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

ANTIOXIDANTS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES ...

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ANTIOXIDANTS 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

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Antioxidants: 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: 0-597-83736-8 1. Antioxidants-Popular works. I. Title.

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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.

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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 antioxidants. 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.

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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.

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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

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON ANTIOXIDANTS ......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Antioxidants ................................................................................. 6 E-Journals: PubMed Central ....................................................................................................... 61 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND ANTIOXIDANTS ............................................................................... 83 Overview...................................................................................................................................... 83 Finding Nutrition Studies on Antioxidants ................................................................................ 83 Federal Resources on Nutrition ................................................................................................... 89 Additional Web Resources ........................................................................................................... 89 CHAPTER 3. ALTERNATIVE MEDICINE AND ANTIOXIDANTS ......................................................... 99 Overview...................................................................................................................................... 99 The Combined Health Information Database............................................................................... 99 National Center for Complementary and Alternative Medicine................................................ 100 Additional Web Resources ......................................................................................................... 107 General References ..................................................................................................................... 130 CHAPTER 4. DISSERTATIONS ON ANTIOXIDANTS ......................................................................... 131 Overview.................................................................................................................................... 131 Dissertations on Antioxidants ................................................................................................... 131 Keeping Current ........................................................................................................................ 134 CHAPTER 5. CLINICAL TRIALS AND ANTIOXIDANTS ................................................................... 135 Overview.................................................................................................................................... 135 Recent Trials on Antioxidants ................................................................................................... 135 Keeping Current on Clinical Trials ........................................................................................... 139 CHAPTER 6. PATENTS ON ANTIOXIDANTS.................................................................................... 141 Overview.................................................................................................................................... 141 Patents on Antioxidants ............................................................................................................ 141 Patent Applications on Antioxidants ........................................................................................ 172 Keeping Current ........................................................................................................................ 208 CHAPTER 7. BOOKS ON ANTIOXIDANTS ....................................................................................... 209 Overview.................................................................................................................................... 209 Book Summaries: Federal Agencies............................................................................................ 209 Book Summaries: Online Booksellers......................................................................................... 212 The National Library of Medicine Book Index ........................................................................... 219 Chapters on Antioxidants .......................................................................................................... 221 CHAPTER 8. MULTIMEDIA ON ANTIOXIDANTS ............................................................................ 223 Overview.................................................................................................................................... 223 Video Recordings ....................................................................................................................... 223 Audio Recordings....................................................................................................................... 224 CHAPTER 9. PERIODICALS AND NEWS ON ANTIOXIDANTS ......................................................... 225 Overview.................................................................................................................................... 225 News Services and Press Releases.............................................................................................. 225 Newsletter Articles .................................................................................................................... 228 Academic Periodicals covering Antioxidants............................................................................. 230 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 233 Overview.................................................................................................................................... 233 NIH Guidelines.......................................................................................................................... 233 NIH Databases........................................................................................................................... 235 Other Commercial Databases..................................................................................................... 239

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APPENDIX B. PATIENT RESOURCES ............................................................................................... 241 Overview.................................................................................................................................... 241 Patient Guideline Sources.......................................................................................................... 241 Finding Associations.................................................................................................................. 245 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 247 Overview.................................................................................................................................... 247 Preparation................................................................................................................................. 247 Finding a Local Medical Library................................................................................................ 247 Medical Libraries in the U.S. and Canada ................................................................................. 247 ONLINE GLOSSARIES................................................................................................................ 253 Online Dictionary Directories ................................................................................................... 253 ANTIOXIDANTS DICTIONARY .............................................................................................. 255 INDEX .............................................................................................................................................. 351

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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 antioxidants 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 antioxidants, 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 antioxidants, 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 antioxidants. 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 antioxidants, 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 antioxidants. The Editors

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

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

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and antioxidants, 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 “antioxidants” (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: •

Vitamins, Trace Elements, and Antioxidant Status in Dementia Disorders Source: International Psychogeriatrics. 13(3): 265-275. 2001. Summary: This article examines levels of vitamins and trace elements in the diets of patients with Alzheimer's disease (AD, n=31), vascular dementia (VaD, n=10), and dementia with Lewy bodies (DLB, n=10) and a comparison group of healthy caregivers (n=30). Blood levels of total antioxidant capacity (TAC) also were assessed. Dietary intake of most measured vitamins and trace elements was decreased in severe AD but not in the other dementia groups. There was no significant difference in TAC among any of the dementia groups. However, a significant correlation was found between intakes of vitamin B1, vitamin B12, zinc, and selenium and blood levels of TAC in the VaD group but not in the AD and DLB groups. No association was observed between zinc and copper intake and Cu/Zn superoxide dismutase activity, or between dietary

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selenium intake and glutathione peroxidase activity, in any of the dementia groups. Results suggest that dietary levels of vitamins and trace elements are associated with overall antioxidant status in VaD patients but not those with AD or DLB. 3 tables, 36 references. (AA- M). •

Dietary Intake of Antioxidants and Risk of Alzheimer Disease Source: JAMA. Journal of the American Medical Association. 287(24): 3223-3229. 2002. Summary: This article examines the association between dietary intake of antioxidants and the risk of Alzheimer's disease (AD) in a population- based study conducted in the Netherlands. At baseline (1990-1993), the 5,395 participants were aged 55 years or older, free of dementia, noninstitutionalized, and had reliable dietary assessment. They were reassessed in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia. After a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had AD. After adjusting for age, sex, baseline cognitive function, alcohol intake, education, smoking status, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intakes of vitamin C and vitamin E were associated with a lower risk of AD. Among current smokers, this relationship was most pronounced and also present for intakes of beta carotene and flavonoids. The associations did not vary by education or apolipoprotein E genotype. Results suggest that high dietary intakes of vitamin C and vitamin E may lower the risk of AD. 6 tables, 34 references. (AA-M).

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Antioxidants May Protect Your Health, Slow Aging Source: Diabetes in the News. 14(3): 20-21. June 1995. Contact: Available from Diabetes in the News. P.O. Box 4548, South Bend, IN 46634. (312) 664-9782. Summary: This article familiarizes readers with antioxidants, a group of micronutrients believed to help protect people from health problems such as heart disease, arthritis, cataracts, and allergies. Vitamins A, C, E, beta carotene, and the trace mineral selenium are the primary micronutrients discussed. Topics include free radicals and their role in disease; foods that are rich in antioxidants; incorporating antioxidants into a diabetes meal plan; the use of vitamin and mineral dietary supplements; the role of vitamin E in blood glucose control; and recommended antioxidant intakes.

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Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study Source: JAMA. Journal of the American Medical Association. 287(24): 3230-3237. June 26, 2002. Summary: This article reports the association between dietary intake of antioxidant nutrients and incident Alzheimer's disease (AD) in a large community study. Data were collected from 1993 to 2000 for a stratified random sample of community-dwelling residents in south Chicago, Illinois. The 815 residents aged 65 years and older were free of AD at baseline and followed up for a mean of 3.9 years. They completed food frequency questionnaires an average of 1.7 years after baseline. The main outcome measure was incident AD diagnosed in clinical evaluations with standardized criteria. After adjusting for age, education, sex, race, apolipoprotein E4 (apoE4), and length of follow-up, increased vitamin E intake from foods was associated with decreased risk of AD. The protective effect of vitamin E was observed only among persons who were

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apoE4 negative. Adjustment for other dietary factors reduced the positive association. Vitamin E intake from supplements and total intakes of vitamin C and beta carotene were not significantly associated with risk of AD. The results suggest that vitamin E from food may be associated with a decreased risk of AD in persons without the apoE4 allele. 4 tables, 42 references. (AA-M). •

Relation between Antioxidants and Memory Performance in the Old and Very Old Source: Journal of the American Geriatrics Society. 45(6): 718-724. June 1997. Summary: This journal article describes a study of the relationship between plasma antioxidant vitamin levels and cognitive performance in healthy older people. Participants were 312 men, 132 women, aged 65 to 94 years, from Basel, Switzerland. Plasma vitamin levels for ascorbic acid, beta-carotene, and alpha-tocopherol, measured previously in 1971, were measured in 1993 along with plasma cholesterol, ferritin, and systolic blood pressure. Participants also completed memory tests assessing priming, working memory, free recall, recognition, and vocabulary (semantic memory). The results suggest significant stability in plasma antioxidant levels between 1971 and 1993. Performances on free recall, recognition, and vocabulary, but not priming or working memory, were significantly correlated with levels of ascorbic acid and beta-carotene in both the cross-sectional 1993 data and the longitudinal 1971-1993 analysis. These two antioxidants remained significant predictors, especially of semantic memory, after controlling for age, education, and gender. The authors conclude that higher plasma levels of some antioxidants may be associated with better memory performance in older people. 2 figures, 3 tables, 36 references.

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Antioxidants in Vegan Diet and Rheumatic Disorders Source: Toxicology. 155(1-3): 45-53. November 30, 2000. Summary: This journal article provides health professionals with information on a study that examined the effectiveness of living food (LF) on fibromyalgia and rheumatoid arthritis symptoms. LF is an uncooked vegan diet and consists of berries, fruits, vegetables and roots, nuts, germinated seeds, and sprouts. These foods are rich sources of carotenoids and vitamins C and E. The study investigated the health parameters of 20 volunteers who were long term users of an LF diet and their controls, as well as 33 people with fibromyalgia who were divided into an LF intervention group and omnivorous controls and 42 patients with RA who were again divided into an LF intervention lasting 3 months and omnivorous controls. All participants reported their food behaviors using questionnaires. Participants eating LF showed greatly increased levels of beta and alfa carotenes, lycopenes, and lutein in their sera. Also, increases in vitamins C and E were statistically significant. Since the berry intake was three time higher than in controls, the intake of polyphenolic compounds like quercetin, myricetin, and kaempherol was also much higher than in the omnivorous controls. The urinary excretion of polyphenols such as enterodiol and enterolactone as well as secoisolaricirecinol was much increased in people eating LF. The shift of fibromyalgia participants to LF resulted in a decrease of their joint stiffness and pain as well as an improvement of their self experienced health. The patients with RA who ate the LF diet also reported similar positive responses, and objective measures supported this finding. The improvement in RA was significantly correlated with the day to day fluctuation of subjective symptoms. The article concludes that the patients with RA subjectively benefited from the vegan diet rich in antioxidants, lactobacilli, and fiber and that this was also seen in objective measures. 4 figures, 2 tables, and 33 references. (AA-M).

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Current Status of Antioxidant Therapy for Alzheimer's Disease Source: JAGS: The Journal of the American Geriatrics Society. 46(12): 1566-1572. December 1998. Summary: This journal article summarizes the oxidative stress hypothesis of Alzheimer's disease (AD) and reviews the strengths and limitations of published antioxidant studies in AD in relation to the role of such therapies in practice. The lay press and increasing numbers of physicians are recommending antioxidant therapies to enhance mental functions and delay cognitive losses associated with aging, with AD, and with other neurodegenerative diseases. High dose vitamin E, ginkgo biloba, and selegiline are three substances that have been tested in randomized, multicenter trial conditions. The authors discuss these trials, state that the available clinical trial data are promising and support continuing investigation, and conclude that convincing evidence supports a role for oxidative stress, particularly lipid peroxidation, in the pathogenesis of AD. 2 tables, 50 references. (AA-M).

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Antioxidants in Pediatric Gastrointestinal Disease Source: Pediatric Clinics of North America. 43(2): 471-488. April 1996. Contact: Available from W.B. Saunders Company. Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: This review article, from an issue on pediatric gastroenterology that focuses on diarrheal diseases in children, describes the role of antioxidants in pediatric gastrointestinal disease. The authors review the pathways of free-radical generation and of antioxidant defenses. They discuss data supporting the role of oxidant stress in inflammatory bowel disease, intestinal ischemia, necrotizing enterocolitis, various pediatric liver diseases, pancreatitis, and cystic fibrosis. Although few diseases have been shown to be responsive to antioxidant therapy, further clinical and basic research in this area is indicated. 2 figures. 1 table. 102 references. (AA-M).

Federally Funded Research on Antioxidants The U.S. Government supports a variety of research studies relating to antioxidants. 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 antioxidants. 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 antioxidants. The following is typical of the type of information found when searching the CRISP database for antioxidants: 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).

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Project Title: ACCESS TO PHYSICAL ACTIVITY AND ITS RELATION TO HEALTH Principal Investigator & Institution: Alessio, Helaine M.; Physical Education, Health and Sports Stud; Miami University Oxford 500 E High St Oxford, Oh 45056 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Animal studies on mechanisms of oxidative stress, aging, and disease often include an experimental group receiving a certain intervention and a sedentary control group to which the experimental group is compared. The common use of a control group having no access to physical activity outside the cage poses a potential intervening variable that may affect results of studies investigating health and stress, in particular, oxidative stress. Animals participating in no physical activity outside of their cage may have different endogenous prooxidant and antioxidant levels, which over time may negatively affect their health. In previous studies where differences in biomarkers of oxidative stress or health were reported between control and experimental groups, investigators may have overestimated the effects of the intervention due to the hypokinetic effects of housing on the sedentary control animals. If animal studies are intended to generalize to other primate populations, including humans, then housing conditions and access to physical activity need to be carefully considered. The purpose of this study is to compare biomarkers of oxidative stress, a variety of health parameters, age and cause of death in animals that are grouped in three distinct ways: a) living solely in a standard cage with no access to physical activity outside the cage, 2) living in a standard cage with twice weekly one hour periods of physical activity in a large box, and 3) living in a standard cage with regular access to exercise on a running wheel. Cardiovascular parameters (blood pressure, heart rate, body weight, blood lipids) will be monitored weekly over the life span of the animals. Blood samples from a tail vein will be collected biannually and analyzed for antioxidants, lipids, and prolactin. Immediately after death, various tissues will be harvested and analyzed using a hematoxin and eosin staining method, and standard autopsy procedures performed by a veterinarian. Brain, ganglia, neurotrophic growth factor, pituitary gland, tumors, and organs and tissues will be analyzed for signs of pathology and differences among the three groups. Results of this study will distinguish cardiovascular parameters, morbidity, mortality, and biomarkers of oxidative stress due to different access to physical activity over the life span. These results will provide insight about the importance of housing and physical activity when designing animal experiments to study aging, selective health parameters, and oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ACUTE LUNG INJURY-MECHANISMS AND THERAPY Principal Investigator & Institution: Crapo, James D.; Executive Vice President for Academic Af; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2001; Project Start 01-MAY-1984; Project End 31-MAR-2005 Summary: PROPOSED PROGRAM (Adapted from Applicant's Abstract) The long-term objectives of this Program Project application are to evaluate basic mechanisms and develop new treatments for acute lung injury. High concentrations of oxygen and septic lung injury are the primary models that will be evaluated. The proposed program consists of four projects and three core units. Project 1 will evaluate the efficacy of small molecular weight catalytic antioxidants in the treatment of both hyperoxic and LPS + sepsis-initiated lung injury. This project will also develop new antioxidant mimetics and

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explore their relationships with the antioxidant properties of heme oxygenase (HO). Project 2 will test the hypothesis that activation of extrinsic coagulation and disordered fibrin turnover are central elements in hyperoxic and septic lung injury. The efficacy of specific blockade of the initiating steps of extrinsic coagulation in reducing inflammation and acute lung injury will be tested using two new anticoagulant drugs that block tissue factor (TF) function and do not cause bleeding. Project 3 will evaluate the regulation and function of the extracellular superoxide dismutase (EC-SOD) in acute lung injury and determine the impact of cleavage of the C-terminal "heparin binding" domain of this enzyme in determining its distribution and function. Project 4 will evaluate control of metabolic pathways and upregulation of lung cell glycolysis in modulating responses to acute injury. This project will test the hypothesis that adaptation to oxidant stress in the lung requires elevated expression of hexokinase (HK), a rate limiting step in glycolysis in the lung. The overall rationale for the Program Project is to use an interdisciplinary approach to define the cellular pathways and cellular adaptive responses involved in acute lung injury and to test new strategies for pharmacologic therapy that can be extended to the treatment of humans with ARDS and sepsis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALDO-KETO REDUCTASES AS PART OF CHEMICAL STRESS RESPONSE Principal Investigator & Institution: Barski, Oleg A.; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 17-AUG-2000; Project End 31-JUL-2003 Summary: Aldo-keto reductases provide protection against environmental and nutritional toxins and carcinogens by detoxification of reactive aldehydes capable of modifying cellular macromolecules. Chemical stress induces the expression of a number of detoxification enzymes. Thus, aflatoxin reductase is induced by ethoxyquin and other antioxidants. Recently it was shown that ethoxyquin and antiobiotic tunicamycin also induce aldehyde reductase, another member of the aldo-keto reductase family. A crucial element of the human aldehyde reductase gene promoter binds transcription factor CHOP, which is induced in cells exposed to chemical stress. Preliminary results suggest that CHOP mediates the induction of aldehyde reductase expression and that both aflatoxin and aldehyde reductases are part of the cellular chemical stress response system, hence their expression is induced in response to toxic insult. The application proposes to: a) evaluate the ability of physiologically relevant compounds to induce aldehyde reductase expression and to find out whether induction of both reductases goes through the CHOP-dependent pathway. B) test the compounds of the two major groups: toxic substrates and chemoprotectors that are known to induce aflatoxin reductase and other drug metabolizing enzymes (e.g. glutathione-S-transferase). C) test the Selected stimuli for their ability to induce CHOP. D) determine whether CHOP plays a role in inducing aflatoxin and aldehyde reductase by testing the effect of CHOP overexpression and deficiency, and known CHOP-inducing agents on the of the reductases expression. e) clone and sequence aflatoxin reductase promoter and examine it for a CHOP-binding element and response elements described to direct antioxidant induction in other detoxification genes. Understanding the nature and mechanism of regulation of aldehyde and aflatoxin reductase expression will potentially assist in the prevention of harmful and carcinogenic effects of toxic aldehydes as well as provide a basis for identifying populations with increased susceptibility to certain environmental agents.

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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 Campus Dr Irvine, Ca 92697 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 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

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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

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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 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 ATHEROSCLEROSIS

PROTECTION

IN

AGE-ASSOCIATED

Principal Investigator & Institution: Carlson, Sara G.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (from application): The Mentored Research Scientist Development Award would allow Dr. Sara G. Carlson, PhD, to make a successful transition into conducting independent research in the field of cardiovascular aging. Since Dr. Carlson has a solid foundation in scientific training, it is reasonable to project that toward the end of the mentored research term, she will have developed a significant body of age-related data that will form a basis for independent research status and funding. The objectives of this application are to enable Dr. Carlson to steer her current efforts toward aging research: the research career development plan consists of Dr. Carlson assuming the primary role in conducting this research project, taking course work in scientific integrity, participating in seminars, journal clubs, workshops, and scientific meetings; reading and discussing original research articles in oxidative damage and atherosclerosis; and meeting with mentors and consultants trained in aging, cardiovascular disease, and apoptosis research. The aims of the research are: 1) to identify specific steps in oxysterolinduced apoptotic pathways that are modulated by altered ROS generation and antioxidants in cultured vascular cells, and 2) to characterize age-associated atherosclerotic lesion development in the senescence-accelerated mouse (SAM) model, and explore the extent to which antioxidant supplementation reduces apoptosis during age-associated atherosclerotic lesion formation. These studies will allow the candidate to test the overall hypothesis that antioxidants exert protective effects in the atherosclerotic processes accompanying aging through inhibition of ROS-mediated apoptosis.

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

Project Title: ANTIOXIDANTS AND NFKAPPAB ACTIVATION IN IDDM Principal Investigator & Institution: Bray, Tammy M.; Professor of Nutrition and Molecular & c; Human Nutrition and Food Mgmt; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-MAY-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTION

ANTIOXIDANTS

AND

OXIDANTS

IN

FOLLICLE/OOCYTE

Principal Investigator & Institution: Behrman, Harold R.; Professor; Obstetrics and Gynecology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2003 Summary: (Adapted from applicant's abstract): The underlying hypothesis of this proposal is that a decrease in antioxidant status of the developing follicle results in abnormal follicular and oocyte function whereas antioxidant depletion is necessary for the sequelae induced by LH that induces ovulation, and the resumption of meiosis. This hypothesis is based largely upon observations in ascorbic acid-deficient animals of follicular atresia and oocyte malfunctions. The studies described herein will investigate ascorbate as the preeminent antioxidant and its role in follicle development. Using several well-established rat models and both in vivo and in vitro cell culture experiments, kinetic analyses of ascorbate uptake will be investigated in granulosa and theca cells, and cumulus enclosed and denuded oocytes. The regulatory endocrine factors governing uptake will be identified. Antioxidant levels present in developing follicles, during ovulation and in atresia will be determined. The role of ascorbic acid in the responsiveness of follicles to gonadotropins and in the inhibition of meiosis will be determined. The hypothesis that cell secretion as a mechanism underlying follicular ascorbate depletion will be tested and the endocrine factors and pathologic conditions which regulate secretion will be determined. Lastly, the origins, nature, and regulation of follicular reactive oxygen species will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POPULATION

ANTIOXIDANTS

NUTRIENTS

AMONG

A

BRAZILIAN

Principal Investigator & Institution: Giuliano, Anna R.; Associate Professor; None; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2001; Project Start 16-JUN-2000; Project End 31-MAY-2003 Summary: (Adapted from the Applicant's Abstract): Epidemiologic research conducted over the past couple of decades has shown that infection with the human papilloma virus (HPV) is a cause of most cases of cervical cancer. Prospective studies have shown that women infected with HPV are more likely to develop cervical intraepithelial neoplasia (CIN), and that those with persistent oncogenic type HPV infections are at a significantly increased risk of developing CIN compared with women transiently infected. In addition, persistently HPV positive women appear to be four times more likely to have persistent cervical lesions. Although HPV infection is a cause of cervical cancer, it may be an insufficient cause requiring the presence of other factors for the

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infection to progress to a significant cervical lesion. Nutritional status may be an important cofactor affecting both HPV persistence and progression of persistent HPV infection to CIN. However, the association between nutritional status and cervical carcinogenesis has not been adequately tested. The overall goal of this application is to determine, using prospectively collected HPV and cytology data, the association between serum carotenoid and tocopherol status and cervical carcinogenesis among a cohort of high risk study participants in the Brazilian HPV Natural History Cohort (RO1 CA70269). This project will provide the first prospective analysis of serum carotenoid and tocopherol concentrations and risk for persistent HPV infection; it will be based on sensitive and specific methods for assessing type of HPV infection over a 12 month period, and evaluate subsequent 5 year risk of progression to CIN. This proposed study is unique in that if focuses on early events in cervical carcinogenesis: HPV infection, HPV persistence, and progression to CIN. It is cost-effective, utilizing previously collected serum samples and questionnaire data. The study utilizes state of the art methods for determining both PV status and serum carotenoid and tocopherol status. Furthermore, it incorporates multiple measurements of both HPV status and serum nutrient concentrations minimizing the probability that measurement imprecision resulting from temporal fluctuations will obscure the true association between nutrients status, and HPV persistence and risk of CIN. Results from this study will efficiently further our understanding of the role of antioxidant nutrients and cervical carcinogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AP-1 AS A XENOBIOTIC RECEPTOR Principal Investigator & Institution: Karin, Michael; Professor; Pharmacology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-JUN-1993; Project End 31-MAY-2002 Summary: Transcription factors AP-1 and NF-kB are activated by a variety of physiological and pathological stimuli. Xenobiotics and therapeutic agents also modulate the activities of these transcription factors and thereby affect expression of their target genes. AP-1 activation is linked to the control of cell proliferation and is effected by tumor promoters, while anti-tumor promoters inhibit AP-1 activity. Therefore, agents that modulate the AP-1 activity have profound effects of cell proliferation and neoplastic transformation. NF-kB activation, on the other hand, plays a key role in induction of immunity and inflammatory responses. Therefore, xenobiotics that activate NF-kB can cause inflammatory disorders, while those that interfere with NF-kB activation are immunosuppressive. Dr. Karin proposes to examine the molecular mechanisms by which xenobiotics affect AP-1 and NF-kB activities, by studying their effects on several protein kinases, JNK, p38 and IkB kinase that play key roles in AP-1 and NF-kB activation. These studies will provide molecular explanation to effects of various xenobiotics, including alkylating agents, oxidants and antioxidants on cellular gene expression. There are conflicting indications that AP-1 and the protein kinases that stimulate its activity, JNK and p38, could be involved in either protection against adverse environmental conditions or in induction of apoptosis and cytotoxicity. He will examine the physiological role of AP-1 and proteins that regulate AP-1 activity in conferring resistance or sensitivity to various drugs by the use of cell lines derived from "knockout" mice deficient in these factors. More specifically, he will: 1) Determine whether JAB1 (a coactivator for c-Jun or JunD) and its targets are involved in conferring drug resistance in mammalian cells; 2) Determine the mechanism by which certain translation and glycosylation inhibitors lead to activation of JNK and p38; 3) Determine the mechanism by which alkylating agents lead to JNK and p38 activation; 4) Investigate

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the role of c-Jun and AP-1 in cellular sensitivity or resistance to alkylating agents; 5) Investigate the role of JNK and p38 in mediating cellular responses to alkylating agents and other xenobiotics and; 6) Identify the IkB kinase and investigate its regulation by oxidants and antioxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APOPTOSIS AND OXIDANTS AFTER MURINE CARDIAC ARREST Principal Investigator & Institution: Becker, Lance B.; Director of Research; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Using a murine cardiac arrest model, we will define oxidant-mediated apoptosis in the post-resuscitation phase of cardiac arrest. Our proposal extends work by others and our own cellular studies that implicate oxidantmediated apoptosis as a cause of significant cell and organ injury after reperfusion following ischemia. This post resuscitation injury may be particularly important following the global ischemia of cardiac arrest, after which almost 90% of patients go on to die hours to days later even after an initially "successful" immediate resuscitation. The Emergency Resuscitation Center at the University of Chicago has developed a translational murine model of cardiac arrest which reflects this post-resuscitation injury, demonstrates activation of cellular apoptotic markers and oxidant-mediated transcriptional changes 18 hours after cardiac arrest, and will allow use of genetically altered animals to further define post-resuscitation processes. Specifically, we aim to use this new model to define the role of intrinsic and extrinsic apoptotic pathways in key organs during post-resuscitation injury and death following murine cardiac arrest. We will test the contribution of the intrinsic apoptotic pathway during cardiac arrest by treatment of mice with a caspase 9 inhibitor, and by using Bcl-2 and Bax knockout mice, which exhibit alterations in apoptotic function. We will test the contribution of the extrinsic apoptotic pathway by studying cardiac arrest in mice treated with a caspase 8 inhibitor, and by using Fas-deficient and Fas ligand-deficient mice. We also aim to define the contribution of oxidants to the sequence of apoptosis. To do this, we will study cardiac arrest while treating mice with antioxidants and by using superoxide dismutase (SOD1) transgenic mice, both alterations known to be protective during ischemia. Outcomes in these studies will include multiple markers of apoptosis, oxidant generation, hemodynamics, neurologic function, cardiac function and survival to 7 days. The highlight of this translational model is its ability to provide insights into integrative physiology, test for similarities and differences between organs exposed to the same ischemic insult, and test for the remote effects that one organ may have on distant organs. Finally we will ask whether antiapoptotic and antioxidant therapies can improve survival and function after cardiac arrest, a leading cause of death in our society. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ATM, P53, GADD45 AND P21 EFFECTS ON RECOMBINATION Principal Investigator & Institution: Schiestl, Robert H.; Professor of Pathologyi; Pathology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: DNA lesions such as double-stranded breaks (DSBs), DNA adducts and DNA strand cross links cause cancer. Such lesions may result in cell cycle arrest and if

14

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repairable, initiate repair reactions including recombination which may lead to genomic rearrangements. The following genes may be involved in DNA damage detection or processing and executing cellular responses. ATM may signal the presence of DNA damage, p53 activates transcription of p21 and Gadd45, which are involved in cell cycle arrest, stopping DNA synthesis in response to the damage and in coordinating repair reactions. Mouse models lacking these genes have been developed. Genome rearrangements such as deletions are associated with carcinogenesis. We have previously shown that X-rays, benzo(a)pyrene (B(a)P) and cisplatin cause DNA DSBs, DNA adducts and DNA cross links respectively increase the frequency of deletions between repeated DNA sequences in the mouse genome. Disruption of the p gene by a DNA duplication, the p/un mutation, results in a diluted coat color and pink eyes. The reversion of this duplication to wildtype in the embryo results in black spots on the fur and the retinal pigment epithelium in the eyes. We have previously shown p53 is involved in X-ray but not in B(a)P induced p/un reversions. Furthermore, X-rays but not B(a)P acts in a p53 independent manner. X-rays induce p53 in an ATM dependent way and in contrast, cisplatin induces p53 in an ATM independent way. These carcinogens will be used to dissect the ATM/p53/p21/Gadd45 DNA damage recognition and repair in mouse embryos. These data will be correlated with induction profiles of these gene products induced by the carcinogenesis in embryos. It has also been proposed that oxidative stress plays a role in the pathogenesis of AT. We propose to determine whether oxidative stress is involved in any different responses of ATM mice to ionizing radiation and we will determine whether nutritional factors such as pro-oxidants and anti-oxidants have any effect on such oxidative stress parameters. If the frequency of deletions in ATM deficient mice can be reduced by exposure to antioxidants this may indicate that oxidative stress may at least partially be responsible for the high incidence of carcinogenesis which in turn may raise the possibility of intervention with nutritional antioxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOCHEMISTRY AND PHARMACOLOGY OF THE MACULAR CAROTENOIDS Principal Investigator & Institution: Bernstein, Paul S.; Assistant Professor; Ophthalmology and Visual Scis; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: The human macula, the specialized region of the retina responsible for high resolution visual acuity, selectively accumulates two xanthophy11 carotenoids derived from the diet, lutein and zeaxanthin. Several recent epidemiological studies have demonstrated a strong inverse correlation between dietary intake of lutein and zeaxanthin and the risk of progression Age-Related Macular Degeneration (AMD) the leading cause of blindness among the elderly in the United States. It is thought that the macular carotenoids protect against least-induced damage to the retina by filtering out damaging wavelengths of light and by acting as antioxidants. The biochemical mechanisms that mediate the selective uptake, concentration, and stabilization of the macular carotenoids are unknown. In lower animals, such as lobsters and cyanobacteria, specialized carotenoid-binding proteins perform these tasks. It is hypothesized that comparable carotenoid-binding proteins may have a similar role in the human macula. A major goal of this project is to understand the biochemical processes responsible for the specific deposition of lutein and zeaxanthin the macula, with special emphasis on the search for potential carotenoid-binding proteins. This project will also investigate the

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properties of carotenoid- protein and carotenoid-lipid interactions through quantitative binding studies and various spectroscopic methods, including resonance Raman spectroscopy, in model systems and in intact retinal tissue. The experiments of this proposal may provide new insights into the biochemical basis of the specific uptake lutein and zeaxanthin into the macula. Derangements of the mechanisms of uptake and stabilization of the macular carotenoids could have profound impact on the progression of AMD and inherited retinal dystrophies. Anticipated interventional clinical studies may be able to take advantage of the specific uptake systems to increase the level of macular carotenoid pigment and perhaps retard or prevent the progressive blindness produced by these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CATECHOLAMINES, INFLAMMATION

ANTIOXIDANTS

AND

BRAIN

Principal Investigator & Institution: Bickford, Paula C.; Professor; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2001; Project Start 01-MAR-1984; Project End 31-MAR-2006 Summary: The cerebellar noradrenergic system is important for plasticity related to motor learning. As animals age, there is a decline in Beta-adrenergic receptor (BetaAR) function that is associated with a decline in learning of specific motor learning tasks. We have demonstrated that nutritional sources of antioxidants can reverse age-induced cognitive deficits in rats and reverse declines in cerebellar BAR function and motor learning. We propose to further these studies by examining the effects of nutritional sources of antioxidants on hippocampal plasticity (LTP). We have observed that in aged rats, there is a reactive oxygen species mediated increase in bcl-2 in Purkinje neurons. We will test the hypothesis that this increase in bcl-2 and an abnormal nuclear localization of bc1-2 underlies an imbalance of cellular homeostasis and is part of a key molecular mechanism underlying the age-related decline in cerebellar BetaAR function and motor learning. A second line of inquiry in this proposal will be to study a line of rats that is resistant to normobaric hyperoxia. These rats do not show the normal agerelated declines in cerebellar BetaAR function and motor learning, and thus are an interesting model of aging. It is hypothesized that leukocyte function associated antigen (LFA-1) is deficient in these rats, and that this is the mechanism of resistance to hyperoxia. We will test the hypothesis that this is the mechanism underlying the resistance to aging by examining immune function in the brains of these rats. In addition, LFA-1 knockout mice will be studied to further test the hypothesis that LFA-1 is a critical contributor to the resistance to aging-related declines in cerebellar BetaAR function and motor learning. We have been examining the signal transduction system of the BetaAR in aged rats. Our results have focused our investigation on protein kinase A (PKA) subunit expression and localization. Important regulators of PKA are A-kinase anchoring proteins (AKAP). AKAP have been shown to localize PKA to specific subcellular domains. We plan to investigate alterations in PKA subunit expression as well as alterations in AKAP with the hypothesis that changes in the subcellular localization of PKA will resemble an apparent loss of PKA activity, as we have observed. Understanding the molecular mechanisms that underlie the age-related loss of cerebellar BetaAR function is critical for designing appropriate pharmacological interventions to improve cerebellar plasticity in aged animals. In very simplified terms, our overall hypothesis is that aging results in an increase in inflammatory processes that, in turn, results in an increase in oxidative stress that results in a disruption of cellular homeostasis and a decline in cognition.

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Antioxidants

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

Project Title: CAUSES AGGREGATION

AND

CONSEQUENCES

OF

ALPHA-SYNUCLEIN

Principal Investigator & Institution: Masliah, Eliezer; Professor; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Parkinson's disease (PD) and related Lewy body diseases are associated with the abnormal intraneuronal accumulation of alpha-synuclein. Mutations that enhance the propensity of alpha-synuclein to aggregate cause early onset familial PD. Notably, the majority of patients with Alzheimer's disease (AD) also have alpha-synuclein immunoreactive Lewy bodies and a substantial proportion of them develop a form of parkinsonism that defies conventional therapeutic approaches. This suggests that factors involved in the pathogenesis of AD might promote the development of particularly recalcitrant forms of PD. We have shown that amyloid beta peptides (Abeta), which play a central role in AD pathogenesis, promote the intracellular accumulation of alphasynuclein and accelerate alpha-synuclein-dependent motor deficits in alphasynuclein/amyloid precursor protein transgenic mice, an animal model that mimics aspects of Lewy body disease. However, the mechanisms underlying these effects remain unknown. The main objectives of this proposal are to elucidate these mechanisms and to determine whether blocking Abeta effects might prevent or ameliorate PD and other Lewy body diseases. In Aim 1 we will determine whether the increase in neuronal alpha-synuclein accumulation and in alpha-synuclein-dependent deficits in a transgenic mouse model of Lewy body disease depends on the ratio of the two predominant Abeta species (Abeta1-42/Abeta1-40). For this purpose, alphasynuclein transgenic mice will be crossed with wildtype or mutant human amyloid precursor protein (hAPP) transgenic mice and detailed biochemical, neuropathological and behavioral analysis will be performed. These experiments will be complemented with in vitro studies in alpha-synuclein-transfected cell fines treated with Abeta1-42 or Abeta1-40 or a mixture of both. In Aim 2 we will determine whether the increase in neuronal alpha-synuclein accumulation and in alpha-synuclein-dependent deficits in a transgenic mouse model of Lewy body disease depends on the uptake of secreted Abeta via the LDL receptor-related protein (LRP). For this purpose, mice expressing both alpha-synuclein and wildtype or mutant hAPP will be crossed with receptor associated protein-deficient mice, which have reduced LRP expression. These experiments will be complemented with in vitro studies in alpha-synuclein-transfected cell lines. In Aim 3 we will determine whether Abeta-dependent alpha-synuclein aggregation and alphasynuclein-dependent neuronal deficits can be reduced by antioxidants. For this purpose, alpha-synuclein/hAPP mice will be crossed with superoxide dismutase 1 or 2 transgenic mice. These experiments will be complemented with in vitro studies in synuclein-transfected cell lines treated with antioxidants. These experiments will shed light on the overlap between AD and PD and on the role of hAPP/Abeta in the pathogenesis of PD and other Lewy body diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CER ON CAM ANTIOXIDANT THERAPIES (CERCAT) Principal Investigator & Institution: Frei, Balz B.; Professor and Endowed Chair; None; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-MAY-2008

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Summary: This Program Project is based in the Linus Pauling Institute, an emerging international leader in research and education on micronutrients and antioxidants, and one of a few centers in the US to focus entirely on health promotion and disease prevention by dietary and CAM approaches. The Center of Excellence for Research on Complementary and Alternative Medicine (CAM) Antioxidant Therapies (CERCAT) will investigate two specific categories of CAM antioxidants: (i) Antioxidants that modulate the cellular redox environment and, thus, cell signaling and transcriptional activation, e.g. by affecting critical thiols with a low pKa or upregulating endogenous antioxidant systems. The CAM antioxidants to be investigated from this category are dithiol compounds (e.g. alpha-Iipoic acid) and metal chelators (e.g. EDTA and desferrioxamine). (ii) Highly conjugated or aromatic compounds that inhibit tyrosine nitration by peroxynitrite and other reactive nitrogen species. The principal antioxidant to be examined in this category is uric acid. Using cell culture studies and relevant animal models, CERCAT will determine the molecular and cellular mechanisms of action of these CAM antioxidants, and their safety and efficacy in treating amyotrophic lateral sclerosis (ALS) and cardiovascular diseases (CVD) and reversing the loss of cellular resistance to stress that occurs with aging. These goals of CERCAT are buttressed by NCCAM's "increased emphasis on studies of the mechanism underlying CAM approaches" and its "FY 2003 Research Priorities" of "studies of the biology of EDTA chelation therapy in animal models of CVD" and "neurodegenerative disorders using in vitro studies and animal models." CERCAT's research goals will be accomplished through three highly interactiveprojects: 1) "Metal chelators and thiols in endothelial function, and CVD" (Balz Frei); 2) "Lower vulnerability to toxins in aging by treatment with lipoic acid" (Tory Hagen); and 3) "CAM antioxidants and ALS" (Joseph Beckman). Center Investigators will be aided by an Administrative Core, which handles budgetary, reporting, and external advisory needs. In summary, CERCAT will investigate the efficacy of CAM antioxidants in ALS, CVD and aging, and provide the essential knowledge about the underlying mechanisms, dose-response effects, and relevant biological targets to advance these CAM therapies to human trials; equally important, the studies will test for untoward effects that might discourage CAM antioxidant therapies from proceeding to human studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHEMICO-PHYSICAL PROPERTIES OF METAL-FLAVONOID Principal Investigator & Institution: Cheng, Francis I.; Chemistry; University of Idaho Moscow, Id 838443020 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant) Flavonoids are recognized as an important class of nutrient that may be responsible for the chemoprevention of a myriad of degenerative diseases. This action is attributed to their putative antioxidant action. Many investigators have recognized that metal chelation is an important determinate in the prediction of the antioxidant action of flavonoids. However, there is a paucity of data accumulated concerning the chemico-physico properties of metal-flavonoid complexes. A previous investigation from this laboratory has found that four flavonoids, baicilein, luteolin, naringenin, and quercetin, chelate pro-oxidant iron ions into a complex that is not Fenton Reaction active. Another plant-borne product, salicylate has been the subject of previous investigations from this laboratory and found to chelate pro-oxidant iron into a form that is again not Fenton Reaction active. The proposed investigations will study the similarity of action between the four aforementioned flavonoids and salicylate, i.e. the ability to bind pro-oxidant metals both as free ions and in low

18

Antioxidants

molecular-weight complexes. The pro-oxidant metals of concern in this study are Fe, Cu, and Mn ions and also in complexed forms with EDTA, ATP/ADP and in porphyrins. The redox potential of each metal complex will predict the antioxidant characteristics in terms of Fenton Reaction activity, other redox-dependent actions such as superoxide dismutase and catalase activity. Metal-flavonoid binding constants will aid in determining if the flavonoids are effective in vivo chelation agents. These data will be derived by potentiometric titrations augmented with UV-vis absorbance. The four flavonoids chosen for this study will give insights into structure-activity relationships. It is hoped that the subject of this investigation will give a new paradigm for the design, and discovery of antioxidants, and anti-inflammatory agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COCHLEAR VULNERABILITY/REACTIVE OXYGEN SPECIES Principal Investigator & Institution: Ohlemiller, Kevin K.; Associate Research Scientist; Central Institute for the Deaf 4560 Clayton Ave St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Acquired hearing loss represents a complex interplay of genes and environment. Although there is much support for the existence of genes that influence the vulnerability of the cochlea to noise and ototoxins, few candidate genes or processes have been identified. One candidate process involves the generation and regulation of reactive oxygen species (ROS). Both chronic neurodegenerative disease and acute CNS injury involve elevated ROS, and deficiency of antioxidant enzymes promotes vulnerability to injury. We hypothesize that some genetic defects that predispose people to acquired hearing loss involve impairment of ROS regulatory mechanisms, rendering the cochlea more vulnerable to injury. We will apply hearing loss-prone and -resistant mouse models (C57BL/6, BALB/c, CBA/Ca), and 'knockout' mice deficient in antioxidant enzymes (superoxide dismutase and glutathione peroxidase), of carefully considered ages to the following Specific Aims: (1) Correlating the dynamics of cochlear ROS production following noise exposure with specific cochlear injury. We will establish the relation between the magnitude and time course of cochlear ROS production following acute noise exposure and cochlear injury, as measured by auditory brainstem responses, light and electron microscopy, and hair cell counts. (2) Identifying genetic influences on the relation between ROS production and noiseinduced cochlear injury. We will determine the impact of genetic defects of hearing and ROS regulation on the relation between cochlear ROS production and noise-induced cochlear injury. (3) Uncovering the basis of genetic and age influences on the efficacy of antioxidants. We will determine the impact of age and genetic defects of hearing on the ability of exogenous antioxidants to attenuate both ROS production and noise-induced cochlear injury. Our experiments will establish how well the dynamics of ROS production predict cochlear injury, and whether progressive deafness genes may impair cochlear ROS regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--FREE RADICAL CORE FACILITY Principal Investigator & Institution: Kalyanaraman, Balaraman; Professor/Director; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: The Free Radical Core (FRC) will make state-of-the-art radical detection methodologies available to all of the investigators associated with the PPG. Multiple

