 'adjunctive treatment.'

Academic Periodicals covering Vitamin E Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to vitamin E. In addition to these sources, you can search for articles covering vitamin E that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

263

CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for vitamin E. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with vitamin E. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

264

Vitamin E

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to vitamin E: Vitamin E •

Systemic - U.S. Brands: Amino-Opti-E; E-Complex-600; Liqui-E; Pheryl-E http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202598.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

265

APPENDICES

267

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

13

These publications are typically written by one or more of the various NIH Institutes.

268

Vitamin E

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

269

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

14

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.

270

Vitamin E

•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “vitamin E” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “vitamin E” (or synonyms) into the “For these words:” box. The following is a sample result: •

Progress Report on Alzheimer's Disease 1998 Source: Silver Spring, MD: Alzheimer's Disease Education and Referral Center. 1998. 58 p. Contact: ADEAR Center. PO Box 8250, Silver Spring, MD 20907-8250. (800) 438-4380; (301) 495-3311; FAX (301) 495-3334. Internet: http://www.alzheimers.org. PRICE: Free. Item number: Z-149. Summary: This annual report on Alzheimer's disease (AD) from the National Institute on Aging (NIA) and other branches of the National Institutes of Health provides up-todate information on research about AD and the latest efforts to treat and prevent it. The report describes the structure and function of the brain, and changes in the brain including amyloid plaques and neurofibrillary tangles. Sections describe: genetic factors in AD; advances in understanding AD, including transgenic mouse models, the role of amyloid and presenilins, African Americans and AD, and oxidative damage; advances in diagnosis; and advances in treating and preventing AD, including estrogen replacement therapy, anti-inflammatory drugs, and the use of selegiline and vitamin E. The report also provides information about economic impact, and prevalence of AD. Also available in Braille (AZDC07545). 95 references.

•

Nutrient Supplementation Needs in HIV Infection Contact: Carl Vogel Center, 1012 14th St NW Ste 707, Washington, DC, 20005, (202) 6380750. Summary: This paper examines nutrient supplement needs in HIV infection and agrees that replenishment of the missing nutrients may be critical for restoration of immune function and to prevent disease progression. Some of the nutrients considered appropriate for all those diagnosed with HIV infection are: Multiple vitamins and/or minerals, antioxidant formula, ascorbic acid/ascorbate, beta carotene, B12, coenzyme Q10, vitamin E, essential fatty acids, glutathione, and zinc. The paper reviews research pointing to the benefit of nutrient replenishment in HIV-infected patients and to nutrient replenishment's advantage in increasing tolerance for and/or help to counter the negative effects of some drugs commonly used with HIV infection.

Physician Resources

271

The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “vitamin E” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 22788 137 860 37 1 23823

HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “vitamin E” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI 16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

17

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19 20

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 21 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

272

Vitamin E

staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Vitamin E In the following section, we will discuss databases and references which relate to the Genome Project and vitamin E. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “vitamin E” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for vitamin E:

22

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

Physician Resources

•

Tocopherol Transfer Protein, Alpha Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600415

•

Vitamin E, Familial Isolated Deficiency of Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?277460

273

Genes and Disease (NCBI - Map) The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

274

•

Vitamin E

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “vitamin E” (or synonyms) into the search box and click “Go.”

Physician Resources

275

Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “vitamin E” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

25

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

277

APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on vitamin E can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to vitamin E. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to vitamin E. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “vitamin E”:

278

•

Vitamin E

Other guides Antioxidants http://www.nlm.nih.gov/medlineplus/antioxidants.html Cancer Alternative Therapy http://www.nlm.nih.gov/medlineplus/canceralternativetherapy.html Vitamin and Mineral Supplements http://www.nlm.nih.gov/medlineplus/vitaminandmineralsupplements.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on vitamin E. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Questions and Answers: SELECT (Selenium and Vitamin E Cancer Prevention Trial) Source: Bethesda, MD: National Cancer Institute. 2001. 6 p. Contact: Available from National Cancer Institute. Publications Ordering Service, P.O. Box 24128, Baltimore, MD 21227. (800) 4-CANCER or (800) 422-6237; TTY: (800) 3328615; FAX: (301) 330-7968. PRICE: Free. Summary: This fact sheet from the National Cancer Institute (NCI) discusses SELECT (the Selenium and Vitamin E Cancer Prevention Trial), an NCI-funded clinical trial to see if selenium, vitamin E, or both dietary supplements prevent prostate cancer in men. In a question and answer format, it provides information on a man's chances of developing prostate cancer, selenium and vitamin E, and why the supplements are being studied for prostate cancer prevention. It also explains what SELECT is; what researchers hope to learn from the trial; participant eligibility and other requirements; who pays for the tests involved in the trial; the doses of selenium and vitamin E being used; possible risks of participation in the trial; and why men should participate in SELECT. In addition, the fact sheet gives information on how potential participants and physicians can get more information about SELECT, and other clinical trials under way for prostate cancer prevention. It lists Web sites for additional information and SELECT audio-visual materials.

•

Dietary Supplement Fact Sheet: Vitamin E Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2000. 10 p.

Patient Resources

279

Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D021. Summary: This fact sheet is designed to provide basic information about the role of vitamin E in health and disease and to guide decisions about the use of a vitamin E supplement. First, it explains what vitamin E is and how it is used by the body, which foods provide vitamin E, what Recommended Dietary Allowance for adults is, when a vitamin E deficiency can occur, and who may need extra vitamin E. Then, it discusses current issues and controversies related to vitamin E and heart disease, cancer, and cataracts. Finally, it examines the health risk of too much vitamin E. The fact sheet includes a table listing selected food sources of vitamin E and 25 references. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Facts About Dietary Supplements: Vitamin E Summary: Answers basic questions about the antioxidant vitamin E, such as what it is, what foods provide it, and what intake is needed to provide the recommended dietary allowance. Source: Warren Grant Magnuson Clinical Center, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6441 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to vitamin E. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

280

Vitamin E

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to vitamin E. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with vitamin E. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about vitamin E. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “vitamin E” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “vitamin E”. Type the following hyperlink into your

Patient Resources

281

Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “vitamin E” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “vitamin E” (or a synonym) into the search box, and click “Submit Query.”

283

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

27

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

284

Vitamin E

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

28

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

285

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

286

Vitamin E

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

287

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

288

Vitamin E

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

289

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on vitamin E: •

Basic Guidelines for Vitamin E Vitamin E Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002406.htm

•

Signs & Symptoms for Vitamin E Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm

•

Nutrition for Vitamin E Balanced diet Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002449.htm Vitamin K Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002407.htm Vitamins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002399.htm

290

•

Vitamin E

Background Topics for Vitamin E Food guide pyramid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002093.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

291

VITAMIN E DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-Hydroxytryptophan: Precursor of serotonin used as antiepileptic and antidepressant. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscisic Acid: Abscission-accelerating plant growth substance isolated from young cotton fruit, leaves of sycamore, birch, and other plants, and from potatoes, lemons, avocados, and other fruits. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as

292

Vitamin E

dressing, ambulation, eating, etc., in rehabilitation. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH]

Dictionary 293

Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Air Pollutants: Substances which pollute the air. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Aldose Reductase Inhibitor: A class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes. Aldose reductase is an enzyme that is normally present in the eye and in many other parts of the body. It helps change glucose (sugar) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Drugs that prevent or slow (inhibit) the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alfalfa: A deep-rooted European leguminous plant (Medicago sativa) widely grown for hay

294

Vitamin E

and forage. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allo: A female hormone. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Aloe: A genus of the family Liliaceae containing anthraquinone glycosides such as aloinemodin or aloe-emodin (emodin). [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-helix: One of the secondary element of protein. [NIH] Alpha-Linolenic Acid: A fatty acid that is found in plants and involved in the formation of prostaglandins. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH]

Dictionary 295

Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminobenzoic Acids: Benzoic acid substituted with an amino group. They can either be mono-, di-, or tri- substituted. Para-aminobenzoic acid (see 4-aminobenzoic acid) is considered a member of the vitamin B complex. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local

296

Vitamin E

inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Anhydrides: Chemical compounds derived from acids by the elimination of a molecule of water. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Animal Welfare: The protection of animals in laboratories or other specific environments and the promotion of their health through better nutrition, housing, and care. This may be carried out through legislation or regulation. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH]

Dictionary 297

Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthocyanins: Glycosidic pigments in blue, red, and purple flowers and also found as metabolic byproducts in blood and urine. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU]

298

Vitamin E

Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiproliferative: Counteracting a process of proliferation. [EU] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Apheresis: Components plateletpheresis. [NIH]

being

separated

out,

as

leukapheresis,

plasmapheresis,

Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes

Dictionary 299

associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is

300

Vitamin E

considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Endopeptidases: A sub-subclass of endopeptidases that depend on an aspartic acid residue for their activity. EC 3.4.23. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition,

Dictionary 301

or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Avian: A plasmodial infection in birds. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azoxymethane: A potent carcinogen and neurotoxic compound. It is particularly effective in inducing colon carcinomas. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basal Metabolism: Heat production, or its measurement, of an organism at the lowest level of cell chemistry in an inactive, awake, fasting state. It may be determined directly by means of a calorimeter or indirectly by calculating the heat production from an analysis of the end products of oxidation within the organism or from the amount of oxygen utilized. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of

302

Vitamin E

donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine. Also called benign prostatic hypertrophy or BPH. [NIH] Benzaldehyde: A colorless oily liquid used as a flavoring agent and to make dyes, perfumes, and pharmaceuticals. Benzaldehyde is chemically related to benzene. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. [NIH] Benzoates: Salts and esters of benzoic acid that possess antibacterial and antifungal properties. They are used as preservatives in pharmaceutical formulations including oral preparations, cosmetics, and food. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [NIH] Beta Rays: A stream of positive or negative electrons ejected with high energy from a disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH]

Dictionary 303

Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU]

304

Vitamin E

Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH]

Dictionary 305

Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone Remodeling: The continuous turnover of bone matrix and mineral that involves first, an increase in resorption (osteoclastic activity) and later, reactive bone formation (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium homeostasis. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as osteoporosis. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Borates: Inorganic or organic salts and esters of boric acid. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain metastases: Cancer that has spread from the original (primary) tumor to the brain. [NIH]

Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU]

306

Vitamin E

Bronchopulmonary Dysplasia: A chronic lung disease appearing in certain newborn infants treated for respiratory distress syndrome with mechanical ventilation and elevated concentration of inspired oxygen. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Buthionine sulfoximine: A drug that may help prevent resistance to some anticancer drugs. [NIH]

Butylated Hydroxytoluene: Antioxidant used in foods, cosmetics, petroleum products, etc. It may inhibit some neoplasms and facilitate others. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Calorimeter: Measures the amounts of heat absorbed or given off by a solid, a liquid, or a gas. [NIH] Camphor: A bicyclic monoterpene ketone found widely in plant (primarily the camphor

Dictionary 307

tree, Cinnamomum camphora). Natural camphor is used topically as a skin antipruritic and as an anti-infective agent. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Canthaxanthin: A trans-carotenoid pigment widely distributed in nature. The compound is used as an oral suntanning agent and as a food and drug coloring agent. It is believed that it inhibits development of tumor cells and neoplastic transformation through its antioxidant properties. Oral ingestion of the compound causes canthaxanthin retinopathy. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiotoxic: Having a poisonous or deleterious effect upon the heart. [EU] Cardiotoxicity: Toxicity that affects the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate

308

Vitamin E

gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell

Dictionary 309

adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Degranulation: The process of losing secretory granules (secretory vesicles). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by exocytosis. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum.

310

Vitamin E

Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cerium: An element of the rare earth family of metals. It has the atomic symbol Ce, atomic number 58, and atomic weight 140.12. Cerium is a malleable metal used in industrial applications. [NIH] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorpyrifos: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecalciferol: An antirachitic oil-soluble vitamin. [NIH]

Dictionary 311

Cholecystitis: Inflammation of the gallbladder. [NIH] Choleretic: A choleretic agent. [EU] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH]

312

Vitamin E

Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the

Dictionary 313

amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]

Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic

314

Vitamin E

foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Concretion: Minute, hard, yellow masses found in the palpebral conjunctivae of elderly people or following chronic conjunctivitis, composed of the products of cellular degeneration retained in the depressions and tubular recesses in the conjunctiva. [NIH] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU]

Dictionary 315

Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]

Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital

316

Vitamin E

can care for. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] Corrosion: Irreversible destruction of skin tissue. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cottonseed Oil: Oil obtained from the seeds of Gossypium herbaceum L., the cotton plant. It is used in dietary products such as oleomargarine and many cooking oils. Cottonseed oil is commonly used in soaps and cosmetics. [NIH] Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or

Dictionary 317

whether there is an associated hemorrhage. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Creatinine clearance: A test that measures how efficiently the kidneys remove creatinine and other wastes from the blood. Low creatinine clearance indicates impaired kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryotherapy: Any method that uses cold temperature to treat disease. [NIH] Crystallins: A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. The presence of these proteins accounts for the transparency of the lens. The family is composed of four major groups, alpha, beta, gamma, and delta, and several minor groups, which are classed on the basis of size, charge, immunological properties, and vertebrate source. Alpha, beta, and delta crystallins occur in avian and reptilian lenses, while alpha, beta, and gamma crystallins occur in all other lenses. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curcumin: A dye obtained from tumeric, the powdered root of Curcuma longa Linn. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes. [NIH] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclodextrins: A homologous group of cyclic glucans consisting of alpha-1,4 bound glucose units obtained by the action of cyclodextrin glucanotransferase on starch or similar substrates. The enzyme is produced by certain species of Bacillus. Cyclodextrins form inclusion complexes with a wide variety of substances. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cystamine: A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage. [NIH] Cysteamine: A radiation-protective agent that oxidizes in air to form cystamine. It can be given intravenously or orally to treat radiation sickness. The bitartrate has been used for the oral treatment of nephropathic cystinosis. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH]

318

Vitamin E

Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytochrome b5: A cytochrome occurring in the endoplasmic reticulum that acts as an intermediate electron carrier in some reactions catalyzed by mixed function oxidases, e.g., fatty acid desaturation. It further activates molecular oxygen for an attack on the substrate. MW 16kDa. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]

Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH]

Dictionary 319

Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]

Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased

320

Vitamin E

risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dextran Sulfate: Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4+ Tlymphocytes. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]

Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the

Dictionary 321

alimentary enzymes of man. It comprises various polysaccharides and lignins. [NIH] Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]

Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used

322

Vitamin E

to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties. [NIH] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diverticula: Plural form of diverticulum. [NIH] Diverticulitis: Inflammation of a diverticulum or diverticula. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dormancy: The period when an organism (i. e., a virus or a bacterium) is in the body but not producing any ill effects. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the

Dictionary 323

effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dwarfism: The condition of being undersized as a result of premature arrest of skeletal growth. It may be caused by insufficient secretion of growth hormone (pituitary dwarfism). [NIH]

Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dysphoria: Disquiet; restlessness; malaise. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dysprosium: Dysprosium. An element of the rare earth family that has the atomic symbol Dy, atomic number 66, and atomic weight 162.50. Dysprosium is a silvery metal used primarily in the form of various salts. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing

324

Vitamin E

embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Ellagic Acid: A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye. [NIH]

Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emodin: Purgative anthraquinone found in several plants, especially Rhamnus frangula. It was formerly used as a laxative, but is now used mainly as tool in toxicity studies. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion

Dictionary 325

medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxemia: A condition characterized by the presence of endotoxins in the blood. If endotoxemia is the result of gram-negative rod-shaped bacteria, shock may occur. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences,

326

Vitamin E

or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [NIH] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Ergometer: An instrument for measuring the force of muscular contraction. [NIH] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH]

Dictionary 327

Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eucalyptus: A genus of Australian trees of the Myrtaceae family that yields gums, oils, and resins which are used as flavoring agents, astringents, and aromatics, and formerly to treat diarrhea, asthma, bronchitis, and respiratory tract infections. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Europium: An element of the rare earth family of metals. It has the atomic symbol Eu, atomic number 63, and atomic weight 152. Europium is used in the form of its salts as coatings for cathode ray tubes and in the form of its organic derivatives as shift reagents in NMR spectroscopy. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evaluable patients: Patients whose response to a treatment can be measured because enough information has been collected. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the

328

Vitamin E

extent of its role as a transmitter is unclear. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU]

Dictionary 329

Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fenbendazole: Antinematodal benzimidazole used in veterinary medicine. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Finasteride: An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Fluorescein Angiography: Visualization of a vascular system after intravenous injection of a fluorescein solution. The images may be photographed or televised. It is used especially in studying the retinal and uveal vasculature. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH]

330

Vitamin E

Food Technology: The application of knowledge to the food industry. [NIH] Forced Expiratory Volume: Measure of the maximum amount of air during a forced vital capacity determination that can be expelled in a given number of seconds. It is usually given as FEV followed by a subscript indicating the number of seconds over which the measurement is made, although it is sometimes given as a percentage of forced vital capacity. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fornix: A bundle of nerves connected to the hippocampus. [NIH] Freeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fructose Intolerance: An autosomal recessive fructose metabolism disorder due to deficient fructose-1-phosphate aldolase (EC 2.1.2.13) activity, resulting in accumulation of fructose-1phosphate. The accumulated fructose-1-phosphate inhibits glycogenolysis and gluconeogenesis, causing severe hypoglycemia following ingestion of fructose. Prolonged fructose ingestion in infants leads ultimately to hepatic failure and death. Patients develop a strong distaste for sweet food, and avoid a chronic course of the disease by remaining on a fructose- and sucrose-free diet. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Galenical: 1. Usually cap: of or relating to Galen or his medical principles or method. 2. Constituting a galenical. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens

Dictionary 331

and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH]

332

Vitamin E

Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gibberellins: A class of plant growth hormone isolated from cultures of Gibberella fujikuroi, a fungus causing Bakanae disease in rice. There are many different members of the family as well as mixtures of multiple members; all are diterpenoid acids based on the gibberellane skeleton. [NIH] Ginger: Deciduous plant rich in volatile oil (oils, volatile). It is used as a flavoring agent and has many other uses both internally and topically. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH]

Dictionary 333

Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Gossypol: Poisonous pigment found in cottonseed and potentially irritating to gastrointestinal tract. [NIH]

334

Vitamin E

Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Government Agencies: Administrative units of government responsible for policy making and management of governmental activities in the U.S. and abroad. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Annulare: Benign granulomatous disease of unknown etiology characterized by a ring of localized or disseminated papules or nodules on the skin and palisading histiocytes surrounding necrobiotic tissue resulting from altered collagen structures. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of

Dictionary 335

habit, customary. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Fairs: Community health education events focused on prevention of disease and promotion of health through audiovisual exhibits. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodialyzer: Apparatus for hemodialysis performing the functions of human kidneys in place of the damaged organs; highly specialized medical equipment used for treating kidney failure by passing the body's toxic substances through an external artificial kidney. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma

336

Vitamin E

glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin C: A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an "ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatic Veins: Veins which drain the liver. [NIH] Hepatic Veno-Occlusive Disease: Blockage of the small- or medium-sized hepatic veins due to nonthrombotic subendothelial edema which may progress to fibrosis. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH]

Dictionary 337

Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hyaluronidase: An enzyme that splits hyaluronic acid and thus lowers the viscosity of the acid and facilitates the spreading of fluids through tissues either advantageously or disadvantageously. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH]

338

Vitamin E

Hydration: Combining with water. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]

Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperoxaluria: Excretion of an excessive amount of oxalate in the urine. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in

Dictionary 339

the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hysterectomy: Excision of the uterus. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idarubicin: An orally administered anthracycline antibiotic. The compound has shown activity against breast cancer, lymphomas and leukemias, together with potential for reduced cardiac toxicity. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization

340

Vitamin E

involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Imperforate Anus: A birth defect in which the anal canal fails to develop. The condition is treated with an operation. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Industrial Waste: Worthless, damaged, defective, superfluous or effluent material from industrial operations. It represents an ecological problem and health hazard. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH]

Dictionary 341

Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Integrins:

A

family

of

transmembrane

glycoproteins

consisting

of

noncovalent

342

Vitamin E

heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to

Dictionary 343

fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iron Compounds: Inorganic compounds that contain iron as an integral part of the molecule. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight,

344

Vitamin E

speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isoprenoids: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in

Dictionary 345

blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Knee Injuries: Injuries to the knee or the knee joint. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Lanthanum: The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Latent period: A seemingly inactive period, as that between exposure of tissue to an injurious agent and the manifestation of response, or that between the instant of stimulation and the beginning of response. [EU] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek,

346

Vitamin E

gums, or tongue and may become cancerous. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to

Dictionary 347

ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Extracts: Extracts of liver tissue containing uncharacterized specific factors with specific activities; a soluble thermostable fraction of mammalian liver is used in the treatment of pernicious anemia. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl

348

Vitamin E

coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lubricants: Oily or slippery substances. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and

Dictionary 349

spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Maple Syrup Urine Disease: A genetic disorder involving deficiency of an enzyme necessary in the metabolism of branched-chain amino acids, and named for the characteristic odor of the urine. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Meat Products: Articles of food which are derived by a process of manufacture from any portion of carcasses of any animal used for food (e.g., head cheese, sausage, scrapple). [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH]

350

Vitamin E

Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metalloendopeptidases: Endopeptidases which use a metal, normally zinc, in the catalytic mechanism. This group of enzymes is inactivated by metal chelators. EC 3.4.24. [NIH] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body

Dictionary 351

functions. It is a chelating agent for heavy metals. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsome: One of the specific metabolic pathways of the liver. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineral Oil: A mixture of liquid hydrocarbons obtained from petroleum. It is used as laxative, lubricant, ointment base, and emollient. [NIH] Miscible: Susceptible of being mixed. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH]

352

Vitamin E

Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mixed Function Oxidases: Catalyse the insertion of one oxygen atom of molecular oxygen into the organ substrate. Require a second substrate to donate electrons for the reduction of the second atom in the oxygen molecule to water. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Morula: The early embryo at the developmental stage in which the blastomeres, resulting from repeated mitotic divisions of the fertilized ovum, form a compact mass. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Multivariate Analysis: A set of techniques used when variation in several variables has to

Dictionary 353

be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables. [NIH] Muscle Fatigue: A state arrived at through prolonged and strong contraction of a muscle. Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH]

354

Vitamin E

Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]

Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] N-acetyl: Analgesic agent. [NIH] N-acetyl cysteine: An antioxidant drug that may keep cancer cells from developing or reduce the risk of growth of existing cancer. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nearsightedness: The common term for myopia. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neodymium: Neodymium. An element of the rare earth family of metals. It has the atomic symbol Nd, atomic number 60, and atomic weight 144.24, and is used in industrial applications. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU]

Dictionary 355

Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain.

356

Vitamin E

Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cellsurface receptors on the neutrophil. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in

Dictionary 357

tobacco smoke. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitrogen Dioxide: Nitrogen oxide (NO2). A highly poisonous gas. Exposure produces inflammation of lungs that may only cause slight pain or pass unnoticed, but resulting edema several days later may cause death. (From Merck, 11th ed) It is a major atmospheric pollutant that is able to absorb UV light that does not reach the earth's surface. [NIH] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [NIH]

Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio

358

Vitamin E

of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmic: Pertaining to the eye. [EU] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum;

Dictionary 359

lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteodystrophy: Defective bone formation. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overactive bladder: A condition in which the patient experiences two or all three of the following conditions: [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

360

Vitamin E

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Oxytetracycline: An antibiotic substance isolated from the actinomycete Streptomyces rimosus and used in a wide variety of clinical conditions. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paratyphoid Fever: A prolonged febrile illness commonly caused by serotypes of Salmonella paratyphi. It is similar to typhoid fever but less severe. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other

Dictionary 361

route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perineal: Pertaining to the perineum. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs

362

Vitamin E

of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pernicious: Tending to a fatal issue. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Peroxisome Proliferators: A class of nongenotoxic carcinogens that induce the production of hepatic peroxisomes and induce hepatic neoplasms after long-term administration. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacists: Those persons legally qualified by education and training to engage in the practice of pharmacy. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions

Dictionary 363

between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebitis: Inflammation of a vein. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoreceptors: Cells specialized to detect and transduce light. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age.

364

Vitamin E

[NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Plastoquinone: Polyunsaturated side-chain quinone derivative which is an important link in the electron transport chain of green plants during the photosynthetic conversion of light energy by photophosphorylation into the potential energy of chemical bonds. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH]

Dictionary 365

Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Policy Making: The decision process by which individuals, groups or institutions establish policies pertaining to plans, programs or procedures. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short

366

Vitamin E

oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Porphyria, Hepatic: Porphyria in which the liver is the site where excess formation of porphyrin or its precursors is found. Acute intermittent porphyria and porphyria cutanea tarda are types of hepatic porphyria. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of

Dictionary 367

muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Praseodymium: Praseodymium. An element of the rare earth family of metals. It has the atomic symbol Pr, atomic number 59, and atomic weight 140.91. [NIH] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (hydroxymethylglutaryl CoA reductases). [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pre-Eclampsia: Development of hypertension with proteinuria, edema, or both, due to pregnancy or the influence of a recent pregnancy. It occurs after the 20th week of gestation, but it may develop before this time in the presence of trophoblastic disease. [NIH] Pre-eclamptic: A syndrome characterized by hypertension, albuminuria, and generalized oedema, occurring only in pregnancy. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH]

368

Vitamin E

Primary Prevention: Prevention of disease or mental disorders in susceptible individuals or populations through promotion of health, including mental health, and specific protection, as in immunization, as distinguished from the prevention of complications or after-effects of existing disease. [NIH] Primary tumor: The original tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane).

Dictionary 369

The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatectomy: Complete or partial surgical removal of the prostate. Three primary approaches are commonly employed: suprapubic - removal through an incision above the pubis and through the urinary bladder; retropubic - as for suprapubic but without entering the urinary bladder; and transurethral (transurethral resection of prostate). [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH]

370

Vitamin E

Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]

Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]

Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Prune Belly Syndrome: A syndrome characterized by abdominal wall musculature deficiency, cryptorchism, and urinary tract abnormalities. The syndrome derives its name from its characteristic distended abdomen with wrinkled skin. [NIH] P-Selectin: Cell adhesion molecule and CD antigen that mediates the adhesion of neutrophils and monocytes to activated platelets and endothelial cells. [NIH] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH]

Dictionary 371

Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quality of Life: A generic concept reflecting concern with the modification and

372

Vitamin E

enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radical prostatectomy: Surgery to remove the entire prostate. The two types of radical prostatectomy are retropubic prostatectomy and perineal prostatectomy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the

Dictionary 373

kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Cytokine: Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells. [NIH] Recessive gene: A gene that is phenotypically expressed only when homozygous. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Reishi: A mushroom, Ganoderma lucidum, of the aphyllophorales order of basidomycetous fungi. It has long been used in traditional Chinese medicine in various forms. Contains sterols, coumarin, mannitol, polysaccharides, and triterpenoids. [NIH]

374

Vitamin E

Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinae: A congenital notch or cleft of the retina, usually located inferiorly. [NIH]

Dictionary 375

Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retropubic: A potential space between the urinary bladder and the symphisis and body of the pubis. [NIH] Retropubic prostatectomy: Surgery to remove the prostate through an incision made in the abdominal wall. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH]

376

Vitamin E

Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Ruthenium: A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for platinum and palladium. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonellosis: Infection by salmonellae. [NIH] Saponification: The hydrolysis of an ester into an alcohol and acid. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is

Dictionary 377

usually highly malignant. [NIH] Scandium: Scandium. An element of the rare earth family of metals. It has the atomic symbol Sc, atomic number 21, and atomic weight 45. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [NIH]

378

Vitamin E

Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Senile Plaques: Spherical masses consisting of amyloid fibrils and neuronal processes. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the

Dictionary 379

one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Care: Maintenance of the hygienic state of the skin under optimal conditions of cleanliness and comfort. Effective in skin care are proper washing, bathing, cleansing, and the use of soaps, detergents, oils, etc. In various disease states, therapeutic and protective solutions and ointments are useful. The care of the skin is particularly important in various occupations, in exposure to sunlight, in neonates, and in decubitus ulcer. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH]

380

Vitamin E

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solar radiation: Sunbathing as a therapeutic measure. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by

Dictionary 381

refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprue: A non febrile tropical disease of uncertain origin. [NIH] Squamous: Scaly, or platelike. [EU] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Steatosis: Fatty degeneration. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH]

382

Vitamin E

Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH]

Dictionary 383

Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH]

384

Vitamin E

Tea Tree Oil: Essential oil extracted from Melaleuca alternifolia (tea tree). It is used as a topical antimicrobial due to the presence of terpineol. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]

hydroxyethyl)-4-

Thiobarbituric Acid Reactive Substances: Low-molecular-weight end products, probably malondialdehyde, that are formed during the decomposition of lipid peroxidation products. These compounds react with thiobarbituric acid to form a fluorescent red adduct. [NIH] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level

Dictionary 385

(absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tilapia: A freshwater fish used as an experimental organism and for food. This genus of the family Cichlidae inhabits Central and South America (one species extends north into Texas), West Indies, Africa, Madagascar, Syria, and coastal India. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [NIH] Tobacco Use Cessation: Cessation of the habit of using tobacco products for smoking or chewing, including the use of snuff. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired

386

Vitamin E

drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoids: Preparations of pathogenic organisms or their derivatives made nontoxic and intended for active immunologic prophylaxis. They include deactivated toxins. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3.

Dictionary 387

Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trichloroacetic Acid: A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Triolein: (Z)-9-Octadecenoic acid 1,2,3-propanetriyl ester. [NIH] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs

388

Vitamin E

from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants. [NIH]

Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Unsaturated Fats: A type of fat. [NIH] Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH]

Dictionary 389

Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uroporphyrinogen Decarboxylase: One of the enzymes active in heme biosynthesis. It catalyzes the decarboxylation of uroporphyrinogen III to coproporphyrinogen III by the conversion of four acetic acid groups to four methyl groups. EC 4.1.1.37. [NIH] Ursodeoxycholic Acid: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginal Smears: Collection of pooled secretions of the posterior vaginal fornix for cytologic examination. [NIH] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects. [NIH] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged

390

Vitamin E

exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH]

Dictionary 391

Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vital Capacity: The volume of air that is exhaled by a maximal expiration following a maximal inspiration. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitamin E: Vitamin found largely in plant materials, especially wheat germ, corn, sunflower seed, rapeseed, soybean oils, alfalfa, and lettuce. It is used as an antioxidant in vegetable oils and shortenings. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH]

392

Vitamin E

Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called observation. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] Weight Lifting: A sport in which weights are lifted competitively or as an exercise. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]

Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Ytterbium: Ytterbium. An element of the rare earth family of metals. It has the atomic symbol Yb, atomic number 70, and atomic weight 173. Ytterbium has been used in lasers and as a portable X-ray source. [NIH] Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers. [NIH] Zinc Compounds: Inorganic compounds that contain zinc as an integral part of the molecule. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

393

INDEX 5 5-Hydroxytryptophan, 195, 291 A Abdomen, 175, 291, 304, 305, 326, 342, 347, 360, 362, 370, 381, 384, 391 Abdominal, 72, 147, 229, 291, 343, 346, 350, 360, 362, 370, 375 Abdominal Pain, 291, 343 Aberrant, 29, 145, 291 Abscisic Acid, 234, 291 Acatalasia, 291, 308 Acceptor, 291, 346, 359, 386 Accommodation, 291, 354 Acetone, 215, 291, 344 Acetylcholine, 291, 311, 357 Acetylcholinesterase, 11, 183, 291 Acetylcysteine, 43, 50, 102, 251, 291 Acne, 79, 147, 291, 344 Acne Vulgaris, 79, 291, 344 Acrylonitrile, 291, 376 Actin, 291, 355 Activities of Daily Living, 5, 7, 51, 291 Acuity, 175, 292, 391 Acyl, 50, 292, 350 Adaptability, 292, 309 Adaptation, 292, 341, 357, 364 Adduct, 134, 292, 384 Adenine, 292 Adenocarcinoma, 28, 72, 90, 292 Adenosine, 182, 207, 292, 295, 300, 306, 363, 384 Adenylate Cyclase, 14, 292 Adipose Tissue, 30, 292, 347 Adjunctive Therapy, 8, 292 Adjustment, 211, 291, 292 Adjuvant, 36, 72, 130, 142, 143, 241, 292, 331 Adrenal Cortex, 292, 316, 327, 368 Adsorption, 194, 197, 292 Adsorptive, 292 Adverse Effect, 211, 238, 292, 344, 378 Aerobic, 59, 215, 292, 351, 360, 388 Aerobic Metabolism, 215, 292, 360 Aerobic Respiration, 292, 360 Aerosol, 293, 357 Affinity, 293, 300, 320, 347, 380 Agar, 293, 364 Age of Onset, 293, 388

Ageing, 131, 246, 293 Agonist, 182, 293, 322, 356 Air Pollutants, 218, 293 Airway, 43, 123, 293 Albumin, 90, 206, 240, 293, 364 Aldehydes, 180, 293 Aldose Reductase Inhibitor, 50, 293 Alertness, 293, 306 Alfalfa, 159, 293, 391 Algorithms, 294, 304 Alimentary, 294, 321, 360 Alkaline, 61, 74, 131, 294, 295, 306, 362 Alkaloid, 294, 307, 312, 313, 356, 384 Alleles, 29, 30, 294 Allo, 186, 294 Allylamine, 294 Aloe, 159, 185, 220, 221, 294 Alpha Particles, 294, 372 Alpha-1, 294, 317 Alpha-helix, 294, 344 Alpha-Linolenic Acid, 30, 195, 294 Alternative medicine, 129, 165, 172, 261, 294, 314 Aluminum, 200, 253, 294, 392 Ameliorating, 240, 294 Amenorrhea, 148, 294, 365 Amine, 200, 294, 337 Amino Acid Sequence, 234, 294, 297, 331, 368 Amino Acids, 48, 195, 198, 227, 294, 295, 303, 327, 331, 349, 356, 361, 366, 370, 378, 382, 388 Aminobenzoic Acids, 230, 295 Amino-terminal, 295, 368 Amiodarone, 120, 140, 159, 295 Ammonia, 294, 295, 333, 383, 388 Amphetamine, 295, 303 Amplification, 38, 295 Ampulla, 295, 311 Amyloid, 9, 11, 51, 133, 217, 270, 295, 378 Anaemia, 85, 90, 135, 142, 295, 349 Anaerobic, 231, 295 Anaesthesia, 95, 137, 295, 340 Anal, 295, 326, 340, 353, 360 Analgesic, 295, 313, 320, 339, 346, 354, 357 Analog, 31, 210, 211, 217, 219, 295, 320, 357 Analogous, 295, 365, 386

394

Vitamin E

Analysis of Variance, 11, 295 Anaphylatoxins, 295, 314 Anaplasia, 296 Anastomosis, 28, 296 Anatomical, 296, 300, 321, 325, 340, 377 Anemia, 84, 87, 121, 131, 148, 157, 274, 296, 302, 312, 329, 347, 362, 384 Anesthesia, 293, 296, 325 Aneurysm, 72, 296, 298, 390 Angina, 6, 148, 296, 297 Angina Pectoris, 6, 296 Anginal, 208, 296, 297 Angiogenesis, 53, 89, 103, 121, 136, 229, 296 Angiography, 5, 45, 175, 296, 329 Angioplasty, 45, 83, 296, 353 Anhydrides, 202, 296 Animal model, 19, 26, 296 Animal Welfare, 63, 296 Anionic, 221, 239, 296 Anions, 293, 296, 343, 382 Annealing, 296, 366 Anorexia, 148, 184, 195, 296 Anovulation, 296, 365 Antagonism, 42, 297, 306, 384 Anthocyanins, 205, 297 Anthracycline, 297, 339 Antianginal, 295, 297 Antiarrhythmic, 295, 297 Antibacterial, 185, 297, 302, 381 Antibiotic, 65, 297, 339, 360, 361, 381 Antibodies, 240, 297, 336, 339, 340, 348, 364, 372 Antibody, 31, 107, 137, 139, 293, 297, 314, 337, 340, 341, 343, 349, 352, 372, 380, 392 Anticarcinogenic, 15, 297 Anticoagulant, 91, 297, 320, 369, 392 Anticonvulsant, 297, 376 Antidepressant, 291, 297 Antiepileptic, 171, 291, 297 Antifungal, 297, 302 Antigen, 16, 53, 70, 186, 242, 293, 297, 314, 319, 332, 337, 339, 340, 341, 342, 349, 369, 370 Antigen-Antibody Complex, 297, 314 Antigen-presenting cell, 186, 297, 319 Anti-infective, 297, 307, 338, 343, 379 Anti-inflammatory, 41, 42, 164, 204, 213, 232, 270, 297, 300, 320, 332, 339 Anti-Inflammatory Agents, 297, 300 Antimicrobial, 139, 180, 181, 297, 312, 320, 384

Antineoplastic, 229, 298, 331, 332, 360, 365, 390 Antiproliferative, 14, 204, 298 Antipruritic, 298, 307 Antipsychotic, 298, 355, 376 Antipyretic, 298, 320 Antiseptic, 291, 298 Antitussive, 298, 320 Antiviral, 291, 298, 320, 331, 342 Anuria, 298, 344 Anus, 254, 295, 298, 300, 305, 340 Aorta, 16, 298, 307, 390 Aortic Aneurysm, 72, 298 Apathy, 298, 355 Apheresis, 77, 298 Apolipoproteins, 32, 298, 347 Applicability, 206, 299 Aqueous, 68, 217, 218, 225, 239, 250, 299, 301, 318, 325, 338, 345, 347 Arachidonate 12-Lipoxygenase, 299, 347 Arachidonate 15-Lipoxygenase, 299, 347 Arachidonate Lipoxygenases, 299, 347 Arachidonic Acid, 28, 50, 299, 346, 347, 368 Arcuate Nucleus, 17, 299 Arginine, 27, 59, 187, 192, 237, 295, 299, 357 Aromatic, 203, 299, 303, 363, 382 Arterial, 18, 87, 199, 208, 294, 299, 311, 339, 370, 383 Arteries, 199, 219, 258, 259, 298, 299, 300, 304, 305, 316, 343, 348, 351, 353, 371, 385 Arterioles, 299, 304, 307, 351, 353, 390 Arteriolosclerosis, 299 Arteriosclerosis, 64, 75, 96, 98, 145, 148, 299, 316, 339, 353 Articular, 299, 359 Ascorbic Acid, 12, 47, 73, 93, 124, 133, 212, 219, 231, 253, 270, 299, 338, 359 Aspartate, 300, 320 Aspartic, 300, 312, 325, 327 Aspartic Endopeptidases, 300, 325 Asphyxia, 300, 357 Aspirin, 13, 41, 53, 55, 61, 99, 119, 133, 134, 160, 177, 235, 260, 300 Assay, 38, 42, 50, 61, 66, 74, 131, 300 Asthenia, 195, 300 Astringents, 300, 327 Astrocytes, 17, 300, 352 Asymptomatic, 291, 300, 302, 336 Ataxia, 20, 68, 71, 74, 87, 88, 97, 259, 273, 300, 310, 384

Index 395

Atherogenic, 16, 57, 300 Atmospheric Pressure, 300, 338 ATP, 182, 207, 292, 300, 322, 332, 343, 363, 369, 370, 386 Atresia, 254, 300 Atrial, 295, 300, 392 Atrial Fibrillation, 300, 392 Atrium, 300, 307, 390 Atrophy, 220, 273, 300, 346, 353, 355 Attenuated, 241, 301 Atypical, 301, 376 Auditory, 63, 301 Autoimmune disease, 211, 301 Avian, 132, 301, 317 Axillary, 301, 305 Axillary Artery, 301, 305 Axons, 301, 355, 358 Azoxymethane, 145, 301 B Bacterial Infections, 186, 211, 301, 309 Bactericidal, 301, 327, 388 Bacteriophage, 301, 364, 386, 391 Bacterium, 301, 322, 336 Basal cell carcinoma, 193, 301 Basal cells, 301 Basal Ganglia, 298, 300, 301, 311, 331 Basal Ganglia Diseases, 300, 301, 311 Basal Metabolism, 198, 301 Base, 8, 35, 180, 220, 223, 238, 292, 301, 319, 329, 331, 334, 344, 345, 351, 362, 365 Basement Membrane, 302, 328 Basophils, 186, 302, 309, 334, 345 Behavioral Symptoms, 7, 302 Benign, 108, 139, 148, 252, 299, 302, 329, 331, 334, 335, 355, 369, 372, 392 Benign prostatic hyperplasia, 108, 139, 302, 329 Benzaldehyde, 180, 302 Benzene, 302 Benzo(a)pyrene, 19, 95, 302 Benzoates, 180, 302 Benzoic Acid, 302 Beta carotene, 75, 113, 199, 205, 207, 251, 270, 302 Beta Rays, 302, 324 Beta-pleated, 295, 302 Beta-Thalassemia, 104, 302 Bewilderment, 302, 315 Bilateral, 302, 365, 375 Bile, 18, 44, 161, 198, 302, 303, 310, 330, 331, 337, 347, 381, 383, 389 Bile Acids, 302, 303, 331, 381, 383

Bile Acids and Salts, 302, 303 Bile Ducts, 303, 330 Biliary, 19, 303, 306, 311 Biliary Tract, 303, 306 Bilirubin, 293, 303, 330 Binding Sites, 32, 303 Bioavailability, 75, 76, 94, 120, 189, 226, 303 Bioavailable, 57, 226, 303 Biochemical reactions, 303, 384 Biogenic Amines, 61, 303 Biological Markers, 9, 303 Biological response modifier, 303, 342 Biological therapy, 303, 334 Biomarkers, 11, 19, 20, 27, 61, 71, 130, 303 Biopsy, 252, 303, 327 Biosynthesis, 15, 69, 110, 123, 205, 226, 227, 234, 299, 303, 348, 369, 378, 379, 389 Biotechnology, 67, 70, 137, 249, 261, 269, 272, 273, 274, 304 Biotic, 304, 388 Biotin, 184, 198, 212, 231, 232, 252, 253, 304 Bladder, 143, 187, 256, 258, 302, 304, 311, 330, 340, 359, 369, 374, 375, 389 Blastocyst, 143, 304, 314, 364, 387 Bloating, 304, 343 Blood Coagulation, 11, 304, 306, 385 Blood Coagulation Factors, 304 Blood Glucose, 12, 196, 197, 304, 335, 339, 341 Blood Platelets, 304, 378, 385 Blood pressure, 55, 132, 175, 199, 219, 304, 307, 339, 352, 357, 362, 371, 380 Body Fluids, 303, 304, 306, 323, 380, 387 Body Mass Index, 55, 304, 359 Bone Cements, 103, 304 Bone Density, 38, 39, 40, 304 Bone Marrow, 38, 39, 40, 89, 112, 185, 186, 302, 304, 305, 317, 326, 334, 340, 348, 380 Bone Marrow Transplantation, 89, 112, 305 Bone Remodeling, 216, 305 Bone Resorption, 305 Borates, 180, 305 Boron, 200, 202, 305, 317 Boron Neutron Capture Therapy, 305 Bowel, 22, 36, 254, 295, 305, 321, 342, 343, 345, 357, 362, 381 Bowel Movement, 305, 321, 381 Brachial, 27, 45, 305 Brachial Artery, 27, 45, 305 Brachytherapy, 305, 342, 343, 372, 392