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assays will be performed, wherever feasible, to provide rigorous identification and characterization of reactive oxygen and nitrogen species, their reactions and products. Following extensive discussions between Project Leaders and FRC research personnel, experimental protocols will be designed. In some instances, particularly in Electron Spin Resonance (ESR)-based protocols, the FRC staff will initially carry out the proposed work and subsequently train other research personnel in ESR. For other routine free radical analysis (i.e., TBARS_, the FRC personnel will advise the investigator on how to perform the experiments. The Free Radical Corre will provide the necessary technical facilities, custom- made free radical traps, and provide scientific expertise to pursue experiments in the following general areas: 1) Direct ESR detection of less reactive free radicals (e.g., ascorbate radical) and detection of more reactive and unstable free radicals (e.g., superoxide anion and hydroxyl radicals( by ESR spin- trapping using a variety of nitrone-based spin traps. 2) Detection of NO and NO-derived products (NO2-, NO3-, RSNO). 3) Detection of marker products of oxidation and nitration (e.g., dityrosine and nitrotyrosine) and lipid hydroperoxide/TBARS in peroxynitrite-mediated reactions. 4) HPLC detection of antioxidants (e.g., alpha-tocopherol) and their radical reaction products (e.g., alpha-tocopherylquinone). 5) Determination of cellular antioxidants (e.g., GSH) and anti-oxidant enzymes (GPx, SOD, catalase). In addition, the FRC will continue to refine and develop new assays for detection of ROS and RNS and synthesize novel radical traps that will enable project leads to pursue new research directions. The ultimate goal of Core B will be to ensure completions of the proposed aims in Projects 15 that require that above-mentioned facilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYTOKINES IN GLIAL CELLS AND EAE BRAIN Principal Investigator & Institution: Singh, Inderjit; Distinguished Professor; Pediatrics; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: The presence of proinflammatory cytokines and induction of inducible nitric oxide synthase (iNOS) in brain lesions of patients with multiple sclerosis (MS) provided evidence that NO/ONOO' along with free radicals of oxygen (02-) play an important role in the pathophysiology of MS. Studies from our laboratory have shown that cAMP inhibitors of protein phosphatases 1/2 A regulate the production of NO and induction of iNOS in astrocytes and macrophages by different mechanisms. NO alters the cellular redox by altering the expression of antioxidant enzymes. We have also shown that antioxidants (N-acetyl cysteine) and mevalonate inhibitors (lovastatin and sodium phenylacetate) block the induction of proinflammatory cytokines and that of iNOS and the production of NO in activated cultured astrocytes, macrophages and microglia. The objective of this proposal is to decipher the mechanism of the induction or regulation of iNOS in astrocytes and macrophages by PKA and protein phosphatases 1/2 A and the role of iNOS in the disease process of experimental allergic encephalitis (EAE), an animal model of MS. Achievement of these goals will be facilitated by understanding the molecular mechanism of activation of NFkB in the differential induction of iNOS by PKA and protein phosphatases 1/2 A in astrocytes and macrophages. Studies are proposed to identify the protein phosphatase (protein phosphatase I or protein phosphatase 2A) that is responsible for the induction of proinflammatory cytokines NFkB and activation of iNOS in astrocytes and macrophages. The possible role of NO/ONOO' in the pathophysiology of EAE will be investigated by using mice models which lack iNOS (iNOS knock out) and those which express increased levels of iNOS. We also propose to test the possible therapeutic effect of antioxidants drugs (N-

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Antioxidants

acetylcysteine) and mevalonate inhibitors (lovastatin and sodium phenylacetate) in halting/slowing the progression of the disease process in EAE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEHYDROASCORBIC ACID AS THERAPY FOR ISCHEMIC STROKE Principal Investigator & Institution: Boyd, Thomas A.; Progenics Pharmaceuticals, Inc. 777 Old Saw Mill River Rd Tarrytown, Ny 10591 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2003 Summary: adapted from applicant's abstract): A major goal of stroke research is the development of new treatment modalities to limit the extent of brain injury following acute ischemic injury. Ischemic stroke is associated with a rapid increase in free radical content in the brain and a depletion of natural antioxidants such as ascorbic acid. Delivery of ascorbic acid to the site of ischemic injury is limited by its inability to cross the blood-brain barrier. Dehydroascorbic acid, the oxidized form of ascorbic acid, readily crosses the blood-brain barrier via a facilitative transport mechanism and is converted into ascorbic acid after entering the brain. Dehydroascorbic acid has shown preliminary evidence of efficacy in a murine stroke model. This compound thus has significant potential as a therapeutic agent for stroke. The first aim of this Phase I project is to prepare an adequate supply of pure dehydroascorbic acid for testing. As large quantities of pure compound are not presently available, a new preparative, large-scale route will be developed. New analytical methods will be developed for determining the compound's identity and purity and for quantitating levels of unwanted impurities. The second aim is to formulate a convenient and stable solution for injection. This is feasible provided the buffer components are tightly optimized and the stability is confirmed by analytical testing. The final aim is to demonstrate in a small animal model that ehydroascorbic acid decreases neuronal injury after an occlusive infarct. This will be done in the mouse middle cerebral artery occlusion model. Dehydroascorbic acid will be administered intravenously at various doses and intervals following the onset of ischemia, and its effects on infarct volume, neurological function, cerebral blood flow, and mortality will be determined. A significant beneficial effect in this model in comparison with either vehicle or ascorbic acid controls will provide in vivo proof-of concept of the approach and will confine the value of additional studies of dehydroascorbic acid as a therapeutic agent in ischemic stroke. PROPOSED COMMERCIAL APPLICATIONS: Dehydroascorbic acid is a novel treatment for patients who have suffered an ischemic stroke. Dehydroascorbic acid has a unique ability to enter the brain and to elevate tissue levels of ascorbic acid, a natural antioxidant. This project seeks to demonstrate that dehydroascorbic acid is efficacious in a murine stroke model in the interval of time immediately following an ischemic event, a critical period for patients with ischemic stroke. These studies will support eventual clinical testing of the compound. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIET, COLON CANCER, AND CANCER COMMUNICATIONS Principal Investigator & Institution: Abouta, Jessie S.; Nutrition; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): This application describes a career development/transition plan for Jessie A. Satia, PhD, MPH, a newly appointed Assistant Professor in the Department of Nutrition at the University of North Carolina,

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Chapel Hill. The candidate's overall career goal is to establish an interdisciplinary research career combining her background in epidemiology, nutrition, and laboratory sciences to conduct methodologic, observational, and intervention studies of diet and human cancers. In particular, she would like to conduct studies to identify risk factors for cancer and design appropriate interventions for prevention and control in minority and underserved populations. The candidate proposes a career development plan that includes: teaching and mentoring students; submitting research manuscripts and pilot project proposals; and a research plan (75% of her effort) with two proposed projects. Project 1 titled "Cancer Communications among African American Adolescents" aims to collect information necessary to design diet-related cancer prevention messages for African American adolescents; and evaluate the effectiveness of messages framed in different ways on knowledge, attitudes, beliefs, and intentions to improve diet in this population. Qualitative methods will be used to collect information on various factors that affect dietary behavior among African American adolescents (14 to 16 years) in Durham, NC. This information will then be used to design messages focused on lowering dietary fat intake in this population that will be delivered via the Internet. Participants will be randomized into four groups based on Prospect theory and message framing, and will complete pre- and post-tests and cognitive interviews to assess the short-term impact of the framed messages. Project 2, "Diet and Colon Cancer in African Americans and Whites in North Carolina" describes proposed analyses using previously collected data from a study of 654 colon cancer cases (40-80 years) and 1067 populationbased controls, with equal numbers of African Americans and whites, in a 33-county area of North Carolina. The specific aims of the analyses proposed here are to examine effects of dietary factors (e.g., fat, fruits, vegetables, antioxidants, fiber, alcohol, and total calories) and food intake patterns (meal frequency and snacking timing) on colon cancer risk. Potential future research opportunities using biological specimens from this study are described. The long-term success of cancer research efforts rests, in part, on building the career of talented young faculty. Obtaining this award will greatly broaden and strengthen the candidate's focus on cancer prevention and control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIETARY AND GENETIC RISK FACTORS FOR COGNITIVE DECLINE Principal Investigator & Institution: Pope, Sandra K.; Geriatrics; University of Arkansas Med Scis Ltl Rock 4301 W Markham St Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This application for a Mentored Research Career Development Award proposes a 5-year career plan for the PI to develop into an independent researcher who will contribute on a national level to understanding risk factors for cognitive decline in older African-American and Caucasian adults. Through a program of mentoring, consultation, coursework, hands-on training, and directed readings, the PI will study the influence of dietary and genetic antioxidant risk factors and their interaction on cognitive decline. Specifically, the candidate will develop expertise in 1) the epidemiology of cognitive decline and dementia; 2) nutritional epidemiology, particularly dietary and supplement intake of antioxidants; 3) molecular epidemiology, particularly genetic polymorphisms and dietary biomarkers; and 4) advanced methods for longitudinal data analyses. The PI's long-term career goal is to build on the expertise and collaborations developed during this KO1 to 1) examine other longitudinal studies that have collected biological samples, nutritional data, and cognitive data, but have not explored antioxidant risk factors and cognitive decline; 2)

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Antioxidants

add cognitive assessments to ongoing studies that have collected dietary data and biological samples, but have not collected cognitive data; and 3) develop research studies to examine genetic and environmental risk factors in populations at high risk for cognitive decline. The overall hypothesis of the proposed studies is that cognitive decline is associated with low antioxidant intake and with genetic polymorphisms that modify this association. To address this hypothesis, the proposed research will focus on three specific aims: 1) examine the relationship of dietary and supplemental intake of antioxidants with cognitive decline; 2) examine the relationship between cognitive decline and specific genetic polymorphisms related to oxidative stress, including apolipoprotein-E, myeloperoxidase, manganese superoxide dismutase, and glutathione peroxidase; and 3) determine whether associations of antioxidant risk factors and cognitive decline are modified by genetic risk. These aims will be addressed in the Healthy Aging and Body Composition (HEALTH ABC) cohort, a 7-year, 2-site study of 3,075 adults (41.77/0 African-American and 58.3 percent Caucasian) aged 70-79 years at baseline. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIETARY ANTIOXIDANTS AND INCIDENCE OF ADULT-ONSET ASTHMA Principal Investigator & Institution: Hartert, Tina V.; Assistant Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The objectives of this application are to study the association of dietary and serum antioxidants and oxidative stress on adult-onset asthma incidence among a cohort of 75,000 women. We hypothesize that dietary antioxidants play a role in the development of asthma, particularly in persons with a family history of atopic disease. Questions related to dietary antioxidant intake that this application aims to address are whether dietary and serum antioxidants protect against development of adult-onset asthma, whether persons with atopic disease have higher indices of oxidative stress, and whether those with a genetic susceptibility to be atopic are protected by higher intake of dietary antioxidants. To examine these hypotheses, we will utilize an existing large prospective cohort, the Shanghai Women's Health Study (SWHS), which tracks detailed information on dietary intake and environmental factors as they relate to cancer incidence and other chronic diseases. This prospective cohort study is being conducted among approximately 75,000 female residents of Shanghai, China between the ages of 35 and 69, where there is marked heterogeneity in dietary intake and 97 percent of the cohort are non-smokers. Measurements of free radicals will be made in baseline urine samples using an assay for isoprostanes, recently described lipid peroxidation products, to determine if there is a correlation between adult-onset asthma and increased markers of lipid peroxidation. Isoprostanes are considered the most accurate marker of oxidative stress currently available. Measurements of serum antioxidants will be made using baseline serum samples. We propose in this project: (1) an incidence study to determine the association between dietary antioxidants and incident asthma, and (2) a nested case control study examining (a) the correlation between a urinary measure of oxidative stress and incident asthma, and (b) the relationship between serum antioxidants and incident asthma. This series of studies, with the combination of three measures of antioxidant exposure and oxidant stress, are designed to uncover antioxidant-specific effects in the development of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIETARY PATTERNS AND RISK OF CARDIOVASCULAR DISEASE Principal Investigator & Institution: Hu, Frank B.; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: This new application presents plans to study, prospectively, the association between dietary patterns and risk of coronary heart disease (CHD), ischemic stroke, and hemorrhagic stroke in cohort studies of 121,700 women age 30 to 55 years at baseline in 1976 (the Nurses; Health Study; NHS) and 51,529 men aged 40-75 years at baseline in 1986 (the Health Professionals Follow-up Study; HPFS). Food consumption data were collected through semiquantitative food frequency questionnaires at baseline and during follow-up in each of the cohorts. Dietary patterns are derived from the food consumption data using factor analysis, cluster analysis, and dietary indexes (based on prevailing dietary recommendations). In addition, using existing datasets from dietary validation studies in sub-samples of the two cohorts, the investigators propos to evaluate the reproducibility and validity of dietary patterns defined by factor/cluster analysis and dietary indexes. Further, using prospectively collected and stored bloods in the NHS (n-32, 826) during 1989-1990 and the HPFS (n-18, 000) during 1993-1994, we propose to examine whether observed associations between dietary patterns and CHD are explained by (or mediated through) plasma biochemical measurements (including serum lipids, thrombotic factors, antioxidants, fasting insulin, and homocysteine levels) in a nested case-control design; and they propose to assess prospectively the relationship between dietary patterns and these biomarkers in the control samples. The funded NHS and HPFS will provide follow-up and documentation of CHD and stroke in addition to covariate information. Assays of biomarkers in the two cohorts are funded through other grants. Overall, the large size of these cohorts, the prospective design, the high follow-up rates, and the availability of archived blood specimens provide a unique opportunity to study the relationship between overall dietary patterns and cardiovascular disease in an extremely cost-efficient manner. This would be the first study to characterize dietary patterns in large cohorts of men and women and relate dietary patterns to CHD and stroke. Finally, this project will enable evaluation of prevailing dietary recommendations in relation to both biomarkers of risk as well as clinical cardiovascular diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIETARY PREVENTION OF CARDIAC MITOCHONDRIAL AGING Principal Investigator & Institution: Hagen, Tory M.; None; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Her heart undergoes several adverse age-related changes that lead to loss of performance and ultimately to heart failure, the major cause of death for people over the age of 65 in the U.S. Oxidative damage, loss of energy supply, and tissue atrophy are thought to be underlying factors causing cardiac dysfunction with age, which in turn are likely caused by mitochondrial decay. However, little is known about the extent or nature of mitochondrial decay in the aging heart and whether dietary supplements that ameliorate mitochondrial decline improves cardiac function. Some studies on mitochondrial decay have been performed using isolated mitochondria, but results are conflicting and difficult to interpret. This is primarily due to a technical problem: extensive mitochondrial lysis and damage during isolation from aged tissue. We proposed to characterize and compare mitochondrial function in intact freshly isolated

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Antioxidants

cardiac myocytes from old and young rats. Advances in methodology now make analysis of mitochondrial function within intact cells feasible, and we now have preliminary evidence that mitochondrial decay occurs in isolated cardiac myocytes from old rats. Advances in methodology now make analysis of mitochondrial functions within intact cells feasible, and we now have preliminary evidence that mitochondrial decay occurs is isolated cardiac myocytes from old rats. Thus, the questions to be addressed in this proposal are A) what is the nature and extent of mitochondrial decay in cardiac myocytes with age? B) does mitochondrial decay affect cardiac function? C) does feeding old rats acetyl-L-carnitine (ALCAR) and (R)-lipoic acid (LA), compounds that we showed to enhance mitochondrial function and quench mitochondrial oxidants in isolated hepatocytes, also improve mitochondrial function in cardiac myocytes? We propose to investigate these questions in 3 specific aims: 1) Characterize and compare mitochondrial functions in isolated cardiac myocytes form young, adult, mature and old rats. Characterization will include oxygen consumption characteristics, bioenergics, and cardiolipin content in quiescent cells and in myocytes stimulated to contract. Other studies using isolated cardiac myocytes or isolated perfused hearts will determine the consequences of mitochondrial decay to cardiac performance. 2) Examine age-related changes in mitochondrial antioxidants, oxidant production, and myocardial oxidative damage. These studies will be instrumental in determining not only the impact of mitochondrial decay on oxidant production, but also the effect of mitochondrial production on the cell as a whole. 3) Assess whether feeding rats ALCAR and/or LA improves mitochondrial function, lowers oxidative stress in cardiac myocytes and improves cardiac performance. These experiments will measure the same experimental end-points as in specific aims 1 and 2. This project will thus be the first step in our long term goals of determining the importance of mitochondrial decay in pathologies of the aging human heart and whether dietary regimens that improve mitochondrial performance can be inexpensive yet effective therapies for cardiac dysfunction in aging. 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

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cells will be studied for gene expression profiling using oligonucleotide probe arrays. Statistical methods encompass gene image analysis, and we will use a computer 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: DISPOSITION OF GINKGO FLAVONOIDS VIA RECYCLING Principal Investigator & Institution: Hu, Ming; Associate Professor; Pharmaceutical Sciences; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: The present proposal will focus on sequential anaerobic and aerobic metabolism of ginkgo-flavones by intestinal microflora, large intestine, and liver. This sequential metabolism of ginkgo-flavones is expected to be efficient and extensive, because flavonoids and their metabolites are expected to go through repeated enterohepatic recycling. The long-term goal of our study is to determine how this sequential metabolism plus repeated recycling affects the disposition of flavonoids, an important class of antioxidants presented in Ginkgo biloba and many other herbs (e.g., garlic, tea, chamomile, and others). The special focus of the present study is on how bacterial metabolism affects the overall disposition of ginkgo- flavonoids. The specific aims are to: (l) determine if bacteria will only take up ginkgo-flavones but not ginkgoflavone glycosides, because of expected poor permeability of glycosides through the bacterial walls; (2) determine the metabolism of each ginkgo-flavone and as a mixture in Ginkgo biloba extract by various groups of bacteria normally residing in human and rat large intestine under anaerobic conditions.; (3) determine how parent compounds and metabolites formed through bacteria metabolism are absorbed in the large intestine,; (4) determine how these metabolites are further metabolized by the large intestine and the liver; and (5) determine how metabolite reshuffling, perhaps for multiple times, into the enterohepatic recycling loop will affect the over metabolic fate of ginkgo flavones and their metabolites. Through these exploratory studies, we would be able to test if a grand recycling scheme which involve sequential metabolism and/or secretion of flavonoids, their microbial and mammalian metabolites, is functionally critical to the disposition of ginkgo-flavonoids. By combining expertise from the two independent disciplines of microbiology and pharmaceutical sciences, we have the capability and the know-how to effectively test this complex hypothesis. if proven, this complex metabolic process will have profound impact on safety and efficacy of this herbal extract and other flavonoidrich herbal products. Through future animal and human studies in vivo, we would then determine how this grand recycling scheme influences the disposition of a variety of herbal and pharmaceutical products that also undergo, perhaps repeatedly, enterohepatic recycling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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Project Title: EPIDEMIOLOGY PARKINSON'S

OF

COGNITIVE

DYSFUNCTION

AND

Principal Investigator & Institution: Ascherio, Alberto; Associate Professor; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): We propose to conduct a pilot study for the prospective investigation of the early stages of cognitive decline in patients with Parkinson's disease and their relation with diet, lifestyle factors, and APOE genotype. Specific factors that will be addressed include cigarette smoking, caffeine consumption, dietary antioxidants, use of anti-inflammatory drugs, and, in women, use of postmenopausal hormones. The investigation would take advantage of two large prospective cohorts: the Health Professionals Follow-up Study (HPFS; 51,529 male health professionals followed since 1986), and the Nurses' Health Study (NHS; 121,600 female registered nurses followed since 1976). The occurrence of incident cases of PD in these cohorts is already being documented as part of an NIH funded study (we have

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confirmed 470 cases, 250 in men and 220 in women, and follow-up is ongoing). Moreover, diet and other lifestyle factors have been repeatedly assessed in these populations, and cognitive tests have already been administered to several thousands of NHS participants without PD (as part of a separate project). Blood samples or cheek-cell samples for DNA analyses have already been collected from most participants. Cognitive assessment will be accomplished by administering seven tests of cognitive function: the Telephone Interview for Cognitive Status (TICS), the East Boston Memory Test (EBMT, immediate and delayed recall), a category fluency test, a letter fluency task, a digits backward test, and a delayed recall of the 10-word list given in the TICS. The interview will be conducted by telephone and take approximately 20-25 minutes to complete. As part of the proposed project, we will administer these tests to men and women with PD and age-matched healthy controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPIDEMIOLOGY: ATHEROSCLEROSIS

OXIDATIVE

STRESS

AND

EARLY

Principal Investigator & Institution: Jacobs, David R.; Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from Investigator's Abstract) The risk of coronary heart disease (CHD) can be diminished significantly by the modification of dietary intakes and the cessation of smoking. A reduction of saturated fat intake and an increase in plant foods has both been associated with beneficial effects on serum cholesterol, hypertension, atherosclerosis and mortality. These dietary and lifestyle modifications are hypothesized to act by increasing antioxidant protection and reducing oxidative damage. Such damage is a primary mechanism in the development of atherosclerosis, as demonstrated by numerous basic science studies and suggested by several small human feeding trials. Specific oxidatively modified macromolecules have been found in advanced atherosclerotic lesions. However, no information is available on the early time course of oxidative damage in human subjects. The investigators propose to measure oxidation products from several classes of compounds, thereby studying multiple pathways in atherogenesis, and serum antioxidants. They will study a cohort of about 3500 black and white young men and women. Between June, 2000 and June, 2001 (15 years after baseline), CARDIA participants will be assessed for subclinical CHD by the measurement of coronary calcification at the earliest stages of detectability. In addition, endothelial dysfunction will be assessed by measurement of plasma adhesion molecules and microalbuminuria. By measuring several kinds of antioxidants and assessing oxidative damage in classes of compounds, this project will test the association of oxidative damage and early/subclinical CHD. In addition, utilizing the extensive biochemical and sociodemographic data collected over the first 15 years of CARDIA, they will define the confounding effects of traditional CHD risk factors. The investigators state that the analyses will allow testing several major hypotheses about the early evolution atherosclerosis and CHD. They further state that the conclusions will identify new strategies for the prevention of CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETHANOL, NITRIC OXIDE AND CORONARY HEART DISEASE Principal Investigator & Institution: Demaster, Eugene G.; Pharmacology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070

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Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2003 Summary: Epidemiological studies conducted over the last several decades consistently show that light to moderate alcohol consumption protects the heart against coronary artery disease. The major protective properties of alcoholic beverages reside with ethanol itself rather than with bioflavinoids/ antioxidants present in some of these beverages, although the latter may possess certain beneficial biological properties distinct from ethanol. Historically, this protection has been attributed to an ethanolinduced increase in one of the subfractions of HDL in plasma; however, this increase in HDL is now regarded to account for only a minor part of the observed protection by ethanol. The antithrombotic properties of alcohol also continue to it beneficial effect, but a specific molecular mechanism connecting these properties to alcohol has not been forthcoming. We are proposing that nitric oxide (NO) mediates the protective effects of ethanol on the cardiovasculature, including the antithrombotic properties of ethanol, through the NO-cyclic GMP (cGMP) signal transduction pathway. According to our mechanism, protection by ethanol occurs via an enhancement of the NO activation of guanylate cyclase by products of ethanol metabolism. The key specific objectives of this proposal are to show that (a) ethanol metabolism promotes the catalase-catalyzed oxidation of NO to NO2 and (b) NO2 is a more potent activator of guanylate cyclase than NO itself. We propose that ethanol drives the catalase-mediated NO oxidation reaction via a cascade of well established metabolic conversions that result in increased production of hydrogen peroxide. The two-electron oxidation of NO to NO2 by catalase and the subsequent activation of guanylate cyclase by NO2 are two biochemical steps that we have undertaken to establish as fact. These two steps are critical to our understanding of the overall mechanism for the protection of the cardiovasculature provided by ethanol. Moreover, because ethanol and its metabolites as well as NO alter or regulate cellular processes in almost every tissue and body organ, we anticipate that the biochemical mechanisms described here for the interaction between ethanol and the NO-cGMP signaling pathway likely have relevance beyond the cell types located within the cardiovascular system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVALUATION OF ANTIOXIDANT SUPPL IN FOCAL CNS ISCHEMIA Principal Investigator & Institution: Clark, Wayne M.; Neurology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Stroke is a major cause of death and disability in the United States. Evidence suggests that even if blood flow is initially restored additional "reperfusion injury" processes can occur that can potentiate brain injury and reduce existing blood flow. Some of the mediators of this "reperfusion injury" appear to be due to an inflammatory responsive involving free radical generation, activated leukocytes, and platelet activated factor. Various commercially available "antioxidant supplements" appear to produce clinical benefit in several diseases. These supplements including Ginkgo biloba extract (EGb) and alpha lipoic acid (LA) have multitude of biologic effects including reducing free radical generation, inhibiting PAF and leukocyte activation (inhibit NFalphaB), and improving cerebral blood flow. Antioxidants have shown benefits in multiple disease models involving reperfusion injury but have yet to be fully evaluated in reperfusion injury related to stroke. This project will investigate the treatment potential and protective mechanisms of selected antioxidants using an animal model that closely approximates clinical stroke. The specific aims of the study are as

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follows: Aim 1: To confirm and characterize the neuroprotective efficacy of EGb in focal CNS ischemia, determine the effects of EGb on the inflammatory response and CBF, and evaluate safety interventions with other medications used in stroke. Aim 2: To confirm and characterize the neuroprotective efficacy of LA and dihydro lipoic (DHLA) in focal CNS ischemia and determine their effects on the inflammatory response and CBF. This study will use the middle cerebral artery filament occlusion (MCAO) model in the mouse and will utilize a combination of ischemic damage (lesion size) and neurologic functional measurements to determine efficacy. Potential mechanisms of efficacy for each antioxidant will be assessed including effects on in vivo cerebral blood flow (laser doppler measurement of blood flow) and the inflammatory response (molecular and flow cytometry). The information obtained from this project will be critical in planning future clinical stroke trials involving these agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEINS

FUNCTIONAL

STUDIES

OF

CYTOSOLIC

ANTIOXIDANT

Principal Investigator & Institution: Valentine, Joan S.; Professor; Chemistry and Biochemistry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-1993; Project End 31-MAR-2002 Summary: Life in air is possible because uncatalyzed reactions of dioxygen in living organisms are usually slow. In addition, oxidative damage to components of healthy cells is frequently prevented or repaired by antioxidant, replacement, or repair systems that exist in the cells for the purpose of maintaining and restoring redox balance. Our approach is to study the roles of superoxide, hydrogen peroxide, metal ions, and small molecule antioxidants in the yeast S. cerevisiae. The yeast S. cerevisiae is a simple eucaryote for which extensive genetics and molecular biology exist. Many genes from higher organism have been shown to substitute functionally for their yeast analogs, and more are expected now the entire yeast genome has been sequenced and is available. When grown on a non-fermentable carbon source, yeast cells metabolize dioxygen in a fashion similar to human cells, and the cellular systems for prevention, repair, and replacement of oxidatively damaged cell components are also similar. Yeast is thus an excellent system in which to study how redox balance is maintained in healthy eucaryotic cells. These studies are expected to lead to a better understanding of redox balance in eucaryotic organisms and the role of "oxidative stress" in processes leading to human aging, cell death, and disease. We will determine the major natural sources of superoxide and hydrogen peroxide in yeast and measure their concentrations and those of small molecule antioxidants (reduced and oxidized) within the cells. These methods will be applied to the wild type strains and to a variety of mutant strains in which antioxidant systems and/or dioxygen metabolism have been modified; the results will be used to interpret the phenotypes observed for these mutant strains. Naturally occurring sensors of hydrogen peroxide levels that are involved in regulation of gene expression will be studied. Levels of copper, zinc, manganese, and calcium metal ions will be determined in wild type and mutant strains in which levels of various antioxidant systems have been modified. Effects of addition or depletion of metal ions on the nature and rates of antioxidant and pro-oxidant processes and the maintenance of redox balance will be examined in the wild type and mutant strains as well. The roles played by the different metal ions will also be examined in yeast model systems designed to investigate processes related to aging, cell death and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Antioxidants

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Project Title: GASTROINTESTINAL PROGRAM PROJECT Principal Investigator & Institution: Potter, John D.; Member & Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 18-AUG-1998; Project End 31-MAY-2003 Summary: Research in colorectal and pancreas cancer is proposed. It takes as its theme the following model: the interaction of cells with DNA damaging agents can result in three classes of cells-normal cells with intact DNA; cells with damaged DNA that undergo apoptosis; and cells which, despite DNA damage, fail to suicide. We propose to explore aspects of the differences in these three classes of cells to increase our understanding of the carcinogenesis process, to monitor interventions, identify markers that may be used for population screening, and to exploit for therapeutic purposes. Project 1 focuses on oxidative damage and apoptosis among a high-risk human populations- with pancreatitis- and an animal model in order to establish the roles of oxidative DNA damage and antioxidants in pancreatitis and pancreas cancer, and to develop a clinical screening test. Project 2 also focuses on a high-risk inflammatory disease- ulcerative colitis-in order to determine the role of DNA damage and mutagenesis in the progression of UC dysplasia. In addition, an intervention with antioxidants is proposed to reverse of slow the dysplasia neoplasia sequence. Project 3 focuses on colonoscopy patients with the specific aim of identifying several processes in the pathways to neoplasia, including oxidative damage and changes in expression of apoptosis-related proteins, that will allow the early identification of high-risk individuals in a low-cost, minimally invasive manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENES, HORMONES & ENVIRONMENT IN AN OVARIAN CANCER MODEL Principal Investigator & Institution: Cramer, Daniel W.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 17-APR-1992; Project End 31-JUL-2008 Summary: (provided by applicant): This New England-based case-control study has sought to identify risk factors for ovarian cancer mediated through depletion of ovarian germ cells and gonadotropin excess. New theories with a molecular basis and considering roles for ovarian steroids, inflammation, and certain genetic polymorphisms now need to be incorporated. In our new model, gonadotropins remain important with risk factors operating at the pituitary or hypothalamic level. Elements within the ovary include germ cells regulating pituitary feedback, stromal cells producing steroids and proteins, and epithelial cells responding to growth factors. Epithelial cells trapped in inclusion cysts or deriving from endometriosis may be more susceptible to local or circulating growth factors. Epithelial proliferation in the setting of reactive oxygen species (ROS), generated from catechol estrogen or inflammation, leads to DNA damage. Selection of cells destined to become cancer may occur when inherited DNA repair mechanisms are faulty and oncogenes or tumor suppressors are damaged. Other genetic factors include variants of genes in pathways for steroid production or xenobiotic metabolism, while a variety of exposures may impact on risk. In the continuation proposed, existing and new epidemiologic data and DNA from 1700 controls and 1800 cases with ovarian, fallopian tube, or primary peritoneal cancer (including a subset identified pre-operatively) will be used to examine how hormonal factors, genes, and environment interact in this model. Through pituitary effects, pregnancy and lactation protect better than pregnancy alone and opposed regimens of

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menopausal therapy protect better than unopposed regimens. As a marker for poor germ cell reserve, short cycle lengths in very early reproductive life increase risk for ovarian cancer. By affecting steroid production, genetic variants of 3 and 17betaHSD, CYP11A, CYP17, and CYP 19 may affect risk for ovarian cancer. Steroid production is also enhanced by caffeine use, a predicted risk factor interacting with dietary cholesterol or caffeine metabolism. Genetic polymorphisms affecting the production or clearance of catechol estrogen or ROS generated by inflammation also influence ovarian cancer risk, including Ahr, CYP1A1, COMT, MnSOD, GST, and NAT and may interact with exposures like genital talc. Protection from ovarian cancer is associated with a variety of antioxidants including lycopene, carotene, ginkgo, and indoles from Brassica vegetables as well as anti-inflammatory agents. Our continued goal is to identify modifiable risk factors and chemo preventive agents for a common and lethal cancer in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLUCOCORTICOID RECEPTOR-MEDIATED CATARACT Principal Investigator & Institution: James, Eric R.; Ophthalmology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2004 Summary: (Applicant's Abstract) Cataracts are a serious risk to those undergoing steroid therapy, restricting the efficacy of these compounds. Steroid-induced cataracts are posterior subcapsular, frequently occlude the central visual axis and often require early surgical removal. The main action of steroids is via the glucocorticoid receptor (GR) which mediates gene transactivation and transrepression; the role of GR activation in steroid-induced cataract has not received due attention to date. Reduced levels of glutathione (GSH) in the lens are an early event following glucocorticoid administration. GSH synthesis is negatively regulated by GR activation and this effect is reversed by RU486, a potent GR antagonist. Reduction in GSH levels would perturb the cellular redox balance, increasing cell sensitivity to reactive oxygen species (ROS). Oxidants have long been considered to play an important role in cataract development, and in vitro, lens opacification due to steroid administration can be ameliorated with antioxidants. GSH depletion is also an early event in apoptosis. ROS can trigger apoptosis, as can activation of p53, a protein that has recently been shown also to bind to GR. Additionally, the ratio of the pro- and anti-apoptotic members of the Bcl-2 family of proteins is altered by GR activation. Thus a second pathway to steroidinduced cataract may involve 'apoptosis' induction in the lens epithelial cells with consequences for the underlying developing and maturing lens fiber cells. We hypothesize that steroidinduced cataracts are mediated via GR through its effects on gene expression. The following specific aims are proposed: 1). Steroid-mediated gene regulation of redox: We aim to test the hypothesis that steroid-GR binding leads to GSH depletion through gene transrepression followed by elevation of ROS. Studies will be conducted to determine a). the localization of GR in the lens epithelium, b). the effect of glucocorticoids on Y-GCS expression and on ROS levels in lens epithelial cells, and c). the oxidation of lens proteins following glucocorticoid. treatment of lenses. 2). Steroid-induced (apoptotic) disruption of lens cell development: We will test the hypothesis that steroid-GR binding leads to activation of proteins involved in the intrinsic, mitochondrial, pathway of lapoptosis' in lens epithelial cells which culminates in disturbance of their normal maturation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Antioxidants

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Project Title: HERBS CARDIOTOXICITY

PROTECT

AGAINST

DOXORUBICIN-INDUCED

Principal Investigator & Institution: Shao, Zuo-Hui; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Doxorubicin (Dox) is an anthracycline antineoplastic drug commonly used against hematologic malignancies and solid tumors for over 30 years. However, its use is largely limited by a cumulative dose-related cardiotoxicity, which includes cardiomyopathy and congestive heart failure. A central mechanism of cardiotoxicity involves generation of reactive oxygen species (ROS), in which Dox generates superoxide, hydrogen peroxide, and hydroxyl radicals leading to mitochondrial damage. Many antioxidants have been used to prevent and minimize Dox-induced cardiotoxicity, but with mixed results. Based upon our cellular studies of ischemia/reperfusion injury, some herbal antioxidants may be more potent than traditional antioxidants in attenuating mitochondrial oxidant injury, and thus could play an important role in preventing cardiac side effects of Dox. The proposed work tests whether two highly effective herbal antioxidants, grape seed proanthocyanidin extract (GSPE) and Scutellaria baicalensis extract (SbE), can prevent Dox-induced cardiotoxicity in our cardiomyocyte model. We will test whether 1) Dox increases mitochondrial oxidant stress and injury in cardiomyocytes, testing whether exposure (124 hours) to increasing doses of Dox (1 -100 uM) increases oxidant stress and death in chick cardiomyocytes, measuring oxidation of DCFH and DHE as indicators of hydrogen peroxide, hydroxyl radicals and superoxide generation respectively, and uptake of propidium iodide as a marker of cell death. We will also observe changes in cell membrane morphology and synchronous contractions as a result of Dox exposure to test its effect on contractile function in this model. We will also test whether Doxinduced ROS generation originates from mitochondrial versus nonmitochondrial sources. We will then test whether 2) GSPE (1-100 _ug/ml) and SbE (0.1 -1 mg/ml) individually or in combination, can attenuate Dox-induced ROS generation and ameliorate ROS-mediated injury. We will compare these protective effects to other antioxidants such as tocopherol and N-acetylcysteine. Finally, we will 3) determine whether GSPE or SbE affect the tumoricidal action of Dox on cancer cell lines. This work has the potential to increase our understanding of Dox oxidant cardiotoxicity, and could lead to new applications for herbal antioxidant treatment, which make Dox safer and more effective. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHALED PARTICLE CHARACTERISTICS AND EARLY LUNG EFFECTS Principal Investigator & Institution: Beckett, William S.; Professor; Environmental Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2003 Summary: (Adapted from the Investigator's Abstract) Chronic obstructive pulmonary disease (COPD) is a disabling condition produced by chronic bronchitis (airway inflammation and mucus hypersecretion) and emphysema (loss of alveolar surface area). Epidemiologic studies of the workplace have consistently shown an excess of COPD associated with dusty work environments, yet only a few substances (coal, silica, cadmium) causing COPD in the workplace have been characterized based on chemical composition and respirable particle size. These findings suggest that the much broader

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range of workplace dusts may in certain conditions contribute to COPD based on characteristics other than chemical composition alone. Pulmonary inflammation plays a role in early events leading to COPD. Particles less than 10 micron aerodynamic diameter are considered to be able to penetrate the upper airways and reach the respiratory tract, and are thus designated as being in the respirable range. Ambient fine particles (<2.5um) consist of two fractions: ultrafines (0.01 to 0.1 um) and accumulation mode particles (0.1 to 1.0 um). Recent studies of ambient particulates indicate that ultrafine particles may be more harmful than other fine particles on an equal mass exposure basis. In animal models, ultrafine particles have a higher alveolar deposition fraction, translocate more easily from the airways to the interstitium, induce greater activation of macrophages and cytokine release, and cause greater impairment of macrophage clearance function.One reason for the greater toxicity of equal masses of these smaller particles is their much greater surface area. We hypothesize that the size of inhaled fine particles, in addition to their chemical and other physical characteristics, plays a critical role in determining occupational health effects. To test this we will study early lung and systemic inflammatory responses as well as cardiac effects in adults after carefully controlled inhalation exposure to ultrafine and accumulation mode zinc oxide, a particle we have previously characterized for the dose-response relationship of its short term pulmonary and systemic inflammatory effects. Studies will be conducted in the Environmental Exposure Facility of the Adult General Clinical Research Center. We will compare ultrafine to larger, accumulation mode particles (on an equal mass exposure basis) in their ability to produce symptoms, fever, markers of airway inflammation, antioxidants, systemic acute phase proteins, and alterations in the blood clotting cascade, cytokine release, heart rate, rhythm, and repolarization. We anticipate that the results will help to determine whether there are differential effects for equal mass exposures to fine particles of different size fractions in the pathogenesis of COPD 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

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Antioxidants

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 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: LUNG SURFACE ANTIOXIDANT KINETICS MEDIATE OXIDANT INJURY Principal Investigator & Institution: Postlethwait, Edward M.; Professor and Vice Chair; Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Pulmonary epithelial cells are continuously subjected to a variety of oxidant stresses. Of substantial concern are the potential health impacts induced by the environmental oxidants ozone (O3) and nitrogen dioxide (NO2), which likely contribute to the pathogenesis of lung disease. The lung surfaces are covered by an aqueous layer (epithelial lining fluid; ELF) which inhaled gases first encounter. The ELF is a complex mixture that contains significant concentrations of small molecular weight antioxidants, principally ascorbic acid (AH2), glutathione (GSH), and uric acid (UA), that directly react with O3 and NO2 during their absorption. The standard paradigm proposes that ELF antioxidants provide a protective screen against the injurious effects of inhaled oxidants. However, because (i) injury unequivocally occurs during exposure despite the high antioxidant concentrations, and (ii) recent data suggests that antioxidants may themselves participate in the cascade(s) leading to membrane damage, the applicant proposes that the dynamics of ELF antioxidants critically mediate the balance between oxidant quenching and production of secondary bioactive species. Thus, if ELF antioxidants cannot be maintained in sufficient concentration, pro-oxidant conditions may develop within the site-specific regions where airway injury occurs. It is hypothesized that the efflux and turnover of ELF antioxidants are rate-limiting determinants governing the epithelial toxicity of inhaled environmental oxidants. This hypothesis will be addressed by an interrelated progression of experimental aims utilizing the application of labeled antioxidants and tightly controlled investigational models to elucidate the kinetics of AH2, GSH, and UA appearance (efflux) and turnover within the ELF. Accomplishment of the proposed aims will: 1) provide novel information regarding ELF antioxidant kinetics and define rate limitations during inhaled O3 and NO2 exposures, 2) quantify the associations among exposure-induced epithelial injury, oxidant dosimetry, and antioxidant kinetics, and 3) establish new mathematical paradigms that, based on oxidant and antioxidant ELF flux rates, will reveal new information regarding mechanisms governing the pathogenesis of oxidant lung injury, potential basis of differential susceptibility, and the importance of lung surface phenomena in predicting human health effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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 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 OF NEUROPROTECTION BY C60 DERIVATIVES Principal Investigator & Institution: Dugan, Laura L.; Associate Professor; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 15-MAY-1998; Project End 31-JUL-2002 Summary: There is substantial evidence that oxidative injury plays a role in many types of cytotoxic insults, and that the role of free radical damage may be especially prominent in neurological disease states, such as stroke, trauma and neurodegenerative disorders such as Parkinson's disease. Recently, the applicant reported that watersoluble derivatives of C60 were highly effective neuroprotective agents capable of

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Antioxidants

rescuing cortical neurons from a broad range of insults, including excitotoxicity induced by NMDA or AMPA, apoptosis produced by growth factor withdrawal or application of A-Beta (1-42), and neuronal death following oxygen-glucose deprivation. In addition, intraperitoneal administration of these compounds to a mouse model of familial ALS delayed both the onset of motor deterioration and death. Electron paramagnetic resonance spectroscopic studies confirmed that these water-soluble malonic acid derivatives of C60 retain the potent free radical scavenging capabilities of native C60 with the ability to eliminate both hydroxyl and superoxide radicals. Based on these observations, the applicants believe that neuroprotection provided by these antioxidants reflects their ability to scavenge not only hydroxyl radical but superoxide radical (O2-) at concentrations in the micromolar range. This application proposes to test the specific hypothesis that superoxide radical scavenging by C60 derivatives is a critical determinant of neuroprotective efficacy by C60 derivatives. They plan to study mechanisms of neuroprotection by generating C60 derivatives substituted with similar functional groups, but possessing differing degrees of O2- scavenging ability. The rankorder potency of derivatives will be compared for both neuroprotection and superoxide scavenging to see if these properties correlate. In addition, using Sod2mlucsf mice, which have a specific impairment in the ability to eliminate mitochondrial O2-, they will test the protective efficacy of these agents on neurons cultured from these mice, and in neonatal mice. The broader goals of this proposal are: 1) to develop these molecules as tools to study the role of O2- as both signaling molecule and neurotoxin, 2) to continue exploration of the contribution of mitochondrial O2- to neuronal cell death, 3) and to begin to define structure-function relationships for these promising compounds as a necessary step towards pre-clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METHYLATION EPIDEMIOLOGY

AND

OXIDATION

IN

BREAST

CANCER

Principal Investigator & Institution: Freudenheim, Jo L.; Professor and Interim Chair; Social and Preventive Medicine; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: (provided by applicant): There is considerable epidemiologic evidence that alcohol intake is related to risk of breast cancer and that intake of vegetables and fruits may reduce risk. Utilizing an existing case control study, we propose to examine two etiological mechanisms, one-carbon metabolism and/or oxidative stress and breast cancer. Our first aim is to examine the relation of elements related to one-carbon metabolism with risk. We propose a) to investigate genetic variation in enzymes important in one-carbon metabolism (methylene tetrahydrofolate reductase (MTHFR), methionine synthase (MS) and cystathione B-synthase (CBS)) in relation to risk and to investigate interaction of these genetic factors with dietary folate and alcohol with breast cancer risk; b) to investigate the association of dietary folate and alcohol and these genetic factors with total p53 mutations and with particular p53 mutations and c) to investigate the association of dietary folate and alcohol and these genetic factors with hypermethylation of the p16 gene, the BRCA1 gene and the estrogen receptor gene in breast tumors. Our second aim is to examine elements related to oxidative stress and antioxidants with risk. We propose to a) examine the relation of genetic variation in an enzyme important in the control of oxidative balance (manganese superoxide dismutase (MnSOD)) and to examine interactions of this genetic factor with dietary factors both oxidants and antioxidants; and b) to investigate the association between dietary sources

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of oxidants and antioxidants with total and particular p53 mutations. By combining information on intake, genetic susceptibility and tumor characteristics, it will be possible to make clearer inferences about the role of these two mechanisms in breast cancer etiology, with potentially important public health implications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MITOCHONDRIAL NEURODEGENERATION

OXIDATIVE

STRESS

AND

Principal Investigator & Institution: Melov, Simon; Assistant Professor; Buck Institute for Age Research Novato, Ca 94945 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2005 Summary: (Verbatim from the Applicant's Abstract) Oxidative stress has been hypothesized to be a major factor in the etiology of many progressive age related neurodegenerative diseases including Alzheimer and Parkinson disease, amytrophic lateral sclerosis, Friedreichs ataxia, and the prion diseases. The chief source of oxidative stress within the cell is the mitochondrion. The main ROS produced is the superoxide radical ( O'~) which under normal circumstances is reduced to H2O2 via the mitochondrial form of superoxide dismutase (Sod2). We have previously reported that inactivation of this gene results in neonatal lethality accompanied by a dilated cardiomyopathy, hepatic lipid accumulation, oxidative DNA damage, organic aciduria, spongiform encephalopathy, gliosis, and mitochondrial enyzmatic abnormalities. We have also demonstrated that many of these phenotypes can be ameliorated by synthetic antioxidant treatment. The long term goals of these studies are to 1) understand the molecular targets of mitochondrial oxidative stress both at the genetic and protein level within the brain, & 2) characterize the efficacy of synthetic antioxidants in preventing many of the CNS disorders which present due to mitochondrial oxidative stress within the brain. The specific aims are 1) Characterize the metabolism of the affected areas of the brain to determine if there is a metabolic differential relative to unaffected areas; 2) Determine whether cell loss contributes to the progression of the spongiform changes; 3) Characterize at the biochemical and enzymatic level the changes due to mitochondrial oxidative stress within the brain and the efficacy of various synthetic antioxidants in attenuating such changes; 4) Investigate gene expression changes in the brain in relation to endogenous mitochondrial oxidative stress via microarray analysis. Experimental methods include; growth and harvesting of Sod2 mutant mice and controls with and without synthetic antioxidant treatment, histopathological analysis, stereological cell counting, metabolic measurements via 2-deoxyglucose labeling, biochemical analysis of mitochondria from control and experimental groups, and microarray analysis of RNA from control and experimental groups of both affected and unaffected areas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR INTERVENTION PREVENT NOISE INDUCED HEARING LOS Principal Investigator & Institution: Miller, Josef M.; Professor & Director of Research; Otolaryngology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: The goal of this research project is to assess the role of oxidative stress as a factor in noise-induced hearing loss (NIHL), the primary cause of hearing loss in the industrialized world. Noise induced metabolic activity of inner ear as well as direct

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Antioxidants

mechanical trauma may result in the formation of reactive oxygen species (ROS). We propose a model in which ROS represent a major causal factor in NIHL leading to downstream cascades that result in cell death. The model proposes that noise induces the formation of ROS, and that ROS and their byproducts directly cause pathology of the inner ear tissues, as well as indirectly cause a reduction in inner ear blood flow that exacerbates tissue damage. The model also proposes interventions that can block the formation and direct effects of ROS (antioxidants) or their downstream cascades (neurotrophic factors, NTF), and thus may protect the inner ear from noise damage. The studies proposed will test the hypotheses that: 1) noise induces ROS and inner ear pathology, and that antioxidant treatment prior to noise exposure will reduce ROS (lipid peroxidation) and NAIL (measured electrophysiologically and by sensory cell damage in guinea pigs); 2) cochlear blood flow is reduced by isoprostanes, products of lipid peroxidation, further contributing to NIHL; 3) NTF will significantly reduce NIHL while minimally reducing ROS; 3) post noise-exposure treatment will afford reduced, but significant, protection (compared to pretreatment). These studies are geared towards identifying the specific ROS formed and the time course of their formation. They will allow us to specifically assess the relative effectiveness of antioxidants and NTFs to reduce ROS-induced cell destruction. These studies will provide a critical test of this model of NIHL and may lead to interventions that are effective in preventing NIHL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NASAL INJURY DUE TO EXPOSURE TO OZONE Principal Investigator & Institution: Harkema, Jack R.; Professor; University of Alabama Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Ozone, the major oxidant pollutant in photochemical smog, causes toxic injury to nasal and pulmonary airways. The overall goal of Project 3 is to determine the nature and distribution of airway mucosal injury, adaptation and repair in the nasal passages of neonatal and infant monkeys episodically exposed to ozone. Intranasal distribution and severity of the ozone-induced lesions will be determined by image analysis and standard morphometric techniques. The ozone-induced nasal alterations will be compared to biochemical changes in intracellular and extracellular antioxidants present in the nasal mucosa and extracellular airway lining fluid, respectively. The identified, site-specific alterations in mucosal morphology and in regional tissue/fluid biochemistry caused by episodic ozone exposures will also be compared to computerassisted estimates of intranasal, regional dosimetry of ozone. The site-specific comparisons throughout the nasal passages will be used to determine how tissue susceptibility and airflow-driven dosimetry contribute to the pathogenesis of nasal epithelial and subepithelial injury and remodeling caused by acute and chronic ozone exposures. The results of these studies will provide a better understanding of how episodic ozone exposure affects the growth and development of the nasal airways at the macroscopic, microscopic and molecular levels of analysis. Our premise is that the developing nasal mucosa in neonatal and infant monkeys is more susceptible to the toxic effects of ozone than is the fully developed nasal mucosa of adult monkeys. We hypothesize that this disparity in mucosal responses is due to differences between infant and adult animals in the regulation of intracellular and extracellular antioxidants in the nasal airways. Project 3 is also designed to test the hypothesis that the ozone-induced morphologic, biochemical, and molecular responses of the nasal mucosa are sentinels for ozone-induced alterations in the distal pulmonary airways. Furthermore, this project will test the hypothesis that the episodic nature of the environmental exposure to ozone alters the House Dust Mite Allergen (HDMA)-induced allergic rhinitis in infant

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monkeys by fundamentally altering postnatal development of the nasal airway mucosa. This project will have critical input into all other projects and is crucial to the overall success of the program. In turn, this project will rely heavily on projects 1,2 and 4 to accomplish the proposed research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEURODEGENERATION AND MITOCHONDRIAL DYSFUNCTION IN AGING Principal Investigator & Institution: Bondy, Stephen C.; Professor of Toxicology; Community and Environ Medicine; University of California Irvine Campus Dr Irvine, Ca 92697 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) neurodegenerative diseases involve promotion of a pathological process by events associated with normal aging. Senescence is generally an essential concomitant of the progression of neurological disease and if this were retarded, the incidence of many such disorders would be significantly reduced. Prevention of deficits is more readily accomplished than attempts to compensate for impaired neurological function. This application posits that the cerebral mitochondrion is a susceptible target of age-related pro-oxidant events within the CSN, that the administration of exogenous factors may modify the velocity of these events and that this can influence other biological and behavioral consequences of aging. Maturational changes in mitochondrial function, structural integrity and mtDNA characteristics will be studied throughout the lifespan of C57BL/6 mice. Attempts to retard the onset of changes in mitochondrial parameters including gene deletions, membrane stability and levels of key enzymes, will be made by dietary supplementation with antioxidants, specifically targeted toward protection against free radicals produced by the reduced efficiency of the respiratory chain encountered with advancing age. Results will be substantiated with those obtained from mitochondria derived from neural cell lines exposed to low oxidant conditions for several generations. The role of both active oxygen and nitrogen species as contributory factors in these events and their potential modulation by antioxidants will be taken into account. The protective potential of antioxidants in combination, targeted toward several sources of oxidative events, will be evaluated. While the onset of neurological disease generally does not represent merely an acceleration of normal aging, there may be biological loci common to both. The identification and protection of such common targets will help in the development of agents that can reduce the incidence of neurodegenerative disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROSCIENCES ANTIOXIDANTS

TECHNOLOGY

DEVELOPMENT

FOR

Principal Investigator & Institution: Kumar, Dinender; Director; Brain Research Laboratories, Inc. (Brl) 115 Mill St Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: adapted from applicant's abstract): There is growing evidence that ROS may be implicated in aging and a variety of age-related human degenerative disorders. In this context, exogenous antioxidants are beginning to assume an unprecedented importance in the arsenal of therapeutic agents that are continuously being developed in order to combat age related diseases and the phenomenon of aging itself. These antioxidants are supposed to supplement and reinforce the natural defenses of the body

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Antioxidants

and to protect it when the endogenous antioxidant levels are diminished as a result of disease or aging. The current problems in the in vitro assay of antioxidants are many and varied: (a) different laboratories use different species of ROS and different target molecules under different experimental conditions in formulating their assay systems; (b) there are no comparative studies to evaluate the reliability of one method over an other, (c) many have been mainly employed for investigating the mechanisms of action of specific oxygen free radicals and are not particularly relevant as procedures for the assay of antioxidants; (d) since many of the methods are not specifically designed for antioxidant assay, they have not been optimized taking into consideration the prooxidant or antioxidant properties of certain substances under different conditions; and (e) they often require expensive instrumentation and highly sophisticated technical skill to perform the analysis and to interpret the resulting data. In the first step in this project, our goal will be to develop in vitro assay systems for the measurement of individual biological activities of coenzyme Q, lipoic acid and melatonin, using pure commercial preparations of these compounds, taking into consideration the properties of both the ROS and the antioxidants involved. In the second step, we will develop an in vivo method using for determining antioxidant activity using intact cells and intracellular macromolecules as targets. The results of the two systems will be analyzed to yield an approach which can be employed for the determination of biological activities of known or unknown mixtures of antioxidants using a minimum number of simple assay procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NITRIC OXIDE REGULATION OF VASCULAR OXIDANT INJURY Principal Investigator & Institution: Freeman, Bruce A.; Professor and Vice Chair; Anesthesiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 15-JAN-1998; Project End 31-MAY-2003 Summary: The focus of this proposed research is to define mechanisms underlying the production and reactions of.NO and peroxynitrite (ONOO-) with lipids and lipid radicals (LO. And LOO.) formed during membrane and lipoprotein oxidation. Special attention will also be paid to the direct reactions and indirect protective effects that.NO exerts towards the key membrane and lipoprotein antioxidants, alpha-tocopherol and ascorbate in chemical and cell studies. To understand the conditions and reactions underlying the dual protective and toxic aspects of the free radical reactivities of.NO, four experimental aims will be pursued to test the hypothesis that.NO can regulate oxidant/inflammatory injury in the vascular compartment by accelerating oxidative events via peroxynitrite (ONOO-) formation or alternatively, by chemically terminating free radical species. This will lead to modulation of inflammatory events and yield nitrogen-containing products having unique reactivities. Specifically, the principal investigator will 1) examine the reactions of.NO, reactive oxygen species and ONOOwith free and esterified unsaturated fatty acids (linoleic and arachidonic acids), 2) characterize the principal.NO/ONOO- derivatives of oxidized lipids (e.g. LONO/LNO2 and LOONO/LONO2 species) formed in oxidizing lipid systems and define their biochemical properties, 3) define the impact of.NO on integrated membrane and lipoprotein antioxidant defenses, focusing on the direct and indirect interactions of.NO with alpha-tocopherol, -tocopherol and ascorbic acid and 4) examine the actions of.NO in a cell model of oxidative and inflammatory injury. Successful accomplishment of the proposed aims will develop and solidify the concept that reactions between oxidized biomolecules and.NO a) mitigate pathologic events and b) yield reactive nitrogen-

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containing products. In particular, the principal investigator will reveal mechanisms and conditions underlying the dual capacity of.NO to mediate both tissue protection and injury, especially within the context of.NO serving as both a prooxidant and antioxidant species. The proposed research also provides a framework for the characterization of newly described lipid species that are formed during vascular inflammatory events. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NITROXIDE THERAPY FOR INFLAMMATORY BOWEL DISEASE Principal Investigator & Institution: Hsia, Carleton Jc.; Synzyme Technology, Inc. 1 Technology Dr, E-309 Irvine, Ca 92618 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-OCT-2001 Summary: (Adapted from the application): Free radicals play important roles in inflammatory bowel disease (IBD), and the reduction or elimination of the adverse effects of these oxidants could provide novel therapies. Antioxidants have been reported to reduce tissue injury in colitis models, but more potent, stable and bioavailable antioxidant compounds are required. This project will test a new class ofantioxidants based on polynitroxylation technology, or linkage of nitroxides (stable Noxyl radicals) to biological macromolecules. In a preliminary study, polynitroxyl-starch (PNS) acted synergistically with the free (unbound) nitroxide compound Tempol to reduce oxidants (especially superoxide) and attenuate inflammation in TNBS-induced murine colitis. We hypothesize that TNBS colitis involves significant superoxidemediated injury, and that PNS and Tempol can attenuate this injury. Specific aims are: (1) Produce PNS and characterize its antioxidant activity. (2) Pharmacokinetically define optimal dose and route of administration. (3) Define efficacy in TNBS-induced mouse colitis. If this is successful, Phase II will define mechanisms of action in animal models of IBD (including the IL-10-/- knockout mouse which spontaneously develops colitis) and other studies required for progression to clinical testing in IBD. PROPOSED COMMERCIAL APPLICATION: Inflammatory bowel disease is a significant health problem. If successful this research will lead to the development of a novel therapeutic agent(s) for the treatment of IBD. This would represent a significant commercial opportunity and provide substantial benefit to patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NUTRITIONAL INFLUENCES ON LUNG FUNCTION Principal Investigator & Institution: Cassano, Patricia A.; Div/Nutritional Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2003 Summary: (provided by applicant): This proposal investigates the relation of nutritional factors to lung function and chronic obstructive pulmonary disease (COPD). The project will use three data sources to investigate the following hypotheses. First, do antioxidants protect the lung from damage caused by endogenous and exogenous oxidants? This research question will be addressed with longitudinal data from the Normative Aging Study (NAS), a prospective study of 2,280 men. Dietary intake data on vitamins C and E and betacarotene from food frequency questionnaires (first administered 1987) will be examined in relation to pulmonary outcomes over the subsequent 13-year period, including forced expiratory volume in the first second (FEV1), methacholine airways responsiveness, and incident COPD. Longitudinal evidence is needed to assess causality. Second, do lower lipid levels increase the risk of respiratory outcomes? Three data sources will be used to address this research question.

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Using cross-sectional data from the Third National Health and Nutrition Examination Survey, we will investigate the relation of lipid profile (total, LDL and HDL cholesterol; apolipoproteins AI and B) to lung function and to prevalent COPD risk. The relation of lipids to lung function also will be investigated in the NAS cohort. The prospective data allow consideration of questions with a time dimension, for example whether changes in lipid profile predict changes in pulmonary outcomes. Finally, cross-sectional data from China, a population with naturally low cholesterol, will be studied to consider the hypothesis in a population with a different range of exposure. We will also consider the possible joint effects of lipids and antioxidant exposures on lung outcomes, given that some of the candidate antioxidants, for example vitamin E and betacarotene, are lipidsoluble. The overall objectives are to understand how nutrition affects lung function, including absolute measures as well as rate of decline, and how nutrition affects the risk of lung disease. An integrated approach to the study of nutritional factors and their potential influences on lung outcomes is proposed. 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 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

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Project Title: ORGANOCHLORINE EXPOSURE, GENETIC POLYMORPHISM AND PARKINSON'S DISEASE Principal Investigator & Institution: Berkowitz, Gertrud S.; Professor; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-MAR-2006 Summary: (Taken from application) Parkinson?s disease (PD) is a progressive, disabling disorder of the central nervous system characterized by tremors at rest, muscle rigidity, slowness, imbalance and, in later stages, often dementia. It is caused by loss of neurons in the substantial nigra that produce dopamine. Approximately half a million Americans are estimated to be affected by PD. Recent data suggest that environmental exposure, possibly in concert with genetically determined vulnerabilities, contribute to causation of PD; particularly in patients with onset of disease above age 50. The study will examine 300 cases of PD whose diagnoses have been confirmed by strict, standardized criteria and 300 controls with "minor" neurologic disorders not involving the basal ganglia. A blood sample will be obtained and a detailed questionnaire will be administered to each case and control. The groups will be half male, half female. All eligible minority patients will be enrolled. Cases and controls will be matched on age, gender, and race. This proposal has two inter-related biomedically based, epidemiologic objectives. We propose to determine: 1) whether serum organochlorine levels and/or a past history of exposure to pesticides are elevated in patients with Parkinson s disease; 2) whether polymorphisms in specific enzymes related to pesticide metabolism are more common in patients with PD; and 3) whether there is evidence for a gene-environment interaction. A more exploratory objective is to evaluate whether diet, particularly intake of antioxidants, may protect against development of PD. To test the hypothesis that organochlorine levels, the most common type of chemical pesticide used between 1940 and 1970, are increased in PD patients, DDT, DDE, Dieldrin, and oxychlordane will be determined and compared between cases and controls. PCB, its congeners and transnonachlor will also be measured since these are organochlorine compounds as well. The gene polymorphism hypotheses will focus specifically on CYP2D6, GSTP1, and PON1. To evaluate the possible protective role of antioxidants, a detailed dietary history will be taken to obtain extensive information on usual antioxidant intake before diagnosis, including Vitamins A, C and E, carotenoids, lycopene, tocopherol and polyphenols (phytoestrogens). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: OXIDATIVE DAMAGE IN SMOKERS AND PASSIVE SMOKERS Principal Investigator & Institution: Block, Gladys; None; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2004 Summary: We propose to perform further epidemiological analyses of data collected in a previous study of oxidative damage in humans. We conducted a randomized intervention trial of smokers and passive smokers, with measurement of two biomarkers of lipid peroxidation (malondialdehyde, MDA; and F2-isoprostanes, Iso-P). Laboratory data support a relationship between oxidative damage and cancer, and epidemiological studies have shown an inverse association between consumption of fruit and vegetables or specific antioxidants and risk of some cancers. Demonstration of a causal relationship will require evidence that anti-oxidant treatment can decrease oxidative damage, and ultimately that decreasing oxidative damage will reduce disease. Our study will provide information needed by other researchers to study oxidative damage and antioxidants in

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cancer prevention. 325 Subjects were recruited (142 smokers, 81 passive smokers and 102 non-smokers), 750 clinic visits conducted, 3700 vacutainers of blood collected and 10,000 vials of plasma frozen. After two baseline visits, smokers and passive smokers were randomized to either placebo, vitamin C or an anti-oxidant cocktail. All assays have been completed, including MDA, Iso-P, vitamins C, E, A carotenoids, lipids, Creactive protein and continine. We have already completed statistical of the effect of anti-oxidant supplementation on Iso-P in smokers, the effect of smoking status on the level of several anti-oxidants in the blood, and predictors of lipid peroxidation. We are seeking funding to carry out further statistical analyses of these data. SPECIFIC AIMS 1) To determine effects of antioxidant treatment on F2-isoprostanes in passive smokers 2) To determine effects of anti-oxidant treatment on MDA in both smokers and passive smokers 3) To determine effects of antioxidant treatment on C-reactive protein in both smokers and passive smokers 4) To estimate the intra-individual variability of oxidative damage, of plasma anti-oxidants and of plasma continue 5) To establish the predictors of C-reactive protein in smokers, non- smokers and passive smokers 6) To determine the level of vitamin C required by smokers to attain the plasma vitamin C levels of nonsmokers 7) To study the effect of supplemental vitamin C or antioxidant cocktail on other plasma antioxidants Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE INJURY IN PARKINSONS DISEASE Principal Investigator & Institution: Ferrante, Robert J.; Professor; Neurology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: Oxidative stress has been proposed as a critical mechanism underlying metabolic dysfunction in diseases and aging and has been implicated in both apoptotic and necrotic cell death. Oxygen-derived free radicals are a normal byproduct of respiration and oxidative metabolism. Normally cells have efficient protective mechanisms which can quench radicals. When there is a compromise in cellular antioxidants or an increase in production of free radical species, neuronal damage occurs. An increasing body of evidence has implicated oxidative damage in the pathogenesis of Parkinson's disease (PD), including evidence of increased lipid peroxidation, protein oxidation, and oxidative damage to both nuclear and mitochondrial DNA directly associated with the known topographic and neuronal distribution of pathology observed within PD. The investigators preliminary studies may provide the strongest evidence yet, and they hypothesize that a connection exists between the pathology observed in PD and oxidative damage leading to metabolic dysfunction in this disorder. Their first Specific Aim is to determine the topographic distribution of markers for oxidative damage to protein, lipid, and DNA fractions in postmortem PD brains, using antibodies to several epitopes associated with oxidative damage. They will provide a direct assessment of markers for oxidative damage to determine if they are altered and subsequently correlate them with the selective neuronal vulnerability and the neuro-pathologic hallmarks associated with PD. Their goal will be to develop biochemical markers which may be useful for diagnostic purposes, monitoring disease progression, and the effectiveness of therapeutic interventions. The second Specific Aim will utilize transgenic animal models and therapeutic interventions to assess the role of oxidative stress in MPTP neurotoxicity. The systemic administration of the toxin MPTP in experimental animals replicates the neuropathological, neurochemical, and clinical features in PD, causing cell death by inducing oxidative stress. They will examine whether transgenic mice with a knockout

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of the manganese superoxide dismutase gene and neuronal nitric oxide synthase gene, as well as those overexpressing bcl-2 show increased vulnerability or resistance, respectively, to MPTP neurotoxicity. They will investigate the use of novel therapeutic strategies, using free radical spin traps, neuronal nitric oxide synthase inhibitors, and dietary creatine supplementation to block MPTP neurotoxicity. These studies will have direct relevance to understanding the pathogenesis of PD and to developing new therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE MODIFICATIONS IN ATHEROGENESIS Principal Investigator & Institution: Fitzgerald, Garret A.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): This SCOR will explore the role of the oxidative modification of diverse targets in the atherogenic process. Although oxidant injury has been implicated in pathogenesis, the process is poorly characterized in integrated systems, such as humans. Recent developments offer novel opportunities to integrate assessment of free radical based modification of protein, lipids and DNA in vivo. A central theme of this proposal is the opportunity to assess the effects of potential prooxidants and antioxidants on these novel biomarkers. A second broad feature of this proposal is the close integration of genomic (A) and proteomic (B) analysis. In Project 1, we shall address the hypothesis that nicotine sustains the endothelial dysfunction observed in chronic smokers and accelerates atherogenesis in the Apobec-l/LDL receptor double knock out mouse (DKO) by acting as a prooxidant integrating biomarkers developed in Projects 2, 3 and 4 and utilizing Cores A and B to relate alterations in gene and protein expression in circulating cells to those in the vasculature. In Project 2, the biophysical and cell biological consequences of fibrinogen nitration will be assessed. As polymorphisms that result in elevated fibrinogen interact with cigarette smoking in the prediction of cardiovascular risk, we shall investigate the effects of nitration on the interaction of fibrinogen with platelets and vascular cells. In Project 3, we shall address the possibility that hyaluronan, a major extracellular matrix protein and its CD 44 receptor may be modified by oxidative stimuli in both model systems and in humans in collaboration with Projects 1 and 5. Again, we shall utilize the resources of the cores to elucidate the modifications that are induced in these targets. In Project 4, we shall characterize further the covalent modifications to DNA resulting from hydroperoxide derived electrophiles; investigate the role of oxygenases in this process; determine from studies in Projects 1 and 5 whether vitamin C administration results in such DNA modifications in vivo and, using the Cores, assess their role in the apoptotic pathway, using endothelial cells as a model system. In Project 5, we shall address the possibility that HDL, inversely associated with cardiovascular risk, may have functional relevance, at least in part, by acting as an endogenous antioxidant. We will investigate the antioxidant potential of HDL components in vitro and by using genetic manipulation of ApoA in mice. We shall also follow progression of plaque burden in humans with electron beam computerized tomography relating HDL to the integrated indices of oxidative stress developed in Projects 1, 2, 3 and 4 as well as the genomic and proteomic analyses developed in the Cores to both the studies in humans and mice. This highly integrated SCOR will broaden consideration of oxidative targets of potential relevance to atherogenesis and utilize a highly integrated series of studies in mice and humans to assess the role of pro- and anti-oxidant interventions on a novel series of biomarkers of oxidant stress in vivo.

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

Project Title: OXIDATIVE DEVELOPMENT

STRESS

AND

FUNCTIONAL

LYMPHOCYTE

Principal Investigator & Institution: Karp, David R.; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The prevalence of childhood asthma is increasing dramatically in industrialized societies. The reasons for this are not completely understood, although persistent indoor aeroallergen challenge, exposure to industrial pollutants and tobacco smoke, and infant bronchiolitis have all been implicated. From these studies, the concept emerges that asthma is the result of a preponderance of accumulated risk factors occurring in a critical sequence, at a critical time in development. Primary prevention of asthma will result from elimination or interruption of any of these risks. One such risk may be the balance between oxidative stress and antioxidants, particularly in the lung. Recent evidence has suggested that oxidative stress may influence the polarization of T cell responses in mice. The effects of oxidative stress on the development of Th2 responses in humans are unknown, as are the effects of antioxidants. The Specific Aims of this Project are: 1. To determine how exposure to oxidative and nitrosative stress affects the function of various antigen presenting cells. 2. To test whether oxidative stress alters the Th1/Th2 balance of a T cell response to antigen. 3. To determine whether antioxidant treatment of antigen presenting cells, and/or T cells, will alter the type of T cell response to antigen. Different types of antigen presenting cells, including monocytic cell lines and primary cells (e.g., dendritic cells) will be subjected to relevant stressors and tested for their ability to modulate the expression of co-stimulatory molecules, cytokines, and chemokines. The APC that are generated under different conditions of oxidative stress will then be tested for the ability to support or modulate the polarization of T cell responses to Th1 or Th2. Finally, the ability of thiol and non-thiol antioxidants to modulate the induction of Th1 or Th2 responses will be determined. These experiments will both answer fundamental questions about the development of immune responses, but also provide a framework for rational clinical trials of specific antioxidants used at critical times for the primary prevention of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS AND POST-MI HEART FAILURE IN DIABETES (PILOT) Principal Investigator & Institution: Hill, Michael F.; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: Patients with Diabetes Mellitus (DM) manifest an increased incidence of congestive heart failure (CHF) following myocardial infarction (MI), which presages a reduced survival rate. This has been shown not to be due to a greater extent of infarction associated with DM. The long-term goals of our studies is to understand the mechanisms that contribute to the progressive deterioration of cardiac function and eventual development of CHF in the diabetic heart following an MI. The current project is based on observations that hyperglycemia secondary to diabetes and non-diabetic post-MI heart failure are associated with increased oxidative stress and an antioxidant deficit. Based on these observations, we propose that the coexistence of diabetes and MI

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exacerbates the existing imbalance between the antioxidant defense system and freeradical production already present in each of these pathologies individually, leading to a quantitative deficiency of antioxidants that predisposes the surviving diabetic myocardium to cumulative, uncontrolled oxidant damage and subsequent failure after MI. The specific aims of the proposed project are: 1) to assess myocardial enzymatic and non-enzymatic antioxidants and concomitant oxidative stress in the remaining, viable diabetic myocardium after MI; 2) to determine the protein expression of the myocardial antioxidant enzymes, and 3) to determine the effects of long-term antioxidant therapy on the occurrence of heart failure following MI in the diabetic heart. The proposed studies will be conducted in streptozotocin (STZ)-induced diabetic rats using the wellestablished coronary-artery ligation model of post-MI heart failure. The objectives of these studies are to delineate the mechanisms by which diabetes adversely affects the functioning of the surviving myocardium after MI and to establish novel therapies aimed at reversing the functional deficit associated with diabetes during the post-MI period. The results of this project will provide a new understanding of the factors that contribute to CHF among diabetics with MI and may form the basis for developing more effective therapeutic interventions for the management of diabetic MI patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OXIDATIVE STRESS IN HEART FAILURE: MECHANISMS Principal Investigator & Institution: Hare, Joshua M.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: Decreased cardiac energy supply is likely of pathophysiologic significance in the failing cardiovascular system. Energetic efficiency (work for a given oxygen utilization) limits the ability of the heart to pump blood to the circulation both at rest and during times of stress. Oxidative stress, an imbalance between the formation of reactive oxygen species and antioxidant defenses, has been implicated in the development of heart failure not only by direct toxicity but also by altering metabolic pathways. We have recently shown that inhibition of xanthine oxidase (XO), an enzyme that produces superoxide during purine metabolism, profoundly enhances myocardial mechanoenergetic efficiency (the ratio of myocardial work to oxygen consumed) in an animal model of heart failure. This observation is consistent with in vitro findings that XO inhibition augments LV trabecular muscle force generation for a given amount of calcium entry into the cytoplasm. These data support a contributory role for oxidant stress in reducing cardiac myocardial energy utilization. The purpose of the studies in this proposal is to test the hypothesis that the XO pathway inhibits myocardial energetic efficiency by elaborating reactive oxygen species. Experiments will be conducted in conscious animals instrumented to measure LV work and oxygen consumption. We will first determine the contribution and biochemical mechanism of XO to the heart failureassociated increase in oxidative stress. In order to clarify the mechanism of allopurinol action and to assess the participation of another important signaling molecule (nitric oxide) to cardiac energetics, we will test the predictions that other antioxidants mimic, and that inhibition of nitric oxide attenuates the energetic effect of allopurinol. Finally and most importantly, we will determine whether XO inhibition prevents the development of LV dysfunction and whether the beneficial effects of XO inhibition in heart failure are due to its antioxidant properties. These studies are designed to define new mechanisms by which oxidant stress influences integrated cardiovascular performance in heart failure. The results of these studies will clarify pathophysiologic

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consequences of oxidant stress in heart failure and may have therapeutic implications for humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEROXYNITRITE AND SOD IN MOTOR NEURON APOPTOSIS Principal Investigator & Institution: Estevez, Alvaro G.; Assistant Professor; Anesthesiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2006 Summary: (From the Applicant's Abstract): Our long-term goal is to understand how mutations to SOD can increase oxidative stress and cause the death of motor neurons in amyotrophic lateral sclerosis (ALS). We have shown that endogenous formation of the peroxynitrite by the diffusion-limited reaction between superoxide and nitric oxide induces apoptosis in cultured embryonic rat motor neurons deprived of trophic support. Both inhibitors of nitric oxide synthesis as well as Cu, Zn superoxide dismutase (SOD) delivered intracellularly with liposomes protect motor neurons from apoptosis. These data indicate that the interaction between nitric oxide and superoxide has a role in motor neuron apoptosis. Mutations to SOD are implicated in the selective degeneration of motor neurons in ALS and expression of ALS-SOD mutants in transgenic mice produces motor neuron disease. A common phenotype among the ALS-SOD mutations so far investigated is to decrease the affinity for zinc. We have shown that zinc-deficient SOD is both less efficient at scavenging superoxide and a better catalyst of tyrosine nitration. Furthermore, the copper in zinc-deficient SOD can act as a non-specific oneelectron oxidase, robbing electrons from antioxidants like ascorbate and glutathione that can be transferred to oxygen to produce superoxide. In the presence of NO, zincdeficient SOD can catalyze the formation of peroxynitrite. In the previous cycle of funding, we have shown that zinc-deficient SOD induces apoptosis in motor neurons by a nitric oxide-dependent mechanism. For the renewal, our first aim is to further investigate the mechanisms by which zinc-deficient SODs can kill cultured motor neurons and to determine what can protect motor neurons from this toxicity. Our second aim is to characterize the source or sources of superoxide induced in motor neurons by trophic factor is to characterize the source or sources of superoxide induced in motor neurons by trophic factor withdrawal. Our third aim is to test the role of tyrosine nitration by peroxynitrite in the death of motor neurons induced by either trophic factor deprivation or by zinc-deficient SOD. Completion of the specific aims will provide a mechanistic basis for explaining how motor neurons are particularly vulnerable to SOD mutations and establish a link between sporadic and familial SODs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHENOLS/CATECHOLS IN OCCUPATIONAL/CONTACT VITILIGO SKIN Principal Investigator & Institution: Boissy, Raymond E.; Professor; Dermatology; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: Complexion coloration is essential to ones health, self-image, and thus overall wellness, both physically and psychologically. Cutaneous pigmentation protects a person from various environmental assaults, like ultraviolet light, as well as potential cellular injury, that can cause cancer and aging of the skin. Loss of skin pigmentation can result in cancer, aging, and compromised immunity of the skin as well as

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psychological and social problems of self- esteem and personal interactions. Occupational/contact vitiligo is a disease that results in the loss of cutaneous pigmentation. This form of vitiligo occurs relatively frequently in individuals exposed to phenolic/catecholic derivatives primarily in the work place. This disease can be financially and socially devastating for the individual, in addition to it compromising the productivity in the workplace. The general goal of this proposal is to assess the pathological effects of phenolic and catecholic derivatives on melanocytes. These prevalent chemical toxins are responsible for the development of occupational/contact vitiligo in the skin of some individuals exposed to these environmental agents in the workplace. Specifically, we propose to assess the relative cytotoxicity, the interaction with tyrosinase, and the generation of toxic free radical products within melanocytes exposed to various phenolic and catecholic derivatives. In this assessment, we will determine whether melanocytes from all patients with vitiligo, patients with the occupational/contact form of vitiligo, family members of patients with vitiligo, and/or a subset of the population in general, are more sensitive to cytotoxicity by these phenolic/catecholic derivatives. In addition, we will assess [1] genes that are differentially expressed and [2] regulators of apoptosis in cells treated with phenolic/catecholic derivatives. In addition, we will determine whether the response of these molecules is altered in vitiligo melanocytes demonstrated to be more susceptible to cytotoxicity. Finally, we will assess the effectiveness of various antioxidants, especially catalase, in dampening the cytotoxic effect of phenolic/catecholic derivatives using cultured melanocytes, organotypic cultures of human skin, and a guinea pig model. 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 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

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Antioxidants

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: POOLING OF PROSPECTIVE STUDIES OF DIET AND CANCER Principal Investigator & Institution: Hunter, David J.; Director; 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) In this application, the aims of the Pooling of Prospective Studies of Diet and Cancer Project (referred to as the Pooling Project) will expand to examine dietary associations with pancreatic and ovarian cancers in large, prospective cohort studies. Expansion of the Pooling Project to these cancers with intermediate incidence rates will take advantage of the statistical power from combining data from multiple studies and the ability to examine a wide range of intakes and subgroup detail. The pooled analyses also allow standardized analytic approaches with standardized categorization of exposures and covariates across studies. Additional analyses of colorectal cancer, a cancer site that is being evaluated as part of the current grant cycle, also will be conducted. The 11 studies comprising the Pooling Project are the Adventist Health Study, Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, Canadian National Breast Screening Study, Cancer Prevention Study II Nutrition Cohort, Iowa Women?s Health Study, Health Professionals Follow-up Study, Netherlands Cohort Study, New York State Cohort, New York University Women?s Health Study, Nurses? Health Study, and Sweden Mammography Cohort. Analyses will include 4,949 colorectal cancer cases and an estimated 1,553 pancreatic and 1,908 ovarian cancer cases. For colorectal cancer, associations with specific carotenoids and grains will be examined. For pancreatic cancer, analyses will evaluate associations with intakes of fruits, vegetables, specific carotenoids, grains, fiber, alcohol, and meat. Analyses of ovarian cancer risk and intakes of lactose, dairy products, fruits, vegetables, antioxidants, fat, eggs, and cholesterol and body mass index will be conducted. The ongoing annual meetings, and frequent communication among investigators, will be used to facilitate the analysis and interpretation of the findings. These analyses will take full advantage of extensive data already collected to provide powerful insight into the relation between diet and the risk of pancreatic, ovarian, colorectal cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POTENTIAL BRAIN THERAPEUTICS Principal Investigator & Institution: Raptis, Anastasios; American Biotechnology Research Corp 424 E State Pky, Ste 229 Schaumburg, Il 60173 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: (provided by applicant): Use of botanical products such as exogenous antioxidants has gained considerable momentum in the last few years in therapy of

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human degenerative diseases. Among these antioxidants, tumeric, neem, guggul, alphatocopherol, Beta-carotene, and ascorbic acid have been shown to have a special relevance in maintaining the redox equilibrium in various cell types, including those of the nervous system. They have a strong commercial potential as dietary supplements or as potential pharmaceutical agents in the treatment of various human degenerative diseases. In Phase I of the project, our aim is to develop cell free in vitro assay systems for the measurement of the biological activities of these compounds, using biological molecules present in their free form as targets of reactive oxygen species (ROS). In the development of these methods, we will take into account the critical factors that may influence the results, for example: (a) different types of ROS; (b) different systems for the generation of these ROS; (c) different molecular targets of ROS, and (d) different methods for the measurements of the molecular lesions produced by the ROS. In Phase II of the proposed project, we will optimize assay systems in which the target molecule is present as an integral part of the cell (intact-cell systems). The intact-cell systems will use functional neurons and astrocytes in which the effects of ROS and antioxidants will be measured by their effects on the structural integrity of the mitochondrial DNA. Also, in Phase Il, we will develop an approach for assigning antioxidant indices to mixtures of antioxidants, using a minimum number of different assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTION OF PHOTOCARCINOGENESIS BY ANTIOXIDANT Principal Investigator & Institution: Katiyar, Santosh K.; Assistant Professor; Dermatology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant)Chronic exposure to solar ultraviolet (UV) radiation, particularly UVB (290-320 nm), is primarily responsible for more than 1,000,000 new cases of nonmelanoma skin cancer each year in the USA alone, making it the most hazardous environmental carcinogen known for humans. Thus, there is an urgent need to develop strategies to prevent the occurrence of cutaneous malignancies. It is well documented that UV radiation is a potent producer of reactive oxygen species (ROS), which play a critical role in cellular signal transduction pathways. Phosphorylation of cell signaling molecules is implicated in various skin diseases including skin cancer. One approach to reduce the risk of UV-induced ROS-mediated skin cancer is the use of antioxidant agents. Several studies led to a strong suggestion that the regular intake of polyphenolic antioxidants from green tea may be an appropriate and effective strategy to prevent some forms of human cancers. We and others have shown that a potyphenolic fraction isolated from green tea, and particularly its major and the most effective chemopreventive antioxidant constituent (-)-epigallocatechin-3-gallate (EGCG) has remarkable preventive effects against UV-induced skin carcinogenesis in mouse model. We found that treatment with EGCG to human skin before UV exposure inhibits UV-induced oxidative stress. The aim of this application is to defme the mechanism through which EGCG would prevent UV-induced oxidative stress-mediated cell signaling pathways in human skin. The central hypothesis to be tested in this proposal is that UV-induced oxidative stress causes phosphorylation of epidermal growth factor receptor (EGFR), and mitogen-activated protein kinases (MAPK), such as extracellular signal-regulated kinase (ERK1/2) and p38 in human skin. The corollary to our hypothesis is that topical treatment with EGCG before UV exposure of the skin will prevent UV radiation-induced oxidative stress, which in turn will inhibit oxidative stress-mediated phosphorylation of cellular signaling events. The inhibition of UVinduced oxidative stress- mediated signaling pathways by EGCG will prevent the