396

Vitamin E

Bradykinin, 305, 357, 364 Brain metastases, 176, 305 Brain Stem, 305, 355 Branch, 287, 305, 324, 348, 361, 371, 380, 384 Breakdown, 212, 227, 305, 309, 321, 331, 358, 379 Breeding, 205, 305 Bronchi, 305, 326, 384, 386 Bronchial, 305, 337, 384 Bronchitis, 149, 305, 311, 327 Bronchopulmonary, 86, 305, 306 Bronchopulmonary Dysplasia, 86, 306 Buccal, 54, 306, 381 Burns, 87, 149, 183, 306 Burns, Electric, 306 Buthionine sulfoximine, 66, 306 Butylated Hydroxytoluene, 210, 306 Bypass, 106, 306, 307, 353 C Cachexia, 195, 209, 306 Caffeine, 192, 306 Calcification, 45, 299, 306 Calcium Oxalate, 26, 306, 359 Calculi, 26, 306, 334 Callus, 306, 324 Caloric intake, 182, 195, 207, 306 Calorimeter, 301, 306 Camphor, 220, 306 Cancer vaccine, 186, 307 Canthaxanthin, 193, 307 Capillary, 305, 307, 308, 347, 376, 390 Capillary Fragility, 307, 308, 376 Capsaicin, 199, 307 Capsules, 181, 189, 225, 307, 329, 331 Carbohydrate, 52, 195, 235, 237, 238, 246, 251, 307, 332, 333, 366 Carbon Dioxide, 200, 307, 319, 364, 374 Carcinogen, 25, 228, 292, 301, 302, 307, 353 Carcinogenesis, 19, 34, 113, 251, 307, 310 Carcinogenic, 302, 307, 341, 358, 381, 388 Carcinoma, 76, 84, 100, 108, 114, 144, 193, 195, 203, 260, 301, 307, 312, 320 Cardiomyopathy, 10, 47, 208, 307, 321 Cardiopulmonary, 106, 307 Cardiopulmonary Bypass, 106, 307 Cardiotoxic, 10, 307 Cardiotoxicity, 10, 139, 307 Cardiovascular System, 232, 307 Carnitine, 167, 214, 307

Carotenoids, 15, 25, 30, 35, 44, 45, 54, 80, 81, 95, 110, 112, 140, 141, 161, 184, 193, 197, 205, 234, 242, 246, 249, 302, 308 Carrier Proteins, 308, 364 Caspase, 16, 48, 308 Castor Oil, 185, 188, 217, 308 Catabolism, 80, 308, 388 Catalase, 50, 61, 231, 235, 291, 308 Cataract, 4, 54, 55, 74, 100, 214, 308 Catechin, 112, 139, 308 Catecholamines, 308, 322, 352 Catheterization, 296, 308, 353 Cathode, 302, 308, 324, 327 Cations, 308, 343 Caudal, 308, 320, 339, 366 Causal, 308, 326, 336, 342 Cause of Death, 219, 232, 308 Caustic, 308, 379, 387 Cell Adhesion, 17, 18, 83, 146, 308, 342 Cell Adhesion Molecules, 18, 83, 308 Cell Count, 175, 309, 362 Cell Cycle, 23, 27, 100, 309, 312, 317, 327, 370 Cell Death, 22, 31, 33, 70, 298, 309, 327, 332, 354 Cell Degranulation, 63, 309 Cell Differentiation, 309, 379 Cell Division, 273, 301, 309, 327, 334, 349, 352, 364, 368, 377 Cell membrane, 12, 34, 54, 211, 308, 309, 319, 328, 331, 343, 344, 363 Cell proliferation, 16, 20, 34, 53, 100, 229, 299, 309, 379 Cell Respiration, 292, 309, 351, 360, 374 Cell Survival, 309, 334 Cellobiose, 309 Cellular metabolism, 250, 256, 309 Cellulose, 181, 309, 330, 351, 364 Central Nervous System Infections, 309, 335 Cerebellar, 300, 309, 373, 387 Cerebellar Diseases, 300, 309, 387 Cerebral, 6, 300, 301, 305, 310, 315, 326, 336, 354, 371, 380, 384 Cerebrospinal, 9, 310, 378 Cerebrospinal fluid, 9, 310, 378 Cerebrovascular, 177, 208, 301, 307, 310, 384 Cerebrum, 310, 387 Cerium, 201, 310 Ceroid, 143, 310, 347 Character, 296, 310, 319

Index 397

Chemokines, 64, 310 Chemoprevention, 19, 21, 25, 26, 28, 52, 59, 172, 174, 175, 251, 310 Chemopreventive, 15, 19, 29, 310 Chemotactic Factors, 310, 314, 356 Chemotaxis, 240, 310 Chemotherapy, 31, 89, 103, 114, 121, 138, 144, 161, 173, 195, 209, 310 Chenodeoxycholic Acid, 310, 389 Chlorine, 198, 310 Chlorpyrifos, 121, 310 Cholangitis, 254, 310 Cholecalciferol, 231, 310 Cholecystitis, 254, 311 Choleretic, 310, 311, 389 Cholestasis, 83, 102, 119, 120, 133, 311 Cholesterol Esters, 311, 347 Choline, 70, 140, 291, 311 Cholinergic, 183, 217, 298, 311, 356 Cholinesterase Inhibitors, 255, 311, 322 Chorea, 109, 298, 311 Choreatic Disorders, 311 Chorioretinitis, 311, 375 Choroid, 311, 374, 375, 389 Chromatin, 298, 311, 326, 381 Chromium, 137, 184, 231, 252, 311 Chromosomal, 34, 70, 80, 295, 311, 375 Chromosome, 88, 311, 335, 346, 377, 388 Chronic Disease, 4, 46, 50, 66, 306, 311 Chronic Obstructive Pulmonary Disease, 134, 149, 176, 311 Chronic renal, 252, 312, 365 Chylomicrons, 312, 347 Chymopapain, 312, 360 Ciprofloxacin, 80, 312 CIS, 312, 375 Cisplatin, 71, 103, 121, 123, 126, 138, 258, 312 Citrus, 213, 299, 312 Clear cell carcinoma, 312, 320 Clinical Medicine, 140, 312, 367 Clinical study, 312, 315 Cloning, 23, 304, 312 Coagulation, 11, 169, 304, 306, 312, 336, 364, 385, 392 Cobalt, 64, 200, 212, 312 Coca, 312 Cocaine, 10, 312 Cod Liver Oil, 313, 325 Codeine, 313, 320 Coenzyme, 69, 73, 99, 101, 161, 181, 203, 207, 214, 270, 299, 313, 348, 356, 379

Cofactor, 15, 313, 356, 370, 385 Cognition, 9, 169, 313, 355 Cohort Studies, 313, 326 Colchicine, 78, 313 Colitis, 137, 254, 313, 343 Collagen, 185, 216, 219, 221, 252, 302, 308, 313, 329, 331, 334, 365, 368 Collapse, 305, 313 Colloidal, 293, 313, 362 Colorectal, 72, 130, 150, 313 Colorectal Cancer, 72, 130, 150, 313 Colostrum, 96, 313 Combination Therapy, 7, 313, 327 Combinatorial, 10, 313 Communis, 308, 313 Complement, 22, 35, 41, 51, 54, 240, 295, 314, 331, 342, 364 Complementary and alternative medicine, 129, 165, 314 Complementary medicine, 129, 314 Compress, 314, 336 Computational Biology, 269, 272, 314 Conception, 314, 315, 329 Concomitant, 79, 190, 260, 314 Concretion, 306, 314 Conduction, 50, 119, 314 Cones, 315, 375 Confounding, 54, 315 Confusion, 51, 61, 315, 321, 355, 389 Congestion, 298, 315, 326 Congestive heart failure, 47, 184, 315 Conjugated, 103, 190, 302, 303, 310, 315, 318 Conjunctiva, 314, 315, 341 Connective Tissue, 122, 150, 219, 299, 304, 313, 315, 329, 331, 348, 350, 370, 375, 376 Connective Tissue Cells, 315 Consciousness, 295, 315, 319, 321 Constipation, 256, 298, 315, 343 Constitutional, 315, 353, 375 Constriction, 315, 343 Consumption, 10, 19, 26, 47, 190, 238, 250, 315, 320, 357, 374 Contact dermatitis, 89, 116, 144, 315 Contamination, 181, 201, 202, 238, 315, 336 Contraceptive, 142, 315 Contraindications, ii, 315 Control group, 21, 315, 364, 367 Controlled clinical trial, 59, 122, 143, 315 Controlled study, 88, 95, 110, 137, 140, 315 Convulsions, 297, 315, 323, 356, 367 Cooperative group, 59, 315

398

Vitamin E

Cornea, 316, 377, 389 Corneum, 105, 221, 316, 326 Coronary Arteriosclerosis, 316, 353 Coronary Circulation, 296, 316 Coronary Disease, 119, 177, 316 Coronary heart disease, 16, 30, 64, 75, 119, 189, 208, 307, 316 Coronary Thrombosis, 316, 351, 353 Coronary Vessels, 316 Corpus, 316, 368, 384 Corpus Luteum, 316, 368 Corrosion, 180, 316 Cortex, 292, 300, 316, 327, 337, 354, 368, 371, 373 Cortical, 66, 316, 327, 377, 384 Corticosteroids, 211, 316, 332 Cortisol, 293, 316 Cortisone, 224, 316 Cottonseed Oil, 213, 316 Coumarin, 316, 373 Cranial, 316, 335, 355, 358, 361 Craniocerebral Trauma, 301, 316, 335, 384 Creatinine, 4, 5, 92, 317, 345 Creatinine clearance, 5, 92, 317 Criterion, 66, 317 Crossing-over, 317, 373 Cross-Sectional Studies, 317, 326 Cryotherapy, 252, 317 Crystallins, 54, 317 Cultured cells, 26, 112, 317 Curative, 251, 317, 356, 376, 384 Curcumin, 203, 204, 251, 317 Cutaneous, 23, 150, 193, 315, 317, 363 Cyclic, 150, 185, 213, 292, 306, 317, 334, 357, 363, 366, 369, 384 Cyclin, 16, 317 Cyclodextrins, 213, 317 Cyclosporine, 113, 120, 162, 317 Cystamine, 317 Cysteamine, 183, 317 Cysteine, 24, 29, 50, 84, 102, 129, 231, 291, 310, 312, 317, 318, 325, 354, 382 Cysteine Endopeptidases, 317, 325 Cystine, 317, 318 Cytochrome, 15, 61, 63, 80, 121, 182, 318 Cytochrome b, 15, 121, 318 Cytochrome b5, 15, 121, 318 Cytokine, 10, 22, 43, 72, 93, 130, 185, 240, 318, 361, 373 Cytoplasm, 231, 298, 302, 309, 318, 323, 326, 334, 355, 383 Cytoprotection, 43, 318

Cytoskeleton, 24, 318, 342, 351 Cytotoxic, 58, 307, 318, 372, 379 Cytotoxicity, 43, 69, 80, 87, 112, 294, 312, 318 Cytotoxins, 241, 318 D Dairy Products, 190, 242, 318 Data Collection, 23, 60, 318 Databases, Bibliographic, 269, 318 Deamination, 318, 352, 388 Decarboxylation, 303, 319, 337, 389 Decidua, 319, 364 Decubitus, 319, 379 Decubitus Ulcer, 319, 379 Defense Mechanisms, 61, 134, 319, 342 Degenerative, 41, 115, 116, 194, 214, 319, 336, 348, 359, 375 Deletion, 58, 65, 298, 319 Delivery of Health Care, 319, 335 Dementia, 5, 7, 11, 29, 51, 52, 143, 150, 157, 173, 298, 319, 355 Denaturation, 319, 366 Dendrites, 319, 355 Dendritic, 23, 185, 186, 319, 349 Dendritic cell, 23, 185, 186, 319 Dentists, 251, 319 Deoxyguanosine, 37, 98, 319 Depolarization, 319, 379 Dermal, 240, 252, 319 Dermatitis, 89, 116, 144, 150, 315, 319 Dermatology, 76, 79, 113, 115, 252, 319 Dermatosis, 252, 319 DES, 197, 217, 295, 319 Detergents, 320, 329, 379 Deuterium, 47, 107, 320, 338 Developing Countries, 226, 320 Dextran Sulfate, 137, 320 Dextromethorphan, 218, 320 Diabetes Mellitus, 24, 51, 84, 98, 150, 196, 197, 320, 332, 336, 341, 357 Diabetic Retinopathy, 5, 6, 320, 363 Diagnostic procedure, 179, 261, 320, 363 Dialysate, 320 Dialyzer, 90, 92, 93, 96, 108, 114, 320, 335 Diarrhea, 320, 327, 343 Diastolic, 320, 339 Diclofenac, 222, 320 Diclofenac Sodium, 320 Diencephalon, 320, 339, 355, 384 Dietary Fats, 142, 320, 346 Dietary Fiber, 30, 320 Dietitian, 245, 321

Index 399

Diffusion, 321, 335, 341, 343, 356 Digestion, 235, 236, 294, 302, 303, 305, 320, 321, 342, 346, 347, 360, 381, 389 Digestive system, 178, 253, 321, 352 Digestive tract, 321, 379 Dihydrotestosterone, 321, 373 Dihydroxy, 321, 376 Dilatation, 62, 296, 321, 368, 390 Dilatation, Pathologic, 321, 390 Dilated cardiomyopathy, 47, 321 Dilation, 45, 305, 321, 390 Dimethyl, 215, 321 Diploid, 321, 364 Discrimination, 93, 321 Disease Progression, 59, 270, 321 Disinfectant, 321, 327 Disorientation, 315, 321 Dissociation, 293, 321, 343 Distal, 321, 331, 370 Disulfides, 54, 322 Diuresis, 306, 322, 384 Diuretic, 322, 349, 380 Diverticula, 322 Diverticulitis, 254, 322 Diverticulum, 322 DNA Topoisomerase, 322, 332 Domesticated, 322, 334 Donepezil, 4, 7, 78, 83, 176, 322 Dopamine, 295, 298, 313, 322, 346, 352, 363, 376 Dormancy, 121, 322 Dorsal, 50, 322, 355, 366 Dorsum, 322, 331 Dose-dependent, 16, 57, 211, 322 Double-blinded, 60, 95, 137, 172, 322 Drive, ii, vi, 117, 122, 200, 251, 322, 343 Drug Delivery Systems, 191, 322 Drug Interactions, 264, 322 Drug Tolerance, 322, 386 Duct, 295, 308, 310, 323, 328, 360, 376, 383 Duodenum, 302, 323, 360, 381 Dwarfism, 183, 323 Dyes, 295, 302, 323, 357 Dyskinesia, 98, 110, 115, 158, 218, 219, 298, 323 Dyslipidemia, 101, 323 Dyspareunia, 323, 327 Dysphoria, 229, 323 Dysplasia, 86, 149, 251, 274, 306, 323 Dyspnea, 323, 371 Dysprosium, 201, 323 Dystonia, 74, 102, 298, 323

Dystrophy, 88, 155, 273, 323, 354 E Echocardiography, 48, 323 Eclampsia, 103, 323, 367 Ectoderm, 323, 355 Ectopic, 216, 323 Edema, 122, 156, 174, 175, 229, 240, 310, 315, 320, 323, 336, 344, 353, 354, 357, 367, 371 Effector, 43, 60, 186, 291, 314, 323, 356, 363 Effector cell, 43, 186, 323, 356 Efficacy, 5, 6, 7, 10, 19, 28, 36, 42, 45, 51, 53, 56, 174, 192, 225, 241, 323 Egg Yolk, 144, 323 Ejaculation, 324, 378 Elasticity, 299, 316, 324 Elastin, 313, 324 Electrocoagulation, 312, 324 Electrolyte, 324, 345, 367, 380 Electrons, 15, 63, 182, 298, 302, 308, 324, 343, 352, 359, 372 Electrophysiological, 324, 390 Elementary Particles, 324, 356, 370 Ellagic Acid, 61, 206, 324 Emboli, 324, 392 Embolism, 324, 371, 392 Embolization, 324, 392 Embolus, 324, 340 Embryo, 143, 230, 304, 309, 323, 324, 340, 352, 365 Embryogenesis, 230, 324 Emodin, 294, 324 Emollient, 324, 333, 351, 358 Emphysema, 151, 210, 311, 324 Emulsion, 224, 324 Enamel, 325, 344 Endarterectomy, 296, 325 Endopeptidases, 24, 300, 317, 325, 350, 361, 369, 378 Endothelial cell, 23, 27, 28, 46, 60, 64, 89, 107, 136, 325, 370, 385 Endothelium, 27, 59, 62, 85, 325, 357 Endothelium, Lymphatic, 325 Endothelium, Vascular, 325 Endothelium-derived, 325, 357 Endotoxemia, 43, 325 Endotoxic, 325, 346 Endotoxin, 43, 123, 325, 387 End-stage renal, 105, 146, 260, 312, 325, 365 Energetic, 235, 325 Energy Intake, 53, 325

400

Vitamin E

Environmental Exposure, 220, 303, 325, 358 Environmental Health, 268, 270, 325 Enzymatic, 213, 235, 303, 306, 308, 314, 326, 337, 360, 366, 375 Enzyme Inhibitors, 29, 326, 364 Eosinophils, 186, 309, 326, 334, 345 Ependyma, 299, 326, 384 Epidemiologic Studies, 24, 37, 38, 39, 40, 60, 101, 303, 326 Epidemiological, 9, 30, 64, 208, 326 Epidermal, 113, 326, 344, 349, 392 Epidermis, 185, 193, 241, 301, 316, 326, 337, 344, 367, 371 Epigastric, 326, 360 Epinephrine, 303, 322, 326, 388 Epithelial, 14, 30, 43, 63, 67, 72, 108, 130, 140, 292, 319, 326, 369 Epithelial Cells, 14, 30, 43, 67, 72, 108, 130, 326, 369 Epithelium, 302, 325, 326 Ergometer, 168, 326 ERV, 212, 271, 326, 328 Erythema, 151, 252, 315, 326, 382 Erythrocytes, 98, 104, 295, 296, 304, 326, 336, 373 Erythropoietin, 84, 85, 121, 135, 326 Esophageal, 28, 107, 139, 326, 331, 348 Esophagitis, 209, 326 Esophagus, 254, 300, 321, 326, 327, 331, 348, 362, 373, 381 Essential Tremor, 273, 327 Estradiol, 98, 103, 327 Estrogen, 13, 17, 29, 36, 115, 182, 231, 232, 270, 327 Estrogen receptor, 17, 327 Estrogen Replacement Therapy, 29, 270, 327 Ethanol, 10, 169, 206, 215, 224, 327, 329 Ether, 31, 327 Etoposide, 34, 224, 327 Eucalyptus, 220, 227, 324, 327 Eukaryotic Cells, 15, 327, 358, 388 Europium, 201, 327 Evacuation, 315, 327, 345 Evaluable patients, 26, 327 Excipient, 217, 327 Excisional, 24, 327 Excitatory, 327, 333, 356 Excitatory Amino Acids, 327, 356 Excitotoxicity, 66, 328 Excrete, 298, 328, 344

Exhaustion, 297, 328 Exocrine, 328, 360 Exocytosis, 309, 328, 383 Exogenous, 60, 97, 134, 182, 184, 207, 292, 328, 369, 388 Expiration, 328, 374, 391 Expiratory, 60, 326, 328, 330 Expiratory Reserve Volume, 326, 328 Extensor, 328, 371, 391 External-beam radiation, 328, 343, 372, 392 Extracellular, 24, 56, 58, 67, 295, 300, 315, 328, 329, 342, 380 Extracellular Matrix, 24, 315, 328, 329, 342 Extracellular Space, 328 Extraction, 198, 242, 328 Extrapyramidal, 7, 90, 298, 322, 328 Extravasation, 240, 328, 335 Eye Movements, 175, 328 F Family Planning, 269, 328 Fatigue, 121, 182, 240, 248, 328, 335, 353 Fatty Liver, 21, 70, 103, 138, 328 Febrile, 328, 360, 381 Feces, 315, 328, 381 Femoral, 307, 328, 329 Femoral Artery, 307, 329 Fenbendazole, 212, 329 Fermentation, 242, 329 Fetus, 326, 329, 364, 367, 389 Fibril, 9, 329 Fibrin, 304, 329, 385 Fibrinogen, 252, 329, 364, 385 Fibroblasts, 57, 106, 108, 216, 315, 329 Fibrosis, 21, 44, 93, 99, 115, 120, 150, 210, 211, 254, 274, 294, 329, 336, 371, 376, 377 Filler, 180, 329 Filtration, 242, 329, 344, 349 Finasteride, 52, 329 Fish Oils, 25, 82, 199, 329 Fistula, 329, 357 Flavoring Agents, 327, 329 Fluorescein Angiography, 5, 329 Folate, 23, 25, 252, 329 Fold, 37, 44, 46, 66, 329, 350 Folic Acid, 80, 124, 184, 187, 190, 198, 203, 204, 212, 218, 231, 232, 245, 252, 253, 329 Follicles, 185, 329, 335, 391 Food Technology, 330, 351 Forced Expiratory Volume, 60, 330 Forearm, 62, 142, 304, 330, 372 Fornix, 330, 389

Index 401

Freeze Drying, 242, 330 Fructose, 132, 253, 254, 330, 343 Fructose Intolerance, 253, 254, 330 Fundus, 175, 330, 358 Fungi, 168, 297, 330, 334, 351, 373, 392 Fungus, 330, 332 G Galactosemia, 253, 254, 330 Galenical, 206, 225, 330 Gallbladder, 151, 291, 303, 311, 321, 330 Gallstones, 303, 310, 330, 389 Gamma Rays, 330, 353, 372 Gamma-interferon, 196, 330 Ganglia, 50, 291, 298, 300, 301, 311, 331, 355, 361 Ganglion, 331, 355, 358 Gap Junctions, 331, 383 Gas, 295, 306, 307, 310, 321, 326, 331, 338, 343, 353, 357, 382, 390 Gasoline, 73, 302, 331 Gastric, 107, 109, 122, 133, 139, 235, 236, 260, 308, 331, 337, 338 Gastrin, 331, 337 Gastritis, 235, 236, 254, 331 Gastroesophageal Reflux, 254, 331 Gastrointestinal, 26, 63, 184, 305, 311, 312, 326, 327, 331, 333, 346, 378, 380, 382, 387 Gastrointestinal tract, 311, 327, 331, 333, 346, 378, 380, 387 Gelatin, 225, 331, 383 Gels, 220, 331 Gene Expression, 13, 16, 17, 26, 27, 37, 46, 56, 58, 65, 120, 274, 331 Genetic Code, 331, 357 Genetic Engineering, 304, 312, 331 Genetic testing, 332, 366 Genistein, 187, 332 Genital, 312, 332 Genotype, 29, 168, 332, 363 Geriatric, 134, 332 Germ Cells, 332, 349, 359, 380, 381, 384 Gestation, 332, 364, 367 Giant Cells, 332, 376 Gibberellins, 234, 332 Ginger, 213, 332 Ginseng, 162, 164, 187, 332 Gland, 292, 316, 332, 339, 348, 360, 361, 369, 377, 381, 383, 385 Glial Fibrillary Acidic Protein, 17, 332 Glomerular, 332, 343, 344, 349, 374 Glucans, 317, 332 Glucocorticoid, 33, 56, 134, 332

Gluconeogenesis, 195, 330, 332 Glucose Intolerance, 195, 320, 332 Glucose tolerance, 332, 333 Glucose Tolerance Test, 332, 333 Glutamate, 66, 68, 320, 328, 333, 376 Glutamic Acid, 329, 333, 336, 368 Glutamine, 89, 112, 209, 333 Glutathione Peroxidase, 12, 13, 26, 43, 50, 61, 231, 333, 377 Glycerol, 195, 225, 333, 363 Glycerophospholipids, 333, 363 Glycogen, 333, 353 Glycols, 333, 338 Glycoprotein, 19, 326, 329, 332, 333, 352, 385, 387 Glycosaminoglycans, 333, 370 Glycosidic, 297, 309, 333, 358 Glycosylation, 24, 119, 235, 333 Goats, 318, 333 Gonadal, 333, 381 Gossypol, 134, 333 Gout, 152, 313, 334 Governing Board, 334, 367 Government Agencies, 253, 334, 367 Grade, 21, 175, 334 Graft, 28, 186, 212, 216, 334, 337, 353, 370 Grafting, 334, 340 Graft-versus-host disease, 334, 370 Gram-negative, 325, 334 Granulocytes, 334, 379, 392 Granuloma, 252, 334 Granuloma Annulare, 252, 334 Grasses, 329, 334 Growth factors, 45, 53, 57, 216, 334 Guanidine, 234, 334 Guanylate Cyclase, 334, 357 Guinea Pigs, 12, 334 H Habitat, 212, 334 Habitual, 193, 310, 334 Haemodialysis, 76, 77, 92, 101, 335 Hair follicles, 185, 335, 391 Haploid, 335, 364 Headache, 155, 158, 229, 289, 306, 335, 341 Headache Disorders, 335 Health Care Costs, 16, 26, 335 Health Education, 335 Health Expenditures, 335 Health Fairs, 36, 335 Heart attack, 6, 82, 189, 219, 258, 260, 307, 335

402

Vitamin E

Heart failure, 48, 59, 182, 184, 259, 315, 335, 371 Heartbeat, 335, 382 Hematoma, 335, 336 Heme, 121, 303, 318, 335, 366, 389 Hemodialysis, 5, 45, 74, 76, 84, 90, 93, 97, 114, 121, 141, 146, 252, 320, 335, 344, 345 Hemodialyzer, 259, 335 Hemoglobin, 5, 6, 8, 73, 89, 196, 197, 200, 296, 302, 326, 335, 336, 344, 345, 366, 384 Hemoglobin C, 89, 336 Hemoglobinuria, 273, 336 Hemolysis, 224, 225, 336 Hemolytic, 336, 384 Hemorrhage, 317, 320, 324, 335, 336, 354, 371, 382, 391 Hemorrhagic stroke, 118, 336 Hemostasis, 336, 342, 378 Hepatic Veins, 336 Hepatic Veno-Occlusive Disease, 89, 336 Hepatitis, 21, 41, 44, 152, 210, 211, 254, 336, 391 Hepatitis A, 211, 336 Hepatitis C, 211, 336 Hepatocyte, 311, 336 Hepatoma, 12, 90, 336 Hepatovirus, 336 Hereditary, 20, 196, 311, 334, 336, 355, 362, 375, 384 Heredity, 291, 331, 337 Hernia, 56, 337 Heterodimers, 337, 342, 387 Heterogeneity, 53, 293, 337 Hippocampus, 330, 337, 355 Histamine, 144, 295, 298, 303, 337 Histidine, 64, 337 Histology, 32, 49, 121, 337, 355 Homeostasis, 15, 19, 58, 66, 223, 305, 337 Homodimer, 337, 386 Homologous, 241, 294, 317, 337, 377, 383 Homozygotes, 30, 337 Hormonal, 13, 22, 26, 53, 59, 196, 228, 301, 327, 337, 391 Hormone Replacement Therapy, 36, 232, 255, 337 Horny layer, 185, 326, 337 Host, 43, 48, 69, 191, 195, 212, 234, 240, 301, 329, 337, 339, 346, 375, 391 Human Development, 174, 212, 268, 337 Humoral, 65, 134, 337 Humour, 337 Hyaluronidase, 222, 337

Hybrid, 15, 20, 132, 205, 337 Hydration, 221, 238, 338 Hydrochloric Acid, 201, 202, 212, 236, 338 Hydrogen Bonding, 239, 338 Hydrogen Peroxide, 231, 308, 333, 338, 346, 382 Hydrolysis, 203, 291, 300, 309, 312, 338, 343, 347, 361, 363, 366, 370, 376 Hydrophilic, 206, 216, 221, 225, 238, 239, 320, 338 Hydrophobic, 213, 221, 224, 225, 239, 320, 333, 338, 344, 347 Hydroxides, 338 Hydroxyl Radical, 48, 338 Hydroxylation, 219, 338 Hydroxylysine, 313, 338 Hydroxyproline, 313, 338 Hygienic, 338, 379 Hyperbaric, 54, 338 Hyperbaric oxygen, 338 Hypercholesterolemia, 28, 45, 94, 153, 208, 323, 338 Hyperglycemia, 11, 24, 338 Hyperlipidemia, 24, 102, 195, 208, 323, 338 Hyperlipoproteinemia, 338, 339, 347 Hyperoxaluria, 141, 338 Hyperplasia, 45, 57, 148, 338, 369 Hypersensitivity, 224, 225, 229, 339, 346, 375 Hypertension, 55, 56, 118, 132, 151, 153, 156, 184, 187, 208, 299, 307, 335, 339, 357, 367, 371 Hyperthyroidism, 153, 184, 339 Hypertriglyceridemia, 323, 339 Hypertrophy, 48, 302, 338, 339 Hypoglycemia, 153, 330, 339 Hypoglycemic, 197, 339 Hypolipidemic, 57, 339 Hypoplasia, 56, 339 Hypothalamic, 17, 339 Hypothalamus, 17, 299, 320, 339, 380, 384 Hysterectomy, 232, 339 I Ibuprofen, 224, 339 Id, 124, 146, 279, 286, 288, 339 Idarubicin, 139, 339 Idiopathic, 339, 376 Imaging procedures, 339, 386 Imidazole, 304, 337, 339 Immune function, 186, 270, 339, 386 Immune response, 43, 58, 65, 134, 186, 190, 292, 297, 301, 316, 339, 340, 382, 388, 391