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occurrence of skin cancer. Validation of this hypothesis would have major implications for the importance of oxidative stress-mediated skin cancer, as well as offering promise for the development of novel intervention approaches to mitigate UV-induced cellular signaling events linked to skin cancer incidence by the use of antioxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMICS OF DEP-INDUCED OXIDATIVE STRESS Principal Investigator & Institution: Nel, Andre E.; Professor of Medicine; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant) An urgent need exists for toxicological profiling of ambient air particulates. The investigators are studying the adjuvant effects of DEP and CAPS in allergic airway inflammation and asthma. In vivo studies in animals and humans have demonstrated that DEP enhance IgE production and allergic inflammation during challenges by common environmental allergens. This effect involves the generation of oxidative stress and can be reversed with thiol antioxidants. The prooxidative and pro-inflammatory effects of DEP can be reproduced in vitro with organic DEP extracts as well as aromatic and polar chemical groups prepared from these particles and fractionated by silica gel chromatography. The investigators hvpothesize that redox cycling polycyclic aromatic hydrocarbons and their oxidized derivatives are responsible for oxidative stress effects in the respiratory tree, and that new biomarkers can be developed around this principle with a proteomics approach. Novel proteome display techniques have recently been developed to identify oxidatively modified proteins in tissue culture cells and bronchoalveolar lavage (BAL) fluid. The principal investigator's long-term goal is to use the comprehensive particle and proteomics infrastructure at UCLA to develop new biomarkers to follow the adverse health effects of particulate matter (PM) in susceptible populations. In order to accomplish this goal, the researchers will use a proteomics approach to identify newly induced as well as oxidatively modified proteins in macrophage and epithelial cell lines during exposure to organic DEP chemicals (Specific Aim 1). These cells will be exposed to crude DEP extracts as well as polar and aromatic chemical groups fractionated from these particles by silica gel chromatography. Whole cell extracts will be resolved by 2-D electrophoresis, followed by protein image analysis and generation of a 2-D database for identifying newly expressed proteins by in-gel digestion and mass spectrometry. The contribution of oxidative stress will be tested by the inclusion of thiol antioxidants in the culture medium, as well as by the implementation of novel techniques for the display of protein carbonyls and nitrotyrosines by 2-D electrophoresis. A complementary approach will be to use proteomics to identify oxidative stress and oxidatively modified proteins in the BAL fluid from an established murine model demonstrating the adjuvant effects of aerosolized DEP towards an inhaled antigen (ovalbumin)(Specific Aim 2). The investigators will determine whether treatment of these animals with a thiol antioxidant can suppress DEP-induced oxidative stress events in the BAL fluid. They will also use a display of protein carbonyls to identity oxidatively modified proteins in the BAL fluid. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REACTIVE OXYGEN SPECIES IN PPHN Principal Investigator & Institution: Black, Stephen M.; Associate Professor; Pediatrics; Northwestern University Office of Sponsored Programs Chicago, Il 60611

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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: With the initiation of ventilation and oxygenation at birth, pulmonary vascular resistance decreases and pulmonary blood flow increases. There is evidence that increased endothelial NO synthase (eNOS) gene expression, eNOS activity, and NO production contribute to these changes. However, in a number of clinical conditions, there is failure of the pulmonary circulation to undergo this normal transition to postnatal life, resulting in persistent pulmonary hypertension of the newborn (PPHN). PPHN complicates more than 1 in 1000 live birth and up to 10% of admissions to intensive care units. PPHN causes substantial morbidity and mortality in otherwise normal term infants. Newborns who die of PPHN have decreased endogenous NO production and an increase in circulating endothelin (ET-1) levels. In addition these children have an increase in pulmonary arterial medial smooth muscle cell thickness and extension of muscle to normally non muscular arteries. The anatomic changes in the pulmonary vessels in newborns with PPHN are thought to be intimately associated with the morbidity and mortality associated with PPHN. However, the mechanisms producing this abnormal smooth muscle cell (SMC) development and the reduction in ENOS gene expression and NO production are not well understood. We hypothesize that the increased circulating levels of ET-1 in infants with PPHN activates the ETS subtype receptor located in the SMC layer leading to an increase in the production of reactive oxygen species (ROS) in these cells. This increase in ROS then stimulates SMC proliferation while decreasing endogenous ENOS expression in endothelial cells by inhibiting the transcription of its gene. To test these hypotheses we will investigate the following: 1) How does ET-1 stimulate ROS generation in SMCs? 2) Are the increased levels of ROS induced by ET-1 linked to an increase in SMC proliferation? 3) Does ROS reduce, while antioxidants increase, eNOS gene expression in endothelial cells? The successful completion of these studies will lead to a better understanding of the mechanisms responsible for the development of PPHN and may lead to new treatments for infants born with pulmonary hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REDOX REGULATION OF ARTERIOLE FUNCTION Principal Investigator & Institution: Flavahan, Nicholas A.; Professor of Medicine & Physiology; Internal Medicine; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 05-MAR-2001; Project End 31-JAN-2006 Summary: (Verbatim from the application): In cultured cells, mechanical strain induces a change in the actin cytoskeleton, mediated in part by the small Gprotein, rac. Rac stimulates actin polymerization, via NADPH oxidase-dependent increase in reactive oxygen species (ROS), which stimulate uncapping of actin filaments. The role of rac in contractile smooth muscle cells (SM) is unknown. We demonstrate that a signaling pathway(s), involving rac, NADPH oxidase, ROS and actin polymerization, plays a key role in the myogenic response, the arteriolar SM constriction caused by elevation in transmural pressure. In mouse arterioles, the myogenic response was: i) selectively abolished by antioxidants or inhibition of NADPH oxidase, ii) depressed in transgenic mice expressing a dominant-negative mutant of rac (RAC-DN) in SM, iii) increased in transgenic mice expressing a constitutively-active rac mutant (RAC-CA) in SM, and iv) associated with increased production of ROS that was absent in RAC-DN arterioles. Inhibition of actin polymerization by cytochalasin D selectively inhibited the myogenic response. Based on these experiments, and on current models of smooth muscle contraction, we propose that the myogenic response involves two distinct signaling

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pathways. One involves the conventional pathway, namely calcium influx, calciumcalmodulin dependent activation of myosin light chain kinase and phosphorylation of myosin light chain. The other pathway involves activation of raci, NADPH oxidase, elevation of ROS production and stimulation of actin polymerization. This latter pathway enables the VSM to withstand elevated pressure and allows the myosin-based system to constrict the artery. Furthermore, since amplification of this response in the RAC-CA mouse was associated with hypertension, we propose that dysregulation of this pathway may contribute to altered vascular function in this disease process. Three specific aims are proposed to analyze the physiological and pathophysiological regulation and role of ROS in arterioles. Experiments will assess the stimuli responsible for ROS production, the mechanisms underlying ROS-induced changes in vasoconstriction and the regulation of this signaling pathway in hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION HOMEOSTASIS

OF

HOMOCYSTEINE-DEPENDENT

REDOX

Principal Investigator & Institution: Banerjee, Ruma; Willa Cather Professor of Biochemistry; Biochemistry; University of Nebraska Lincoln 14Th and R Sts Lincoln, Ne 68588 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Perturbations of redox homeostasis incurred by oxidative stress appear to be a common thread connecting the etiologies of various complex and multifactorial diseases, such as cardiovascular diseases, Parkinson's disease, Alzheimer's disease, arthritis and some cancers. Glutathione is a key component of the intracellular arsenal of antioxidants in eukaryotes, and the limiting reagent in its synthesis is believed to cysteine. The transsulfuration pathway which converts homocysteine to cysteine is a quantitatively significant contributor to the intracellular cysteine pool in the liver and -50 percent of the cysteine in glutathione is derived via this pathway. Homocysteine is a sulfur containing amino acid whose elevated levels are correlated with a number of multifactorial diseases such as cardiovascular diseases, neural tube defects and Alzheimer's disease. However, intracellular regulation of this amino acid and of the metabolic link to the major cellular redox buffer pool of glutathione are poorly understood. This proposal focuses on three key loci important in regulation of homocysteine concentrations: methionine synthase, methionine synthase reductase and cystathionine beta-synthase. Mutations in each of these enzymes is correlated with hereditary hyperhomocystenemia which is inherited as an autosomal recessive disorder. Using a combination of biophysical, cell biological and mouse model studies for cystathionine beta-synthase deficiency, we will; (i) characterize how polymorphic variations and hereditary mutations in methionine synthase reductase influence redox activation of methionine synthase-dependent transmethyiation of homocysteine, (ii) elucidate the mechanism of translational regulation of methionine synthase and (iii) elucidate the mechanism of redox regulation of homocysteine metabolism and its influence on glutathione homeostasis. These studies will provide important insights into multiple levels of regulation of homocysteine metabolism and will assess the effects of modulating the transsulfuration pathway on glutathionedependent antioxidant defense in cell culture and in mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF NAD(P)H: QUINONE OXIDOREDUCTASES Principal Investigator & Institution: Jaiswal, Anil Kumar.; Associate Professor; Pharmacology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1991; Project End 31-MAR-2006 Summary: (provided by applicant): Quinone oxidoreductases (NQO1 and NQO2) catalyze the detoxification of quinines, thus protecting cells from oxidative stress and neoplasia. The NQO1 gene is coordinately induced with other detoxifying enzyme genes in response to xenobiotics (Beta-naphthoflavone (Beta-NF)) and antioxidants (tert-butyl hydroquinone 9t-BHQ)). Deletion mutagenesis of the NQO1 gene promoter identified and antioxidant response element (ARE) that is required for NQO1 gene expression and induction in response to Beta-NF and t-BHQ. The nuclear factors Nrf2 and Nrf1 heterodimerize with Jun proteins and bind to the ARE. This complex upregulates basal expression and coordinated induction of NQO1 and other genes. The Nrf-Jun dimerization requires unknown cytosolic factors. A cytosolic inhibitor of Nrf2 that retains it in the cytoplasm, Inrf2, was cloned and sequenced. Treatment of cells with t-BHQ caused the release of Nrf2 which moved into nucleus, inducing NQO1 gene expression. The mechanism of the release of Nrf2, from Inrf2, remains unknown. The role of the newly identified Nrf3 and large Maf proteins, in ARE-mediated regulation of NQO1 and other genes, also remains unknown. Analysis of NQO1 gene expression showed large variations among human tissues. The major goals of this proposal are to elucidate the mechanisms that regulate the ARE-mediated expression and coordinated induction of NQO1 and other detoxifying enzyme genes in response to xenobiotics and antioxidants. We will perform transfection, band/super shift and immunoprecipitation assays to investigate the role of Nrf3 and large Maf proteins in this process. PCR generated deletions of INrf2 will be used in nuclear translocation, transfection and immunoprecipitation assays to precisely map the domain of INrf that interacts with Nrf2. Similar assays will be used to determine xenobiotic and antioxidant induced phosphorylation/dephosphorylation and/or redox regulation of INrf2, Nrf2 and/or cJun leading to the release of Nrf2 form INrf2 and stimulation of heterodimerization/binding of Nrf2/c-Jun to the ARE. Mass spectrophotometry will be used to detect the phosphorylation/dephosphorylation sites of INrf2, Nrf2 and/or cJun. Deletion mapping and transfection studies are also planned to identify cis-elements and trans-acting factors that regulate expression and induction of the NQO2 gene. We will use Northern, Western, DNaseI hypersensitivity, footprinting, band/super shift assays and transgenic NQO1-/- mice that express the human NQO1 gene to study the mechanism of tissue specific expression and induction NQO1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 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: RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS Principal Investigator & Institution: Silverman, David J.; Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-DEC-1980; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): The long-term objectives and specific aims of this application are to understand the pathogenesis of Rickettsia rickettsii, and other members of the spotted fever group of rickettsiae by better studying the processes involved in causing cell injury. The investigators are interested in the interaction of R. rickettsii (Rocky Mountain spotted fever) with the endothelial cell, the target cell in human infection, and the mechanism(s) of cell injury caused by this obligate intracellular bacterium. It has been determined by the Principal Investigator's laboratory that cell injury appears to be initiated by reactive oxygen species produced during internalization and intracellular rickettsial growth. With an interest in abrogating endothelial cell injury, they have incorporated antioxidants into infected cell culture systems. One antioxidant, (alpha-lipoic acid, was able to effectively reverse the leading predictors of cell injury due to reactive oxygen species and to substantially prolong the viability of infected cell cultures. Studies to date have been carried out both in human umbilical vein endothelial cells and the permanent human endothelial cell line, EA.hy926. The investigators will continue to carry out experiments in these cells to characterize changes in the cytoskeleton of endothelial cells following R. rickettsii infection and to evaluate the link between these changes and increases in endothelial permeability. They will determine whether R. rickettsii-induced oxidative injury is responsible for the alterations in the actin pools and whether these changes can be prevented (controlled) by the use of antioxidants. They believe that it is also important to test our in vitro observations on oxidant-mediated injury in a relevant animal model to determine whether oxidant injury occurs and if antioxidants are effective in altering the course of disease. The most suitable model for these studies is the Rickettsia conoriiC3H/HeN mouse model which has been extensively studied by Walker and his colleagues. R. conorii is closely related to R. rickettsii, causes Mediterranean spotted

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fever, a syndrome clinically similar to RMSF, and as they have demonstrated, results in the same dramatic morphological manifestations of cell injury as R. rickettsii in human endothelial cells. These preliminary in vitro studies and those in the mouse model, indicate that this rickettsia is also able to cause oxidative stress. They propose to test the hypothesis that oxidant injury contributes to the pathologic changes within the animal. They will determine whether oxidative injury correlates with the local presence of rickettsiae within particular organs and tissues and whether the antioxidant, alphalipoic acid, can ameliorate oxidative injury as they have shown in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ANTIOXIDANTS IN BREAST CANCER PREVENTION Principal Investigator & Institution: Gupta, Ramesh C.; Professor of Toxicology; Prev Med & Environmental Hlth; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Epidemiological studies have identified an association of elevated levels of estrogens with breast cancer development. In particular, the natural hormone, 17b-estradiol (E2) and its hydroxylated metabolites, particularly, 4-hydroxyestradiol (4-E2), which are known animal carcinogens, have been implicated and it is proposed that these substances cause free radical-mediated DNA damage, a key step involved in the development of breast cancer. We have detected novel, polar DNA adducts in rat and human tissues, including mammary tissue, by a newly developed 32p-postlabeling/TLC assay. Chromatographic similarity with reference hydroxylated and cyclic adducts suggested that the endogenous DNA adducts presumably resulted from oxygen free radical-mediation. Adduct levels in rats were increased after treatment with E2 and 4-E2, further supporting the involvement of free radicals in the adduct formation. Cu2+-mediated activation of 4-E2 in the presence of DNA also resulted in polar adduct formation. Some of the adducts formed in vitro and in vivo were chromatographically similar. Taken together these results suggest that the polar adducts may result, in part, from redox cycling or E2 metabolites. We hypothesize that oxidative DNA adducts induced by the estrogen, E2 can be inhibited by intervention with known or potential cancer chemopreventive agents of antioxidant potential. Our main objective is to identify effective antioxidants to inhibit E2-mediated oxidative DNA damage. Specifically, 1) To determine the efficacy of known or potential chemopreventive agents for their antioxidant potential in vitro against oxidative DNA adducts induced nonenzymatically and enzymatically. 2) To determine the efficacy of selected agents to inhibit oxidative DNA adducts using E2-rat mammary carcinogenesis model. Data resulting from this project will formulate the basis of detailed investigations (RO1 grant) to correlate intermediate biomarkers (oxidative DNA damage, DNA repair activity, apoptosis, gene mutations and cell proliferation) with the disease endpoint at different intervals of rat mammary tumorigenesis. Studies can subsequently be planned with human subjects. Thus, the intermediate biomarker approach may ultimately identify women who may be at higher risk of developing breast cancer, before the onset of pathologically detectable lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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: SYNTHETIC SOD/CATALASE MIMICS FOR STROKE Principal Investigator & Institution: Doctrow, Susan R.; Vice President, Research; Eukarion, Inc. 6-F Alfred Circle Bedford, Ma 01730 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAR-2002 Summary: Stroke is the third leading cause of death in the United States and is considered to be the most common cause of adult disability. Pharmacological intervention has made little, if any, impact in preventing neurological damage that occurs during the hours and days following stroke onset. Reactive oxygen species (ROS) are strongly implicated in this damage. Eukarion has developed a series of low molecular weight synthetic compounds that are catalytic ROS scavengers, mimicking the antioxidants superoxide dismutase (SOD) and catalase, and are highly protective in rodent stroke models. This SBIR project will investigate the potential therapeutic value of these SOD/catalase mimics in stroke. During Phase I, several of the compounds were evaluated for their neuroprotective activity in the rodent stroke model, and for other relevant properties such as solubility and stability. Based on this research three compounds were selected as candidate molecules for preclinical and clinical development. Research proposed for Phase II will involve: (l) Safety screening studies to

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enable selection of one compound as the lead molecule ("EUK-n"); (2) Development of an injectable formulation for clinical administration of EUK-n; (3) Formal toxicity studies; and (4) Pharmacokinetic and biodistribution studies. This will provide necessary information to file an Investigational New Drug application with the FDA in order to initiate clinical trials with EUK-n. PROPOSED COMMERCIAL APPLICATION: Stroke affects about 500,000 patients annually in the U.S. and there is no satisfactory treatment to prevent the neurological darn age that results. Eukarion's novel SOD/catalase mimics are highly neuroprotective in rodent stroke models. This SBIR research will provide key preclinical information that will enable Eukarion to apply to the FDA for permission to initiate clinical trials with an SOD/catalase mimic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE NEUROPATHY

ROLE

OF

NUTRITION

IN

VIRUS-INDUCED

OPTIC

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 15-APR-1999; Project End 31-MAR-2007 Summary: (provided by applicant): Coxsackievirus A9 (CA9) and a variant, impaired in replication but persistently present in CSF over several months, were isolated from patients' CSF specimens during an epidemic of optic and peripheral neuropathy in Cuba in the early 1990's. The epidemic was clearly related to dietary deficiencies in several nutrients, including the antioxidants selenium, vitamin E, and lycopene. We are studying these isolates in the context of our previous work in mice, which demonstrated that deficiency of selenium or vitamin E can lead to increased severity of both Coxsackievirus B3 myocarditis and influenza pneumonia, with concomitant mutations in the viral genome. These mutations are reproducible, and the mutant strains have increased virulence for mice with normal nutriture. We hypothesize that host nutritional deficiencies induced mutations in CA9, leading to a new viral variant with altered pathogenic potential. We have completed genomic sequence analysis of three Cuban CA9 isolates from neuropathy patients and of five meningitis isolates from before the epidemic. Phylogenetic analysis shows the neuropathy isolates to be different, with a unique mutation near the active site of 2a protease that may contribute to the altered capsid proteins previously demonstrated in the variant virus. Using homologous regions among the CA9 already sequenced, we designed improved primers for sequencing the variant, which required special methods for RNA isolation because of apparent instability and/or very limited quantity. We have produced full-length cDNA from the variant, and sequences in the 5' non-translated region are consistent with a CA9 not identical to the other isolates. Using electron microscopy, we have demonstrated typical picornavirus virions in thin sections of CA9, but not of the variant, although the latter produces abundant viral antigen as demonstrated by immunofluorescence with homologous antiserum. We have produced mutations in CB3 by in vitro exposure to hydrogen peroxide in cell culture, and we will now apply the methods developed to CA9. In this continuation proposal, our objectives are 1) to characterize the quasispecies populations of the CA9 and variant isolates from Cuban patients; 2) to determine the role of the 2a protease and other mutations in altering the capsid proteins and replication patterns of the variant; 3) to determine the effects of repeated passage of CA9 and variant viruses in cells exposed to, or protected from, oxidative stress; and 4) to study the capsid morphology of the variant by comparing it to normal CA9 using cryo-electron microscopy.

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

Project Title: TRANSFORMATION SPECIFIC APOPTOSIS BY ANTIOXIDANTS Principal Investigator & Institution: Brash, Douglas E.; Professor; Therapeutic Radiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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Project Title: UROLITHIASIS AND PEROXIDATIVE INJURY Principal Investigator & Institution: Thamilselvan, Sivagnanam; Urology; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 31-JUL-2004 Summary: Urolithiasis is a major health problem in the United States, and the incidence and frequency of stone formation appears to be increasing in this country. The current cost to the nation for treating kidney stones is approximaately 2.39 billion dollars/year. About two thirds of the stones contain calcium oxalate. Chances of recurrences within 10 years are nearly 60 percent. Treatment program includes medications, open surgery, percutaneous techniques and extra corporeal shock wave lithotripsy. Despite recent advances in treatment, stone recurrence can be reduced by only 50 percent. To reduce the likelihood of stone recurrence it is necessary to determine and understand the mechanisms involved in stone formation. Our working hypothesis is that cell injury is central to the process of urolithiasis and that prevention of cell injury will prevent calcium oxalate formation, retention and deposition. Hyperoxaluria and calcium oxalate crystalluria are often associated with increased excretion of tubular marker enzymes, a finding consistent with damage to renal tubular cells. Moreover, these changes are observed even in the absence of crystalluria, suggesting that oxalate induced membrane damage is not due solely to injury produced by calcium oxalate crystals. Our studies have suggested that oxalate induces peroxidative injury to the kidney tubules which can alter membrane permeability, and result in the deterioration of ability of the cells to maintain normal ionic environment. The oxidant and antioxidant balance is therefore likely to be a critical determinant of cell sensitivity to free radical injury and a major impact on the magnitude of stone crystal nucleation on the injured renal tubular epithelium and the development of stone nidus. We propose to test this hypothesis in an animal model and renal epithelial cell culture (LLC-PK1 and MDCK). In an animal model hyperoxaluria is induced in male rats. In cell culture experiments, renal epithelial cells in culture are exposed to oxalate and calcium oxalate monohydrate crystals. The effect of antioxidants on these experimental models will be tested. These studies will provide valuable information on the importance of antioxidants in decreasing oxalate synthesis and deposition and, whether antioxidants offer promise as a therapeutic agent for recurrent stone formation. 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 “antioxidants” (or synonyms) into the search box. This search gives you access to

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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.

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full-text articles. The following is a sample of items found for antioxidants in the PubMed Central database: •

A catalytic antioxidant metalloporphyrin blocks hydrogen peroxide-induced mitochondrial DNA damage. by Milano J, Day BJ.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=102572

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A crucial role for thiol antioxidants in estrogen-deficiency bone loss. by Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA, Urry ZL, Chambers TJ.; 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193670

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A new automated method for the determination of the Total Antioxidant Capacity (TAC) of human plasma, based on the crocin bleaching assay. by Kampa M, Nistikaki A, Tsaousis V, Maliaraki N, Notas G, Castanas E.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128814

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Acclimation of Foliar Antioxidant Systems to Growth Irradiance in Three BroadLeaved Evergreen Species. by Grace SC, Logan BA.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158097

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Amphotericin B protects cis-parinaric acid against peroxyl radical-induced oxidation: amphotericin B as an antioxidant. by Osaka K, Ritov VB, Bernardo JF, Branch RA, Kagan VE.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163786

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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

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Antiatherogenic effects of the antioxidant BO-653 in three different animal models. by Cynshi O, Kawabe Y, Suzuki T, Takashima Y, Kaise H, Nakamura M, Ohba Y, Kato Y, Tamura K, Hayasaka A, Higashida A, Sakaguchi H, Takeya M, Takahashi K, Inoue K, Noguchi N, Niki E, Kodama T.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21472

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Antioxidant Activities of Some Tryptophan Metabolites: Possible Implication for Inflammatory Diseases. by Christen S, Peterhans E, Stocker R.; 1990 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53718

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Antioxidant activity of Ferrozine --iron --amino acid complexes. by Berlett BS, Levine RL, Chock PB, Chevion M, Stadtman ER.; 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14607

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Antioxidant Defenses in the Peripheral Cell Layers of Legume Root Nodules. by Dalton DA, Joyner SL, Becana M, Iturbe-Ormaetxe I, Chatfield JM.; 1998 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35178

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Antioxidant Enzyme Expression in Clinical Isolates of Pseudomonas aeruginosa: Identification of an Atypical Form of Manganese Superoxide Dismutase. by Britigan BE, Miller RA, Hassett DJ, Pfaller MA, McCormick ML, Rasmussen GT.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=98827

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Antioxidant function of melanin in black fungi. by Jacobson ES, Hove E, Emery HS.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173711

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Antioxidant Functions Required for Insusceptibility of Saccharomyces cerevisiae to Tetracycline Antibiotics. by Angrave FE, Avery SV.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90759

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Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. by Hagfors L, Leanderson P, Skoldstam L, Andersson J, Johansson G.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194256

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Antioxidant Systems and O2.[minus sign]/H2O2 Production in the Apoplast of Pea Leaves. Its Relation with Salt-Induced Necrotic Lesions in Minor Veins. by Hernandez JA, Ferrer MA, Jimenez A, Barcelo AR, Sevilla F.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129254

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Antioxidant-induced changes in oxidized DNA. by Malins DC, Hellstrom KE, Anderson KM, Johnson PM, Vinson MA.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122880

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Antioxidant-induced changes of the AP-1 transcription complex are paralleled by a selective suppression of human papillomavirus transcription. by Rosl F, Das BC, Lengert M, Geletneky K, zur Hausen H.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191059

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Antitumor Promotion by Phenolic Antioxidants: Inhibition of AP-1 Activity Through Induction of Fra Expression. by Yoshioka K, Deng T, Cavigelli M, Karin M.; 1995 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41829

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Association of Helicobacter pylori Antioxidant Activities with Host Colonization Proficiency. by Olczak AA, Seyler, Jr. RW, Olson JW, Maier RJ.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=143418

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Bucillamine, a thiol antioxidant, prevents transplantation-associated reperfusion injury. by Amersi F, Nelson SK, Shen XD, Kato H, Melinek J, Kupiec-Weglinski JW, Horwitz LD, Busuttil RW, Horwitz MA.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124398

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Cannabidiol and ([minus sign])[Delta]9-tetrahydrocannabinol are neuroprotective antioxidants. by Hampson AJ, Grimaldi M, Axelrod J, Wink D.; 1998 Jul 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20965

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Changes in Salicylic Acid and Antioxidants during Induced Thermotolerance in Mustard Seedlings. by Dat JF, Foyer CH, Scott IM.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34763

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Changes in the Antioxidant Systems as Part of the Signaling Pathway Responsible for the Programmed Cell Death Activated by Nitric Oxide and Reactive Oxygen Species in Tobacco Bright-Yellow 2 Cells. by de Pinto MC, Tommasi F, De Gara L.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166599

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Cloning and Sequencing of Thiol-Specific Antioxidant from Mammalian Brain: Alkyl Hydroperoxide Reductase and Thiol-Specific Antioxidant Define a Large Family of Antioxidant Enzymes. by Chae HZ, Robison K, Poole LB, Church G, Storz G, Rhee SG.; 1994 Jul 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44329

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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

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Dietary Antioxidants Preserve Endothelium-Dependent Vessel Relaxation in Cholesterol-Fed Rabbits. by Keaney JF Jr, Gaziano JM, Xu A, Frei B, Curran-Celentano J, Shwaery GT, Loscalzo J, Vita JA.; 1993 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48088

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Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis. by Miller MJ, Angeles FM, Reuter BK, Bobrowski P, Sandoval M.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61450

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Differential accumulation of antioxidant mRNAs in Arabidopsis thaliana exposed to ozone. by Conklin PL, Last RL.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157577

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Differential Localization of Antioxidants in Maize Leaves. by Doulis AG, Debian N, Kingston-Smith AH, Foyer CH.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158391

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Dimerization of Thiol-Specific Antioxidant and the Essential Role of Cysteine 47. by Chae HZ, Uhm TB, Rhee SG.; 1994 Jul 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44330

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Distinct Effects of Thioredoxin and Antioxidants on the Activation of Transcription Factors NF-[kappa]B and AP-1. by Schenk H, Klein M, Erdbrugger W, Droge W, Schulze-Osthoff K.; 1994 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43225

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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

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Effects of the Antioxidant [alpha]-Lipoic Acid on Human Umbilical Vein Endothelial Cells Infected with Rickettsia rickettsii. by Eremeeva ME, Silverman DJ.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=108194

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Electrophile and Antioxidant Regulation of Enzymes that Detoxify Carcinogens. by Prestera T, Talalay P.; 1995 Sep 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41088

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Enhanced Expression of the Transcription Factor Nrf2 by Cancer Chemopreventive Agents: Role of Antioxidant Response Element-Like Sequences in the nrf2 Promoter. by Kwak MK, Itoh K, Yamamoto M, Kensler TW.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=133753

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Functional antioxidant responsive elements. by Wasserman WW, Fahl WE.; 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24683

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Immunization with a Polyprotein Vaccine Consisting of the T-Cell Antigens ThiolSpecific Antioxidant, Leishmania major Stress-Inducible Protein 1, and Leishmania Elongation Initiation Factor Protects against Leishmaniasis. by Coler RN, Skeiky YA, Bernards K, Greeson K, Carter D, Cornellison CD, Modabber F, Campos-Neto A, Reed SG.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128156

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Improving stable transfection efficiency: antioxidants dramatically improve the outgrowth of clones under dominant marker selection. by Brielmeier M, Bechet JM, Falk MH, Pawlita M, Polack A, Bornkamm GW.; 1998 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147536

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Induction of Heme Oxygenase 1 in the Retina by Intense Visible Light: Suppression by the Antioxidant Dimethylthiourea. by Kutty RK, Kutty G, Wiggert B, Chader GJ, Darrow RM, Organisciak DT.; 1995 Feb 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42661

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Local and Systemic Responses of Antioxidants to Tobacco Mosaic Virus Infection and to Salicylic Acid in Tobacco (Role in Systemic Acquired Resistance). by Fodor J, Gullner G, Adam AL, Barna B, Komives T, Kiraly Z.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158437

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Low Ascorbic Acid in the vtc-1 Mutant of Arabidopsis Is Associated with Decreased Growth and Intracellular Redistribution of the Antioxidant System. by VeljovicJovanovic SD, Pignocchi C, Noctor G, Foyer CH.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125079

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Methionine residues as endogenous antioxidants in proteins. by Levine RL, Mosoni L, Berlett BS, Stadtman ER.; 1996 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26351

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Methionine sulfoxide reductase (MsrA) is a regulator of antioxidant defense and lifespan in mammals. by Moskovitz J, Bar-Noy S, Williams WM, Requena J, Berlett BS, Stadtman ER.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60800

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Nitric Oxide Acts as an Antioxidant and Delays Programmed Cell Death in Barley Aleurone Layers. by Beligni MV, Fath A, Bethke PC, Lamattina L, Jones RL.; 2002 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166752

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Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene. by Venugopal R, Jaiswal AK.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26245

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Overexpression of glutathione reductase but not glutathione synthetase leads to increases in antioxidant capacity and resistance to photoinhibition in poplar trees. by Foyer CH, Souriau N, Perret S, Lelandais M, Kunert KJ, Pruvost C, Jouanin L.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=161408

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Oxidants, Antioxidants, and the Degenerative Diseases of Aging. by Ames BN, Shigenaga MK, Hagen TM.; 1993 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47258

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Ozone Quenching Properties of Isoprene and Its Antioxidant Role in Leaves. by Loreto F, Mannozzi M, Maris C, Nascetti P, Ferranti F, Pasqualini S.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116456

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Pathogen-Induced Changes in the Antioxidant Status of the Apoplast in Barley Leaves. by Vanacker H, Carver TL, Foyer CH.; 1998 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34926

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Positive Control of a Global Antioxidant Defense Regulon Activated by SuperoxideGenerating Agents in Escherichia coli. by Greenberg JT, Monach P, Chou JH, Josephy PD, Demple B.; 1990 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54496

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Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: The indirect antioxidant effects of sulforaphane. by Gao X, Dinkova-Kostova AT, Talalay P.; 2001 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=65010

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Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. by Tanaka Y, Gleason CE, Tran PO, Harmon JS, Robertson RP.; 1999 Sep 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17973

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Reduced Activity of Antioxidant Machinery Is Correlated with Suppression of Totipotency in Plant Protoplasts. by Papadakis AK, Siminis CI, Roubelakis-Angelakis KA.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102316

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Regulation of p53 by metal ions and by antioxidants: dithiocarbamate down-regulates p53 DNA-binding activity by increasing the intracellular level of copper. by Verhaegh GW, Richard MJ, Hainaut P.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232418

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Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2. by Huang HC, Nguyen T, Pickett CB.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18788

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Responses of Antioxidants to Paraquat in Pea Leaves (Relationships to Resistance). by Donahue JL, Okpodu CM, Cramer CL, Grabau EA, Alscher RG.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=158137

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Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice. by Hardman WE, Munoz J Jr, Cameron IL.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140128

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Shaken, not stirred: bioanalytical study of the antioxidant activities of martinis. by Trevithick CC, Chartrand MM, Wahlman J, Rahman F, Hirst M, Trevithick JR.; 1999 Dec 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28303

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The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. by Moosmann B, Behl C.; 1999 Aug 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17699

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The tobacco salicylic acid-binding protein 3 (SABP3) is the chloroplast carbonic anhydrase, which exhibits antioxidant activity and plays a role in the hypersensitive defense response. by Slaymaker DH, Navarre DA, Clark D, del Pozo O, Martin GB, Klessig DF.; 2002 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129322

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The yeast peptide-methionine sulfoxide reductase functions as an antioxidant in vivo. by Moskovitz J, Berlett BS, Poston JM, Stadtman ER.; 1997 Sep 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23225

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Total and corrected antioxidant capacity in hemodialyzed patients. by Malliaraki N, Mpliamplias D, Kampa M, Perakis K, Margioris AN, Castanas E.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166281

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Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: protection by the antioxidant N-acetylcysteine and the genes bcl-2 and crmA. by Talley AK, Dewhurst S, Perry SW, Dollard SC, Gummuluru S, Fine SM, New D, Epstein LG, Gendelman HE, Gelbard HA.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230464

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Ubiquinol-10 is an Effective Lipid-Soluble Antioxidant at Physiological Concentrations. by Frei B, Kim MC, Ames BN.; 1990 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54222

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Ultraviolet-B- and ozone-induced biochemical changes in antioxidant enzymes of Arabidopsis thaliana. by Rao MV, Paliyath G, Ormrod DP.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157701

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Uric Acid is a Major Antioxidant in Human Nasal Airway Secretions. by Peden DB, Hohman R, Brown ME, Mason RT, Berkebile C, Fales HM, Kaliner MA.; 1990 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54803

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Why do antioxidants fail to provide clinical benefit? by Warnholtz A, Munzel T.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59596

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 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 antioxidants, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “antioxidants” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for antioxidants (hyperlinks lead to article summaries): •

2nd International Meeting on Free Radicals in Health and Disease. The role of oxidants and antioxidants in the regulation of chronic diseases, may 8-12, 2002, Istanbul, Turkey. Author(s): Rahman I, Tomasi A. Source: Free Radical Research. 2003 April; 37(4): 349-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747728&dopt=Abstract

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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

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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.

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Age, antioxidants, and atherogenesis. Author(s): Gronholdt ML. Source: Stroke; a Journal of Cerebral Circulation. 2001 November; 32(11): 2479-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12617083&dopt=Abstract

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Alterations in the erythrocyte antioxidant system of blood stored in blood bags. Author(s): Korgun DK, Bilmen S, Yesilkaya A. Source: Res Commun Mol Pathol Pharmacol. 2001; 109(5-6): 357-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889518&dopt=Abstract

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Antioxidant effect of lercanidipine. Author(s): Tomlinson B, Benzie IF. Source: Hypertension. 2003 October; 42(4): E10-1; Author Reply E10-1. Epub 2003 September 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953020&dopt=Abstract

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Antioxidant protection of low density lipoprotein by procyanidins: structure/activity relationships. Author(s): da Silva Porto PA, Laranjinha JA, de Freitas VA. Source: Biochemical Pharmacology. 2003 September 15; 66(6): 947-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12963481&dopt=Abstract

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Antioxidant status and levels of different vitamins determined by high performance liquid chromatography in diabetic subjects with multiple complications. Author(s): Merzouk S, Hichami A, Madani S, Merzouk H, Berrouiguet AY, Prost J, Moutairou K, Chabane-Sari N, Khan NA. Source: Gen Physiol Biophys. 2003 March; 22(1): 15-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870698&dopt=Abstract

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Antioxidant therapy in intensive care. Author(s): Lovat R, Preiser JC. Source: Current Opinion in Critical Care. 2003 August; 9(4): 266-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883280&dopt=Abstract

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Antioxidant vitamins C and E improve endothelial function in children with hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial. Author(s): Engler MM, Engler MB, Malloy MJ, Chiu EY, Schloetter MC, Paul SM, Stuehlinger M, Lin KY, Cooke JP, Morrow JD, Ridker PM, Rifai N, Miller E, Witztum JL, Mietus-Snyder M. Source: Circulation. 2003 September 2; 108(9): 1059-63. Epub 2003 August 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912807&dopt=Abstract

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Antioxidant vitamins for prevention of cardiovascular disease. Author(s): Paolini M, Sapone A, Canistro D, Chieco P, Valgimigli L. Source: Lancet. 2003 September 13; 362(9387): 920; Author Reply 921. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678992&dopt=Abstract

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Antioxidant vitamins improves hemoglobin level in children with group a beta hemolytic streptococcal infection. Author(s): Ahmed J, Zaman MM, Ali K. Source: Mymensingh Med J. 2003 July; 12(2): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894046&dopt=Abstract

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Antioxidants and atherosclerosis: don't throw out the baby with the bath water. Author(s): Jialal I, Devaraj S. Source: Circulation. 2003 February 25; 107(7): 926-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600900&dopt=Abstract

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Antioxidants and fetal protection against ethanol teratogenicity. I. Review of the experimental data and implications to humans. Author(s): Cohen-Kerem R, Koren G. Source: Neurotoxicology and Teratology. 2003 January-February; 25(1): 1-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633732&dopt=Abstract

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Antioxidants and healthy aging. Author(s): Hasnis E, Reznick AZ. Source: Isr Med Assoc J. 2003 May; 5(5): 368-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12811959&dopt=Abstract

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Antioxidants and oxidative stress in BAL fluid of atopic asthmatic children. Author(s): Schock BC, Young IS, Brown V, Fitch PS, Shields MD, Ennis M. Source: Pediatric Research. 2003 March; 53(3): 375-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595583&dopt=Abstract

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Antioxidants in treatment of idiopathic sudden hearing loss. Author(s): Joachims HZ, Segal J, Golz A, Netzer A, Goldenberg D. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2003 July; 24(4): 572-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851547&dopt=Abstract

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Antioxidants inhibit the human cortical neuron apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42. Author(s): Medina S, Martinez M, Hernanz A. Source: Free Radical Research. 2002 November; 36(11): 1179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592670&dopt=Abstract

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Antioxidants, statins, and atherosclerosis. Author(s): Gotto AM. Source: Journal of the American College of Cardiology. 2003 April 2; 41(7): 1205-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679223&dopt=Abstract

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Binding of fatty acids facilitates oxidation of cysteine-34 and converts copperalbumin complexes from antioxidants to prooxidants. Author(s): Gryzunov YA, Arroyo A, Vigne JL, Zhao Q, Tyurin VA, Hubel CA, Gandley RE, Vladimirov YA, Taylor RN, Kagan VE. Source: Archives of Biochemistry and Biophysics. 2003 May 1; 413(1): 53-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706341&dopt=Abstract

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Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Author(s): Di Matteo V, Esposito E. Source: Current Drug Targets. Cns and Neurological Disorders. 2003 April; 2(2): 95-107. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769802&dopt=Abstract

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Bronchopulmonary dysplasia-oxidative stress and antioxidants. Author(s): Saugstad OD. Source: Seminars in Neonatology : Sn. 2003 February; 8(1): 39-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667829&dopt=Abstract

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cDNA gene expression profile homology of antioxidants and their antiapoptotic and proapoptotic activities in human neuroblastoma cells. Author(s): Weinreb O, Mandel S, Youdim MB. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 May; 17(8): 935-7. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626434&dopt=Abstract

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Changes in blood antioxidants and several lipid peroxidation products in women with age-related macular degeneration. Author(s): Nowak M, Swietochowska E, Wielkoszynski T, Marek B, Karpe J, Gorski J, Glogowska-Szelag J, Kos-Kudla B, Ostrowska Z. Source: Eur J Ophthalmol. 2003 April; 13(3): 281-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747649&dopt=Abstract

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Children's lung function and antioxidant vitamin, fruit, juice, and vegetable intake. Author(s): Gilliland FD, Berhane KT, Li YF, Gauderman WJ, McConnell R, Peters J. Source: American Journal of Epidemiology. 2003 September 15; 158(6): 576-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965883&dopt=Abstract

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Circulating antioxidants and lipid peroxidation products in untreated tuberculosis patients in Ethiopia. Author(s): Madebo T, Lindtjorn B, Aukrust P, Berge RK. Source: The American Journal of Clinical Nutrition. 2003 July; 78(1): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816780&dopt=Abstract

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Clinical pharmacokinetics of antioxidants and their impact on systemic oxidative stress. Author(s): Schwedhelm E, Maas R, Troost R, Boger RH. Source: Clinical Pharmacokinetics. 2003; 42(5): 437-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739983&dopt=Abstract

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Contribution of the Ah receptor to the phenolic antioxidant-mediated expression of human and rat UDP-glucuronosyltransferase UGT1A6 in Caco-2 and rat hepatoma 5L cells. Author(s): Munzel PA, Schmohl S, Buckler F, Jaehrling J, Raschko FT, Kohle C, Bock KW. Source: Biochemical Pharmacology. 2003 September 1; 66(5): 841-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948865&dopt=Abstract

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Delivering antioxidants by zip code. Author(s): Li Y, Davis JM. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2003 August; 285(2): L281-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851208&dopt=Abstract