Index 403

Immune Sera, 339, 340 Immune system, 63, 186, 190, 193, 297, 303, 323, 339, 340, 346, 348, 362, 389, 392 Immunity, 65, 132, 186, 248, 318, 339, 340, 358, 386 Immunization, 58, 339, 368 Immunodeficiency, 86, 136, 273, 340 Immunogenic, 58, 340, 346 Immunoglobulin, 137, 141, 252, 297, 340, 352 Immunohistochemistry, 27, 64, 340 Immunologic, 217, 310, 339, 340, 361, 372, 386 Immunology, 13, 27, 65, 186, 190, 292, 293, 340 Immunosuppressive, 211, 332, 340 Impairment, 11, 52, 219, 232, 300, 302, 311, 323, 340, 350 Imperforate Anus, 254, 340 Implant radiation, 340, 342, 343, 372, 392 Implantation, 216, 314, 340, 387 Impotence, 214, 340 Incision, 234, 340, 343, 369, 375 Incompetence, 331, 340 Incontinence, 232, 256, 340 Incubated, 60, 340 Incubation, 16, 340 Indicative, 45, 207, 246, 340, 361, 390 Induction, 20, 43, 57, 61, 94, 108, 186, 298, 340, 379 Industrial Waste, 181, 340 Infantile, 340, 346 Infarction, 6, 30, 46, 62, 82, 136, 155, 177, 189, 316, 336, 340, 351, 353, 374, 392 Infiltration, 43, 341, 356 Influenza, 43, 65, 211, 341 Informed Consent, 4, 341 Infusion, 84, 341, 354, 387 Ingestion, 93, 181, 182, 187, 188, 189, 242, 307, 330, 333, 341, 350, 365 Inhalation, 62, 293, 341, 351, 365 Initiation, 19, 22, 37, 230, 251, 341 Inlay, 341, 374 Inorganic, 180, 191, 192, 236, 305, 312, 322, 338, 341, 343, 357, 363, 392 Inotropic, 322, 341, 389 Insecticides, 341, 392 Insight, 32, 34, 46, 57, 65, 341 Institutionalization, 5, 7, 341 Insulin-dependent diabetes mellitus, 98, 341 Insulin-like, 53, 57, 341, 389

Integrins, 18, 341 Interferon, 78, 173, 196, 210, 211, 330, 342 Interferon-alpha, 342 Interleukin-1, 196, 342 Interleukin-2, 342 Intermediate Filaments, 342, 355 Intermittent, 62, 153, 342, 347, 362, 366 Internal radiation, 342, 343, 372, 392 Interstitial, 57, 240, 305, 328, 342, 343, 374, 392 Intervention Studies, 135, 342 Intestinal, 26, 63, 132, 182, 207, 237, 308, 310, 333, 342, 348, 391 Intestine, 303, 305, 310, 313, 323, 337, 342, 345, 373, 379 Intoxication, 61, 342, 390 Intracellular, 14, 18, 24, 31, 33, 58, 223, 306, 341, 342, 350, 357, 366, 369, 373, 377, 379 Intracellular Membranes, 342, 350 Intraepithelial, 251, 342 Intravascular, 223, 342 Intravenous, 95, 137, 219, 224, 225, 329, 341, 342, 361 Intrinsic, 64, 66, 293, 302, 342 Inulin, 142, 342 Invasive, 45, 339, 343 Involuntary, 301, 311, 327, 343, 354, 373, 379 Iodine, 198, 212, 226, 231, 252, 343 Ion Channels, 300, 343, 356, 383 Ion Transport, 343, 389 Ionization, 31, 73, 343 Ionizing, 212, 294, 325, 343, 372, 388 Ions, 201, 202, 212, 301, 321, 324, 334, 338, 343, 352, 370, 389 Iron Compounds, 226, 343 Irradiation, 54, 168, 211, 305, 343, 392 Irritable Bowel Syndrome, 254, 343 Ischemia, 6, 10, 89, 122, 177, 296, 300, 316, 319, 336, 343, 353, 356, 374 Ischemic stroke, 6, 343 Isoleucine, 195, 344 Isoprenoids, 234, 344 Isopropyl, 227, 236, 344 Isotretinoin, 79, 126, 172, 173, 260, 344 Isozymes, 15, 344 J Joint, 22, 49, 194, 252, 262, 299, 312, 344, 345, 359, 383 K Kb, 268, 344 Keratin, 221, 344, 377

404

Vitamin E

Keratinocytes, 144, 344 Ketone Bodies, 291, 344 Kidney Disease, 3, 74, 84, 173, 178, 268, 274, 344 Kidney Failure, 114, 253, 325, 335, 344, 345, 349 Kidney Failure, Acute, 344 Kidney Failure, Chronic, 344, 345 Kidney stone, 26, 345, 359 Kinetic, 343, 345 Knee Injuries, 38, 39, 40, 345 L Labile, 211, 314, 345 Lactation, 313, 345 Lanthanum, 201, 345 Large Intestine, 313, 321, 342, 345, 373, 379 Latent, 51, 62, 345 Latent period, 51, 62, 345 Laxative, 293, 310, 324, 345, 351, 380 Lectin, 345, 350 Lens, 54, 308, 317, 345, 391 Lesion, 16, 45, 334, 345, 347, 378, 383 Lethal, 13, 70, 301, 345, 353 Leucine, 195, 345 Leukapheresis, 298, 345 Leukemia, 34, 153, 174, 195, 273, 345 Leukocytes, 18, 95, 186, 302, 304, 310, 326, 334, 342, 345, 362, 387 Leukocytosis, 240, 345 Leukopenia, 211, 345 Leukoplakia, 153, 216, 217, 345 Leukotrienes, 115, 299, 346, 347 Levodopa, 346, 377 Levorphanol, 320, 346 Library Services, 286, 346 Life Expectancy, 194, 217, 346 Ligament, 346, 369 Ligands, 58, 308, 342, 346 Linkage, 22, 33, 309, 346 Lip, 173, 346 Lipase, 195, 346, 347 Lipid A, 33, 346 Lipid Bilayers, 12, 346 Lipid Peroxides, 6, 112, 346 Lipodystrophy, 254, 346 Lipofuscin, 310, 346 Lipolysis, 21, 195, 347 Lipophilic, 213, 224, 225, 347 Lipopolysaccharides, 346, 347 Lipoprotein Lipase, 195, 347 Liposome, 56, 347 Lipoxygenase, 16, 67, 299, 346, 347

Lipoxygenase Inhibitors, 17, 347 Liver Cirrhosis, 94, 153, 347 Liver Extracts, 198, 347 Localization, 10, 97, 98, 340, 347 Localized, 26, 251, 252, 334, 335, 341, 346, 347, 352, 364 Locomotion, 347, 364 Long-Term Care, 65, 347 Loop, 337, 347 Lovastatin, 126, 347, 379 Low-density lipoprotein, 31, 72, 77, 79, 91, 98, 99, 130, 144, 323, 347, 348 Lower Esophageal Sphincter, 331, 348 Lubricants, 348, 362 Lumen, 46, 63, 325, 348 Lycopene, 30, 37, 53, 99, 106, 163, 187, 203, 204, 208, 348 Lymph, 63, 301, 325, 337, 348, 376 Lymph node, 63, 301, 348, 376 Lymphatic, 325, 341, 348, 350, 365, 380, 381, 385 Lymphatic system, 348, 380, 381, 385 Lymphocyte, 70, 190, 297, 348, 349 Lymphoid, 297, 316, 348 Lymphoma, 90, 154, 273, 348 Lysine, 336, 338, 348, 368 Lytic, 348, 391 M Macrophage, 17, 58, 342, 348 Macula, 175, 242, 348 Macula Lutea, 348 Macular Degeneration, 55, 70, 144, 154, 235, 242, 348 Malabsorption, 35, 44, 47, 99, 273, 348 Malaise, 323, 348 Malignancy, 195, 348 Malignant, 91, 193, 195, 217, 251, 273, 292, 298, 299, 348, 355, 369, 372, 377 Malnutrition, 47, 184, 195, 293, 300, 306, 349, 353 Malondialdehyde, 11, 16, 98, 168, 349, 384 Mammary, 14, 30, 84, 234, 313, 347, 349 Mammogram, 306, 349, 351 Mannitol, 349, 373 Maple Syrup Urine Disease, 254, 349 Meat, 37, 135, 242, 320, 349 Meat Products, 320, 349 Medial, 44, 299, 349, 358 Mediate, 14, 15, 308, 322, 349 Mediator, 24, 46, 342, 349, 378 Medical Records, 13, 24, 349 Medical Staff, 322, 349

Index 405

Medicament, 196, 235, 236, 349, 383 MEDLINE, 269, 272, 274, 349 Medullary, 320, 349, 371 Megaloblastic, 329, 349 Meiosis, 349, 383, 388 Melanin, 193, 349, 363, 388 Melanocytes, 349, 350 Melanoma, 121, 193, 273, 305, 350 Membrane, 15, 28, 34, 54, 56, 66, 69, 77, 79, 84, 92, 93, 98, 105, 121, 122, 211, 212, 221, 223, 232, 234, 242, 249, 300, 302, 309, 311, 314, 315, 319, 320, 326, 327, 328, 331, 334, 335, 343, 344, 350, 352, 354, 358, 359, 363, 366, 374, 379, 383, 391 Membrane Fluidity, 28, 350 Membrane Proteins, 15, 350 Memory, 11, 29, 52, 154, 173, 255, 296, 319, 350 Meninges, 309, 316, 350 Menopause, 13, 79, 154, 232, 350, 366 Menstrual Cycle, 350, 368 Menstruation, 294, 319, 350, 358 Mental Disorders, 178, 350, 368 Mental Health, iv, 9, 178, 268, 271, 350, 368, 371 Menthol, 220, 227, 350 Mesenchymal, 57, 350 Mesenteric, 63, 350 Mesentery, 350, 362 Metabolite, 41, 67, 94, 103, 173, 210, 225, 227, 240, 321, 347, 350, 367, 368, 372 Metalloendopeptidases, 325, 350 Metaplasia, 16, 350 Metastasis, 53, 309, 350 Metastatic, 26, 53, 195, 350, 377 Methanol, 73, 206, 350 Methionine, 43, 83, 187, 231, 321, 350, 382 Methylcellulose, 216, 351 Methylene Chloride, 192, 236, 351 MI, 6, 103, 133, 227, 290, 351 Microbe, 351, 386 Microcalcifications, 306, 351 Microcirculation, 100, 347, 351 Micronutrients, 25, 35, 75, 112, 230, 351 Microorganism, 227, 313, 351, 361, 391 Microscopy, 63, 302, 351 Microsome, 133, 351 Microtubule-Associated Proteins, 351, 355 Microtubules, 342, 351, 355, 360 Migration, 22, 28, 123, 351 Milligram, 190, 351 Milliliter, 304, 351

Mineral Oil, 221, 227, 232, 233, 351 Miscible, 115, 217, 351 Mitochondria, 20, 181, 207, 231, 351, 354, 358 Mitochondrial Swelling, 351, 354 Mitosis, 298, 352 Mitotic, 327, 352 Mixed Function Oxidases, 318, 352 Modeling, 53, 352 Modification, 29, 70, 80, 98, 331, 352, 371 Molecular, 8, 12, 15, 23, 25, 30, 31, 37, 48, 50, 53, 54, 56, 58, 60, 64, 65, 90, 101, 104, 110, 111, 132, 135, 136, 181, 185, 191, 193, 194, 207, 240, 269, 272, 295, 304, 314, 318, 329, 333, 346, 351, 352, 355, 376, 382, 384, 388 Molecular Structure, 185, 352 Monitor, 317, 352, 357 Monoamine, 7, 295, 352, 377, 388 Monoamine Oxidase, 7, 295, 352, 377, 388 Monoclonal, 343, 352, 372, 392 Monocyte, 18, 58, 352 Mononuclear, 74, 98, 101, 185, 334, 352, 387 Morphological, 17, 50, 58, 92, 222, 293, 324, 330, 349, 352 Morphology, 27, 186, 191, 308, 352 Morula, 304, 352 Mucolytic, 291, 352 Mucosa, 63, 341, 352, 354, 381 Mucositis, 209, 352 Multivariate Analysis, 54, 352 Muscle Fatigue, 240, 353 Muscle Fibers, 353 Muscular Atrophy, 273, 353 Muscular Dystrophies, 323, 353 Musculature, 353, 370 Mustard Gas, 353 Mutagen, 228, 302, 353 Mutagenesis, 19, 353 Mutagenic, 68, 353, 388 Myalgia, 341, 353 Myasthenia, 334, 353 Mydriatic, 321, 353 Myocardial infarction, 6, 30, 36, 46, 62, 82, 189, 208, 316, 351, 353, 392 Myocardial Ischemia, 89, 122, 177, 296, 316, 353 Myocardial Reperfusion, 353, 354, 374 Myocardial Reperfusion Injury, 353, 354, 374 Myocardium, 296, 351, 353, 354

406

Vitamin E

Myopathy, 131, 207, 354 Myopia, 54, 354, 373 Myotonic Dystrophy, 88, 273, 354 N N-acetyl, 24, 29, 50, 102, 231, 291, 333, 354 N-acetyl cysteine, 24, 29, 231, 354 Narcotic, 346, 351, 354, 357 Nasal Mucosa, 341, 354 Nausea, 298, 354, 389 NCI, 1, 52, 173, 174, 176, 177, 229, 267, 278, 312, 354 Nearsightedness, 354 Necrosis, 57, 82, 196, 298, 340, 351, 353, 354, 374, 376, 387 Neocortex, 354, 355 Neodymium, 201, 354 Neonatal, 50, 85, 135, 354 Neoplasia, 175, 251, 273, 355 Neoplasm, 355, 376, 388 Neoplastic, 14, 229, 296, 307, 348, 355 Nephropathy, 3, 5, 94, 240, 344, 355 Nerve Fibers, 23, 355 Nervous System, 17, 20, 91, 273, 291, 295, 302, 306, 309, 311, 312, 331, 333, 335, 346, 349, 355, 356, 358, 361, 378, 380, 382, 383, 384, 388 Neural, 99, 103, 123, 295, 337, 352, 355 Neural Crest, 99, 355 Neurodegenerative Diseases, 41, 240, 301, 355 Neurofibrillary Tangles, 270, 355 Neurofilaments, 355 Neuroleptic, 91, 298, 355 Neurologic, 20, 119, 355 Neuromuscular, 291, 355 Neuromuscular Junction, 291, 355 Neuronal, 17, 20, 51, 66, 68, 123, 143, 355, 378 Neurons, 17, 20, 66, 313, 319, 327, 328, 331, 346, 354, 355, 356, 383 Neuropathy, 20, 50, 71, 293, 355 Neuropeptide, 15, 24, 355 Neuroprotective Agents, 29, 356 Neuropsychological Tests, 29, 356 Neuroretinitis, 356, 375 Neurotic, 356, 389 Neurotoxic, 301, 356 Neurotoxicity, 103, 258, 320, 356 Neurotransmitters, 327, 356 Neutrons, 294, 305, 343, 356, 372 Neutrophil, 43, 80, 108, 259, 356 Neutrophil Activation, 108, 356

Neutrophil Infiltration, 43, 356 Niacin, 184, 198, 212, 213, 251, 253, 260, 356, 387 Niacinamide, 231, 356 Nickel, 200, 356 Nicotine, 120, 129, 210, 356 Night Blindness, 357, 375 Nitrates, 122, 357 Nitric acid, 357 Nitric Oxide, 59, 62, 74, 79, 81, 146, 357 Nitrogen, 48, 68, 69, 195, 294, 333, 345, 357, 360, 387 Nitrogen Dioxide, 68, 69, 357 Nitrous Oxide, 200, 357 Normotensive, 97, 357 Nuclear, 16, 33, 54, 58, 86, 121, 301, 312, 324, 327, 330, 331, 354, 357 Nuclei, 294, 324, 331, 352, 356, 357, 358, 370 Nucleic acid, 227, 234, 331, 357 Nutritional Status, 28, 35, 43, 44, 84, 190, 357 O Octreotide, 122, 357 Odds Ratio, 357, 374 Odour, 299, 358 Office Visits, 25, 358 Ointments, 358, 379 Oligomenorrhea, 358, 365 Oligosaccharides, 213, 358 Oliguria, 344, 349, 358 Omega-3 fatty acid, 53, 214, 358 Oncogene, 114, 273, 358, 360, 370 Oncogenic, 342, 358, 370 Oncology, 26, 34, 36, 58, 71, 84, 103, 108, 109, 130, 138, 173, 174, 209, 358 Opacity, 308, 319, 358 Ophthalmic, 74, 100, 358 Opsin, 358, 375 Optic Chiasm, 339, 358 Optic Disk, 320, 348, 358 Optic Nerve, 356, 358, 374, 375, 377 Organ Culture, 358, 385 Organelles, 181, 207, 318, 349, 358, 364 Orthostatic, 298, 357, 359 Osmosis, 359 Osmotic, 223, 293, 351, 359 Osteoarthritis, 38, 39, 40, 110, 140, 155, 184, 259, 359 Osteodystrophy, 359 Osteoporosis, 154, 232, 305, 327, 359 Outpatient, 172, 359

Index 407

Ovaries, 359, 365, 378 Ovary, 57, 316, 327, 359, 365 Overactive bladder, 187, 359 Overweight, 38, 39, 40, 123, 359 Ovulation, 192, 296, 359 Ovum, 316, 319, 332, 352, 359, 368, 387 Oxalate, 26, 306, 338, 359 Oxalic Acid, 306, 359 Oxidants, 18, 47, 48, 56, 57, 60, 65, 134, 198, 199, 242, 359 Oxidation-Reduction, 359, 360 Oxidative metabolism, 292, 346, 360 Oxidative Stress, 6, 10, 13, 16, 17, 18, 20, 22, 26, 28, 34, 43, 44, 45, 46, 47, 48, 49, 54, 56, 57, 59, 61, 66, 68, 73, 77, 84, 90, 95, 97, 102, 103, 104, 108, 109, 110, 111, 114, 120, 122, 130, 132, 135, 137, 138, 140, 142, 143, 145, 173, 184, 214, 215, 360 Oxygenation, 231, 336, 360 Oxygenator, 307, 360 Oxytetracycline, 212, 360 P Paclitaxel, 129, 164, 224, 229, 360 Palate, 360, 381 Palladium, 201, 360, 376 Palliative, 360, 384 Pancreas, 195, 197, 291, 303, 304, 321, 341, 346, 360, 377, 380, 387 Pancreatic, 44, 72, 155, 273, 308, 331, 360 Pancreatic cancer, 273, 360 Pancreatic Insufficiency, 44, 155, 360 Pancreatic Juice, 331, 360 Papain, 222, 360 Paralysis, 237, 360, 380 Paratyphoid Fever, 242, 360 Parenteral, 109, 325, 360 Parotid, 361, 376 Paroxysmal, 273, 296, 335, 361 Particle, 68, 347, 361, 380, 386 Patch, 345, 361 Pathogen, 340, 361 Pathogenesis, 10, 49, 52, 62, 65, 208, 241, 252, 361 Pathologic, 18, 298, 303, 316, 321, 339, 361, 371, 374, 390 Pathologic Processes, 298, 361 Pathophysiology, 28, 45, 49, 57, 103, 361 Patient Education, 278, 284, 286, 290, 361 Pelvic, 155, 256, 361, 369 Penicillin, 297, 361, 389 Pentoxifylline, 164, 210, 258, 361 Pepsin, 235, 236, 361

Peptide, 51, 183, 218, 325, 344, 361, 366, 368, 369, 370 Peptide Hydrolases, 325, 361 Perennial, 361, 387 Perfusion, 27, 361, 385 Perineal, 361, 372 Peripheral blood, 74, 186, 342, 361 Peripheral Nervous System, 355, 361, 380, 382 Peripheral Vascular Disease, 6, 107, 156, 208, 361 Peritoneal, 252, 320, 362 Peritoneal Cavity, 362 Peritoneal Dialysis, 252, 320, 362 Peritoneum, 350, 362 Pernicious, 347, 349, 362 Pernicious anemia, 347, 362 Peroxidase, 13, 17, 26, 50, 61, 96, 231, 299, 333, 346, 362, 377 Peroxide, 64, 75, 97, 231, 308, 333, 338, 346, 362, 382 Peroxisome Proliferators, 22, 362 Petrolatum, 325, 362 Petroleum, 232, 233, 306, 331, 351, 362 PH, 70, 108, 139, 202, 304, 362 Phagocyte, 48, 215, 359, 362 Pharmaceutical Preparations, 309, 327, 331, 362, 368 Pharmacists, 224, 225, 362 Pharmacologic, 8, 98, 296, 362, 385, 386 Pharynx, 331, 341, 362 Phenolphthalein, 325, 362 Phenotype, 20, 88, 186, 303, 362 Phenylalanine, 227, 363, 388 Phlebitis, 224, 225, 363 Phlebotomy, 62, 363 Phosphates, 180, 363 Phosphodiesterase, 361, 363 Phospholipases, 363, 379 Phospholipids, 19, 49, 169, 328, 347, 350, 363 Phosphorous, 188, 363 Phosphorus, 198, 212, 231, 252, 306, 363 Phosphorylated, 313, 363 Phosphorylation, 18, 56, 81, 363, 370 Photocoagulation, 312, 363 Photodynamic therapy, 363 Photoreceptors, 315, 363 Photosensitivity, 156, 363, 366 Photosensitizer, 211, 363 Physical Examination, 175, 363 Physical Fitness, 181, 363

408

Vitamin E

Physiologic, 16, 18, 21, 32, 55, 240, 293, 303, 343, 350, 351, 363, 368, 373, 374, 387 Physiology, 15, 32, 63, 65, 73, 80, 86, 94, 132, 140, 183, 242, 250, 292, 303, 324, 364, 390 Pigment, 72, 107, 130, 205, 206, 242, 303, 307, 310, 333, 346, 348, 349, 350, 364 Pigmentation, 193, 205, 206, 364 Pilot study, 45, 51, 71, 80, 364 Placebos, 52, 364 Placenta, 84, 327, 364, 368 Plaque, 11, 145, 199, 296, 300, 364 Plasma cells, 297, 364 Plasma protein, 198, 293, 325, 364, 370 Plasmapheresis, 298, 364 Plasticity, 17, 131, 336, 364 Plastids, 359, 364 Plastoquinone, 234, 364 Platelet Activation, 37, 364, 379 Platelet Aggregation, 81, 295, 357, 361, 365, 385 Plateletpheresis, 298, 365 Platelets, 18, 107, 200, 299, 304, 309, 357, 364, 365, 370, 378, 385 Platinum, 201, 312, 347, 360, 365, 376 Pleated, 295, 302, 344, 365 Plethysmography, 59, 365 Plexus, 252, 365 Podophyllotoxin, 327, 365 Point Mutation, 20, 365 Poisoning, 34, 181, 227, 342, 354, 365 Policy Making, 334, 365 Pollen, 187, 196, 228, 365, 372 Polycystic, 57, 274, 365 Polycystic Ovary Syndrome, 57, 365 Polyethylene, 44, 102, 194, 210, 222, 224, 229, 365 Polymerase, 27, 38, 365 Polymerase Chain Reaction, 27, 38, 365 Polymers, 222, 366, 370, 382 Polymorphism, 95, 366 Polypeptide, 16, 294, 295, 313, 329, 366, 368, 369, 380, 384, 392 Polyposis, 254, 313, 366 Polysaccharide, 297, 309, 366, 370 Polyunsaturated fat, 13, 25, 90, 93, 137, 144, 366, 385 Porphyria, 91, 136, 253, 254, 363, 366 Porphyria Cutanea Tarda, 91, 136, 363, 366 Porphyria, Hepatic, 366 Porphyrins, 366

Posterior, 295, 300, 311, 322, 360, 366, 377, 389 Postmenopausal, 13, 79, 327, 359, 366 Postnatal, 366, 381 Postoperative, 106, 366 Postsynaptic, 366, 379, 383 Potassium, 25, 188, 198, 211, 212, 238, 366, 379 Potentiates, 105, 342, 367 Potentiation, 123, 229, 311, 367, 379 Practice Guidelines, 271, 367 Praseodymium, 201, 367 Pravastatin, 90, 367 Precancerous, 310, 367 Precipitation, 54, 367 Preclinical, 31, 229, 367 Preeclampsia, 97, 106, 156, 367 Pre-Eclampsia, 103, 367 Pre-eclamptic, 323, 367 Premalignant, 251, 367 Prenatal, 56, 324, 367 Presumptive, 42, 367 Presynaptic, 367, 383 Prevalence, 11, 25, 35, 47, 270, 358, 367 Prickle, 344, 367 Primary endpoint, 5, 21, 367 Primary Prevention, 13, 19, 50, 53, 55, 61, 99, 177, 368 Primary tumor, 251, 368 Probe, 26, 63, 334, 368 Procollagen, 219, 368 Prodrug, 368, 372 Progesterone, 192, 368, 381 Projection, 319, 358, 368, 373 Proline, 313, 338, 368 Prophase, 368, 383, 388 Prophylaxis, 368, 386, 392 Propylene Glycol, 225, 368 Prospective study, 71, 107, 129, 139, 189, 368 Prostaglandin, 29, 41, 42, 85, 368, 385 Prostaglandins A, 50, 368, 369 Prostaglandins D, 369 Prostate, 22, 26, 36, 37, 50, 52, 53, 59, 60, 70, 100, 118, 156, 174, 175, 195, 258, 259, 260, 273, 278, 302, 303, 369, 372, 375, 387 Prostate gland, 369 Prostatectomy, 26, 53, 369, 372, 375 Prostate-Specific Antigen, 53, 70, 369 Prostatic Hyperplasia, 108, 139, 148, 302, 329, 369 Prosthesis, 234, 369

Index 409

Protease, 27, 221, 313, 369 Protease Inhibitors, 27, 369 Protein Binding, 369, 385 Protein C, 200, 293, 294, 298, 301, 344, 347, 369, 388 Protein Conformation, 294, 344, 369 Protein Kinases, 46, 56, 369 Protein S, 67, 108, 235, 236, 249, 274, 304, 331, 369, 370 Protein-Tyrosine Kinase, 332, 370 Proteinuria, 367, 370 Proteoglycan, 32, 370 Proteolytic, 294, 314, 329, 360, 370 Prothrombin, 12, 370, 385 Protocol, 33, 38, 62, 364, 370 Protons, 63, 294, 338, 343, 370, 372 Proto-Oncogene Proteins, 360, 370 Proto-Oncogene Proteins c-mos, 360, 370 Protozoa, 351, 370 Proximal, 26, 321, 367, 370 Proxy, 4, 370 Prune Belly Syndrome, 254, 370 P-Selectin, 37, 370 Psoralen, 252, 370 Psoriasis, 156, 182, 232, 353, 370, 371 Psychiatric, 303, 350, 371 Psychic, 371, 377 Psychomotor, 355, 371 Psychopathology, 21, 371 Puberty, 183, 371 Public Health, 13, 25, 30, 38, 39, 40, 47, 51, 60, 61, 122, 271, 302, 371 Public Policy, 269, 371 Publishing, 67, 251, 253, 371 Pulmonary Artery, 304, 371, 390 Pulmonary Edema, 156, 310, 344, 371 Pulmonary Embolism, 371, 392 Pulmonary Fibrosis, 120, 371 Pulmonary hypertension, 56, 371 Pulse, 175, 352, 371 Pupil, 316, 321, 353, 371 Purifying, 242, 320, 371 Purpura, 84, 371 Pustular, 291, 371 Pyramidal Tracts, 328, 371 Q Quality of Life, 29, 44, 90, 172, 176, 371 Quaternary, 191, 369, 372 Quercetin, 126, 235, 372 R Race, 49, 351, 372

Radiation, 36, 54, 80, 105, 137, 156, 173, 176, 193, 212, 220, 235, 296, 317, 322, 324, 325, 328, 330, 338, 340, 342, 343, 372, 380, 382, 392 Radiation therapy, 173, 176, 235, 322, 328, 338, 342, 343, 372, 392 Radical prostatectomy, 26, 372 Radioactive, 338, 340, 342, 343, 357, 358, 372, 388, 392 Radioimmunotherapy, 372 Radioisotope, 372, 386 Radiolabeled, 343, 372, 392 Radiotherapy, 209, 258, 305, 343, 372, 392 Radius, 36, 372 Ramipril, 4, 372 Randomized clinical trial, 3, 60, 71, 372 Reabsorption, 237, 372 Reactive Oxygen Species, 17, 28, 34, 46, 57, 61, 63, 66, 67, 373 Reagent, 310, 320, 338, 359, 373 Receptors, Cytokine, 58, 373 Recessive gene, 205, 373 Recombinant, 15, 211, 373, 390 Recombination, 35, 373 Rectum, 298, 305, 313, 321, 331, 340, 345, 369, 373, 383 Recurrence, 173, 175, 310, 373 Red blood cells, 101, 200, 211, 212, 326, 336, 366, 373, 376 Red Nucleus, 300, 373 Reductase, 12, 50, 69, 82, 293, 329, 348, 367, 373, 379, 384 Refer, 1, 203, 205, 254, 306, 314, 330, 347, 348, 355, 356, 372, 373 Reflex, 328, 373 Reflux, 28, 254, 331, 373 Refraction, 354, 373, 381 Refractive Power, 354, 373 Refractory, 210, 211, 324, 373 Regimen, 7, 174, 209, 323, 373 Regurgitation, 331, 373 Reishi, 203, 204, 373 Relapse, 53, 374 Relative risk, 52, 374 Reliability, 11, 374 Remission, 373, 374 Renal failure, 105, 252, 259, 336, 365, 374 Renal pelvis, 345, 374 Reperfusion, 89, 122, 214, 353, 354, 374 Reperfusion Injury, 89, 122, 353, 354, 374 Research Design, 4, 374 Resorption, 169, 305, 373, 374