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Dietary antioxidant intake in patients at risk for second primary cancer. Author(s): Steward DL, Wiener F, Gleich LL, Falciglia G. Source: The Laryngoscope. 2003 September; 113(9): 1487-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12972921&dopt=Abstract

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Disturbed glutathione metabolism and decreased antioxidant levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy-potential immunomodulatory effects of antioxidants. Author(s): Aukrust P, Muller F, Svardal AM, Ueland T, Berge RK, Froland SS. Source: The Journal of Infectious Diseases. 2003 July 15; 188(2): 232-8. Epub 2003 June 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854078&dopt=Abstract

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DNA damage of tumor-associated lymphocytes and total antioxidant capacity in cancerous patients. Author(s): Liu X, Zhao J, Zheng R. Source: Mutation Research. 2003 August 5; 539(1-2): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948809&dopt=Abstract

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Do dietary antioxidants prevent Alzheimer's disease? Author(s): Sano M. Source: Lancet. Neurology. 2002 October; 1(6): 342. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849394&dopt=Abstract

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Effect of antioxidants on glucose metabolism and plasma lipids in HIV-infected subjects with lipoatrophy. Author(s): McComsey G, Southwell H, Gripshover B, Salata R, Valdez H. Source: Journal of Acquired Immune Deficiency Syndromes (1999). 2003 August 15; 33(5): 605-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902805&dopt=Abstract

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Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants on antioxidant status in patients with acute respiratory distress syndrome. Author(s): Nelson JL, DeMichele SJ, Pacht ER, Wennberg AK; Enteral Nutrition in ARDS Study Group. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 March-April; 27(2): 98104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665164&dopt=Abstract

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Effect of epoetin on HO-1 mRNA level and plasma antioxidants in hemodialysis patients. Author(s): Calo LA, Stanic L, Davis PA, Pagnin E, Munaretto G, Fusaro M, Landini S, Semplicini A, Piccoli A. Source: Int J Clin Pharmacol Ther. 2003 May; 41(5): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776808&dopt=Abstract

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Effect of exercise intensity and training on antioxidants and cholesterol profile in cyclists. Author(s): Aguilo A, Tauler P, Pilar Guix M, Villa G, Cordova A, Tur JA, Pons A. Source: The Journal of Nutritional Biochemistry. 2003 June; 14(6): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873713&dopt=Abstract

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Effect of orange juice intake on vitamin C concentrations and biomarkers of antioxidant status in humans. Author(s): Sanchez-Moreno C, Cano MP, de Ancos B, Plaza L, Olmedilla B, Granado F, Martin A. Source: The American Journal of Clinical Nutrition. 2003 September; 78(3): 454-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936929&dopt=Abstract

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Effects of lipid peroxidation and antioxidant status on peak flow in a population aged 59-71 years: the EVA study. Author(s): Molinie F, Favier A, Kauffmann F, Berr C. Source: Respiratory Medicine. 2003 August; 97(8): 939-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924522&dopt=Abstract

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Effects of oxygen on the antioxidant responses of normal and transformed cells. Author(s): Allen RG, Balin AK. Source: Experimental Cell Research. 2003 October 1; 289(2): 307-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499631&dopt=Abstract

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Exercise training and antioxidants: relief from oxidative stress and insulin resistance. Author(s): Henriksen EJ, Saengsirisuwan V. Source: Exercise and Sport Sciences Reviews. 2003 April; 31(2): 79-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715971&dopt=Abstract

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Free radical toxicity and antioxidants in Parkinson's disease. Author(s): Sudha K, Rao AV, Rao S, Rao A. Source: Neurology India. 2003 March; 51(1): 60-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865518&dopt=Abstract

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Fruit, vegetables, and antioxidants in childhood and risk of adult cancer: the Boyd Orr cohort. Author(s): Maynard M, Gunnell D, Emmett P, Frankel S, Davey Smith G. Source: Journal of Epidemiology and Community Health. 2003 March; 57(3): 218-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594199&dopt=Abstract

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Gene-environment interactions between the codon 194 polymorphism of XRCC1 and antioxidants influence lung cancer risk. Author(s): Ratnasinghe DL, Yao SX, Forman M, Qiao YL, Andersen MR, Giffen CA, Erozan Y, Tockman MS, Taylor PR. Source: Anticancer Res. 2003 January-February; 23(1B): 627-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12680158&dopt=Abstract

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Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Author(s): Grosser N, Abate A, Oberle S, Vreman HJ, Dennery PA, Becker JC, Pohle T, Seidman DS, Schroder H. Source: Biochemical and Biophysical Research Communications. 2003 September 5; 308(4): 956-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927812&dopt=Abstract

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Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease. Author(s): Kruidenier L, Kuiper I, Van Duijn W, Mieremet-Ooms MA, van Hogezand RA, Lamers CB, Verspaget HW. Source: The Journal of Pathology. 2003 September; 201(1): 17-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950013&dopt=Abstract

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Immune system and antioxidants, especially those derived from Indian medicinal plants. Author(s): Devasagayam TP, Sainis KB. Source: Indian J Exp Biol. 2002 June; 40(6): 639-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587713&dopt=Abstract

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Influence of UVB, UVA and UVA1 irradiation on histamine release from human basophils and mast cells in vitro in the presence and absence of antioxidants. Author(s): Kronauer C, Eberlein-Konig B, Ring J, Behrendt H. Source: Photochemistry and Photobiology. 2003 May; 77(5): 531-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812296&dopt=Abstract

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Interplay between high energy impulse noise (blast) and antioxidants in the lung. Author(s): Elsayed NM, Gorbunov NV. Source: Toxicology. 2003 July 15; 189(1-2): 63-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821283&dopt=Abstract

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Intestinal oxidative damage in inflammatory bowel disease: semi-quantification, localization, and association with mucosal antioxidants. Author(s): Kruidenier L, Kuiper I, Lamers CB, Verspaget HW. Source: The Journal of Pathology. 2003 September; 201(1): 28-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950014&dopt=Abstract

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Intramuscular heat shock protein 72 and heme oxygenase-1 mRNA are reduced in patients with type 2 diabetes: evidence that insulin resistance is associated with a disturbed antioxidant defense mechanism. Author(s): Bruce CR, Carey AL, Hawley JA, Febbraio MA. Source: Diabetes. 2003 September; 52(9): 2338-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941774&dopt=Abstract

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L-5-Hydroxytryptophan: antioxidant and anti-apoptotic principle of the intertidal sponge Hymeniacidon heliophila. Author(s): Lysek N, Kinscherf R, Claus R, Lindel T. Source: Z Naturforsch [c]. 2003 July-August; 58(7-8): 568-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939046&dopt=Abstract

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Levels of enzymatic antioxidants activities in mononuclear cells and skin reactivity to sodium dodecyl sulphate. Author(s): Camera E, Lisby S, Dell'Anna ML, Santucci B, Paganelli R, Baadsgaard O, Picardo M. Source: Int J Immunopathol Pharmacol. 2003 January-April; 16(1): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578731&dopt=Abstract

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Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study. Author(s): Maggio D, Barabani M, Pierandrei M, Polidori MC, Catani M, Mecocci P, Senin U, Pacifici R, Cherubini A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 1523-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679433&dopt=Abstract

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Micronutrients, antioxidants, and carcinoma of the gallbladder. Author(s): Shukla VK, Adukia TK, Singh SP, Mishra CP, Mishra RN. Source: Journal of Surgical Oncology. 2003 September; 84(1): 31-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949988&dopt=Abstract

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Mitochondria-targeted antioxidants protect Friedreich Ataxia fibroblasts from endogenous oxidative stress more effectively than untargeted antioxidants. Author(s): Jauslin ML, Meier T, Smith RA, Murphy MP. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 October; 17(13): 1972-4. Epub 2003 August 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923074&dopt=Abstract

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Neuroprotection by dietary antioxidants: new age of research. Author(s): Aruoma OI. Source: Die Nahrung. 2002 December; 46(6): 381-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12577583&dopt=Abstract

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New method to study oxidative damage and antioxidants in the human small bowel: effects of iron application. Author(s): Troost FJ, Saris WH, Haenen GR, Bast A, Brummer RJ. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2003 August; 285(2): G354-9. Epub 2003 April 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724133&dopt=Abstract

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Nrf2, not the estrogen receptor, mediates catechol estrogen-induced activation of the antioxidant responsive element. Author(s): Lee JM, Anderson PC, Padgitt JK, Hanson JM, Waters CM, Johnson JA. Source: Biochimica Et Biophysica Acta. 2003 October 1; 1629(1-3): 92-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522084&dopt=Abstract

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Oxidant-antioxidant system: role and significance in human body. Author(s): Irshad M, Chaudhuri PS. Source: Indian J Exp Biol. 2002 November; 40(11): 1233-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677624&dopt=Abstract

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Oxidants and antioxidants in alcohol-induced liver disease. Author(s): Arteel GE. Source: Gastroenterology. 2003 March; 124(3): 778-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612915&dopt=Abstract

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Oxidants, antioxidants and carcinogenesis. Author(s): Ray G, Husain SA. Source: Indian J Exp Biol. 2002 November; 40(11): 1213-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677623&dopt=Abstract

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Oxidative stress and antioxidant defense system in healthy, elderly men: relationship to physical activity. Author(s): Karolkiewicz J, Szczesniak L, Deskur-Smielecka E, Nowak A, Stemplewski R, Szeklicki R. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2003 June; 6(2): 100-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898794&dopt=Abstract

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Oxidative stress and gene transcription in asthma and chronic obstructive pulmonary disease: antioxidant therapeutic targets. Author(s): Rahman I. Source: Curr Drug Targets Inflamm Allergy. 2002 September; 1(3): 291-315. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561194&dopt=Abstract

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Oxygen free radicals and antioxidants. Author(s): Kuhn MA. Source: The American Journal of Nursing. 2003 April; 103(4): 58-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677123&dopt=Abstract

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Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, is under-expressed in Down syndrome fetal brains. Author(s): Sanchez-Font MF, Sebastia J, Sanfeliu C, Cristofol R, Marfany G, GonzalezDuarte R. Source: Cellular and Molecular Life Sciences : Cmls. 2003 July; 60(7): 1513-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943237&dopt=Abstract

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Plasma antioxidants and type 2 diabetes mellitus. Author(s): Palanduz S, Ademoglu E, Gokkusu C, Tamer S. Source: Res Commun Mol Pathol Pharmacol. 2001; 109(5-6): 309-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889514&dopt=Abstract

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Plasma antioxidants from chocolate. Author(s): Serafini M, Bugianesi R, Maiani G, Valtuena S, De Santis S, Crozier A. Source: Nature. 2003 August 28; 424(6952): 1013. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944955&dopt=Abstract

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Plasma electrolytes, total cholesterol, liver enzymes, and selected antioxidant status in protein energy malnutrition. Author(s): Etukudo MH, Agbedana EO, Akinyinka OO, Osifo BO. Source: Afr J Med Med Sci. 1999 March-June; 28(1-2): 81-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953993&dopt=Abstract

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Prolonged copper depletion induces expression of antioxidants and triggers apoptosis in SH-SY5Y neuroblastoma cells. Author(s): Lombardo MF, Ciriolo MR, Rotilio G, Rossi L. Source: Cellular and Molecular Life Sciences : Cmls. 2003 August; 60(8): 1733-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513838&dopt=Abstract

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Protective effect of soybean saponins and major antioxidants against aflatoxin B1induced mutagenicity and DNA-adduct formation. Author(s): Jun HS, Kim SE, Sung MK. Source: Journal of Medicinal Food. 2002 Winter; 5(4): 235-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639399&dopt=Abstract

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Reactive oxygen species and antioxidants in apoptosis of esophageal cancer cells induced by As2O3. Author(s): Shen ZY, Shen WY, Chen MH, Shen J, Zeng Y. Source: International Journal of Molecular Medicine. 2003 April; 11(4): 479-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632101&dopt=Abstract

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Relation between homocysteine concentrations and the consumption of different types of alcoholic beverages: the French Supplementation with Antioxidant Vitamins and Minerals Study. Author(s): Mennen LI, de Courcy GP, Guilland JC, Ducros V, Zarebska M, Bertrais S, Favier A, Hercberg S, Galan P. Source: The American Journal of Clinical Nutrition. 2003 August; 78(2): 334-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885718&dopt=Abstract

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Semiquinone radical intermediate in catecholic estrogen-mediated cytotoxicity and mutagenesis: chemoprevention strategies with antioxidants. Author(s): Samuni AM, Chuang EY, Krishna MC, Stein W, DeGraff W, Russo A, Mitchell JB. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 29; 100(9): 5390-5. Epub 2003 Apr 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702779&dopt=Abstract

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Serum and plasma concentration of oxidant and antioxidants in patients of Helicobacter pylori gastritis and its correlation with gastric cancer. Author(s): Khanzode SS, Khanzode SD, Dakhale GN. Source: Cancer Letters. 2003 May 30; 195(1): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767508&dopt=Abstract

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Serum antioxidant vitamin levels of people in Khon Kaen, northeastern Thailand. Author(s): Sripanidkulchai B, Vaikrutta S, Sriamporn S, Vatanasapt P, Sripanidkulchai K, Sirisangtrakul W. Source: Asian Pac J Cancer Prev. 2003 April-June; 4(2): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875628&dopt=Abstract

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The activities of antioxidant nutrients in human plasma depend on the localization of attacking radical species. Author(s): Yeum KJ, Aldini G, Chung HY, Krinsky NI, Russell RM. Source: The Journal of Nutrition. 2003 August; 133(8): 2688-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12888659&dopt=Abstract

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The antioxidant responsive element (ARE) may explain the protective effects of cruciferous vegetables on cancer. Author(s): Finley JW. Source: Nutrition Reviews. 2003 July; 61(7): 250-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918878&dopt=Abstract

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The importance of exhaled air condensate in assessing the oxidant-antioxidant system in patients with chronic obstructive pulmonary disease. Author(s): Makarevich AE, Ivashkevich DL. Source: Wiad Lek. 2003; 56(1-2): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901263&dopt=Abstract

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The interaction of cigarette smoking and antioxidants. Part III: ascorbic acid. Author(s): Kelly G. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2003 February; 8(1): 43-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611560&dopt=Abstract

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The metabolic syndrome and antioxidant concentrations: findings from the Third National Health and Nutrition Examination Survey. Author(s): Ford ES, Mokdad AH, Giles WH, Brown DW. Source: Diabetes. 2003 September; 52(9): 2346-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941775&dopt=Abstract

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The role and functions of dietary antioxidants in relation to human health. Author(s): Blaauw R, Labadarios D. Source: Sadj. 2000 June; 55(6): 327-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608273&dopt=Abstract

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The role of oxidants and antioxidants in generalized vitiligo. Author(s): Yildirim M, Baysal V, Inaloz HS, Kesici D, Delibas N. Source: The Journal of Dermatology. 2003 February; 30(2): 104-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692376&dopt=Abstract

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The role of oxidants and antioxidants in psoriasis. Author(s): Yildirim M, Inaloz HS, Baysal V, Delibas N. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 January; 17(1): 34-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602965&dopt=Abstract

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The synergistic effect of conventional and sustained delivery of antioxidants on LNCaP prostate cancer cell line. Author(s): Richards LR, Benghuzzi H, Tucci M, Hughes J. Source: Biomed Sci Instrum. 2003; 39: 402-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724927&dopt=Abstract

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The use of antioxidants in Friedreich's ataxia treatment. Author(s): Rustin P. Source: Expert Opinion on Investigational Drugs. 2003 April; 12(4): 569-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665413&dopt=Abstract

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The use of antioxidants with first-line chemotherapy in two cases of ovarian cancer. Author(s): Drisko JA, Chapman J, Hunter VJ. Source: Journal of the American College of Nutrition. 2003 April; 22(2): 118-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672707&dopt=Abstract

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Thioredoxin reductase in human hepatoma cells is transcriptionally regulated by sulforaphane and other electrophiles via an antioxidant response element. Author(s): Hintze KJ, Wald KA, Zeng H, Jeffery EH, Finley JW. Source: The Journal of Nutrition. 2003 September; 133(9): 2721-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949356&dopt=Abstract

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Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. Author(s): Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M, Brighenti F. Source: The Journal of Nutrition. 2003 September; 133(9): 2812-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949370&dopt=Abstract

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United they go: conjunct regulation of aortic antioxidant enzymes during atherogenesis. Author(s): Palinski W. Source: Circulation Research. 2003 August 8; 93(3): 183-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907662&dopt=Abstract

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Vascular thrombogenicity induced by progressive LDL oxidation: protection by antioxidants. Author(s): Banfi C, Camera M, Giandomenico G, Toschi V, Arpaia M, Mussoni L, Tremoli E, Colli S. Source: Thrombosis and Haemostasis. 2003 March; 89(3): 544-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624640&dopt=Abstract

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Vitamins, antioxidants and endothelial function in coronary artery disease. Author(s): Hornig B. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2002 September; 16(5): 401-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652109&dopt=Abstract

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What should we advise our patients about taking antioxidants? Author(s): Pickering TG. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 May-June; 5(3): 231-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826791&dopt=Abstract

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

Finding Nutrition Studies on Antioxidants 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 “antioxidants” (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.

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

Antioxidants for the uninitiated. Source: Smart, J.M. Vegetarian-times (USA). (April 1994). (no. 200) page 26, 28. antioxidants nutrients human nutrition health services health carotenoids vitamin e 0164-8497

•

Do antioxidant supplements harm rather than help? A hard look at the Finnish study. Source: Smith, S.M. Environmental-nutrition (USA). (June 1994). (no. suppl.) page 9-10. fats finland diet antioxidants disease control medical sciences research supplements carotenoids vitamin e nutrients 0893-4452

Additional consumer oriented references include: •

Antioxidant properties of a Tinospora cordifolia polysaccharide against ironmediated lipid damage and gamma-ray induced protein damage. Author(s): Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. Source: Subramanian, M Chintalwar, G J Chattopadhyay, S Redox-Repage 2002; 7(3): 137-43 1351-0002

•

Antioxidant properties of carboxymethyl glucan: comparative analysis. Author(s): Department of Biophysics and Chemical Physics, Comenius University, Bratislava, Slovakia. [email protected] Source: Babincova, M Bacova, Z Machova, E Kogan, G J-Med-Food. 2002 Summer; 5(2): 79-83 1096-620X

•

Antioxidant status and muscle cell leakage during endurance exercise. Author(s): Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061-0306, USA. Source: Hargreaves, B J Kronfeld, D S Waldron, J N Lopes, M A Gay, L S Saker, K E Cooper, W L Sklan, D J Harris, P A Equine-Vet-J-Suppl. 2002 September; (34): 116-21

•

Antioxidants, oxidative damage and oxygen deprivation stress: a review. Author(s): Department of Biosciences, Division of Plant Physiology, Viikki Biocenter, FIN-00014 Helsinki University, Finland. Source: Blokhina, O Virolainen, E Fagerstedt, K V Ann-Bot-(Lond). 2003 January; 91 Spec No: 179-94 0305-7364

•

Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Author(s): Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78229-3900, USA. Source: Tan, D X Reiter, R J Manchester, L C Yan, M T El Sawi, M Sainz, R M Mayo, J C Kohen, R Allegra, M Hardeland, R Curr-Top-Med-Chem. 2002 February; 2(2): 181-97 1568-0266

•

Diet during pregnancy and total antioxidant capacity in maternal and umbilical cord blood. Author(s): Nutrition Section of Department of Internal Medicine, University of Perugia, Italy. Source: Alberti Fidanza, A Di Renzo, G C Burini, G Antonelli, G Perriello, G J-MaternFetal-Neonatal-Med. 2002 July; 12(1): 59-63 1476-7058

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Effect of a novel NSAID derivative with antioxidant moiety on oxidative damage caused by liver and cerebral ischaemia-reperfusion in rats. Author(s): Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54006, Greece. [email protected] Source: Kourounakis, A P Tsiakitzis, K Paramithiotis, D Kotzampassi, K Kourounakis, P N J-Pharm-Pharmacol. 2002 August; 54(8): 1091-6 0022-3573

•

Effect of excessive intake of thermally oxidized sesame oil on lipids, lipid peroxidation and antioxidants' status in rats. Author(s): Department of Biochemistry, Annamalai University, Annamalainagar, Tamilnadu 608 002, India. Source: Srinivasan, K N Pugalendi, K V Indian-J-Exp-Biol. 2000 August; 38(8): 777-80 0019-5189

•

Effect of preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine. Author(s): Department of Pharmaceutics, College of Pharmacy ( University of Delhi ), Pushp Vihar, Sector-III, New Delhi 110 017, India. Source: Malhotra, M Majumdar, D K Indian-J-Exp-Biol. 2002 May; 40(5): 555-9 0019-5189

•

Effects of a low carbohydrate diet and graded exercise during the follicular and luteal phases on the blood antioxidant status in healthy women. Author(s): Department of Physiological and Medical Sciences, Academy of Physical Education, 40-065 Katowice, ul Mikolowska 72A, Poland. [email protected] Source: Klapcinska, B Sadowska Krepa, E Manowska, B Pilis, W Sobczak, A Danch, A Eur-J-Appl-Physiol. 2002 August; 87(4-5): 373-80 1439-6319

•

Effects of photodynamic treatment on biological antioxidant systems in rats. Author(s): Biochemistry & Nutrition Discipline, Defence Food Research Laboratory, Siddarthanagar, Mysore 570 011, India. Source: AnilakuMarch, K R Khanum, F Swamy, M S Santhanam, K Indian-J-Exp-Biol. 2001 June; 39(6): 558-63 0019-5189

•

Enhanced contact activity of fluconazole in association with antioxidants against fluconazole-resistant organisms. Author(s): University of Rome La Sapienza, Institute of Microbiology, Faculty of Pharmacy, Piazzale Aldo Moro 5, 00185 Rome, Italy. Source: Simonetti, G Villa, A Simonetti, N J-Antimicrob-Chemother. 2002 August; 50(2): 257-9 0305-7453

•

Flavonoid antioxidant silymarin and skin cancer. Author(s): Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Source: Singh, R P Agarwal, R Antioxid-Redox-Signal. 2002 August; 4(4): 655-63 15230864

•

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Source: Patrick, L Altern-Med-Revolume 2002 December; 7(6): 456-71 1089-5159

•

On the antioxidant properties of therapeutic drugs: quenching of singlet molecular oxygen by aminosalicylic acids. Author(s): Departamento de Quimica y Fisica, Universidad Nacional de Rio Cuarto, Rio Cuarto, Argentina. Source: Yppolito, R Pappano, N Debattista, N Miskoski, S Bertolotti, S G Garcia, N A Redox-Repage 2002; 7(4): 229-33 1351-0002

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On-line antioxidant activity determination: comparison of hydrophilic and lipophilic antioxidant activity using the ABTS*+ assay. Author(s): Department of Plant Biology (Plant Physiology), Campus Espinardo, University of Murcia, 30100-Murcia, Spain. Source: Cano, A Alcaraz, O Acosta, M Arnao, M B Redox-Repage 2002; 7(2): 103-9 13510002

•

Oxidative stress and cardiac microvascular structure in ischemia and reperfusion: the protective effect of antioxidant vitamins. Author(s): William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London 0E1 4NS, United Kingdom. Source: Molyneux, C A Glyn, M C Ward, B J Microvasc-Res. 2002 September; 64(2): 26577 0026-2862

•

Role of chelating agents and antioxidants in beryllium induced toxicity. Author(s): Laboratory of Toxicology & Reproductive Biology, School of Studies in Zoology, Jiwaji University, Gwalior, 474 011, India. Source: Johri, S Shukla, S Sharma, P Indian-J-Exp-Biol. 2002 May; 40(5): 575-82 0019-5189

•

Role of oxidative stress and antioxidants in neurodegenerative diseases. Author(s): Department of Nutritional Sciences, University of Toronto, Ont., Canada. [email protected] Source: Rao, A V Balachandran, B Nutr-Neurosci. 2002 October; 5(5): 291-309 1028-415X

•

Structural aspects of antioxidant activity of substituted pyridoindoles. Author(s): Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic. Source: Rackova, L Stefek, M Majekova, M Redox-Repage 2002; 7(4): 207-14 1351-0002

•

The effects of antioxidants and nitric oxide modulators on hepatic ischemicreperfusion injury in rats. Author(s): Department of Emergency Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea. Source: Rhee, J E Jung, S E Shin, S D Suh, G J Noh, D Y Youn, Y K Oh, S K Choe, K J JKorean-Med-Sci. 2002 August; 17(4): 502-6 1011-8934

•

Total antioxidant capacity of colostrum, and transitional and mature human milk. Author(s): Department of Internal Medicine, University of Perugia, Italy. Source: Alberti Fidanza, A Burini, G Perriello, G J-Matern-Fetal-Neonatal-Med. 2002 April; 11(4): 275-9 1476-7058

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

Antioxidant properties of a Tinospora cordifolia polysaccharide against ironmediated lipid damage and gamma-ray induced protein damage. Author(s): Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. Source: Subramanian, M Chintalwar, G J Chattopadhyay, S Redox-Repage 2002; 7(3): 137-43 1351-0002

•

Antioxidant status and muscle cell leakage during endurance exercise. Author(s): Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg 24061-0306, USA.

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Source: Hargreaves, B J Kronfeld, D S Waldron, J N Lopes, M A Gay, L S Saker, K E Cooper, W L Sklan, D J Harris, P A Equine-Vet-J-Suppl. 2002 September; (34): 116-21 •

Antioxidants, oxidative damage and oxygen deprivation stress: a review. Author(s): Department of Biosciences, Division of Plant Physiology, Viikki Biocenter, FIN-00014 Helsinki University, Finland. Source: Blokhina, O Virolainen, E Fagerstedt, K V Ann-Bot-(Lond). 2003 January; 91 Spec No: 179-94 0305-7364

•

Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Author(s): Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78229-3900, USA. Source: Tan, D X Reiter, R J Manchester, L C Yan, M T El Sawi, M Sainz, R M Mayo, J C Kohen, R Allegra, M Hardeland, R Curr-Top-Med-Chem. 2002 February; 2(2): 181-97 1568-0266

•

Diet during pregnancy and total antioxidant capacity in maternal and umbilical cord blood. Author(s): Nutrition Section of Department of Internal Medicine, University of Perugia, Italy. Source: Alberti Fidanza, A Di Renzo, G C Burini, G Antonelli, G Perriello, G J-MaternFetal-Neonatal-Med. 2002 July; 12(1): 59-63 1476-7058

•

Effect of a novel NSAID derivative with antioxidant moiety on oxidative damage caused by liver and cerebral ischaemia-reperfusion in rats. Author(s): Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Thessaloniki 54006, Greece. [email protected] Source: Kourounakis, A P Tsiakitzis, K Paramithiotis, D Kotzampassi, K Kourounakis, P N J-Pharm-Pharmacol. 2002 August; 54(8): 1091-6 0022-3573

•

Effect of excessive intake of thermally oxidized sesame oil on lipids, lipid peroxidation and antioxidants' status in rats. Author(s): Department of Biochemistry, Annamalai University, Annamalainagar, Tamilnadu 608 002, India. Source: Srinivasan, K N Pugalendi, K V Indian-J-Exp-Biol. 2000 August; 38(8): 777-80 0019-5189

•

Effect of preservative, antioxidant and viscolizing agents on in vitro transcorneal permeation of ketorolac tromethamine. Author(s): Department of Pharmaceutics, College of Pharmacy ( University of Delhi ), Pushp Vihar, Sector-III, New Delhi 110 017, India. Source: Malhotra, M Majumdar, D K Indian-J-Exp-Biol. 2002 May; 40(5): 555-9 0019-5189

•

Effects of a low carbohydrate diet and graded exercise during the follicular and luteal phases on the blood antioxidant status in healthy women. Author(s): Department of Physiological and Medical Sciences, Academy of Physical Education, 40-065 Katowice, ul Mikolowska 72A, Poland. [email protected] Source: Klapcinska, B Sadowska Krepa, E Manowska, B Pilis, W Sobczak, A Danch, A Eur-J-Appl-Physiol. 2002 August; 87(4-5): 373-80 1439-6319

•

Effects of photodynamic treatment on biological antioxidant systems in rats. Author(s): Biochemistry & Nutrition Discipline, Defence Food Research Laboratory, Siddarthanagar, Mysore 570 011, India. Source: AnilakuMarch, K R Khanum, F Swamy, M S Santhanam, K Indian-J-Exp-Biol. 2001 June; 39(6): 558-63 0019-5189

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Enhanced contact activity of fluconazole in association with antioxidants against fluconazole-resistant organisms. Author(s): University of Rome La Sapienza, Institute of Microbiology, Faculty of Pharmacy, Piazzale Aldo Moro 5, 00185 Rome, Italy. Source: Simonetti, G Villa, A Simonetti, N J-Antimicrob-Chemother. 2002 August; 50(2): 257-9 0305-7453

•

Flavonoid antioxidant silymarin and skin cancer. Author(s): Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Source: Singh, R P Agarwal, R Antioxid-Redox-Signal. 2002 August; 4(4): 655-63 15230864

•

Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Source: Patrick, L Altern-Med-Revolume 2002 December; 7(6): 456-71 1089-5159

•

On the antioxidant properties of therapeutic drugs: quenching of singlet molecular oxygen by aminosalicylic acids. Author(s): Departamento de Quimica y Fisica, Universidad Nacional de Rio Cuarto, Rio Cuarto, Argentina. Source: Yppolito, R Pappano, N Debattista, N Miskoski, S Bertolotti, S G Garcia, N A Redox-Repage 2002; 7(4): 229-33 1351-0002

•

On-line antioxidant activity determination: comparison of hydrophilic and lipophilic antioxidant activity using the ABTS*+ assay. Author(s): Department of Plant Biology (Plant Physiology), Campus Espinardo, University of Murcia, 30100-Murcia, Spain. Source: Cano, A Alcaraz, O Acosta, M Arnao, M B Redox-Repage 2002; 7(2): 103-9 13510002

•

Oxidative stress and cardiac microvascular structure in ischemia and reperfusion: the protective effect of antioxidant vitamins. Author(s): William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London 0E1 4NS, United Kingdom. Source: Molyneux, C A Glyn, M C Ward, B J Microvasc-Res. 2002 September; 64(2): 26577 0026-2862

•

Role of chelating agents and antioxidants in beryllium induced toxicity. Author(s): Laboratory of Toxicology & Reproductive Biology, School of Studies in Zoology, Jiwaji University, Gwalior, 474 011, India. Source: Johri, S Shukla, S Sharma, P Indian-J-Exp-Biol. 2002 May; 40(5): 575-82 0019-5189

•

Role of oxidative stress and antioxidants in neurodegenerative diseases. Author(s): Department of Nutritional Sciences, University of Toronto, Ont., Canada. [email protected] Source: Rao, A V Balachandran, B Nutr-Neurosci. 2002 October; 5(5): 291-309 1028-415X

•

Structural aspects of antioxidant activity of substituted pyridoindoles. Author(s): Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Slovak Republic. Source: Rackova, L Stefek, M Majekova, M Redox-Repage 2002; 7(4): 207-14 1351-0002

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The effects of antioxidants and nitric oxide modulators on hepatic ischemicreperfusion injury in rats. Author(s): Department of Emergency Medicine, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea. Source: Rhee, J E Jung, S E Shin, S D Suh, G J Noh, D Y Youn, Y K Oh, S K Choe, K J JKorean-Med-Sci. 2002 August; 17(4): 502-6 1011-8934

•

Total antioxidant capacity of colostrum, and transitional and mature human milk. Author(s): Department of Internal Medicine, University of Perugia, Italy. Source: Alberti Fidanza, A Burini, G Perriello, G J-Matern-Fetal-Neonatal-Med. 2002 April; 11(4): 275-9 1476-7058

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/

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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/

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/

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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 antioxidants; 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/vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,936,00.html Multiple Vitamin-mineral Supplements Source: Healthnotes, Inc.; www.healthnotes.com Provitamin A Source: Integrative Medicine Communications; www.drkoop.com Vitamin A Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10066,00.html Vitamin B2 Source: Healthnotes, Inc.; www.healthnotes.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 E Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-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 •

Minerals Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Chromium Source: Healthnotes, Inc.; www.healthnotes.com Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com Copper Source: Healthnotes, Inc.; www.healthnotes.com Copper Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,886,00.html D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Hmg-coa Reductase Inhibitors (statins) Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Iron Source: Prima Communications, Inc.www.personalhealthzone.com

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Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Manganese Source: Healthnotes, Inc.; www.healthnotes.com Manganese Source: Integrative Medicine Communications; www.drkoop.com Manganese Source: Prima Communications, Inc.www.personalhealthzone.com Quercetin Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: Integrative Medicine Communications; www.drkoop.com Quercetin Source: Prima Communications, Inc.www.personalhealthzone.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 Zinc Source: Healthnotes, Inc.; www.healthnotes.com •

Food and Diet Artichoke Source: Healthnotes, Inc.; www.healthnotes.com Arugula Source: Healthnotes, Inc.; www.healthnotes.com Asparagus Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Asparagus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,7,00.html Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Avocado Source: Healthnotes, Inc.; www.healthnotes.com Avocados Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,46,00.html Beet Greens Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,309,00.html Beets Source: Healthnotes, Inc.; www.healthnotes.com Blackberries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,142,00.html Blueberries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,101,00.html Bok Choy Source: Healthnotes, Inc.; www.healthnotes.com Brazil Nuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,115,00.html Broccoflower Source: Healthnotes, Inc.; www.healthnotes.com Broccoli Source: Healthnotes, Inc.; www.healthnotes.com Brussels Sprouts Source: Healthnotes, Inc.; www.healthnotes.com

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Cabbage Source: Healthnotes, Inc.; www.healthnotes.com Carrots Source: Healthnotes, Inc.; www.healthnotes.com Cauliflower Source: Healthnotes, Inc.; www.healthnotes.com Cherries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,49,00.html Chicory Source: Healthnotes, Inc.; www.healthnotes.com Chocolate Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,179,00.html Collards Source: Healthnotes, Inc.; www.healthnotes.com Complex Carbohydrates Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,993,00.html Dandelion Greens Source: Healthnotes, Inc.; www.healthnotes.com Diet Drinks Source: Healthnotes, Inc.; www.healthnotes.com Endive Source: Healthnotes, Inc.; www.healthnotes.com Feingold Diet Source: Healthnotes, Inc.; www.healthnotes.com Flaxseeds Source: Healthnotes, Inc.; www.healthnotes.com Garlic Alternative names: Allium sativum Source: Healthnotes, Inc.; www.healthnotes.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com

Nutrition

Garlic Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,786,00.html Hazelnuts Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,307,00.html Honey Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,283,00.html Jerusalem Artichoke Source: Healthnotes, Inc.; www.healthnotes.com Jicama Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,127,00.html Kohlrabi Source: Healthnotes, Inc.; www.healthnotes.com Leeks Source: Healthnotes, Inc.; www.healthnotes.com Mackerel Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,310,00.html Mustard Greens Source: Healthnotes, Inc.; www.healthnotes.com Okra Source: Healthnotes, Inc.; www.healthnotes.com Onions Source: Healthnotes, Inc.; www.healthnotes.com Onions Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,27,00.html Parsnips Source: Healthnotes, Inc.; www.healthnotes.com Pomegranates Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,216,00.html Radishes Source: Healthnotes, Inc.; www.healthnotes.com Romaine Lettuce Source: Healthnotes, Inc.; www.healthnotes.com Rutabagas Source: Healthnotes, Inc.; www.healthnotes.com Snow Peas Source: Healthnotes, Inc.; www.healthnotes.com Soy Source: Healthnotes, Inc.; www.healthnotes.com Soybeans Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,105,00.html Spinach Source: Healthnotes, Inc.; www.healthnotes.com Spinach Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,35,00.html Sprains and Strains Source: Healthnotes, Inc.; www.healthnotes.com Strawberries Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,108,00.html Summer Squash Source: Healthnotes, Inc.; www.healthnotes.com Sunflower Seeds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

Nutrition

Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,158,00.html Sweet Peppers Source: Healthnotes, Inc.; www.healthnotes.com Sweet Potatoes Source: Healthnotes, Inc.; www.healthnotes.com Tomatoes Source: Healthnotes, Inc.; www.healthnotes.com Turnips Source: Healthnotes, Inc.; www.healthnotes.com Winter Squash Source: Healthnotes, Inc.; www.healthnotes.com Yams Source: Healthnotes, Inc.; www.healthnotes.com Zucchini Source: Healthnotes, Inc.; www.healthnotes.com

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

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “antioxidants” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •

Antioxidant Vitamins and Zinc Reduce Risk of Vision Loss from Age-Related Macular Degeneration Source: Bethesda, MD: National Eye Institute. 2001. 5 p. Contact: Available from National Eye Institute. National Institutes of Health, 2020 Vision Place, Bethesda, MD 20892. (301) 496-5248. PRICE: Free. Summary: This National Eye Institute (NEI) news release reports on the nationwide clinical trial "Age Related Eye Disease Study," which found that high levels of antioxidants and zinc reduce the risk of advanced age-related macular degeneration and its associated vision loss. It describes the methodology and results of the trial, and includes quotes from the trial investigators and the director of the NEI.

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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 antioxidants 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 “antioxidants” (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 antioxidants: •

A Natural Antioxidant Mixture from Spinach Does Not Have Estrogenic or Antiestrogenic Activity in Immature CD-1 Mice. Author(s): Lomnitski L, Padilla-Banks E, Jefferson WN, Nyska A, Grossman S, Newbold RR. Source: The Journal of Nutrition. 2003 November; 133(11): 3584-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14608077&dopt=Abstract

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Ability of antioxidants to prevent oxidative mutations in Salmonella typhimurium TA102. Author(s): Grey CE, Adlercreutz P. Source: Mutation Research. 2003 June 19; 527(1-2): 27-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787911&dopt=Abstract

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An in vivo study of the antioxidant potentials of a plant food concentrate. Author(s): Ziccarelli VE, Basu TK. Source: Journal of the American College of Nutrition. 2003 August; 22(4): 277-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897041&dopt=Abstract

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Antioxidant action of Moringa oleifera Lam. (drumstick) against antitubercular drugs induced lipid peroxidation in rats. Author(s): Ashok Kumar N, Pari L. Source: Journal of Medicinal Food. 2003 Fall; 6(3): 255-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585192&dopt=Abstract

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Antioxidant activities of chitobiose and chitotriose. Author(s): Chen AS, Taguchi T, Sakai K, Kikuchi K, Wang MW, Miwa I. Source: Biological & Pharmaceutical Bulletin. 2003 September; 26(9): 1326-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12951480&dopt=Abstract

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Antioxidant activity of Arbutus unedo leaves. Author(s): Pabuccuoglu A, Kivcak B, Bas M, Mert T. Source: Fitoterapia. 2003 September; 74(6): 597-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946724&dopt=Abstract

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Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. Author(s): Frei B, Higdon JV. Source: The Journal of Nutrition. 2003 October; 133(10): 3275S-84S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519826&dopt=Abstract

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Antioxidant activity of the anthocyanin from carrot (Daucus carota) callus culture. Author(s): Ravindra PV, Narayan MS. Source: International Journal of Food Sciences and Nutrition. 2003 September; 54(5): 34955. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907406&dopt=Abstract

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Antioxidant and anti-inflammatory activities of Mallotus oppositifolium in model systems. Author(s): Farombi EO, Ogundipe O, Moody JO. Source: Afr J Med Med Sci. 2001 September; 30(3): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510131&dopt=Abstract

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Antioxidant effects of tea: evidence from human clinical trials. Author(s): Rietveld A, Wiseman S. Source: The Journal of Nutrition. 2003 October; 133(10): 3285S-3292S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519827&dopt=Abstract

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Antioxidant effects of tetrahydro-beta-carboline derivatives identified in aged garlic extract. Author(s): Ichikawa M, Ryu K, Yoshida J, Ide N, Yoshida S, Sasaoka T, Sumi S. Source: Biofactors (Oxford, England). 2002; 16(3-4): 57-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530594&dopt=Abstract

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Antioxidant intake and primary open-angle glaucoma: a prospective study. Author(s): Kang JH, Pasquale LR, Willett W, Rosner B, Egan KM, Faberowski N, Hankinson SE. Source: American Journal of Epidemiology. 2003 August 15; 158(4): 337-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915499&dopt=Abstract

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Antioxidant intake, plasma antioxidants and oxidative stress in a randomized, controlled, parallel, Mediterranean dietary intervention study on patients with rheumatoid arthritis. Author(s): Hagfors L, Leanderson P, Skoldstam L, Andersson J, Johansson G. Source: Nutrition Journal [electronic Resource]. 2003 July 30; 2(1): 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952549&dopt=Abstract

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Antioxidant isoflavones in Osage orange, Maclura pomifera (Raf.) Schneid. Author(s): Tsao R, Yang R, Young JC.

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Source: Journal of Agricultural and Food Chemistry. 2003 October 22; 51(22): 6445-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14558760&dopt=Abstract •

Antioxidant properties of extracts from Alchornea laxiflora (Benth) Pax and Hoffman. Author(s): Olatunde Farombi E, Ogundipe OO, Samuel Uhunwangho E, Adeyanju MA, Olarenwaju Moody J. Source: Phytotherapy Research : Ptr. 2003 August; 17(7): 713-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12916064&dopt=Abstract

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Antioxidant properties of low molecular weight phenols present in the mediterranean diet. Author(s): Briante R, Febbraio F, Nucci R. Source: Journal of Agricultural and Food Chemistry. 2003 November 19; 51(24): 6975-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14611157&dopt=Abstract

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Antioxidant systems and their relationship with the response of pepper fruits to storage at 20 degrees C. Author(s): Jimenez A, Romojaro F, Gomez JM, Llanos MR, Sevilla F. Source: Journal of Agricultural and Food Chemistry. 2003 October 8; 51(21): 6293-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14518958&dopt=Abstract

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Antioxidants in tears and plasma: Inter-relationships and effect of vitamin C supplementation. Author(s): Choy C, Benzie I, Cho P. Source: Current Eye Research. 2003 July; 27(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868009&dopt=Abstract

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Antioxidants protect primary rat hepatocyte cultures against acetaminophen-induced DNA strand breaks but not against acetaminophen-induced cytotoxicity. Author(s): Lewerenz V, Hanelt S, Nastevska C, El-Bahay C, Rohrdanz E, Kahl R. Source: Toxicology. 2003 September 30; 191(2-3): 179-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965121&dopt=Abstract

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Antioxidants: a possible role in kidney protection. Author(s): Tylicki L, Rutkowski B, Horl WH. Source: Kidney & Blood Pressure Research. 2003; 26(5-6): 303-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14610334&dopt=Abstract

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Apple and pear peel and pulp and their influence on plasma lipids and antioxidant potentials in rats fed cholesterol-containing diets. Author(s): Leontowicz M, Gorinstein S, Leontowicz H, Krzeminski R, Lojek A, Katrich E, Ciz M, Martin-Belloso O, Soliva-Fortuny R, Haruenkit R, Trakhtenberg S.

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Source: Journal of Agricultural and Food Chemistry. 2003 September 10; 51(19): 5780-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952433&dopt=Abstract •

Beneficial effect of combined administration of some naturally occurring antioxidants (vitamins) and thiol chelators in the treatment of chronic lead intoxication. Author(s): Flora SJ, Pande M, Mehta A. Source: Chemico-Biological Interactions. 2003 June 15; 145(3): 267-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732454&dopt=Abstract

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Chemical characterization and biological effects of Sicilian Opuntia ficus indica (L.) mill. Fruit juice: antioxidant and antiulcerogenic activity. Author(s): Galati EM, Mondello MR, Giuffrida D, Dugo G, Miceli N, Pergolizzi S, Taviano MF. Source: Journal of Agricultural and Food Chemistry. 2003 August 13; 51(17): 4903-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903943&dopt=Abstract

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Comparative study of eight well-known polyphenolic antioxidants. Author(s): Cos P, Hermans N, Calomme M, Maes L, De Bruyne T, Pieters L, Vlietinck AJ, Vanden Berghe D. Source: The Journal of Pharmacy and Pharmacology. 2003 September; 55(9): 1291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14604473&dopt=Abstract

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Delineation of signalling pathway leading to antioxidant-dependent inhibition of dexamethasone-mediated muscle cell death. Author(s): Orzechowski A, Jank M, Gajkowska B, Sadkowski T, Godlewski MM, Ostaszewski P. Source: Journal of Muscle Research and Cell Motility. 2003; 24(1): 33-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953835&dopt=Abstract

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Determination of total antioxidant activity in three types of local vegetables shoots and the cytotoxic effect of their ethanolic extracts against different cancer cell lines. Author(s): Rahmat A, Kumar V, Fong LM, Endrini S, Sani HA. Source: Asia Pacific Journal of Clinical Nutrition. 2003; 12(3): 292-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14505992&dopt=Abstract

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Effect of Coccinia indica leaf extract on plasma antioxidants in streptozotocininduced experimental diabetes in rats. Author(s): Venkateswaran S, Pari L. Source: Phytotherapy Research : Ptr. 2003 June; 17(6): 605-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12820225&dopt=Abstract

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Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]- quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification

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capacity in the rat. Author(s): Breinholt VM, Molck AM, Svendsen GW, Daneshvar B, Vinggaard AM, Poulsen M, Dragsted LO. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2003 October; 41(10): 1315-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12909264&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

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Effects of Nigella sativa L. and Urtica dioica L. on lipid peroxidation, antioxidant enzyme systems and some liver enzymes in CCl4-treated rats. Author(s): Kanter M, Meral I, Dede S, Cemek M, Ozbek H, Uygan I, Gunduz H. Source: Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine. 2003 June; 50(5): 264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567515&dopt=Abstract

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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

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Influence of a drink containing different antioxidants and Lactobacillus plantarum 299v on plasma total antioxidant capacity, selenium status and faecal microbial flora. Author(s): Onning G, Berggren A, Drevelius M, Jeppsson B, Lindberg AM, Johansson Hagslatt ML. Source: International Journal of Food Sciences and Nutrition. 2003 July; 54(4): 281-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850889&dopt=Abstract

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Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation. Author(s): Trebble T, Arden NK, Stroud MA, Wootton SA, Burdge GC, Miles EA, Ballinger AB, Thompson RL, Calder PC. Source: The British Journal of Nutrition. 2003 August; 90(2): 405-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908901&dopt=Abstract

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Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury. Author(s): Gupta R, Singh M, Sharma A.

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Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2003 August; 48(2): 209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798674&dopt=Abstract •

Nutritional supplementation with antioxidants decreases chromosomal damage in humans. Author(s): Dusinska M, Kazimirova A, Barancokova M, Beno M, Smolkova B, Horska A, Raslova K, Wsolova L, Collins AR. Source: Mutagenesis. 2003 July; 18(4): 371-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840111&dopt=Abstract

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Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic acid induced excitotoxicity. Author(s): Parihar MS, Hemnani T. Source: Journal of Biosciences. 2003 February; 28(1): 121-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682435&dopt=Abstract

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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

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Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Author(s): Trebble TM, Wootton SA, Miles EA, Mullee M, Arden NK, Ballinger AB, Stroud MA, Burdge GC, Calder PC. Source: The American Journal of Clinical Nutrition. 2003 September; 78(3): 376-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936918&dopt=Abstract

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Protective effect of Spirulina on lead induced deleterious changes in the lipid peroxidation and endogenous antioxidants in rats. Author(s): Upasani CD, Balaraman R. Source: Phytotherapy Research : Ptr. 2003 April; 17(4): 330-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722134&dopt=Abstract

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Role of antioxidants in chronic fatigue syndrome in mice. Author(s): Singh A, Garg V, Gupta S, Kulkarni SK. Source: Indian J Exp Biol. 2002 November; 40(11): 1240-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677625&dopt=Abstract

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S-allylcysteine inhibits circulatory lipid peroxidation and promotes antioxidants in N-nitrosodiethylamine-induced carcinogenesis. Author(s): Sundaresan S, Subramanian P. Source: Polish Journal of Pharmacology. 2003 January-February; 55(1): 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856824&dopt=Abstract

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Screening pharmaceutical preparations containing extracts of turmeric rhizome, artichoke leaf, devil's claw root and garlic or salmon oil for antioxidant capacity. Author(s): Betancor-Fernandez A, Perez-Galvez A, Sies H, Stahl W. Source: The Journal of Pharmacy and Pharmacology. 2003 July; 55(7): 981-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12906755&dopt=Abstract

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Several culinary and medicinal herbs are important sources of dietary antioxidants. Author(s): Dragland S, Senoo H, Wake K, Holte K, Blomhoff R. Source: The Journal of Nutrition. 2003 May; 133(5): 1286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730411&dopt=Abstract

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Stilbazulenyl nitrone, a novel antioxidant, is highly neuroprotective in focal ischemia. Author(s): Ginsberg MD, Becker DA, Busto R, Belayev A, Zhang Y, Khoutorova L, Ley JJ, Zhao W, Belayev L. Source: Annals of Neurology. 2003 September; 54(3): 330-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953265&dopt=Abstract

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Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Author(s): Arvindakshan M, Ghate M, Ranjekar PK, Evans DR, Mahadik SP. Source: Schizophrenia Research. 2003 August 1; 62(3): 195-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837515&dopt=Abstract

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The antioxidant conundrum in cancer. Author(s): Seifried HE, McDonald SS, Anderson DE, Greenwald P, Milner JA. Source: Cancer Research. 2003 August 1; 63(15): 4295-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907593&dopt=Abstract

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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. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563626&dopt=Abstract

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The study of phenolic compounds as natural antioxidants in wine. Author(s): Lopez-Velez M, Martinez-Martinez F, Del Valle-Ribes C.

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Source: Critical Reviews in Food Science and Nutrition. 2003; 43(3): 233-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822671&dopt=Abstract •

Toxic metals and antioxidants: Part II. The role of antioxidants in arsenic and cadmium toxicity. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2003 April; 8(2): 106-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777158&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/

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to antioxidants; 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

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Age-related Cognitive Decline Source: Healthnotes, Inc.; www.healthnotes.com Aids and Hiv 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 Amyloidosis Source: Integrative Medicine Communications; www.drkoop.com Angina Source: Healthnotes, Inc.; www.healthnotes.com Angioedema Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Arteriosclerosis Source: Integrative Medicine Communications; www.drkoop.com Ascariasis Source: Integrative Medicine Communications; www.drkoop.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Asthma 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 Benign Prostatic Hyperplasia Source: Integrative Medicine Communications; www.drkoop.com

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Bone Cancer Source: Integrative Medicine Communications; www.drkoop.com Bph Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Burns Source: Healthnotes, Inc.; www.healthnotes.com Burns Source: Integrative Medicine Communications; www.drkoop.com Cancer Prevention (reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention and Diet Source: Healthnotes, Inc.; www.healthnotes.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: Prima Communications, Inc.www.personalhealthzone.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 Colon Cancer Source: Healthnotes, Inc.; www.healthnotes.com

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Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Common Cold Source: Integrative Medicine Communications; www.drkoop.com Congestive Heart Failure Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Integrative Medicine Communications; www.drkoop.com Coronary Artery Disease Source: Integrative Medicine Communications; www.drkoop.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 Herpetiformis Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Emphysema Source: Integrative Medicine Communications; www.drkoop.com Epilepsy Source: Healthnotes, Inc.; www.healthnotes.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com

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Frostbite Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Healthnotes, Inc.; www.healthnotes.com Gastritis Source: Integrative Medicine Communications; www.drkoop.com Gestational Hypertension Source: Healthnotes, Inc.; www.healthnotes.com Guinea Worm Disease Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.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 Histoplasmosis Source: Integrative Medicine Communications; www.drkoop.com Hiv and Aids Source: Integrative Medicine Communications; www.drkoop.com Hiv and Aids Support Source: Healthnotes, Inc.; www.healthnotes.com Hives Source: Healthnotes, Inc.; www.healthnotes.com Hookworm Source: Integrative Medicine Communications; www.drkoop.com

112 Antioxidants

Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.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 Loiasis Source: Integrative Medicine Communications; www.drkoop.com Lung Cancer Source: Healthnotes, Inc.; www.healthnotes.com Lung Cancer Source: Integrative Medicine Communications; www.drkoop.com Lymphatic Filariasis 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

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Male Infertility Source: Prima Communications, Inc.www.personalhealthzone.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Miscarriage Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Night Vision (impaired) Source: Prima Communications, Inc.www.personalhealthzone.com Osteoarthritis Source: Healthnotes, Inc.; www.healthnotes.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Prima Communications, Inc.www.personalhealthzone.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 Peptic Ulcer Source: Healthnotes, Inc.; www.healthnotes.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Pericarditis Source: Integrative Medicine Communications; www.drkoop.com Peripheral Vascular Disease Source: Healthnotes, Inc.; www.healthnotes.com

114 Antioxidants

Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Phenylketonuria Source: Healthnotes, Inc.; www.healthnotes.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Photosensitivity Source: Healthnotes, Inc.; www.healthnotes.com Pinworm Source: Integrative Medicine Communications; www.drkoop.com Preeclampsia Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Healthnotes, Inc.; www.healthnotes.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com Prostate Enlargement Source: Integrative Medicine Communications; www.drkoop.com Prostate Infection Source: Integrative Medicine Communications; www.drkoop.com Prostatitis Source: Healthnotes, Inc.; www.healthnotes.com Prostatitis Source: Integrative Medicine Communications; www.drkoop.com Pulmonary Edema Source: Integrative Medicine Communications; www.drkoop.com Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.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

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Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com River Blindness Source: Integrative Medicine Communications; www.drkoop.com Roundworms Source: Integrative Medicine Communications; www.drkoop.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 Sexually Transmitted Diseases Source: Integrative Medicine Communications; www.drkoop.com Shock Source: Integrative Medicine Communications; www.drkoop.com Sickle Cell Anemia Source: Healthnotes, Inc.; www.healthnotes.com Sinusitis Source: Healthnotes, Inc.; www.healthnotes.com Skin Cancer Source: Integrative Medicine Communications; www.drkoop.com Spontaneous Abortion Source: Integrative Medicine Communications; www.drkoop.com Sprains and Strains Source: Integrative Medicine Communications; www.drkoop.com Stds Source: Integrative Medicine Communications; www.drkoop.com Stomach Inflammation Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com

116 Antioxidants

Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Temporomandibular Joint Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Threadworm Source: Integrative Medicine Communications; www.drkoop.com Tmj Source: Integrative Medicine Communications; www.drkoop.com Trichinosis Source: Integrative Medicine Communications; www.drkoop.com Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Uveitis Source: Integrative Medicine Communications; www.drkoop.com Varicose Veins Source: Prima Communications, Inc.www.personalhealthzone.com Viral Hepatitis Source: Prima Communications, Inc.www.personalhealthzone.com Visceral Larva Migrans Source: Integrative Medicine Communications; www.drkoop.com Whipworm Source: Integrative Medicine Communications; www.drkoop.com Wound Healing Source: Healthnotes, Inc.; www.healthnotes.com •

Alternative Therapy Apitherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,669,00.html Chelation Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,679,00.html Naturopathy Source: Integrative Medicine Communications; www.drkoop.com

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Nutrition Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements Agrimony Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,833,00.html Alpha Lipoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Alpha2-adrenergic Agonists Source: Integrative Medicine Communications; www.drkoop.com Alpha-lipoic Acid Source: Integrative Medicine Communications; www.drkoop.com Alpha-lipoic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10002,00.html Anthocyanins Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1026,00.html 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 Aralia Alternative names: Spikenard; Aralia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Arctostaphylos Alternative names: Bearberry; Arctostaphylos uva-ursi (L.) Spreng. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10006,00.html

118 Antioxidants

Barberry Alternative names: Berberis vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Barberry Alternative names: Berberis vulgaris, Berberry Source: Integrative Medicine Communications; www.drkoop.com B-carotene Source: Integrative Medicine Communications; www.drkoop.com Berberis Vulgaris Source: Integrative Medicine Communications; www.drkoop.com Berberry Source: Integrative Medicine Communications; www.drkoop.com Beta-blockers Source: Integrative Medicine Communications; www.drkoop.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 Beta-carotene Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10103,00.html Betacarotenum Source: Integrative Medicine Communications; www.drkoop.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Bilberry Alternative names: Vaccinium myrtillus Source: Healthnotes, Inc.; www.healthnotes.com Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com Bilberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10007,00.html Blackberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,837,00.html Blue-green Algae Source: Healthnotes, Inc.; www.healthnotes.com Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com Brahmi Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Camellia Sinensis Source: Integrative Medicine Communications; www.drkoop.com Capsaicin Source: Integrative Medicine Communications; www.drkoop.com Capsicum Frutescens Source: Integrative Medicine Communications; www.drkoop.com 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 Cat’s Claw Alternative names: Uncaria tomentosa Source: Healthnotes, Inc.; www.healthnotes.com Catechins Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1023,00.html

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Cayenne Alternative names: Capsicum frutescens, Capsicum spp., Capsaicin, Chili Pepper, Red Pepper Source: Integrative Medicine Communications; www.drkoop.com Centella Source: Integrative Medicine Communications; www.drkoop.com Centella Asiatica Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Chaparral Alternative names: Larrea tridentata Source: Healthnotes, Inc.; www.healthnotes.com Chaparral Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Cherry Fruit Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10015,00.html Chili Pepper Source: Integrative Medicine Communications; www.drkoop.com Chlorophyll Source: Healthnotes, Inc.; www.healthnotes.com Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Clozapine Source: Healthnotes, Inc.; www.healthnotes.com Coenzyme Q Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,768,00.html Coenzyme Q10 Source: Healthnotes, Inc.; www.healthnotes.com

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Coenzyme Q10 Source: Integrative Medicine Communications; www.drkoop.com Coenzyme Q10 (coq10) Source: Prima Communications, Inc.www.personalhealthzone.com Coq10 Source: Integrative Medicine Communications; www.drkoop.com Cranberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10019,00.html Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Crataegus Laevigata Source: Integrative Medicine Communications; www.drkoop.com Crataegus Monogyna Source: Integrative Medicine Communications; www.drkoop.com Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Curcuma Longa Source: Integrative Medicine Communications; www.drkoop.com Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Cysteine Source: Healthnotes, Inc.; www.healthnotes.com Cysteine Source: Integrative Medicine Communications; www.drkoop.com Dapsone Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (dhea) Source: Healthnotes, Inc.; www.healthnotes.com Dha Source: Integrative Medicine Communications; www.drkoop.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com

122 Antioxidants

Docosahexaenoic Acid (dha) Source: Integrative Medicine Communications; www.drkoop.com Doxorubicin Source: Healthnotes, Inc.; www.healthnotes.com Echinacea Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eicosapentaenoic Acid (epa) Source: Integrative Medicine Communications; www.drkoop.com Elderberry Alternative names: Sambucus nigra Source: Healthnotes, Inc.; www.healthnotes.com Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Epa Source: Integrative Medicine Communications; www.drkoop.com Fennel Source: Healthnotes, Inc.; www.healthnotes.com Fibric Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Flavonoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,782,00.html Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com Flurbiprofen Source: Healthnotes, Inc.; www.healthnotes.com Foeniculum Alternative names: Fennel; Foeniculum vulgare Mill Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gamma-oryzanol Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10028,00.html

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Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Biloba Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Ginseng (panax) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10029,00.html Glutamine Source: Healthnotes, Inc.; www.healthnotes.com Glutathione Source: Healthnotes, Inc.; www.healthnotes.com Glutathione Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,854,00.html Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gotu Kola Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com 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

124 Antioxidants

Grapefruit Seed Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,985,00.html Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Alternative names: Camellia sinensis Source: Integrative Medicine Communications; www.drkoop.com Green Tea Source: Prima Communications, Inc.www.personalhealthzone.com Green Tea Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10032,00.html Guggul Alternative names: Commiphora mukul Source: Healthnotes, Inc.; www.healthnotes.com Hawthorn Alternative names: Crataegus laevigata, Crataegus oxyacantha, Crataegus monogyna Source: Healthnotes, Inc.; www.healthnotes.com Hawthorn Alternative names: Crataegus monogyna, Crataegus laevigata Source: Integrative Medicine Communications; www.drkoop.com Hawthorn Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10035,00.html Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hydrocotyle Source: Integrative Medicine Communications; www.drkoop.com Indian Pennywort Source: Integrative Medicine Communications; www.drkoop.com Indole-3-carbinol Source: Healthnotes, Inc.; www.healthnotes.com

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Interferon Source: Healthnotes, Inc.; www.healthnotes.com Ip-6 Source: Healthnotes, Inc.; www.healthnotes.com Leonurus Alternative names: Motherwort; Leonurus cardiaca Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lepidium Sp Alternative names: Cress; Lepidium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Licorice Alternative names: Glycyrrhiza glabra, Glycyrrhiza uralensis Source: Healthnotes, Inc.; www.healthnotes.com Licorice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,801,00.html Lipoic Acid Source: Prima Communications, Inc.www.personalhealthzone.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com Lutein Source: Healthnotes, Inc.; www.healthnotes.com Lutein Source: Prima Communications, Inc.www.personalhealthzone.com Lycopene Source: Healthnotes, Inc.; www.healthnotes.com Lycopene Source: Prima Communications, Inc.www.personalhealthzone.com Lycopene Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,803,00.html Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com

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Marsh Pennywort Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Methionine Source: Healthnotes, Inc.; www.healthnotes.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Alternative names: Silybum marianum, Carduus marianus Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Alternative names: Silybum marianum, St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com Milk Thistle Source: Prima Communications, Inc.www.personalhealthzone.com Milk Thistle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10044,00.html Nac (n-acetylcysteine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,809,00.html N-acetyl Cysteine Source: Healthnotes, Inc.; www.healthnotes.com N-acetyl Cysteine (nac) Source: Prima Communications, Inc.www.personalhealthzone.com Ocimum Alternative names: Basil, Albahaca; Ocimum basilicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Opcs (oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com

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Origanum Alternative names: Oregano; Origanum vulgare Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Phenothiazine Derivatives Source: Integrative Medicine Communications; www.drkoop.com Picrorhiza Alternative names: Picrorhiza kurroa Source: Healthnotes, Inc.; www.healthnotes.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 Plantago Major Alternative names: Plantain; Plantago major/lanceolata Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Potentilla Alternative names: Cinquefoil, Silverweed; Potentilla sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Proanthocyanidins Source: Healthnotes, Inc.; www.healthnotes.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Pyruvate Source: Healthnotes, Inc.; www.healthnotes.com Red Pepper Source: Integrative Medicine Communications; www.drkoop.com Red Yeast Rice Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10054,00.html

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Resveratrol Source: Healthnotes, Inc.; www.healthnotes.com Resveratrol Source: Prima Communications, Inc.www.personalhealthzone.com Resveratrol Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1040,00.html Ribes Alternative names: Black Currant; Ribes nigrum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Rosemary Alternative names: Rosmarinus officinalis Source: Healthnotes, Inc.; www.healthnotes.com Rosmarinus Alternative names: Rosemary; Rosmarinus officinalis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Salicylates Source: Integrative Medicine Communications; www.drkoop.com Same Source: Healthnotes, Inc.; www.healthnotes.com Schisandra Source: Healthnotes, Inc.; www.healthnotes.com Silybum Alternative names: Milk Thistle; Silybum marianum (L.) Gaertn. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Silybum Marianum Source: Integrative Medicine Communications; www.drkoop.com Soy Isoflavones Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10057,00.html Spirulina Alternative names: Blue-green Algae Source: Integrative Medicine Communications; www.drkoop.com St. Mary's Thistle Source: Integrative Medicine Communications; www.drkoop.com

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Sulfonylureas Source: Integrative Medicine Communications; www.drkoop.com Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thiazide Diuretics Source: Integrative Medicine Communications; www.drkoop.com Thioxanthene Derivatives Source: Integrative Medicine Communications; www.drkoop.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 Tricyclic Antidepressants (tcas) Source: Integrative Medicine Communications; www.drkoop.com Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc.; www.healthnotes.com Turmeric Alternative names: Curcuma longa Source: Integrative Medicine Communications; www.drkoop.com Turmeric Source: Prima Communications, Inc.www.personalhealthzone.com Turmeric Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10062,00.html Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Valproic Acid Derivatives Source: Integrative Medicine Communications; www.drkoop.com Vasodilators Source: Integrative Medicine Communications; www.drkoop.com

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Vitis Vinifera Source: Integrative Medicine Communications; www.drkoop.com Wild Yam Alternative names: Dioscorea villosa Source: Healthnotes, Inc.; www.healthnotes.com Willow Bark Alternative names: There are several species of willow includingSalix alba, Salix nigra, Salix fragilis, Salix purpurea, Salix babylonica, White Willow, European Willow, Black Willow, Pussy Willow, Crack Willow, Purple Willow, Weeping Willow, Liu-zhi Source: Integrative Medicine Communications; www.drkoop.com Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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

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CHAPTER 4. DISSERTATIONS ON ANTIOXIDANTS Overview In this chapter, we will give you a bibliography on recent dissertations relating to antioxidants. 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 “antioxidants” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on antioxidants, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Antioxidants 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 antioxidants. 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: •

A Possible Role of Oxygen Metabolism in the Evolution of the Human Life Span: Antioxidants and Aging (genetics, Alzheimers Disease, Aging, Oxygen Radicals) by Delahunty, Dorothy Anne, Phd from Rutgers the State University of New Jersey - New Brunswick, 1984, 208 pages http://wwwlib.umi.com/dissertations/fullcit/8424097

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Antioxidant Assessment in Western Maine Elderly Women Following 30 Days of Wild Blueberry Consumption by Bagnulo, John David; Phd from University of Maine, 2003, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3087697

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Antioxidant Capacity and Identification of Polyphenolics in Plums and Chemical Structure-bioactivity Relationship by Kim, Dae-ok; Phd from Cornell University, 2003, 169 pages http://wwwlib.umi.com/dissertations/fullcit/3075804

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Antioxidant Defense in Exercised Skeletal Muscle of the Aging-delayed Ames Dwarf Mouse by Romanick, Mark Andrew; Phd from The University of North Dakota, 2002, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3058851

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Antioxidant Properties of Sorghum by Awika, Joseph Mobutu; Phd from Texas A&m University, 2003, 118 pages http://wwwlib.umi.com/dissertations/fullcit/3088114

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Antioxidant Protection Mechanisms and Arachidonic Acid Metabolism in Diabetic Rat Nerve and Schwann Cells Cultured in Elevated Glucose by Miinea, Cristinel Paul; Phd from University of Houston, 2002, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3048346

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Antioxidants, Nitric Oxide and Chronic Pancreatitis by Fredstrom, Susan Beth; Phd from University of Minnesota, 2002, 220 pages http://wwwlib.umi.com/dissertations/fullcit/3047627

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Biological Effects of Dietary Antioxidants from Almonds and Cocoa by Gonsalves, Jana L.; Phd from University of California, Davis, 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/3065249

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Biostability of Polyurethane Elastomers: Pacemaker Leads, Effect of Fatigue, and Novel Antioxidant Stabilizers by Wiggins, Michael John; Phd from Case Western Reserve University, 2002, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3058378

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Cigarette Smoking, Antioxidants and Fats and Primary Open-angle Glaucoma by Kang, Jae Hee; Sd from Harvard University, 2002 http://wwwlib.umi.com/dissertations/fullcit/f754561

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Copper Deficiency in Hl-60 Cells Increases Their Susceptibility to Apoptosis When Treated with Antioxidants by Raymond, Laura Jean; Phd from The University of North Dakota, 2002, 120 pages http://wwwlib.umi.com/dissertations/fullcit/3062875

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Development and Application of a Gc/ms Rapid Screening Method for Selected Endocrine Disruptors, Pharmaceuticals, Antioxidants, and Plasticizers by Soliman, Mary Attalah; Phd from University of California, Los Angeles, 2003, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3076637

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Diet, Lifestyle, Antioxidants, and Biomarkers of Cancer Risk: an Epidemiological Report from the Malmo Diet and Cancer Cohort (sweden) by Wallstrom, Peter; Phd from Lunds Universitet (sweden), 2002, 152 pages http://wwwlib.umi.com/dissertations/fullcit/f735553

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Dietary Antioxidants and Breast Cancer Survival by Fleischauer, Aaron Thomas; Phd from The University of North Carolina at Chapel Hill, 2002, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3046989

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Effect of Drying Technologies and Natural Rice Bran Oil Antioxidants on the Stability of Whole Milk Powder by Osorio, Luis Fernando; Phd from Clemson University, 2002, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3071564

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Effects of Dietary Antioxidants on Learning and Memory in Aged Beagle Dogs by Estrada, Jimena; Msc from University of Toronto (canada), 2002, 107 pages http://wwwlib.umi.com/dissertations/fullcit/MQ74104

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Effects of Lipoic Acid in Cats: Pharmacokinetics, Toxicity, and Antioxidant Activity by Hill, Ana Schmidt; Phd from University of California, Davis, 2002, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3074569

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Estimating Interfacial Urea and Antioxidant Concentrations by Zhang, Jianbing; Phd from Rutgers the State University of New Jersey - New Brunswick, 2003, 247 pages http://wwwlib.umi.com/dissertations/fullcit/3077123

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Honey As a Source of Natural Antioxidants by Gheldof, Nele Cecile Monique; Phd from University of Illinois at Urbana-champaign, 2002, 146 pages http://wwwlib.umi.com/dissertations/fullcit/3069996

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Immunological Modulation of Antioxidants in Side-stream Cigarette Smoke (sscs) Exposed Mice by Zhang, Jin; Phd from The University of Arizona, 2002, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3053916

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Isolation, Characterization and Pharmacokinetics of Antioxidants from Hawthorn by Chang, Qi; , Phd from Chinese University of Hong Kong (people's Republic of China), 2002, 225 pages http://wwwlib.umi.com/dissertations/fullcit/3052124

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Optimization of Antioxidant Additives in Carbon-containing Castables by He, Huiqing; Phd from Ecole Polytechnique, Montreal (canada), 2002, 239 pages http://wwwlib.umi.com/dissertations/fullcit/NQ71311

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Phenolic Antioxidants in Wood Smoke by Kjallstrand, Jennica Maria; Phd from Chalmers Tekniska Hogskola (sweden), 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/f692081

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Phenolic Compounds in Mentha Spicata: Quanitification, Identification and Antioxidant Activity by Mcauley, Colette Yvonne; Msc from University of Guelph (canada), 2002, 117 pages http://wwwlib.umi.com/dissertations/fullcit/MQ67365

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Polymorphism in Manganese Superoxide Dismutase, Antioxidant Intake and Allcause, Cancer and Cardiovascular Disease Mortality by Genkinger, Jeanine Marie; Phd from The Johns Hopkins University, 2003, 268 pages http://wwwlib.umi.com/dissertations/fullcit/3080663

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Progression of Carotid Intima-media Thickness and Plasma Antioxidants: the Los Angeles Atherosclerosis Study (california) by Fan, Jing; , Ms from University of Southern California, 2002, 26 pages http://wwwlib.umi.com/dissertations/fullcit/1411785

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Studies on Genetic, Cytogenetic and Radiosensitizing Effects of Phenolic Antioxidants in Drosophila Melanogaster and the Mouse by Gollapudi, Bala Bhaskar; Phd from Dalhousie University (canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK48191

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Syntheses and Structure-activity Relationships of Plant Antioxidant Caffeic Acid Amides and Esters. Possible Roles in Nutraceuticals and Functional Foods by Son, Sopheak; Phd from Cornell University, 2003, 193 pages http://wwwlib.umi.com/dissertations/fullcit/3075901

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Synthesis and Kinetic Testing of Novel Antioxidants by Babic, Gordana; Msc from University of Ottawa (canada), 2003, 149 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76509

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The Role of Antioxidants in Cardiac and Skeletal Muscle during Conditions of Energy Deficit by Klawitter, Paul F.; Phd from The Ohio State University, 2002, 140 pages http://wwwlib.umi.com/dissertations/fullcit/3039490

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The Synergistic Effect of Conventional and Sustained Delivery of Antioxidants on Lncap Prostate Cancer Cell Line by Richards, La'toya Ross; Ms from The University of Mississippi Medical Center, 2002, 86 pages http://wwwlib.umi.com/dissertations/fullcit/1408845

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Transformation of Bioactive Diterpene Lactone Andrographolides from Andrographis Paniculata Nees by Superoxide Radical in Vitro: Structure of Reaction Products and Antioxidant Mechanism of Andrographolides by Kamdem, Ricky Emery Ouaffo; Phd from Rutgers the State University of New Jersey - New Brunswick, 2002, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3066720

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Use of Electrochemically-induced Oxidation As an Evaluation Method for Low Molecular Weight Antioxidants by Dong, Yijie; Phd from Rutgers the State University of New Jersey - New Brunswick, 2003, 192 pages http://wwwlib.umi.com/dissertations/fullcit/3077096

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.

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

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

Laser and Antioxidant Treatment of Diabetic Macular Edema Condition(s): Macular Edema; Diabetes Mellitus Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will compare the side effects of two laser treatments for diabetic macular edema, a common condition in patients with diabetes. In macular edema, blood vessels in the retina-a thin layer of tissue that lines the back of the eyebecome leaky and the retina swells. The macula-the center part of the retina that is responsible for fine vision-may also swell and cause vision loss. Traditional laser treatment (argon blue or green, or yellow) for macular swelling, or edema, causes scarring that can expand and possibly lead to more loss of vision. A different type of laser (diode) may have less damaging effects to the eye and fewer long-term adverse effects, but this is not known. The results of this study on side effects of the treatments will be used to design a larger study of effectiveness. The study will also examine whether vitamin E can reduce the damage caused by laser treatment. Patients with elevated cholesterol levels will be invited to participate in a cholesterol reduction part of the study to compare normal-pace cholesterol reduction with accelerated reduction. Patients 18 years of age and older with type 1 or type 2 diabetes and macular edema may be eligible for this study. Candidates will be screened with the following tests and procedures: - Medical history and physical examination. - Eye examination to assess visual acuity (eye chart test) and eye pressure, and to examine pupils, lens, retina and

8

These are listed at www.ClinicalTrials.gov.

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eye movements. The pupils will be dilated with drops for this examination. - Blood tests to measure cholesterol and vitamin E blood levels, blood clotting time, hemoglobin A1C (a measure of diabetes control), and to evaluate liver and kidney function. - Eye photography to help evaluate the status of the retina and changes that may occur in the future. Special photographs of the inside of the eye are taken using a camera that flashes a bright light into the eye. - Fluorescein angiography to evaluate the eye's blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality. - Multifocal electroretinogram to measure electrical responses generated within the retina. The test, which takes about 1-1/2 hours, is painless. Participants will be randomly assigned to take 1600 IU of vitamin E or placebo (an inactive, look-alike pill) daily. After taking the pills for 3 months or more, patients who require laser treatment will be randomly assigned to one of the two laser therapies. (Patients with macular edema in both eyes will receive both treatments, one in each eye.) For these procedures, eye drops are put in the eye to numb the surface and a contact lens is placed on the eye during the laser beam application. Several visits may be required for additional laser treatments. The maximum number of treatments depends on how well they are working. Patients will return for follow-up visits 1, 3, and 6 months after the first treatment, and then every 6 months until either the patient returns for a 3-year visit; the last enrolled patient returns for the 1-year visit; or the patient requests to leave the study. During the follow-up visits, patients' response to treatment will be evaluated with repeat tests of several of the screening exams. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055042 •

Study of antioxidants and oxidants in malnourished children Condition(s): Protein-Energy Malnutrition; Kwashiorkor; Marasmus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: It is believed that the organs of severely malnourished children malfunction because harmful compounds called oxidants injure the tissues in these organs. In a healthy person oxidants are made harmless because another compound called glutathione neutralizes them. Glutathione is made from three amino acids that we get from the protein we eat in our food. We found that malnourished children were not making enough glutathione because they lacked one of these amino acids called cysteine. In this study we determine why malnourished children do not have sufficient cysteine, and we will feed malnourished children a whey-based diet which is rich in cysteine during their treatment to determine whether they will make more glutathione. This in turn may make their organs recover faster. These findings will let us know whether malnourished children can recover faster if they are given more cysteine during the early phase of treatment. Phase(s): Phase I; MEDLINEplus consumer health information Study Type: Interventional Contact(s): see Web site below

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Web Site: http://clinicaltrials.gov/ct/show/NCT00069134 •

Intimal Thickening and Antioxidants in Hispanics and Anglos (Los Angeles Atherosclerosis Study) Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate the role of serum and dietary antioxidants, serum prooxidants, and smoking on the progression/regression of carotid intima-media thickness (IMT). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005372

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Women's Antioxidant and Cardiovascular Study (WACS) Condition(s): Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Infarction; Myocardial Ischemia Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if supplements of vitamin C, vitamin E, and betacarotene reduce all major cardiovascular events in high risk women with a prior history of atherosclerotic cardiovascular disease. The trial is piggybacked on the Women's Health Study (WHS), a primary prevention trial of vitamin Eand aspirin in a low risk population of women. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000541

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A Study to See if Certain Antioxidants and Vitamins Will Keep Lactate Levels Down in Patients Taking Anti-HIV Drugs Condition(s): HIV Infections Study Status: This study is terminated. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if certain vitamins (C, E, B1, and B2) can keep lactate levels from becoming too high in patients who are taking nucleoside reverse transcriptase inhibitor (NRTI) anti-HIV drugs. Some patients taking anti-HIV drugs develop hyperlactatemia. Hyperlactatemia is a condition in which lactate (a natural substance normally present in the body) levels are too high. Too much lactate in the body can lead to serious health problems. When patients suffer from hyperlactatemia while taking anti-HIV drugs, most doctors temporarily stop the drugs. Patients then restart the anti-HIV drugs when their lactate levels return to normal. If patients restart the same drugs they were taking when they developed hyperlactatemia, there is a risk that they may develop high lactate levels again. This study wants to find

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out if taking antioxidants (substances that reduce tissue damage due to oxygen radicals) and certain B vitamins may help prevent patients from developing hyperlactatemia when they restart the same anti-HIV drugs. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037063 •

Antioxidant Functions of Lipoic Acid Condition(s): Hypercholesterolemia Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The goal of this study is to determine whether a short treatment with lipoic acid, an antioxidant used in the treatment of diabetic neuropathy, improves blood vessel reactivity and decreases oxidant stress in persons with elevated blood cholesterol. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065624

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Antioxidants and Prevention of Early Atherosclerosis Condition(s): Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Heart Diseases; Vascular Diseases; Atherosclerosis Study Status: This study is suspended. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the effects of vitamin E supplementation in retarding the progression of common carotid artery intima-media thickening in African Americans. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000600

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Dietary Antioxidants and Atherosclerosis Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Carotid Stenosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the role of dietary antioxidants in the etiology of atherosclerosis in both sexes and in whites and Blacks. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005412

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Effects of Herbal Antioxidants on cardiovascular disease in Older Blacks Condition(s): Cardiovascular Diseases Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM); National Heart, Lung, and Blood Institute (NHLBI); National Institute on Aging (NIA) Purpose - Excerpt: Older African Americans suffer from disproportionately high rates of cardiovascular disease (CVD) morbidity and mortality. In response to the health disparity between older African Americans and whites, national mandates have called for new research on innovative approaches to CVD prevention in this high risk population. Oxidative stress has recently been implicated in the pathogenesis of atherosclerotic CVD. Available evidence from epidemiological studies, clinical trials, and laboratory mechanistic studies indicate that antioxidant interventions may be useful in the prevention and treatment of atherosclerotic CVD in high risk older populations. Furthermore, it has been hypothesized that dietary or food sources of antioxidant nutrients may be more clinically effective than conventional nonfood-derived vitamin supplementation. Surveys indicate relatively high rates of complementary and alternative medicine (CAM) use, including herbal medicines, in older African Americans. Yet, with the exception of the previous clinical trials of the present Center team, there have been few controlled studies on CAM therapies in older African Americans and no previous controlled studies on efficacy and mechanisms of herbal antioxidants for the prevention of CVD in this high risk population. Preliminary studies have found that a CAM herbal preparation (MAK) derived from traditional Vedic medicine demonstrates potent antioxidant and anti-atherogenic effects in laboratory and pilot human studies. Therefore, the overall goal of the proposed study is to evaluate the effects of this traditional CAM herbal preparation compared to conventional nonfoodderived vitamin supplementation and placebo on pathophysiological markers of CVD in high risk older African Americans. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010725

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 “antioxidants” (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

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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/

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

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

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

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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

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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

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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

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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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/

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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

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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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

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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

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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

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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

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CHAPTER 6. PATENTS ON ANTIOXIDANTS 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 “antioxidants” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on antioxidants, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Antioxidants By performing a patent search focusing on antioxidants, 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 will tell you how to obtain this information later in the chapter. The following is an 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on antioxidants: •

Adhesive compositions containing graft copolymers Inventor(s): Lau; Willie (Ambler, PA), Van Rheenen; Paul Ralph (Warminster, PA) Assignee(s): Rohm and Haas Company (Philadelphia, PA) Patent Number: 6,589,651 Date filed: September 13, 2001 Abstract: The present invention provides adhesive compositions, particularly pressure sensitive adhesive compositions, comprised of from 30 weight percent to 70 weight percent of water insoluble graft copolymers dispersed in an aqueous medium. The graft copolymers are comprised of (i) from 1 weight percent to 30 weight percent of macromonomer, based on the total weight of the copolymer, wherein the macromonomer is water insoluble and has a number average molecular weight of from 2,000 to 50,000 g/mole and comprises from 85 to 100 weight percent polymerized units of at least one first ethylenically unsaturated monomer, 5 mole percent or less of polymerized mercapto-olefin compounds, and 10 weight percent or less polymerized acid-containing monomer; and (ii) from 70 weight percent to 99 weight percent of polymerized units of at least one second ethylenically unsaturated monomer, based on the total weight of the copolymer. In certain preferred embodiments, the adhesive compositions further comprise from 0.1 to 60 weight percent solids of at least one additive. The additive is selected from the group consisting of emulsifiers, defoamers, tackifiers, pigments, humectants, fillers, curing agents, thickeners, wetting agents, biocides, adhesion promoters, colorants, waxes, UV stabilizers, and antioxidants. Excerpt(s): The present invention relates generally to improved adhesive compositions. More particularly, the present invention relates to improved pressure sensitive adhesive compositions containing graft copolymers. Adhesives have been used since antiquity to hold substrates together via surface attachment. The term "adhesive", as used herein, is a substance that is typically a liquid or tacky semisolid, or at least for an instant to contact and wet a surface, and be applied in a relatively thin layer to form a useful joint capable of transmitting stresses from one substrate to another. The term "pressure sensitive", as used herein, refers to adhesives which typically do not undergo hardening after they have been applied to the surface of the substrate and the joint is formed. These adhesives are capable of holding substrates together when the surfaces are mated under briefly applied pressure at room temperature. The properties of tack, peel strength and shear resistance, which are frequently mutually exclusive properties, may be highly important in tailoring an adhesive composition that is suitable for a particular application. Tack is a measure of viscous flow under conditions of fast strain rates and low stress magnitudes and generally relates to the initial attraction of an adhesive to a substrate. Peel strength is a measure of resistance to flow at intermediate strain rates and moderate to high stress magnitudes and generally relates to the measure of bond strength between an adhesive and a substrate. Shear resistance is a measure of resistance to flow at intermediate stress magnitudes and generally relates to the internal or cohesive strength of an adhesive. Web site: http://www.delphion.com/details?pn=US06589651__