410

Vitamin E

Respiration, 292, 307, 309, 351, 352, 360, 374 Respiratory distress syndrome, 306, 374 Restoration, 24, 270, 353, 374, 392 Retina, 122, 139, 174, 242, 311, 315, 320, 345, 348, 354, 356, 358, 374, 375, 376, 389, 391 Retinae, 348, 374 Retinal, 4, 5, 6, 72, 92, 122, 130, 175, 242, 320, 329, 358, 375, 391 Retinitis, 78, 176, 375 Retinitis Pigmentosa, 78, 176, 375 Retinoblastoma, 273, 375 Retinoid, 16, 375 Retinol, 25, 253, 375 Retinopathy, 5, 6, 157, 240, 250, 293, 307, 320, 363, 375 Retropubic, 369, 372, 375 Retropubic prostatectomy, 372, 375 Retrospective, 20, 375 Retrovirus, 10, 375 Rheology, 361, 375 Rheumatic Diseases, 13, 375 Rheumatism, 339, 375 Rheumatoid, 13, 41, 118, 157, 214, 252, 262, 359, 375 Rheumatoid arthritis, 13, 41, 118, 214, 252, 262, 375 Riboflavin, 184, 198, 212, 231, 251, 253, 375 Ribose, 292, 376 Rickets, 376, 391 Rigidity, 364, 376 Riluzole, 71, 75, 236, 237, 376 Risk factor, 4, 13, 20, 22, 24, 32, 37, 38, 39, 40, 44, 53, 55, 98, 208, 218, 326, 368, 374, 376 Risk patient, 85, 113, 376 Risperidone, 91, 165, 376 Rod, 111, 301, 325, 376 Rubber, 238, 291, 376 Ruthenium, 64, 376 Rutin, 199, 235, 372, 376 S Salivary, 321, 360, 376 Salivary glands, 321, 376 Salmonellosis, 241, 376 Saponification, 198, 376 Saponins, 376, 381 Sarcoidosis, 254, 376 Sarcoma, 195, 376 Scandium, 200, 377 Schizophrenia, 157, 376, 377

Sclera, 311, 315, 377, 389 Scleroproteins, 344, 377 Sclerosis, 42, 71, 75, 155, 237, 273, 299, 376, 377, 387 Screening, 13, 22, 26, 52, 175, 229, 312, 377 Sebaceous, 377, 391 Sebum, 291, 377 Secondary tumor, 350, 377 Secretion, 18, 47, 67, 183, 198, 219, 223, 291, 323, 337, 341, 345, 357, 360, 377, 378, 386, 389 Secretory, 309, 377, 383 Secretory Vesicles, 309, 377 Sedative, 313, 377, 389 Sedentary, 181, 377 Segregation, 373, 377 Seizures, 171, 361, 377 Selegiline, 6, 7, 270, 377 Selenomethionine, 26, 60, 214, 377 Self Care, 291, 378 Semen, 110, 121, 133, 138, 140, 324, 369, 378 Semisynthetic, 327, 378 Senescence, 17, 378 Senile, 54, 157, 218, 359, 378 Senile Plaques, 218, 378 Sequencing, 366, 378 Serine, 325, 369, 370, 378 Serine Endopeptidases, 325, 378 Serotonin, 291, 298, 303, 352, 376, 378, 387 Serotypes, 360, 378 Serous, 313, 325, 378 Sex Characteristics, 371, 378, 384 Sex Determination, 273, 378 Sharpness, 232, 378, 391 Shedding, 185, 378 Shock, 73, 108, 131, 325, 378, 387 Shunt, 54, 378 Side effect, 36, 79, 173, 175, 176, 197, 209, 218, 232, 260, 263, 292, 298, 303, 322, 378, 386 Signal Transduction, 31, 46, 49, 56, 66, 379 Signs and Symptoms, 253, 374, 379 Silicon, 200, 379 Silicon Dioxide, 379 Simvastatin, 99, 126, 379 Skeletal, 120, 130, 181, 195, 207, 311, 323, 353, 379 Skeleton, 221, 291, 305, 332, 344, 368, 379 Skin Care, 221, 379 Small cell lung cancer, 172, 176, 379

Index 411

Small intestine, 207, 303, 310, 312, 323, 337, 342, 379 Smooth muscle, 46, 57, 60, 64, 86, 87, 294, 295, 306, 315, 337, 379, 382 Sneezing, 378, 379 Soaps, 185, 316, 329, 379 Social Environment, 372, 380 Sodium, 126, 137, 181, 191, 198, 212, 238, 246, 250, 304, 320, 334, 373, 379, 380, 383 Soft tissue, 304, 379, 380 Solar radiation, 137, 193, 380 Solid tumor, 296, 380 Soma, 380 Somatic, 230, 241, 324, 337, 349, 352, 361, 380 Somatostatin, 183, 357, 380 Sorbitol, 50, 293, 349, 380 Sound wave, 314, 380 Soybean Oil, 30, 366, 380, 391 Spastic, 343, 380 Specialist, 280, 321, 380 Specificity, 14, 52, 293, 299, 325, 380, 385 Spectrum, 317, 380, 388 Sperm, 110, 140, 311, 365, 381 Spermatozoa, 378, 381 Spinal cord, 300, 305, 309, 310, 311, 326, 331, 350, 355, 356, 361, 371, 373, 381 Spinous, 326, 344, 381 Spleen, 348, 376, 381 Sporadic, 355, 366, 375, 381 Sprue, 254, 381 Squamous, 16, 76, 381 Stabilization, 122, 218, 381 Stabilizer, 224, 238, 381 Steatosis, 328, 381 Steel, 381, 389 Stem Cells, 34, 186, 216, 326, 334, 381 Sterile, 200, 227, 381 Steroid, 41, 198, 303, 316, 376, 379, 381 Stimulant, 295, 306, 337, 381, 389 Stimulus, 322, 323, 343, 373, 381, 385 Stomach, 195, 291, 321, 326, 327, 330, 331, 333, 337, 348, 354, 361, 362, 373, 379, 381 Stomatitis, 184, 209, 381 Stool, 340, 343, 345, 381 Strand, 34, 61, 74, 131, 365, 381 Stroke, 6, 97, 113, 118, 158, 178, 214, 260, 268, 307, 336, 344, 356, 382 Structure-Activity Relationship, 42, 382 Styrene, 215, 376, 382 Subacute, 341, 382 Subarachnoid, 335, 382

Subclinical, 341, 377, 382 Subcutaneous, 252, 323, 346, 361, 382 Subspecies, 380, 382 Substance P, 350, 377, 382 Substrate, 55, 59, 180, 206, 318, 326, 347, 352, 382, 388 Suction, 329, 382 Sudden cardiac death, 208, 382 Sudden death, 6, 382 Sulfur, 212, 320, 322, 350, 382 Sunburn, 158, 193, 382 Superoxide, 17, 27, 28, 50, 54, 61, 63, 69, 94, 231, 382 Superoxide Dismutase, 17, 28, 50, 61, 63, 69, 382 Support group, 253, 382 Suppositories, 331, 383 Suppression, 14, 89, 113, 120, 136, 183, 383 Surfactant, 191, 217, 218, 221, 224, 225, 239, 383 Sweat, 185, 383 Sweat Glands, 185, 383 Symphysis, 369, 383 Symptomatic, 38, 39, 40, 383 Synapses, 17, 311, 356, 383 Synapsis, 383 Synaptic, 17, 131, 356, 379, 383 Synaptic Transmission, 356, 383 Synaptic Vesicles, 383 Synergistic, 37, 88, 183, 208, 218, 383 Systemic, 55, 62, 73, 96, 131, 158, 183, 209, 264, 298, 304, 326, 341, 343, 355, 372, 376, 381, 383, 386, 390, 392 Systolic, 339, 383 T Tardive, 98, 110, 115, 158, 218, 219, 298, 383 Taurine, 139, 303, 310, 383 Tea Tree Oil, 227, 384 Telangiectasia, 273, 384 Teratogen, 228, 384 Teratogenic, 344, 384 Testis, 327, 384 Testosterone, 329, 373, 384 Thalamic, 300, 384 Thalamic Diseases, 300, 384 Thalassemia, 104, 302, 384 Theophylline, 185, 384 Therapeutics, 38, 81, 84, 185, 264, 352, 384 Thermal, 305, 321, 356, 366, 384 Thiamine, 184, 198, 212, 231, 253, 384

412

Vitamin E

Thiobarbituric Acid Reactive Substances, 61, 384 Thioredoxin, 12, 43, 384 Third Ventricle, 299, 339, 384 Thorax, 291, 384 Threshold, 339, 384 Thrombin, 12, 329, 365, 369, 370, 385 Thrombocytes, 365, 385 Thrombocytopenia, 211, 385 Thrombomodulin, 369, 385 Thrombosis, 11, 45, 75, 77, 96, 98, 145, 316, 342, 351, 353, 370, 382, 385, 390, 392 Thromboxanes, 299, 385 Thrombus, 316, 340, 344, 353, 365, 385, 390 Thymus, 165, 186, 340, 348, 385 Thyroid, 214, 339, 343, 385, 388 Thyroid Gland, 339, 385 Thyroxine, 142, 293, 363, 385 Tilapia, 132, 385 Tin, 201, 365, 385 Tissue Culture, 186, 385 Tissue Distribution, 14, 385 Tobacco Use Cessation, 19, 385 Tolerance, 186, 250, 270, 292, 322, 332, 333, 385 Tomography, 175, 304, 386 Tonicity, 323, 336, 386 Torsion, 340, 386 Toxaemia, 367, 386 Toxic, iv, 10, 54, 194, 222, 227, 231, 242, 262, 302, 318, 325, 334, 335, 339, 346, 350, 355, 356, 357, 365, 377, 382, 386 Toxicity, 9, 10, 18, 66, 68, 81, 121, 123, 143, 172, 176, 231, 251, 307, 322, 324, 339, 386 Toxicology, 55, 75, 80, 81, 120, 138, 140, 146, 270, 386 Toxins, 198, 297, 341, 372, 386, 390 Toxoids, 241, 386 Trace element, 142, 252, 305, 311, 312, 356, 379, 385, 386 Tracer, 59, 386 Trachea, 305, 362, 385, 386 Transcriptase, 375, 386 Transduction, 31, 46, 49, 51, 56, 66, 379, 386 Transfection, 304, 386 Transfer Factor, 340, 386 Transferases, 333, 386 Transforming Growth Factor beta, 90, 386 Transfusion, 108, 212, 336, 387 Transmitter, 291, 300, 322, 327, 343, 349, 383, 387, 388

Transplantation, 77, 89, 92, 101, 109, 112, 113, 305, 312, 340, 345, 387 Transurethral, 369, 387 Transurethral Resection of Prostate, 369, 387 Trauma, 183, 301, 316, 326, 335, 354, 356, 384, 387 Trees, 230, 327, 376, 387 Tremor, 273, 327, 387 Trichloroacetic Acid, 201, 202, 236, 387 Triglyceride, 6, 188, 225, 338, 339, 387 Triolein, 31, 387 Trophoblast, 304, 387 Tryptophan, 195, 313, 378, 387 Tuberculosis, 315, 387 Tuberous Sclerosis, 273, 387 Tumor marker, 303, 387 Tumor Necrosis Factor, 57, 82, 196, 387 Tumor-derived, 50, 388 Tumorigenic, 31, 388 Tumour, 331, 388 Type 2 diabetes, 106, 119, 138, 388 Typhoid fever, 360, 388 Tyramine, 303, 352, 388 Tyrosine, 48, 64, 227, 308, 322, 332, 370, 388 U Ubiquinone, 181, 234, 388 Ubiquitin, 355, 388 Ultrasonography, 27, 59, 388 Ultraviolet Rays, 206, 388 Unconscious, 319, 339, 388 Univalent, 338, 359, 388 Unsaturated Fats, 329, 388 Urban Population, 36, 388 Urea, 240, 241, 345, 383, 388, 389 Uremia, 45, 344, 374, 389 Ureters, 345, 389 Urethra, 302, 369, 387, 389 Urinary, 26, 48, 60, 98, 112, 187, 232, 256, 306, 311, 312, 340, 358, 369, 370, 375, 388, 389 Urinary tract, 187, 370, 389 Uroporphyrinogen Decarboxylase, 366, 389 Ursodeoxycholic Acid, 99, 211, 389 Uterus, 316, 319, 330, 339, 350, 359, 368, 389 Uvea, 389 Uveitis, 158, 174, 389 V Vaccine, 186, 241, 292, 307, 370, 388, 389

Index 413

Vacuoles, 359, 389 Vagina, 320, 350, 389 Vaginal, 17, 158, 389 Vaginal Smears, 17, 389 Valerian, 187, 389 Valine, 195, 389 Vanadates, 180, 389 Vanadium, 200, 389 Vascular endothelial growth factor, 103, 175, 390 Vascular Resistance, 142, 295, 390 Vasodilatation, 240, 390 Vasodilation, 59, 390 Vasodilator, 60, 305, 322, 337, 353, 390 Vasomotor, 327, 390 VE, 77, 82, 102, 118, 120, 226, 238, 390 Vector, 386, 390 Vein, 175, 296, 342, 357, 361, 363, 390 Venoms, 318, 390 Venous, 45, 59, 370, 390, 392 Venous Thrombosis, 390, 392 Ventilation, 306, 390 Ventral, 299, 339, 390 Ventricle, 299, 337, 339, 371, 383, 384, 390 Ventricular, 10, 48, 62, 295, 354, 389, 390 Ventricular Dysfunction, 10, 390 Ventricular Function, 10, 390 Venules, 304, 307, 325, 351, 390 Veterinary Medicine, 120, 121, 140, 269, 329, 390 Vinca Alkaloids, 390, 391 Vincristine, 138, 391 Viral, 43, 65, 186, 204, 210, 211, 291, 332, 341, 358, 375, 386, 388, 391, 392 Viral Hepatitis, 210, 211, 391 Virulence, 241, 301, 386, 391 Virulent, 43, 391 Virus, 43, 86, 114, 136, 211, 214, 301, 309, 322, 331, 332, 336, 342, 364, 386, 391 Viscera, 350, 380, 391

Viscosity, 291, 337, 375, 391 Visual Acuity, 175, 391 Visual field, 358, 375, 391 Vital Capacity, 330, 391 Vitamin A, 34, 176, 205, 207, 212, 218, 231, 232, 235, 375, 391 Vitamin D, 47, 125, 185, 190, 212, 231, 376, 391 Vitiligo, 370, 391 Vitreous Body, 311, 374, 391 Vitreous Hemorrhage, 320, 391 Vivo, 6, 10, 12, 13, 16, 18, 28, 37, 41, 42, 45, 49, 54, 56, 58, 65, 75, 81, 84, 85, 109, 137, 146, 186, 211, 340, 346, 359, 385, 391 Vulgaris, 79, 165, 291, 344, 391 W Warfarin, 91, 165, 392 Warts, 158, 182, 365, 387, 392 Watchful waiting, 38, 392 Weight Gain, 232, 392 Weight Lifting, 261, 392 White blood cell, 48, 186, 200, 297, 313, 340, 345, 348, 352, 356, 364, 392 Windpipe, 362, 385, 392 Wound Healing, 159, 219, 233, 309, 342, 392 X Xenobiotics, 22, 392 Xenograft, 31, 69, 296, 392 X-ray, 32, 252, 304, 308, 330, 343, 349, 353, 357, 372, 381, 388, 392 X-ray therapy, 252, 343, 392 Y Yeasts, 330, 363, 392 Ytterbium, 201, 392 Yttrium, 200, 392 Z Zinc Compounds, 226, 392 Zymogen, 369, 392

414

Vitamin E

Index 415

416

Vitamin E