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Bis(alkyleneoxybenzophenone) ultraviolet light absorbers Inventor(s): Sassi; Thomas Patrick (Stamford, CT) Assignee(s): Cytec Technology Corp. (Wilmington, DE) Patent Number: 6,537,670 Date filed: November 3, 2000 Abstract: The present invention relates to novel bisbenzophenones and the use thereof as an ultraviolet light absorber. The presently claimed compounds are particularly useful, either alone or in combination with other additives, including other ultraviolet light absorbers, antioxidants and stabilizers, in stabilizing polymers and other materials from degradation by environmental forces such as actinic radiation (ultraviolet light), oxidation, moisture, atmospheric pollutants and combinations thereof. Excerpt(s): This invention relates to bis(alkyleneoxybenzophenone) compositions which are particularly useful as stabilizers for photodegradable polymers against the degradative action of ultraviolet (UV) light. It is well known that UV light or radiation, particularly from sunlight, can cause degradation of polymers. Often this results in the embrittlement or yellowing of polymers, which may be in the form of molded articles, extruded articles, polymer films, fibers, tapes, coatings, and the like. This degradation can be inhibited by the incorporation of stabilizers which retard photooxidative degradation on weathering. Derivatives of benzophenones, benzotriazoles, triazines, benzoxazinones and other compounds have been widely used for the protection of such polymeric materials. The effectiveness of such UV absorbers is reduced if they readily migrate and/or volatilize out of the polymeric substrate, during manufacture and/or use of said substrate. Loss of the absorbers by these mechanisms may be particularly high in certain types of articles, such as stabilized thin films, or in capstock applications. In the latter approach, a thin layer with a very large concentration of the absorber is applied to the top of a molded article by any of several means, in order to protect that article from UV light-induced degradation. The high concentration of absorber in a thin layer, processed at relatively high temperatures, gives a higher likelihood that loss of the absorber will occur. Certain properties of the absorbers themselves are likely to cause greater loss from the substrates during manufacture and/or use. These properties include high volatility, low compatibility with the polymer, water solubility, as well as other characteristics. Absorbers with low volatility (usually those with higher molecular weight), and high polymer solubility/compatibility will be more likely to stay in the polymer during manufacture and throughout the lifetime of the polymer. Of course, these absorbers should also possess other characteristics that are important for effectiveness as stabilizers, such as low initial color in the polymer and prevention of tensile strength reduction during weathering. They should not cause adverse effects, such as significant reduction of molecular weight of the polymer. Web site: http://www.delphion.com/details?pn=US06537670__

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Canola oil having increased oleic acid and decreased linolenic acid content Inventor(s): DeBonte; Lorin R. (Fort Collins, CO), Hitz; William D. (Wilmington, DE) Assignee(s): Cargill, Incorporated (Minneapolis, MN) Patent Number: 6,583,303 Date filed: September 28, 2001

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Abstract: An endogenous oil extracted from Brassica seeds is disclosed that contains, after crushing and extraction, greater than 86% oleic acid and less than 2.5%.alpha.linolenic acid. The oil also contains less than 7% linoleic acid. The Brassica seeds are produced by plants that contain seed-specific inhibition of microsomal oleate desaturase and microsomal linoleate desaturase gene expression. Such inhibition can be created by cosuppression or antisense technology. Such an oil has a very high oxidative stability in the absence of added antioxidants. Excerpt(s): This invention relates to a Brassica canola oil having an elevated oleic acid content and a decreased linolenic acid profile in the seed oil. The invention also relates to methods by which such an oil may be produced. Diets high in saturated fats increase low density lipoproteins (LDL) which mediate the deposition of cholesterol on blood vessels. High plasma levels of serum cholesterol are closely correlated with atherosclerosis and coronary heart disease (Conner et al., Coronary Heart Disease: Prevention, Complications, and Treatment, pp. 43-64, 1985). By producing oilseed Brassica varieties with reduced levels of individual and total saturated fats in the seed oil, oil-based food products which contain less saturated fats can be produced. Such products will benefit public health by reducing the incidence of atherosclerosis and coronary heart disease. The dietary effects of monounsaturated fats have also been shown to have dramatic effects on health. Oleic acid, the only monounsaturated fat in most edible vegetable oils, lowers LDL as effectively as linoleic acid, but does not affect high density lipoproteins (HDL) levels (Mattson, F. H., J. Am. Diet. Assoc., 89:387-391, 1989; Mensink et al., New England J. Med., 321:436-441, 1989). Oleic acid is at least as effective in towering plasma cholesterol as a diet low in fat and high in carbohydrates (Grundy, S. M., New England J. Med., 314:745-748, 1986; Mensink et al., New England J. Med., 321:436-441, 1989). In fact, a high-oleic acid diet is preferable to low fat, high carbohydrate diets for diabetics (Garg et al., New England J. Med., 319:829-834, 1988). Diets high in monounsaturated fats are also correlated with reduced systolic blood pressure (Williams et al., J. Am. Med. Assoc., 257:3251-3256, 1987). Epidemiological studies have demonstrated that the "Mediterranean" diet, which is high in fat and monounsaturates, is not associated with coronary heart disease. Web site: http://www.delphion.com/details?pn=US06583303__ •

Carotenoid esters Inventor(s): Binnington; Richard H. (17 Castle Road, Sandal Wakefield West Yorkshire, WF2 7LU, GB), Levy; Luis W. (c/o Inexa, Industria Extractora C.A., P.O. Box 17-03-4581, Quito, EC), Tabatznik; Anthony S. (75 Sheringham, Queensmead, St John's Wood Park, London, NW8 6RB, GB) Assignee(s): none reported Patent Number: 6,540,654 Date filed: February 22, 2002 Abstract: Monoesters, diesters and polyesters are provided wherein both the acidderived moiety and the alcohol-derived moiety of the esters are carotenoid compounds. The synthetic ester linkage between two or more carotenoids provides new compounds in which the similar and complementary properties of the individual carotenoids are combined. The new all-carotenoid esters may be useful as antioxidants, therapeutic agents, pigmenting ingredients in poultry feed or as coloring agents for fats. The polyesters have the potential to act as molecular wires with unique electrical conductance characteristics. The all-carotenoid esters may be prepared from the

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esterification of at least one hydroxy carotenoid with at least one carboxylic carotenoid, or via the reaction of the acid chloride of a carboxylic carotenoid with a hydroxy carotenoid. Preferred hydroxy carotenoids include lutein, zeaxanthin, cryptoxanthin, violaxanthin, carotene diol, hydroxy carotene, hydroxylycopene, alloxanthin and dehydrocryptoxanthin. Preferred carboxylic carotenoids include bixin, norbixin,.beta.apo-8-carotenoic acid, crocetin, diapocarotenoic acid, carboxylcarotene and azafrin. Excerpt(s): The carotenoids are important natural products which are involved in the photosynthetic process of plants. Carotenoids are used as nutritional supplements for animals and humans, as well as in food colorants and cosmetics. Although carotenoids are important for health, animals and humans cannot produce them, and these compounds must thus be obtained through diet from fruits and vegetables. Several properties of the carotenoids make them important for the health of both animals and humans. For example, these compounds are antioxidants with important quenching effects on free radicals. They protect living tissues against a variety of diseases, either directly or as immunopotentiators. Additionally, carotenoids are involved in gapjunction communication among living cells. Recent epidemiological evidence has suggested an inverse relationship between the consumption of fruits and vegetables with high carotenoid content and the incidence of several types of cancers. Specifically,.beta.-carotene, lutein and lycopene have been shown to exhibit a cancerprevention effect (M. M. Mathews-Roth, Current Chemotherapy and Infectious Diseases (J. D. Nelson and C. Grassi, Eds, Am. Soc. Microbiol., Washington D.C.:1503-1505(1980)); B. P. Chew et al, Anticancer Research 16:3689-3694 (1996); P. H. Gann et al, Cancer Res. 59:1225-1230 (1999)). Additionally, several carotenoids, such as lutein and zeaxanthin, have specific functions in the retina of the eye to assure healthy vision in several animal species, including humans (J. D. Landrum et al., Archives Biochem. Biophys. 385(1):2840(2001)). Finally, some carotenoids have pro-vitamin A activity, whereas others control reproduction and fertility, upregulate the Connexin43 gene, decrease the risk of degenerative disease and prevent coronary heart disease (N. Krinsky, Pure and Appl. Chem. 66(5):1003-1010 (1994)). Web site: http://www.delphion.com/details?pn=US06540654__ •

Cosmetic and dermatological formulations comprising flavonoids Inventor(s): Lanzendorfer; Ghita (Hamburg, DE), Stab; Franz (Echem, DE), Untiedt; Sven (Hamburg, DE) Assignee(s): Beiersdorf AG (Hamburg, DE) Patent Number: 6,562,794 Date filed: March 30, 2000 Abstract: The invention relates to cosmetic and dermatological formulations havinga) a content of a compound or several compounds from the group consisting of flavonoids, or havingb) a content of an active compound combination comprising a compound or several compounds chosen from the group consisting of flavonoids in combination with a compound or several compounds chosen from the group consisting of cinnamic acid derivatives andc) if appropriate an additional content of a compound or several compounds from the group consisting of antioxidants. Excerpt(s): The present invention relates in particular to cosmetic and dermatological formulations comprising flavonoids, their glycosides and, if appropriate, combinations thereof with cinnamic acid derivatives or antioxidants. The damaging effect of the

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ultraviolet component of solar radiation on the skin is generally known. While rays having a wavelength below 290 nm (the so-called UVC range) are absorbed by the ozone layer in the earth's atmosphere, rays in the range between 290 nm and 320 nm, the so-called UVB range, cause erythema, simple sunburn or even burns of greater or lesser severity. The narrower range around 308 nm is stated as the maximum for the erythema activity of sunlight. Web site: http://www.delphion.com/details?pn=US06562794__ •

Cyclic organoselenium compounds, their preparation and their uses Inventor(s): Chaudiere; Jean (Saint Maur des Fosses, FR), Erdelmeier; Irene (Paris, FR), Moutet; Marc (Bagneux, FR), Tailhan-Lomont; Catherine (Boissise-le-Roi, FR), Yadan; Jean-Claude (Montreuil, FR) Assignee(s): Oxis Isle of Man, Limited (Douglas, GB) Patent Number: 6,525,040 Date filed: May 16, 2000 Abstract: The invention is directed to novel cyclic organoselenium compounds useful as antioxidants, pharmaceutical compositions containing them, and methods for their preparation. Excerpt(s): This application is a 371 of PCT/EP97/07295 filed Dec. 23, 1997. a method of preparation of said novel compounds. In aerobic organisms, during the metabolism of oxygen, very reactive entities are generated whose accumulation causes deleterious effects. These organisms possess a system of regulation, composed of enzymes and small is molecules which enable controlling the production of these reactive oxygen entities. Amongst the various components of this regulation system, often called Antioxidant Defense System, glutathione peroxidases play a central role in the prevention of oxidative stress and its deleterious consequences. These antioxidant and cytoprotecting enzymes enable degrading the endogenous or exogenous cytotoxic hydroperoxides. Web site: http://www.delphion.com/details?pn=US06525040__

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Dimethicone copolyol cranberriate as a delivery system for natural antioxidants Inventor(s): Klein; Kenneth (Fair Lawn, NJ), O'Lenick, Jr.; Anthony J. (Docula, GA), Paleksky; Irwin (Fairfield, NJ) Assignee(s): Zenitech LLC (Old Greenwich, CT) Patent Number: 6,646,144 Date filed: November 4, 2002 Excerpt(s): The present invention relates to cranberry seed oil derivatives derived by the reaction of dimethicone copolyol and cold pressed cranberry seed oil. The choice of cold pressed cranberry seed oil as a raw material in the preparation of the compounds of the present invention is critical, since it has been found that the cold pressed cranberry seed oil contains antioxidants, antimicrobial compounds and which when reacted with a water soluble or water dispersible silicone result in products that deliver said actives to the skin and hair, resulting in protection of the skin and hair from environmental factors such as acid rain, ozone attack and UV degradation. U.S. Pat. No. 6,391,345 issued May

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2002 describes the refining of cold pressed cranberry seed oil, and is incorporated herein by reference. American cranberries, Vaccinium macrocarpon, are native plants of open, acid peat bogs in North America. Cranberry plants are evergreen perennial vines that produce runners and upright branches with terminal flower buds. Cranberries have historically been harvested and either ingested as whole berries, such as in cranberry sauce, or have been processed for their juice. Pulp remaining after cranberry juice extraction processing has historically been regarded as an undesirable waste product with little or no utility. Web site: http://www.delphion.com/details?pn=US06646144__ •

Dimethicone copolyol raspberriate as a delivery system for natural antioxidants Inventor(s): Klein; Kenneth (Fair Lawn, NJ), O'Lenick, Jr.; Anthony J. (Dacula, GA), Paleksky; Irwin (Clifton, NJ) Assignee(s): Zenitech LLC (Old Greenwich, CT) Patent Number: 6,630,180 Date filed: November 12, 2002 Abstract: The invention relates to raspberry seed oil derivatives prepared by the reaction of dimethicone copolyol and cold pressed raspberry seed oil. The choice of cold pressed raspberry seed oil as a raw material in the preparation of the compounds is critical, since it has been found that the cold pressed raspberry seed oil contains antioxidants, antimicrobial compounds and which when reacted with a water soluble or water dispersible silicone result in products that deliver said actives to the skin and hair, resulting in protection of the skin and hair from environmental factors such as acid rain, ozone attack and UV degradation. Excerpt(s): The present invention relates to raspberry seed oil derivatives derived by the reaction of dimethicone copolyol and cold pressed raspberry seed oil. The choice of cold pressed raspberry seed oil as a raw material in the preparation of the compounds of the present invention is critical, since it has been found that the cold pressed raspberry seed oil contains a unique antioxidant which when reacted with a water soluble or water dispersible silicone result in products that deliver said actives to the skin and hair, resulting in protection of the skin and hair from environmental factors such as acid rain, ozone attack and UV degradation. U.S. Pat. No. 6,391,345 issued May 2002 describes the refining of cold pressed raspberry seed oil, and is incorporated herein by reference. American cranberries, Vaccinium macrocarpon, are native plants of open, acid peat bogs in North America. Raspberry plants are evergreen perennial vines that produce runners and upright branches with terminal flower buds. Raspberries have historically been harvested and either ingested as whole berries, such as in raspberry sauce, or have been processed for their juice. Pulp remaining after raspberry juice extraction processing has historically been regarded as an undesirable waste product with little or no utility. Web site: http://www.delphion.com/details?pn=US06630180__

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Fertility kit Inventor(s): Sweazy; Jill A. (1747 Village Park Dr., Orangeburg, SC 29118), Sweazy; Scott M. (1747 Village Park Dr., Orangeburg, SC 29118) Assignee(s): none reported Patent Number: 6,610,331 Date filed: May 30, 2002 Abstract: A method and kit for enhancing the natural fertility process. The kit includes a vaginal douche that is used prior to intercourse to enhance the sperm transportation and sustaining properties of the cervical mucous. The douche contains a balanced electrolyte solution, polysaccharides, and pH buffers. The kit also includes nutriceuticals specifically formulated for both the male and female which include amino acids, minerals, vitamins, herbs, phytoestrogens, and antioxidants along with a specified dosing regimen. A basal body temperature thermometer and chart is provided with instructions to confirm when and if ovulation will/did occur. Commercially available urinary chemical reagent strips are provided with instructions so as to predict/confirm if and when ovulation will occur. A lubricating medium will also be provided and utilized at the time of intercourse which is nonspermicidal and which contains polysaccharides which influence natural sperm motility. A detailed instruction book regarding the method and practice is provided along with dietary and lifestyle recommendations which have been shown to affect natural fertility. Excerpt(s): The present invention relates generally to a fertility kit used to enhance the natural fertility potential of both the male and female partner. It utilizes naturally occurring vitamins, minerals, herbs, and saccharides to assist with the normal ovulatory cycle in the female, improve the physicochemical properties of the cervical mucus, and improve the production of sperm in men along with improving the quality of the ejaculatory fluid derived from the prostate gland and seminal vesicles. Approximately 15 % of all married couples experience some form of infertility. Primary infertility occurs in a couple in which a child has not been successfully conceived for a period of greater than one year while performing intercourse during an appropriate schedule. Secondary infertility occurs in a couple which has previously successfully conceived and who has failed to subsequently conceive. Approximately 40 % of all infertility problems are associated with a male factor, 40 % are associated with a female factor, and the remaining 20 % occur in couples when either both partners have an identifiable infertility cause or there is no identifiable reason in either partner that explains their infertility. Male factor infertility may be the result of complete lack of sperm production, azoospermia, which may be the result of primary testicular failure or secondary testicular failure resulting from a previous disease such as the mumps or secondary to chemotherapy administration. Other causes include obstruction of the vas deferen or ejaculatory ducts. Greatly diminished sperm production, oligospermia, may be the result of similar problems or secondary to spermatogenic problems at the level of the testicles. Web site: http://www.delphion.com/details?pn=US06610331__

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Instant granules and process for their formulation Inventor(s): Gergely; Gerhard (Vienna, AT), Gergely; Irmgard (Vienna, AT) Assignee(s): Dr. Gergely & Co. (Vienna, AT) Patent Number: 6,645,529 Date filed: June 5, 2001 Abstract: The pharmaceutical formulation according to the invention is in the form of instant granules, in which the surface of the particles of at least two different soluble carrier materials is covered or coated with at least one layer which contains -of from 50 to 120, preferably from about 60 to about 100, parts by weight of active substance per 100 parts by weight of carrier material -of at least one, preferably insoluble or slightly soluble, active substance, such as amino acids or antioxidants. A first carrier material constitutes from about 50 to about 80% by weight of the total carrier material and is selected from carrier materials having a bulk density of between 58 and 100, preferably between 63 and 90 g/100 ml, while the second carrier material is selected from carrier materials having a bulk density of between 30 to 55, preferably between 33 and 50 g/100 ml. Excerpt(s): The invention relates to a pharmaceutical formulation in the form of instant granules according to the precharacterizing clause of claim 1. Such a formulation is described, for example, in EP-B1-232,277. Said publication discusses the fact that, according to the invention, an amino acid (e.g. tryptophane in Example 1) can be processed as an active substance or a plurality of active substances (e.g. vitamins and mineral salts in Example 2, applied to a carrier material comprising acid, which presents a problem for kidney patients) can be processed, it also being stated that a plurality of layers can be applied to the granular carrier material of soluble carbohydrate by means of a binder solution, for anchoring relatively large amounts of active substance. This last proposal is subject to limits in practice, especially in the case of amino acids, unless special measures are taken. In particular, it has been found that, for amounts of active substance which are greater than the amounts occurring in the examples mentioned in EP-B1-232,277 and for active substances which are very bulky, the active substances on the carbohydrate carriers cannot be sufficiently anchored by the binder layer alone and too much active substance remains free, with the result that neither the desired suspension property nor the flowability of the product can be satisfactorily achieved. In the case of amounts of active substance of from 60 to 100 parts by weight--based on 100 parts by weight of carrier--undesired agglomerations of the active substance occur when the binder is applied repeatedly, so that, on introduction into water, the desired suspension is no longer achievable and the particles sink to the bottom or remain on the surface of the water. Web site: http://www.delphion.com/details?pn=US06645529__

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Lipoic acid derivatives, their preparation, and pharmaceutical compositions containing them Inventor(s): Auguet; Michel (Palaiseau, FR), Chabrier de Lassauniere; Pierre-Etienne (Paris, FR), Harnett; Jeremiah (Gif-sur-Yvette, FR) Assignee(s): Societe de Conseils de Recherches et d'Applications Scientifiques (FR) Patent Number: 6,605,637 Date filed: September 27, 2001

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Abstract: The invention concerns novel lipoic acid derivatives, which have an inhibiting action with respect to NO-synthase enzymes producing nitrogen monoxide NO and/or are agents enabling the regeneration of antioxidants or entities trapping reactive oxygen species (ROS) and intervening in a more general manner in the redox status of thiol groups. The invention also concerns methods for preparing them, pharmaceutical compositions containing them and their use for therapeutic purposes, particularly their use as NO-synthase inhibitors and/or as agents acting more generally in the redox status of thiol groups. Excerpt(s): This application is a 371 of PCT/FR00/00814 filed Mar. 31, 2000. A subject, of the present invention is new derivatives of lipoic acid, which have an inhibitory activity on NO-synthase enzymes producing nitrogen monoxide NO and/or are agents which allow the regeneration of antioxidants or entities which trap the reactive oxygen species (ROS) and which intervene in a more general fashion in the redox status of thiol groups. These antioxidants or entities which trap the reactive oxygen species can be of natural origin, such as for example vitamin E or glutathione, or of synthetic origin such as certain products which trap the ROS or products having both an inhibitory activity on NO-synthase enzymes and an activity which traps the ROS. Examples of such products of synthetic origin can in particular be found in the PCT Patent Applications WO 96/09653, WO 98/42696 and WO 98/58934. Therefore, the invention relates in particular to the derivatives corresponding to general formula (I) defined below, their preparation methods, the pharmaceutical preparations containing them and their use for therapeutic purposes, in particular their use as NO-synthase inhibitors and/or as agents which allow the regeneration of antioxidants or entities which trap the ROS's and which intervene in a more general fashion in the redox status of thiol groups. Web site: http://www.delphion.com/details?pn=US06605637__ •

Long-life lubricating oil with wear prevention capability Inventor(s): Butler; Kevin David (Sarnia, CA) Assignee(s): ExxonMobil Research and Engineering Company (Annandale, NJ) Patent Number: 6,534,452 Date filed: January 8, 2002 Abstract: An industrial lubricant having wear prevention properties without sacrificing oxidation resistance comprises a major portion of a base oil; an effective amount of a sulfur and phosphorus antiwear compound and an effective amount of an anti-oxidant or mixture of antioxidants. Excerpt(s): This invention concerns lubricating compositions for use in industrial equipment requiting antiwear control. More particularly this invention concerns lubricating compositions providing load-carrying (antiwear) control for industrial equipment without sacrificing oxidation resistance. The art of lubricating oil formulation has become increasingly complex with ever more stringent industry standards dictated by developing industrial equipment technology. One requirement for industrial lubricants is to provide wear control. At the same time the lubricant formulation should provide resistance to oxidation and sludge formation in order to achieve operation life of adequate length. Experience has shown that the incorporation of one type of additive in a lubricant composition can have a negative impact on the function of another type of additive in that composition. Indeed, the presence of antiwear additives in lubricants often reduces the oxidation stability and increases sludge formation compared to a

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similar oil where the antiwear additive is absent. Thus, there is a need for industrial lubricants that provide improved antiwear performance without sacrificing oxidation resistance and deposit control. According to the invention, a lubricant composition especially suitable for use in industrial equipment requiring antiwear properties and oxidation resistance is provided, comprising a major portion of a base oil, an effective amount of both a sulfur and phosphorous containing antiwear additive, and an antioxidant or a mixture of antioxidants. Web site: http://www.delphion.com/details?pn=US06534452__ •

Method and assay kit for evaluation of the oxidative modification of proteincontaining substances Inventor(s): Lewin; Gudrun (Scharnhorststrasse 2, D-10115 Berlin, DE), Popov; Igor (Scharnhorststrasse 2, D-10115 Berlin, DE) Assignee(s): none reported Patent Number: 6,607,919 Date filed: June 1, 2000 Abstract: Oxidative stress in living organisms is determined in a photochemiluminescence measuring system after separation of low-molecular weight antioxidants from protein-containing test samples that were withdrawn from these organisms using an assay kit that contains a gel chromatographic column, a photosensitizer solution, a carbonate buffer solution, and a phosphate buffer solution. Excerpt(s): The present invention relates to a method and assay kit for the analysis of the oxidative modification of protein-containing substances and of the oxidative stress in biological samples by measuring the antiradical properties of their protein-containing components. Oxidative stress is a common phenomenon which is implicated in the etiopathogenesis of several diseases such as atherosclerosis, cancer, acute inflammation, etc. Methods determining the concentration of species reactive with thiobarbituric acid (TBA) or of conjugated dienes have been used as routine measurements for the determination of the degree of severity of oxidative stress. Products of lipid peroxidation, for example, malondialdehyde and 4-hydroxynonenal are reactive with thiobarbituric acid. One drawback of the known methods for the determination of oxidative stress is the lack of specificity, because several substances react with thiobarbituric acid. Another drawback is the relative insensitivity because lipid peroxidation does not immediately accompany oxidative stress. In fact, lipid peroxidation occurs only after antioxidants have been exhausted (see FAVIER, A.: Oxidative stress: value of its demonstration in medical biology and problems posed by the choice of a marker, Ann. Biol. Clin. (Paris), Vol. 55, 1997, pp. 9-16). Web site: http://www.delphion.com/details?pn=US06607919__

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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__

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Method of delivering a benefit agent Inventor(s): Howell; Steven (Sharnbrook, GB), Little; Julie (Sharnbrook, GB), Parry; Neil James (Sharnbrook, GB), Van Der Logt; Cornelis Paul (Vlaardingen, NL) Assignee(s): Unilever Home & Personal Care USA division of Conopco, Inc. (Greenwich, CT) Patent Number: 6,642,196 Date filed: December 20, 2000 Abstract: There is provided a method of delivering a benefit agent whereby a benefit agent is first loaded to a surface and subsequently unloaded and transferred and delivered to a second surface. More in particular, the benefit agent is first loaded onto a garment during a laundering process, and subsequently delivered to another surface. The benefit agents can be fragrance agents, perfumes, colour enhancers, fabric softening agents, polymeric lubricants, photoprotective agents, latexes, resins, dye fixative agents, encapsulated materials, antioxidants, insecticides, soil repelling agents, soil release agents, and cellulose fibers. Excerpt(s): The present invention relates to a method of delivering a benefit agent to a surface. More in particular, it relates to a method whereby a benefit agent is loaded to a first surface and subsequently unloaded and transferred and delivered to a second surface. In a preferred embodiment, it relates to the transfer of benefit agent, loaded on to a garment during the washing process, and subsequent delivery of the benefit agent to another surface. Conventionally, benefit agents, such as bleach and perfume, are incorporated in detergent compositions, adsorbed onto surfaces, and act on the

Patents 153

garments during the washing process. After the washing process, the effects are generally short-lived. In addition, large quantities of benefit have to be present to achieve an effect. According to DE-A-196 21 224 (Henkel), the transfer of textile dyes from one garment to another during a washing or rinsing process may be inhibited by adding antibodies against the textile dye to the wash or rinse liquid. Web site: http://www.delphion.com/details?pn=US06642196__ •

Methods of coating an implantable device having depots formed in a surface thereof Inventor(s): Harish; Sameer (Fremont, CA), Scheinpflug; Kurt W. (Santa Clara, CA), Wu; Steven Z. (Santa Clara, CA), Yoe; Brandon (Mountain View, CA) Assignee(s): Advanced Cardiovascular Systems, Inc. (Santa Clara, CA) Patent Number: 6,506,437 Date filed: October 17, 2000 Abstract: The present invention provides methods of coating an implantable device, such as a stent or a graft, having a plurality of depots formed in a surface thereof. An exemplary method includes applying a composition including a polymer and a solvent to the implantable device proximate to the depots. Such application of the composition is performed at a first gas pressure. The method also includes applying a second gas pressure, which is greater than the first gas pressure, to the composition-coated device so that air pockets in the depots are eliminated, or at least reduced in size. The method also includes the act of removing the solvent from the composition to form a coating. An implantable device coated in accordance with the method is also provided.The compositions employed in the methods may include one or more therapeutic substances such as antineoplastics, antimitotics, antiinflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antiproliferatives, antibiotics, antioxidants, antiallergics, radioisotopes, and combinations thereof. Excerpt(s): The present invention relates generally to implantable devices, examples of which include stents and grafts. More particularly, the present invention is directed to a method of coating an implantable device having a plurality of depots formed in a surface thereof. Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radially compress the atherosclerotic plaque of the lesion against the inner wall of the artery to dilate the lumen. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient's vasculature. A problem associated with the above procedure includes formation of intimal flaps or tom arterial linings which can collapse and occlude the vessel after the balloon is deflated. Moreover, thrombosis and restenosis of the artery may develop over several months after the procedure, which may require another angioplasty procedure or a surgical by-pass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis, an implantable device, examples of which include stents and grafts, may be implanted. Web site: http://www.delphion.com/details?pn=US06506437__

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Multi-faceted method to repress reproduction of latent viruses in humans and animals Inventor(s): Van Dyke; Knox (Morgantown, WV) Assignee(s): HIV Diagnostics, Inc. (Lexington, KY) Patent Number: 6,514,955 Date filed: June 7, 1995 Abstract: Disclosed are methods for repressing reproduction of latent viruses, such as HIV, in animals by the generally concurrent administration of (1) antioxidants including a glutathione agent; and (2) an NFKB induction inhibitor. Also disclosed are pharmaceutical compositions and kits for use in repressing reproduction of latent viruses such as HIV. Excerpt(s): Acquired Immunodeficiency Syndrome (AIDS) is one of the most significant infections to appear in the last decade. This epidemic is not confined to a single segment of the population nor is its spread blocked by natural barriers or international boundaries. Millions have died in Africa and many more individuals are infected worldwide. In the United States more than 100,000 people have died and at least 1 million more are presently infected with the virus. This pandemic shows no signs of abating. It is strongly suspected that the causative agent in AIDS is an RNA retrovirus called the human immunodeficiency virus (HIV-1 or HIV-2). HIV possesses an envelope glycoprotein (gp120) that has a high affinity for the CD.sub.4 receptor on T helper cells and other target cells. These other target cells include bone marrow stem cells, macrophages, endothelial cells, glial cells, lymph node, dendritic cells, bowel enterochromaffin cells, cervical eptithlium and possibly Langerhans cells. However, it is the effects of HIV on T-helper cells that are the best known. The infectious process begins when the virus penetrates the body and enters the blood stream. Binding of HIV to CD.sub.4 target cells involves interaction of the external envelope glycoprotein molecule gp120 with the CD.sub.4 molecule, although other cell receptors may be involved. The virus next enters the target cell, or is internalized, through fusion of the viral envelope with the target cell membrane. Through this fusion, the virus loses its coat, and releases its RNA core and reverse transcriptase enzyme into the host cell cytoplasm. The HIV reverse transcriptase enzyme copies the RNA message producing first a single-stranded, and then a double-stranded, DNA (circular complementary DNA). This newly formed double-stranded DNA becomes incorporated into the host chromosomal DNA once it enters the host cell nucleus. This incorporated viral DNA may remain dormant or, upon activation, will produce viral messenger RNA (mRNA). The viral mRNA codes for proteins that are important in viral replication. Glycoprotein will then envelop the RNA genome resulting in the production of infectious viral particles; completed viral particles are then released to infect other cells. Web site: http://www.delphion.com/details?pn=US06514955__

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Nutritional composition containing methionine Inventor(s): Hageman; Robert Johan Joseph (Waddinxveen, NL) Assignee(s): N. V. Nutricia (Zoetermeer, NL) Patent Number: 6,544,547 Date filed: January 31, 2000

Patents 155

Abstract: An enteral food composition for clinical or dietary use, comprises, in addition to carbohydrates and proteins or their hydrolysates the following components or their nutritional equivalents, per daily dosage: methionine (0.6-7 g), cysteine (0.5-2.5 g), folic acid (0.4-8 mg), pyridoxal (vitamin B.sub.6) (3-20 mg), zinc (18-120 mg) and at least 400 kcal energy in the form of carbohydrates. These amounts are well above the Recommended Daily Allowance (RDA) values. Further preferred components include lecithin, cyanocobalamine, betaine and magnesium, as well as transsulfuration metabolites, ATP enhancers and antioxidants. Excerpt(s): The present invention relates to a module of nutritional components which supports total methionine metabolism in man, for use in a universal medicinal food. The invention also relates to food products containing this module and to a method of producing food products by using selected amounts of the module. Methionine is metabolised in man via a multi-step pathway, the transsulfuration pathway. Several intermediate products are formed in this pathway, which play a dominant role in other biochemical pathways as well. For example, the reaction product S-adenosyl methionine is extensively used in many methylation reactions; homocysteine is the main methyl acceptor in folate metabolism and also the conversion of betaine to dimethylglycine (via methylation of homocysteine) strongly influences folate metabolism. Another intermediate in the transsulfuration pathway is cystathionine generated by reaction between homocysteine and serine, that may split into cysteine and 2-oxy-butyrate. The latter is involved in the metabolism of several other compounds (e.g. threonine). Cysteine is metabolised to various useful products such as taurine and sulphates. It is also an important precursor for glutathione in the liver and some other tissues. Glutathione that is produced in the liver has to be transported to cell compartments in some peripheral organs in order to exhibit its activity. Intracellular glutathione levels are in turn strongly influenced by the presence of reducing equivalents and amino acids in the cell. Web site: http://www.delphion.com/details?pn=US06544547__ •

Pharmaceutical levothyroxine preparation Inventor(s): Nischwitz; Marion (Darmstadt, DE), Schreder; Sven (Heidelberg, DE) Assignee(s): Merck Patent Gesellschaft (Darmstadt, DE) Patent Number: 6,491,946 Date filed: January 5, 2001 Abstract: The invention relates to a pharmaceutical preparation comprising levothyroxine sodium, potassium iodide, microcrystalline cellulose and binding agent, which is free of antioxidants or further auxiliaries, and processes for its production. Excerpt(s): The invention relates to a novel stable pharmaceutical preparation comprising levothyroxine sodium, potassium iodide, microcrystalline cellulose and binding agent, which is free of antioxidants or further auxiliaries. Auxiliaries are substances which prevent formation of iodine, e.g. potassium hydroxide. A thyroxine preparation stabilized with thiosulfate as an antioxidant is described in DE 195 41 128. Web site: http://www.delphion.com/details?pn=US06491946__

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Preservation compositions and process for mushrooms Inventor(s): Kravitz; Howard S. (Wayne, PA), Martin; Stefan T. (Flourtown, PA), Romig; William R. (Morrestown, NJ) Assignee(s): EPL Technologies, Inc. (Philadelphia, PA) Patent Number: 6,500,476 Date filed: June 29, 2001 Abstract: Preservative compositions using GRAS (generally recognized as safe) ingredients are incorporated into a commercially viable three-stage preservation process for mushrooms. The process includes contacting the mushrooms with a high pH solution for microbial reduction; a neutralizing step to return the pH of the mushrooms to their about physiological pH; and an anti-browning step that incorporates suitable antioxidants and ancillary compounds to maintain the color of the finished product. Specifically disclosed is a method for preserving fresh mushrooms comprising the steps of exposing the mushrooms to a aqueous anti-microbial solution with a pH of 10.5-11.5; treating the mushrooms with a pH neutralizing buffer consisting of an organic acid and a salt of an organic acid and then subjecting the mushrooms to a combination of an antibrowning agent, a source of calcium and a chelating agent. Excerpt(s): Fresh-cut fruits and vegetables, with minimal processing and ready to eat, are the fastest growing segment of the produce market. Sulfite solutions were historically used to wash fruits, vegetables and mushrooms. Due to the detrimental effects of water and the undesirable effects of sulfites, minimally processed or ready to eat mushrooms with acceptable quality and shelf life for retail markets have not been achieved on a commercially viable basis. Commercial production practices of growing mushrooms in straw-bedded horse manure compost covered with a fine layer of peat or other "casing material" yield harvested mushrooms with undesirable appearance and requires the consumer to wash the mushrooms prior to use. Mushrooms are typically harvested by hand leading to the introduction and spread of fluorescent Pseudomonads and other spoilage organisms that lead to accelerated decay and discoloration of the mushrooms. Consumers identify whiteness and cleanliness of fresh mushrooms (Agaricus bisporus) as the main factors of quality. If an economical process could be developed to remove the casing material and compost from the surface of mushrooms while minimizing bacterial attack, the processors could create new markets and increase the sale of mushrooms. The consumer would prefer to purchase ready to use mushrooms that are free of such contaminants and have the opportunity to readily mix them with other food components. In the view of the grower/processor and end user, mushrooms would then join the category of minimally processed or fresh-cut produce and occupy the convenience section of the produce aisle. Web site: http://www.delphion.com/details?pn=US06500476__

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Process for enriching foods and beverages Inventor(s): Drunen; Jeffrey Van (South Holland, IL), Hranisavljevic; Jovan T. (Belgrade, YU) Assignee(s): VDF Futurceuticals (Momence, IL) Patent Number: 6,572,915 Date filed: June 27, 2000

Patents 157

Abstract: A method of enriching fruit products and coffee with beneficial agents present in processing waste products such as fruit skins and kernels and coffee cherries. The waste products are dried and extracted with an appropriate organic solvent and/or water. The extract is dried, purified if desired, and blended into the food product corresponding to the waste product, such as a fruit processing waste product extract could be combined with fruit juices, canned or frozen fruit, etc., and coffee cherry extract could be combined with ground or freeze-dried coffee. The extracts contain highly beneficial antioxidants and potentially other beneficial agents. Excerpt(s): This invention relates to the enrichment of foods and beverages with added naturally occurring agents and to methods of preparing such agents from waste products generated in agricultural food processing. Many different crops are grown, harvested and processed into foods, beverages, nutritional supplements and the like. Large quantities of agricultural waste products are generated during crop processing. Typically, these include fruit skin and pits resulting from fruit crops such as peaches, apricots, cherries, plums, etc. or the "coffee cherry" husks that are removed from coffee beans in the processing of coffee. Disposing of these waste products can cause serious environmental problems. Such waste products are generally incinerated, sometimes as auxiliary energy sources, or buried in landfills. In the past no significant use has been developed for coffee cherries. Generally, coffee cherry pulp is simply disposed in a land fill. Uses exist for only a small portion of the fruit processing waste material. Web site: http://www.delphion.com/details?pn=US06572915__ •

Process for macromolecularizing phenolic compounds etc. and use thereof Inventor(s): Echigo; Takashi (Chiba, JP), Ohno; Ritsuko (Tokyo, JP) Assignee(s): SDS Biotech K.K. (Tokyo, JP) Patent Number: 6,537,546 Date filed: December 22, 2000 Abstract: A process for macromolecularizing phenolic compounds or aromatic amine compounds by the action of a catalyst comprising an enzyme having a polyphenol oxidizing activity in the alkali region; applications of the compounds obtained by the above process to thickeners, stabilizers, coagulants, emulsifiers, dispersants, water retainers, antioxidants, adhesives, concrete admixtures, dyes, coating materials, petroleum recovering agent, soil conditioner, a blow-applied seed bearing surface soil stabilizer, deodorants, smell eliminators, agricultural chemical spreaders, feeding stuff binders, bactericides, antimicrobial agents, viral infection inhibitors, bioadhesion preventives, biotic repellents, insecticides, poultices, ink bases or wood treating agents; and method of waste water disposal, a method of deoxygenation and a method of treating wood, concrete or soil in which use is made of the above reaction. Excerpt(s): The present invention relates to a process for enzymatic macromolecularization of phenolic compounds or aromatic amine compounds and to applications of the macromolecules obtained by the process. More particularly, the present invention provides a process for producing phenolic compounds or aromatic amine compounds which have increased molecular weights by reacting phenolic compounds or aromatic amine compounds with an enzyme having a polyphenol oxidizing activity in the alkaline pH region, and applications of the reaction method of increasing the molecular weight of phenolic compounds or aromatic amine compounds utilizing the above-described catalytic activity of the enzyme in the alkali regions to

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obtain thickeners, stabilizers, coagulants, emulsifiers, dispersants, water retainers, antioxidants, adhesives, concrete admixtures, dyes, deodorants, smell eliminators, coating materials, petroleum recovering agents, soil conditioners, blow-applied seed bearing surface soil stabilizers, agricultural chemical spreaders, feeding stuff binders, bactericides, antimicrobial agents, viral infection inhibitors, bioadhesion preventives, biotic repellents, insecticides, poultices, ink bases and wood treating agents; a method of producing these various agents; a method of waste water disposal; a method of deoxygenation; and methods of treating wood, concrete and soil, respectively. Hitherto, it has been known that phenolic compounds etc. can be macromolecularized by utilizing an enzyme such as laccase or polyphenol oxidase produced by Basidiomycotina or Deuteromycotina (Journal of Biotechnology, 13, 229-241, 1990 and etc. so on). However, the laccases or polyphenol oxidases produced by fungi have their optimal reaction pH in the acidic region so that the reaction must be carried out in pH region ranging from acidic to neutral in order to catalyze or accelerate the macromolecularization reaction utilizing these enzymes and in addition, the rate of the macromolecularization reaction is not high enough. Also, the natural organic compounds with which these enzymes react are mainly polyphenolic compounds and, hence, the reaction must be carried out in the pH region ranging from acidic to neutral because the optimal reaction pH of the enzyme is in the acidic region despite the fact that the polyphenolic compounds have solubilities which decrease in the pH region from acidic to neutral, resulting in a defect that it is impossible to efficiently macromolecularize polyphenolic compounds in high concentrations. Further, although many polyphenolic compounds are accelerated their autooxidation in the alkaline pH region, enzymatic oxidative macromolecularization has been carried out in the pH region ranging from acidic to neutral, resulting in a defect that the autooxidation cannot be utilized effectively. Web site: http://www.delphion.com/details?pn=US06537546__ •

Prophylactic therapeutic and industrial antioxidant compositions enhanced with stabilized atomic hydrogen/free electrons and methods to prepare and use such compositions Inventor(s): Colic; Miroslav (Goleta, CA) Assignee(s): Henceforth Hibernia Inc. (New York, NY) Patent Number: 6,649,193 Date filed: June 9, 2000 Abstract: The invention is directed to therapeutic antioxidant compositions which are enhanced by the stabilized atomic hydrogen; one of the most potent antioxidants. Such products can be used for prophylactic and therapeutic purposes in treatment of cancer, diabetes, autoimmune diseases, neurodegenerative diseases, cardiovascular diseases, skin diseases etc. The products described can be used independently or in combination with other drugs and treatment modalities. The products can also be used as dietetic products to aid in desired weigh loss. The described products can also be used to prevent oxidative and free radical damage to food and oxidation-prone industrial products. The invention also describes the methods to produce and stabilize atomic hydrogen and prepare and use such stabilized/encaged atomic hydrogen enhanced antioxidant compositions. Excerpt(s): The invention provides prophylactic, therapeutic and industrial antioxidant compositions that are enhanced with stabilized atomic hydrogen/free electrons. The invention also provides methods to prepare and use such antioxidant compositions.

Patents 159

Molecular oxygen is an essential substance for all aerobic organisms, including humans. Oxygen is involved in many metabolic reactions ranging from energy production to the synthesis of vitamin A and prostaglandins and the deoxification and metabolism of drugs, chemicals and foods. Some forms of oxygen and oxygen-containing species are very reactive and can cause significant damage to the organism. Such moieties are termed reactive oxygen species ("ROS"). Organisms, including humans, have evolved ways of handling dangerous ROS. Organisms posses a large number of defenses against the deleterious effects of ROS. [See, for instance, Oxidative Stress, Oxidants and Antioxidants, Academic Press, London, 1991]. Many enzymes and small molecules are used by aerobic cells to protect against the damage caused by ROS. Enzymes which are used to catalyze the removal or transformation of ROS include superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase etc. Small molecules used by aerobic cells to scavenge ROS include vitamins C, E and A, glutathione, ubiquinone, uric acid, carotenoids, etc. Superoxide dismutase is a very efficient catalyst for the removal of superoxide free radicals. Such removal results in the production of hydrogen peroxide. Catalase, in turn, is a very efficient catalyst for the removal of the hydrogen peroxide that is produced. Glutathione peroxidase and transferase enzymes are efficient in the removal of many ROS. Among small molecules, the most important molecule involved in the prevention of damage caused by ROS is a thiol-containing tripeptide, glutathione [see, for instance, Oxidative Stress, Oxidants and Antioxidants, Academic Press, London, 1991]. Glutathione (GSH) is present in all animal cells in millimolar concentrations and is directly involved in the reduction (and, thereby, detoxification) of ROS. Reduction of ROS by glutathione results in oxidation and dimerization of glutathione to the disulfide-linked dimer (GSSG). This oxidized form of glutathione is toxic and oxidizing in itself. Other small molecules such as ascorbate (vitamin C) or tocopherol (vitamin E) also can directly reduce ROS. The difference between enzymes such as superoxide dismutase and small molecules such as vitamin C is that the former can catalytically remove many molecules of ROS, while the latter reacts with oxidants stoichiometrically, usually in a 1:1 or 2:1 ratio. Web site: http://www.delphion.com/details?pn=US06649193__ •

Refractory batch, in particular for the production of a shaped body, and process for producing the shaped body Inventor(s): Bartha; Peter (Bovenden, DE), Jansen; Helge (Friedland, DE), Wienand; Hans (Duesseldorf, DE) Assignee(s): Refractechnik Holding GmbH (Ismaning, DE) Patent Number: 6,645,425 Date filed: June 1, 2000 Abstract: The invention relates to a refractory batch containing at least one refractory metal oxide component, at least one binder component, such as resin or pitch, if appropriate antioxidants, at least one carbon carrier, such as soot and/or graphite, and reinforcement fibers which are formed from a stainless steel material, which at the temperatures of use forms a coat of the refractory metal oxide on its surface, and to a shaped body made from the batch and to a process for producing the shaped body. Excerpt(s): The invention relates to a batch, in particular for the production of a refractory shaped body as described in the preamble of claim 1, to a refractory shaped body in accordance with the preamble of claim 29, and to a process for producing the shaped body in accordance with the preamble of claim 31. In the iron and steelmaking

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industry, the reaction and transport vessels used are brick-lined with refractory materials or lined with ramming compounds. Vessels of this nature are, in particular, converters, such as basic oxygen furnaces or bottom-blowing converters, in which crude steel is obtained from pig iron. Furthermore, steel casting ladles and treatment ladles for secondary metallurgical processes (steel refining), and also downstream units in the steel casting system, are provided with a similar refractory lining. In this case, steel casting ladles, for example, may both be lined with a high alumina content and have an alkaline lining based on MgO or dolomite. Web site: http://www.delphion.com/details?pn=US06645425__ •

Rubber compositions and method for increasing the mooney scorch value Inventor(s): Greene; Peter K. (Goshen, CT), Hannon; Martin J. (Bethany, CT), Hong; Sung W. (Cheshire, CT) Assignee(s): Uniroyal Chemical Company, Inc. (Middlebury, CT) Patent Number: 6,620,875 Date filed: September 4, 2001 Abstract: A rubber composition is disclosed wherein the rubber composition contains at least (a) a rubber component; (b) a silica filler; (c) a coupling agent; (d) a cure-enhancing amount of at least one polyalkylene oxide; and (e) at least one high molecular weight thiuram disulfide. The compositions may also include suitable amounts of other ingredients such as carbon black, antiozonants, antioxidants, etc. Excerpt(s): This invention relates generally to rubber compositions and a method for increasing the mooney scorch value of the rubber compositions. The rubber compositions are particularly useful for tire tread applications in vehicles, e.g., passenger automobiles and trucks. The tire treads of modern tires must meet performance standards which require a broad range of desirable properties. Generally, three types of performance standards are important in tread compounds. They include good wear resistance, good traction and low rolling resistance. Major tire manufacturers have developed tire tread compounds which provide lower rolling resistance for improved fuel economy and better skid/traction for a safer ride. Thus, rubber compositions suitable for, e.g., tire treads, should exhibit not only desirable strength and elongation, particularly at high temperatures, but also good cracking resistance, good abrasion resistance, desirable skid resistance, low tangent delta values at 60.degree. C. and low frequencies for desirable rolling resistance of the resulting treads. Additionally, a high complex dynamic modulus is necessary for maneuverability and steering control. A high mooney scorch value is further needed for processing safety. Presently, silica has been added to rubber compositions as a filler to replace some or substantially all of the carbon black filler to improve these properties, e.g., lower rolling resistance. Although more costly than carbon black, the advantages of silica include, for example, improved wet traction, low rolling resistance, etc., with reduced fuel consumption. Indeed, as compared to carbon black, there tends to be a lack of, or at least an insufficient degree of, physical and/or chemical bonding between the silica particles and the rubber to enable the silica to become a reinforcing filler for the rubber thereby giving less strength to the rubber. Therefore, a silica filler system requires the use of coupling agents. Web site: http://www.delphion.com/details?pn=US06620875__

Patents 161

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Skin whitening composition comprising bearberry and tetrahydrocurcumin Inventor(s): Kyrou; Christos D. (Suffern, NY), Martin; Dennis M. (Cornwall, NY), Ptchelintsev; Dmitri (Mahwah, NJ), Simpson; Susan E. (Wyckoff, NJ), Teal; Janice J. (Old Greenwich, CT) Assignee(s): Avon Products, Inc. (New York, NY) Patent Number: 6,641,845 Date filed: June 2, 2000 Abstract: A preferred composition containing a skin whitening blend containing bearberry and an antioxidant, such as tetrahydrocurcumin, is provided. Also the composition can comprise a hypopigmenting component selected from mulberry, scutellaria, grape, cowberry, bilberry, molasses, pear, guava, licorice, etc. The licorice extract can be in the form of a water soluble extract or an oil soluble extract. Other antioxidants can be selected from rosemary extract, tocopherol, green tea extract, and gamma oryzanol. The skin whitening blend may also have an accelerant that enhances or accelerates the skin cell turnover rate. The skin whitening blend may also include a sunscreen component. Also, the composition may further include a pH adjusting agent, a surfactant, a thickening agent, a preservative, a fragrance, a masking agent, a pigment, an emulsifier, and/or emollient. Excerpt(s): The present invention relates to a novel skin whitening blend that is a synergistic combination of a hypopigmenting component and an antioxidant. The skin whitening blend is further incorporated into a suitable topical vehicle to provide a skin whitening composition. Optionally, the novel skin whitening blend may also incorporate a sunscreen and/or a skin cell turnover rate accelerant. It is an object of the present invention to provide an efficacious skin whitening blend that includes a hypopigmenting component and an antioxidant. It is another object of the present invention to provide an efficacious skin whitening blend that further comprises a sunscreen and/or a skin cell turnover rate accelerant. Web site: http://www.delphion.com/details?pn=US06641845__

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Solid compositions and liquid preparations for oral administration which contain cocoa polyphenols Inventor(s): Buck; Margaret M. (Morristown, NJ), Hammerstone, Jr.; John F. (Nazareth, PA), Romanczyk, Jr.; Leo J. (Hackettstown, NJ) Assignee(s): Mars Incorporated (Mclean, CA) Patent Number: 6,517,841 Date filed: October 11, 2001 Abstract: Disclosed and claimed are cocoa extracts such as polyphenols or procyanidins, methods for preparing such extracts, as well as uses for them, especially as antineoplastic agents and antioxidants. Disclosed and claimed are antineoplastic compositions containing cocoa polyphenols or procyanidins and methods for treating patients employing the compositions. Additionally disclosed and claimed is a kit for treating a patient in need of treatment with an antineoplastic agent containing cocoa polyphenols or procyanidins as well as a lyophilized antineoplastic composition containing cocoa polyphenols or procyanidins. Further, disclosed and claimed is the use

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of the invention in antioxidant, preservative and topiosomerase-inhibiting compositions and methods. Excerpt(s): This invention relates to cocoa extracts such as polyphenols preferably polyphenols enriched with procyanidins. This invention also relates to methods for preparing such extracts, as well as to uses for them; for instance, as antineoplastic agents and antioxidants. Documents are cited in this disclosure with a full citation for each appearing in a References section at the end of the specification, preceding the claims. These documents pertain to the field of this invention; and, each document cited herein is hereby incorporated herein by reference. Polyphenols are an incredibly diverse group of compounds (Ferreira et al., 1992) which widely occur in a variety of plants, some of which enter into the food chain. In some cases they represent an important class of compounds for the human diet. Although some of the polyphenols are considered to be nonnutrative, interest in these compounds has arisen because of their possible beneficial effects on health. For instance, quercitin (a flavonoid) has been shown to possess anticarcinogenic activity in experimental animal studies (Deshner et al., 1991 and Kato et al., 1983). (+)-Catechin and (-)-epicatechin (flavan-3-ols) have been shown to inhibit Leukemia virus reverse transcriptase activity (Chu et al., 1992). Nobotanin (an oligomeric hydrolyzable tannin) has also been shown to possess anti-tumor activity (Okuda et al., 1992). Statistical reports have also shown that stomach cancer mortality is significantly lower in the tea producing districts of Japan. Epigallocatechin gallate has been reported to be the pharmacologically active material in green tea that inhibits mouse skin tumors (Okuda et al., 1992). Ellagic acid has also been shown to possess anticarcinogen activity in various animal tumor models (Bukharta et al., 1992). Lastly, proanthocyanidin oligomers have been patented by the Kikkoman Corporation for use as antimutagens. Indeed, the area of phenolic compounds in foods and their modulation of tumor development in experimental animal models has been recently presented at the 202nd National Meeting of The American Chemical Society (Ho et al., 1992; Huang et al., 1992). Web site: http://www.delphion.com/details?pn=US06517841__ •

Stable gelled surface polish Inventor(s): Collins; James R. (5817 Centralcrest, Houston, TX 77092), Collins; Jock R. (5817 Centralcrest, Houston, TX 77092), Kaiser; Conard E. (5817 Centralcrest, Houston, TX 77092) Assignee(s): none reported Patent Number: 6,533,850 Date filed: February 26, 2001 Abstract: A smooth stable viscous gelled surface polish composition comprising a mixture of water, a gelling agent, a chelating agent, an abrasive, and colorant or pigment and other property enhancing additives evenly dispersed into the mixture, and an alkaline electrolyte viscosity increasing agent that raises the pH of the mixture and forms a smooth homogeneous stable gel with a viscosity level having the consistency of a custard or jelly which prevents separation of the abrasives and additives and does not require shaking or mixing prior to use. Additionally other suitable additives such as antioxidants, waxes, and oils may be used in the composition. The smooth homogeneous stable gel is also resistant to drying and the formation of a surface "skin".

Patents 163

Excerpt(s): This invention relates generally to surface polishes of the type used for polishing metal wood, painted surfaces and other surfaces, and more particularly to a stable viscous gelled surface polish composition that contains abrasives and other additives in a gel base which prevents separation of the abrasives and additives and does not require shaking or mixing prior to use. Polishes for metal, wood, and other surfaces have long been known. The aqueous polishes are extremely effective and handy for use after shaking or mixing. However, they are difficult to use because their abrasive polishing additives commonly settle out of their liquid carriers in the storage containers. Because these products must use clays, starches, polysaccharides and other materials for the sole purpose of assisting in holding the desired abrasives in suspension although these additives serve no polishing purpose and commonly interfere with the polishing efficiency of the end product. Additionally the dried additives often accumulate on the insides of the storage container usually resulting in wastage of much of the contents after only partial use. Making additives in the polish uniformly available when polishing is vital for consistent results. The consumer also desires to utilize the entire contents of the bottle, which cannot be done when a significant portion of the material adheres to the inside walls of the container and are unreachable in smallmouthed vessels. Polishes are usually sold in small-mouthed bottles to facilitate shaking as a method to insure thorough mixing. Small-mouthed containers will limit the amount of polish that can be efficiently removed without spillage and often limiting obtaining desired quantities for use. Web site: http://www.delphion.com/details?pn=US06533850__ •

Succinimide-acid compounds and derivatives thereof Inventor(s): Loper; John T. (Richmond, VA) Assignee(s): Ethyl Corporation (Richmond, VA) Patent Number: 6,548,458 Date filed: November 8, 2001 Abstract: Succinimide-acid compounds prepared by reaction of hydrocarbyl-substituted succinic acylating agents with alpha-omega amino acids are disclosed, as well as derivatives thereof useful as lubricity additives, lubricant dispersants, friction modifiers, liquid hydrocarbonaceous fuel detergents, antioxidants and alkali and/or alkaline-earth metal detergents. Excerpt(s): The present invention is directed to novel succinimide-acid compounds prepared by reaction of hydrocarbyl-substituted succinic acylating agents with amino acids, as well as derivatives thereof useful as lubricity additives, lubricant dispersants, friction modifiers, liquid hydrocarbonaceous fuel detergents, antioxidants and alkali and/or alkaline-earth metal detergents. Hydrocarbyl-substituted succinic anhydride derivatives are widely used as fuel and lubricant additives. The hydrocarbyl-substituted succinic anhydride derivatives are typically prepared by reacting a hydrocarbylsubstituted succinic acylating agent with a polyamine to form a succinimide. For example, hydrocarbyl-substituted succinic anhydrides and derivatives thereof prepared by the thermal reaction of a polyolefin and maleic anhydride, are described, for example in U.S. Pat. Nos. 3,361,673 and 3,676,089. Alternatively, hydrocarbyl-substituted succinic anhydrides can be prepared by the reaction of chlorinated polyolefins with maleic anhydride, are described, for example, in U.S. Pat. No. 3,172,892. Additional examples of hydrocarbyl-substituted succinic anhydrides and derivatives thereof can be found, for example, in U.S. Pat. Nos. 4,234,435; 4,997,456; 5,393,309 and 5,620,486.

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Web site: http://www.delphion.com/details?pn=US06548458__ •

Synergistic combinations of phenolic antioxidants Inventor(s): Koch; Harald (Burgheim, DE), Krohnke; Christoph (BreisachOberrimsingen, DE), Lichtblau; Alexander (Augsburg, DE), Zah; Matthias (Gersthofen, DE) Assignee(s): Clariant Finance (BVI) Limited (Tortola, VG) Patent Number: 6,646,035 Date filed: August 22, 2002 Abstract: The invention relates to synergistic combinations of certain phenolic antioxidants in thermoplastic polymers, especially in polyolefin pipes and other thermoplastic molding materials which are in prolonged contact with water. The instant combinations lead to better resistance against oxidative degradation as measured in terms of oxidation induction times (OIT), color and other technically important parameters as known in the art. Excerpt(s): The invention relates to synergistic combinations of phenolic antioxidants in polyolefine pipes and other thermoplastic molding materials especially those which are in contact with water. The usability and lifetime of--often partially crosslinked-polyolefin pipes and other thermoplastic materials which are in prolonged contact with water such as geotextiles, water pipes, tubing for heating equipment etc. is influenced by numerous parameters such as mechanical properties, density, molar mass and mass distribution of the polymer. Depending on the final use and the local conditions (temperature, stress, and environmental influences) during the use time, a lifetime of up to several decades should be guaranteed. New trends for lifetime expectancy are more than 50 years. In case of their use for water transportation, special requirements must be fulfilled which can be reached by addition of appropriate stabilizers and stabilizer conditions. Their contribution can be determined under accelerated test conditions at elevated temperatures by hot water storage. As important technical criteria oxidation induction time (OIT) and mechanical stability are used to assess the stabilization of polyolefin pipes or other polyolefin-based molding materials. OIT-tests are still established and are used as technically important criteria despite the fact that extrapolations of OIT-data are since a long time discussed to be often too optimistic compared to conventional oven aging results. Effects in the polymer matrix e.g. change in cristallinity, free volume, morphology, and coefficient of diffusion and reaction kinetics cause changes in the degradation mechanism. Nevertheless, especially in the PE-MD- and PE-HD-sector OIT-limits of at least 30 minutes at T=210.degree. C. are required. Another technical criterion which must fulfill certain technical requirements is color determined as yellowness index (YI). Further technical criteria to judge the quality of resins used for contacts with water is the remaining stabilizer content after hot water storage (95.degree. C.) which is part of the standard test program of the involved resin producers and manufacturers of finished articles. Web site: http://www.delphion.com/details?pn=US06646035__

Patents 165

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Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease Inventor(s): Doctrow; Susan Robin (Roslindale, MA), Malfroy-Camine; Bernard (Arlington, MA) Assignee(s): Eukarion, Inc. (Bedford, MA) Patent Number: 6,573,257 Date filed: April 4, 2000 Abstract: The invention provides antioxidant salen-metal complexes, compositions of such antioxidant salen-metal complexes having superoxide activity, catalase activity, and/or peroxidase activity, compositions of salen-metal complexes in a form suitable for pharmaceutical administration to treat or prevent a disease associated with cell or tissue damage produced by free radicals such as superoxide, and cosmetic and free radical quenching formulations of salen metal compounds. Excerpt(s): The invention provides antioxidant compositions, including pharmaceutical compositions, of synthetic catalytic small molecule antioxidants and free radical scavengers for therapy and prophylaxis of disease and prevention of oxyradicalmediated oxidation, methods for using the small molecule antioxidants in prevention and treatment of pathological conditions, methods for using the small molecule antioxidants as preservatives and oxyradical quenching agents in hydrocarbons, methods for using the small molecule antioxidants for targeted protection of tissues and/or cell types during cancer chemotherapy, and methods for using the small molecule antioxidants to prevent toxicologic damage to individuals exposed to irritating oxidants or other sources of oxidative damage, particularly oxygen-derived oxidative species such as superoxide radical. The compositions and methods of the invention are also used for preventing oxidative damage in human transplant organs and for inhibiting reoxygenation injury following reperfusion of ischemic tissues. The compositions and methods of the invention are also useful for chemoprevention of chemical carcinogenesis and alteration of drug metabolism involving epoxide or free oxygen radical intermediates. Molecular oxygen is an essential nutrient for nonfacultative aerobic organisms, including, of course, humans. Oxygen is used in many important ways, namely, as the terminal electronic acceptor in oxidative phosphorylation, in many dioxygenase reactions, including the synthesis of prostaglandins and of vitamin A from carotenoids, in a host of hydroxylase reactions, including the formation and modification of steroid hormones, and in both the activation and the inactivation of xenobiotics, including carcinogens. The extensive P450 system uses molecular oxygen in a host of important cellular reactions. In a similar vein, nature employs free radicals in a large variety of enzymic reactions. Excessive concentrations of various forms of oxygen and of free radicals can have serious adverse effects on living systems, including the peroxidation of membrane lipids, the hydroxylation of nucleic acid bases, and the oxidation of sulfhydryl groups and of other sensitive moieties in proteins. If uncontrolled, mutations and cellular death result. Web site: http://www.delphion.com/details?pn=US06573257__

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Tire, the sidewalls of which contain a varnished film Inventor(s): Bataille; Francois (St-Amant-Tallende, FR), Ringot; Claude (Riom, FR) Assignee(s): Michelin Recherche et Technique S.A. (Granges-Paccot, CH) Patent Number: 6,554,037 Date filed: March 8, 2001 Abstract: The present invention relates to a tire the sidewalls of which comprise a vulcanized elastomeric composition, and a process for forming an even, varnished film on at least one of said sidewalls. According to the invention, the composition comprises in combination:a polymer containing an oxy radical of the formula --O-- therein, the polymer having an alkyl group on one side of the oxy radical and, on the other side of the oxy radical, at least one alkene polyoxide block of the formula (C.sub.n H.sub.2n O).sub.z joined to a hydrogen atom at the chain end thereof, such that the hydrogen atom and the end terminal oxygen of the alkene polyoxide block form an alcohol function, in the amount of between 0.3 and 5 phr (parts by weight per 100 parts elastomer), andan alkali metal salt of an alkylsulphonic or alkylsulphuric acid, in an amount of between 0.5 and 10 phr.The invention also provides process for forming an even, varnished film on sidewalls composed of the composition which involves exposing the sidewalls to an ozone environment of at least 20 parts per 100 million in a chamber for at least 48 hours. The invention applies in particular to the protection of said tire sidewalls against the visible effects of the migration of antioxidants and antiozonants present therein. Excerpt(s): The present invention relates to a tire, the sidewalls of which comprise a vulcanized composition based on at least one elastomer. Also provided is a process for forming an even, varnished film on at least one of said sidewalls. In particular the invention protects the tire against the effects of the migration of antioxidants and antiozonants in the sidewalls that are visible on the respective outer faces of the sidewalls. Certain rubber compositions are very susceptible to the action of ozone, in particular, vulcanized compositions based on diene elastomers. When an article comprising such a vulcanized elastomeric composition is subjected to prolonged static and dynamic stresses in the presence of ozone, visible cracks or fissures that are more or less marked appear on the surface of the article. These cracks are oriented substantially perpendicular to the direction of the stress. Their propagation under the action of persistent stress may eventually cause complete breakage of the article. In order to minimize the effects of ozone, antiozonants intended to reduce the formation and propagation of cracks under the above mentioned stress, have been incorporated into such articles, especially tire sidewalls composed of such vulcanized elastomers. Waxes have also been used to provide a protective coating on the surface of the sidewalls so as to ensure additional protection under static stresses. The use of these antiozonants and waxes has proved effective in minimizing cracks on the surface of the sidewalls. Web site: http://www.delphion.com/details?pn=US06554037__

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Tobacco alternative Inventor(s): Siadto; Modesto E. (10011 Whitefield St., Fairfax, VA 22032) Assignee(s): none reported Patent Number: 6,619,293 Date filed: July 19, 2002

Patents 167

Abstract: An alternative to tobacco for both smokers and chewers is provided. A cigarette is prepared from mature tea leaves which are steamed and dried, but not withered, roasted or fermented. The tea leaves are rolled in paper and may be filtered or non-filtered. Cigarettes prepared with tea leaves processed in this manner provide acceptable taste, and may provide natural antioxidants, such as polyphenols and flavonoids, by inhalation. A chaw prepared according to the present invention is made with tea leaves which have been roasted, but not fermented, and is flavored with vanilla, cinnamon or mint. Both products may be produced with natural caffeine content, or may be partially decaffeinated. Excerpt(s): The present invention relates to a substance which serves as an alternative to tobacco in cigarettes and in chaws, and particularly to fresh tea cigarettes and a method of making the same used as an alternative for cigarettes made from tobacco, and to a flavored chewing tea used as an alternative for chewing, tobacco. The hazards of tobacco are well documented. Smoking tobacco cigarettes greatly increases the risk of cancers, especially lung cancer. In addition, several impairments other than lung cancer have been linked to smoking tobacco products, including pulmonary emphysema, heart attacks, etc. Using tobacco as a chew is not without hazards. Tobacco chewers frequently develop oral cancer. For years, inventors have sought tobacco substitutes which are less hazardous and less expensive. Unfortunately, prior inventions have not been well received by tobacco consumers. A good alternative would at least have two relevant tobacco properties: stimulant and robust flavor. Additional desirable properties would be low cost and health enhancing benefits. Regular, non-herbal drinking tea is made from the Camellia Sinensis plant. All drinking teas preferably use young tea leaves. The younger the tea leaves, the better the quality of drinking tea. Teas are generally classified into type by the steps used in processing the tea leaves. Black tea is processed by withering the tea leaves, then conditioning the tea leaves to distribute the enzymes on the tea leaves, rolling the leaves, fermenting the leaves (allowing the leaves to undergo enzymatic oxidation), and firing the leaves. Green teas are prepared without withering and without fermentation in order to prevent oxidation of various polyphenol and flavonoid constituents, and may be prepared according to the Japanese method (steaming and drying, followed by rolling and firing), or by the Chinese method (roasting, followed by rolling and firing). Various intermediates (yellow and red teas) are prepared by omitting or modifying various steps (yellow tea is not fermented, but is withered, roasted, and fired; red tea [Oolong] is partially fermented) used in preparing black and green, teas. White tea is made from buds which are plucked before they open, and then steamed and dried. White tea takes its name from the silver-white hairs on the new buds and tender young leaves. The types and grades of tea and processing methods are described in Food Chemistry, 2nd ed., H. D. Belitz and W. Grosch, Springer, 1999, pp. 886-893, and in The Tea Companion, J. Pettigrew, Macmillan, 1197, pp. 30-39. Web site: http://www.delphion.com/details?pn=US06619293__ •

Tobacco smoke filter and relative composition made of antioxidant and mineral substances Inventor(s): Pera; Ivo E. (1400 St. Charles Pl., Pembroke Pines, FL 33026) Assignee(s): none reported Patent Number: 6,615,843 Date filed: February 28, 2002

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Abstract: A tobacco smoke filter synergist composition is provided comprised of antioxidants and minerals: the former are effective as free radical scavenger and the latter are capable of reducing the other harmful substances from tobacco smoke. In particular, minerals include the magnetized ferrite, which has great adsorbing capacity. The composition can be disposed within a one or more chambers. Excerpt(s): This application claims the benefit of and priority to European Patent Application No. EP 01125053.7, filed Oct. 22, 2001. The present invention relates to the technical sector of smoking articles and in particular of tobacco smoke filter and relative compositions to insert in cigarettes, cigars and pipes. Accumulated evidence by competent medical authorities indicates that the death rate from disease of the coronary arteries and the death from cancer are much higher among persons with a history of regular cigarette smoking than among persons who did not smoke. Smoke free radicals and contaminants are believed to be the primary agents in cigarette smoke hastening death to coronary artery disease. Attempts have been made to reduce the amount of smoke contaminants and other ingredients in tobacco smoke absorbed by the smoker by causing the smoke to pass through filters, which are either embodied in a filter type cigarette or in a holder for the cigarette, cigars or pipe tobacco. Such filters remove a certain proportion of smoke contaminants and tars from the smoke, but the amount remaining and passing into the smoker's system is still far greater than a safe value and is capable of causing objective damage to the lung and heart lining and other parts of the body. Web site: http://www.delphion.com/details?pn=US06615843__ •

Topical formulation of alkyl-, phenyl-pyridone Inventor(s): Scheiwe; Max Werner (Maulburg, DE), Yamauchi; Shitotomo (Tokyo, JP) Assignee(s): Mepha AG (Aesch, CH) Patent Number: 6,492,395 Date filed: May 23, 2001 Abstract: A pharmaceutically acceptable topical formulation for the treatment and/or prevention of skin ailments, more particularly of fibriotic nature such as fibriotic lesional tissues, contiguous warts, contact dermatitis, and keloids, and to assist the healing of burns after surgery, comprising as active ingredient a substituted pyridone of the formula: n-(R.sup.1)-R.sup.2 -2-(1H)pyridone or a pharmaceutically acceptable salt or ester thereof, where R.sup.1 is selected from methyl, ethyl, propyl, carboxyl and a carboxymethyl or carboxyethyl ester group, R.sup.2 is selected from phenyl, methylphenyl, ethylphenyl, propylphenyl, and a carboxyphenyl or carboxyethylphenyl ester group, and n is 3, 4 or 5, together with an excipient, characterized in that the excipient comprises, one or more plasticisers, one or more antioxidants, one or more gel-forming agents and sufficient pH adjusting agent to bring the pH of the formulation to a value from 4 to 8. The preferred active ingredient is 5-methyl-1-phenyl-2(1H)pyridone (Pirfenidone). Excerpt(s): or a pharmaceutically acceptable salt or ester thereof, where R.sup.1 is selected from methyl, ethyl, propyl, carboxyl and a carboxymethyl or carboxyethyl ester group, R.sup.2 is selected from phenyl, methylphenyl, ethylphenyl, propylphenyl, and a carboxyphenyl or carboxyethylphenyl ester group, and n is 3, 4 or 5 (position of substitution). The preferred active ingredient is Pirfenidone (CAS 53179-13-8, 5-methyl1-phenyl-2-(1H)-pyridone). As described in U.S. Pat. No. 5,310,562 and EP 0 383 591,

Patents 169

Pirfenidone has a broad spectrum of applications in the prevention and treatment of fibrotic diseases, especially for the reparation and prevention of fibrotic lesional tissues, contiguous warts, contact dermatitis, keloids, fibrosis of the lung, fibrosis of the prostate, sclerosis, the healing of burns after surgery and Alzheimer disease. Although the possibility of topical application is mentioned, there is no description of any specific formulation. The application of active ingredients of the class mentioned, (hereafter called alkyl,phenyl pyridones) e.g. Pirfenidone for e.g. the treatment of burns and keloids may possibly be carried out using a solution or a suspension of the agent in aqueous or oily excipient such as emulsions, creams, ointments, gels, microemulsions, liquid emulsions, nanocapsule suspensions, liposome formulations, lotions and the like; however, an ointment, cream or gel formulation is preferable because of their soothing effect and easy application. Because these formulations are used in the treatment of humans they are considered to be pharmaceutical preparations, and as thus have to be proven to be physically and chemically stable before they are permitted on the market. For this reason, each formulation must undergo a stability test. Without the necessary data on stability and shelf life, the formulation cannot be approved by any health authority. Web site: http://www.delphion.com/details?pn=US06492395__ •

Use of.gamma.-tocopherol and its oxidative metabolite LLU-.alpha. in the treatment of disease Inventor(s): Wechter; William J. (Redlands, CA) Assignee(s): Loma Linda University Medical Center (Loma Linda, CA) Patent Number: 6,555,575 Date filed: April 26, 2002 Abstract: The present invention is generally related to the discovery of the therapeutic benefit of administering.gamma.-tocopherol and.gamma.-tocopherol derivatives. More specifically, the use of.gamma.-tocopherol and racemic LLU-.alpha., (S)-LLU-.alpha., or.gamma.-tocopherol derivatives as antioxidants and nitrogen oxide scavengers which treat and prevent high blood pressure, thromboembolic disease, cardiovascular disease, cancer, natriuretic disease, the formation of neuropathological lesions, and a reduced immune system response are disclosed. Excerpt(s): The present invention is generally related to the discovery of the therapeutic benefit of administering.gamma.-tocopherol and.gamma.-tocopherol derivatives. More specifically, the use of.gamma.-tocopherol and racemic LLU-.alpha., (S)-LLU-.alpha., or other.gamma.-tocopherol derivatives as antioxidants and nitrogen oxide scavengers which treat and prevent high blood pressure, thromboembolic disease, cardiovascular disease, cancer, natriuretic disease, the formation of neuropathological lesions, and a reduced immune system response are disclosed. Vitamin E, an essential fat-soluble vitamin, encompasses eight naturally occurring compounds in two classes. The first class, tocopherols, have four members designated alpha, beta, gamma and delta. The two major forms,.alpha.-tocopherol and.gamma.-tocopherol, differ structurally only by a methyl group substitution at the 5-position. The second class, tocotrienols, are molecules related to the tocopherols and also consist of four members designated alpha, beta, gamma and delta. The tocotrienol structure differs from the tocopherols by possessing three double bonds in their side chain rather than being saturated. One of the important chemical features of the tocopherols is that they are redox agents which act under certain circumstances as antioxidants. In acting as an antioxidant, tocopherols

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presumably prevent the formation of toxic oxidation products, such as perioxidation products formed from unsaturated fatty acids. Early on, investigators attributed most if not all of the biological activity of the tocopherols to their ability to act as antioxidants. More recently, however, other biological activities have been associated with tocopherols including the modulation of signal transduction, modulation of phospholipid metabolism, inhibition of protein kinase C, inhibition of phospholipase A and inhibition of prostaglandin production. (Meydani and Mosen, The Lancet 345(8943):170-175 (1995)). Web site: http://www.delphion.com/details?pn=US06555575__ •

Use of bathocuproine for the evaluation of the antioxidant power in liquids and solutions Inventor(s): Da Cruz; Giuseppe (San Germano Vercellese, IT) Assignee(s): Med. Dia SRL. (San Germano Vercelles, IT) Patent Number: 6,613,577 Date filed: May 9, 2001 Abstract: The antioxidant power of an organic or inorganic liquid is determined by causing it to enter into competition with bathocuproine (BC) in a copper sulphate solution. Bathocuproine (BC) forms stable complexes with the monovalent Cu. Such a reaction is specific for Cu(I) and not for divalent Cu(II). Cu(II) in solution can be reduced to Cu(I) by a number of reducing compositions belonging to a class of compositions consisting prevailingly of both liposoluble and water soluble nonenzymatic antioxidants. When the reaction occurs in a bathocuproine (BC) buffer, the complex being formed is characterized by the concentration of the reducing agents and then, by good approximation, of the antioxidants present in the system. The quantitative analysis of such a reaction can be easily made by spectrophotometry at 480 nm both by macro- and micromethods with the use of a number of reducing standard compositions with known concentrations. Excerpt(s): This application is the 35 USC 371 national stage of International Application PCT/IT99/00289 filed on Sep. 15 1999, which designated the United States of America. The present invention relates to the chemical analysis and more particularly a method of determining the antioxidant power of an organic or inorganic liquid and/or solution by using bathocuproine. According to the invention, the antioxidant power of an organic or inorganic liquid and/or solution is determined by causing it to enter into competition with bathocuproine in a copper sulphate solution. The results compared with the reducing action of uric acid in water solution or.alpha.-tocopherol in oil solution with known concentration give values expressed in.mu.mol/litre. causing such solution to enter into competition with the sample to be analyzed in a hydrogen peroxide solution. Web site: http://www.delphion.com/details?pn=US06613577__

Patents 171

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Vitamin supplement composition Inventor(s): Herbert; Victor D. (New York, NY) Assignee(s): Upsher-Smith Laboratories, Inc. (Minneapolis, MN) Patent Number: 6,605,646 Date filed: August 9, 2002 Abstract: A vitamin B.sub.12 supplement composition comprising vitamin B.sub.12 with and/or without added folic acid that is essentially free of antioxidants, such as vitamin C, as well as iron is disclosed. Also disclosed are methods of using this vitamin composition to prevent brain and nervous system damage, such as peripheral nerve damage, as well as pernicious anemia, such as where such anemia is caused by a deficiency of vitamin B.sub.12 deficiency. Excerpt(s): Homocystinuria is characterized by high serum homocysteine levels and leads to blood vessel damage, excretion of homocysteine in the urine, mental retardation, ectopia lentis, sparse blonde hair, convulsive tendency, thromboembolic episodes, and fatty changes of liver and is associated with defective formation of cystathionine synthetase. Homocysteine is a homolog of cysteine and is produced by the demethylation of methionine, and is an intermediate in the biosynthesis of cysteine from methionine via cystathionine by cystathioninase. High serum homocysteine-related blood vessel damage may account for up to 20% of U.S. heart attacks, 40% of strokes and 60% of peripheral venous occlusions, in addition to those in the placenta associated with neural tube defects in about 2,000 infants a year. Web site: http://www.delphion.com/details?pn=US06605646__

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Waterborne crosslinkable coating compositions Inventor(s): Fioravanti, Jr.; Louis Carl (Collegeville, PA), Fischer; Gordon Charles (Horsham, PA), Frazza; Mark Stephen (Philadelphia, PA) Assignee(s): Rohm and Haas Company (Philadelphia, PA) Patent Number: 6,512,042 Date filed: December 18, 1996 Abstract: Disclosed are aqueous, storage-stable, crosslinkable polymer compositions comprising: (a) an aqueous dispersion of a an acrylic polymer component containing certain carbonyl-containing functional-groups; (b) a nitrogen-containing compound having at least two carbonyl-reactive nitrogen groups; and (c) optionally, co-solvents, pigments, fillers, dispersants, wetting agents, anti-foam agents, UV absorbers, antioxidants, biocides, and stabilizers. Such compositions are useful as coatings or binders in coating compositions, or as adhesives. Excerpt(s): The present invention relates generally to crosslinkable waterborne polymer compositions, especially emulsions or dispersions. In particular, the present crosslinkable waterborne polymer compositions are useful as coatings or binders in onepack storage-stable coating compositions which have low moisture permeability. It is well known that the durability and aesthetic value of a variety of substrates can be maintained or enhanced by application of a polymeric coating to the surface of such substrates, and that crosslinking after application improves coating performance (for example, by improving film hardness and strength, as well as chemical resistance properties). These improvements are particularly beneficial to substrates that require

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protection from environmental stresses, or substrates to which abrasives or organic solvents (cleaners) are frequently applied. Where polymer particle dispersions contain amine nitrogen reactive carbonyl functional groups, maintaining dispersion stability in the presence of polyfunctional amines is difficult. One method of obtaining a stable polymer particle dispersion in an aqueous carrier is to incorporate carboxy acid functional groups into the polymer backbone. It is thought that, in an aqueous carrier at a pH equal to or greater than the pKa of the acid group, some of the carboxy acid groups located on the surface of the polymer particles ionize and form a dispersion-stabilizing electric double layer around the polymer particle. Sufficient carboxy acid groups must be present to block effectively the reaction between the amine nitrogen groups of the crosslinking agent and the carbonyl groups present on the dispersed polymer particles. Examples of such compositions are disclosed in EP 555 774 A1 (Kriessmann et al.) and WO 93/16133 (Esser). The main drawback to this method is that, although the carboxy acid groups on the polymer backbone stabilize the dispersion, these groups also increase moisture permeability of the resultant coating. That is, in the resulting polymeric coating, the presence of the carboxy acid groups increases the amount of water which is able to pass through the coating or which is absorbed by the coating itself, thus allowing more water to attack the substrate. Web site: http://www.delphion.com/details?pn=US06512042__

Patent Applications on Antioxidants 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 antioxidants: •

3,4-dihydroxybenzyl-substituted carbonic acid derivatives and the use thereof as antioxidants Inventor(s): Johncock, William; (H?ouml;xter, DE), Langner, Roland; (Bevern, DE), Ley, Jakob Peter; (Holzminden, DE) Correspondence: BAYER POLYMERS LLC; 100 BAYER ROAD; PITTSBURGH; PA; 15205; US Patent Application Number: 20030139470 Date filed: December 19, 2002 Abstract: The invention relates to 3,4-dihydroxybenzyl-substituted carbonic acid derivatives, to their production, and to their use as antioxidants or free-radical scavengers, especially in cosmetic and pharmaceutical preparations and in foodstuffs and stimulants, to protect cells and tissues from the harmful effects of radicals and reactive oxygen compounds that accelerate aging. The invention further relates to cosmetic and pharmaceutical preparations and to foodstuffs and stimulants that comprises the inventive 3,4-dihydroxybenzyl-substituted carbonic acid derivatives. Excerpt(s): The invention relates to 3,4-dihydroxybenzyl-substituted carbonic acid derivatives, to the preparation thereof and to the use thereof as antioxidants and/or free-radical scavengers, in particular in cosmetic and/or pharmaceutical preparations

10

This has been a common practice outside the United States prior to December 2000.

Patents 173

for protecting cells and tissue of humans and animals against the harmful effects of free radicals and reactive oxygen compounds which accelerate aging. The invention further relates to cosmetic and/or pharmaceutical preparations, and to foods and/or luxury products comprising these 3,4-dihydroxybenzyl-substituted carbonic acid derivatives. Ultraviolet light, in particular ultraviolet light in the range from 290 to 400 nm, triggers photooxidative processes on and in the skin, in particular of humans and animals, various reactive oxygen compounds or free radicals being formed starting from oxygen. These may, for example, harm or destroy intracellular molecules and thus weaken the cell in its vitality or even cause it to die. In addition, the reactive oxygen compounds or free radicals can also damage the intracellular molecules or structures. In the case of skin, the lipid layer, which serves as a barrier against the environment, and also the sebum may be destroyed by oxidative processes. A major constituent of the vital sebum is considerably unsaturated squalene. Substances and preparations of these substances which, in physiological systems, support the natural defence mechanisms against free radicals and reactive oxygen compounds and/or, as antioxidants or free radical scavengers, protect the lipid layer of the skin against oxidative processes, safeguard the skin from destruction and aging. Such substances also protect oxygen-sensitive materials, such as oxidation-sensitive constituents of cosmetics, pharmaceuticals or foods and/or luxury products. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

4-Hydroxycinnamamide derivatives as antioxidants and pharmaceutical compositions containing them Inventor(s): Jung, Young-Sik; (Daejeon, KR), Kong, Jae-Yang; (Daejeon, KR), Lim, HeeJong; (Daejeon, KR), Park, No-Sang; (Daejeon, KR), Park, Woo-Kyu; (Cheongju-si, KR), Seong, Churl-Min; (Daejeon, KR), Yoon, Joong-Ho; (Gyeongsangnam-do, KR) Correspondence: Michael N. Mercanti; Roberts and Mercanti, L.L.P.; 105 Lock Street, Suite 203; Newark; NJ; 07103; US Patent Application Number: 20030162789 Date filed: November 22, 2002 Excerpt(s): The present invention relates to 4-hydroxycinnamamide derivatives as antioxidants and pharmaceutical compositions containing them. More particularly, it relates to 4-hydroxycinnamamide derivatives showing superior antioxidant activity compared to the known antioxidant compounds, their pharmaceutically acceptable salt, and pharmaceutical compositions containing them. Oxygen plays an important role in producing ATP by oxidizing nutrients at the mitochondria inside cells. However, inevitably, 2-5% of the oxygen changes into reactive oxygen species such as superoxide radical(.O.sub.2.sup.-), hydrogen peroxide(H.sub.2O.sub.2) and hydroxy radical(HO.) that are harmful to human body. As a protector against reactive oxygen species, antioxidant enzymes such as superoxide dismutase, catalase and peroxidase, and antioxidant substances such as glutathion and coenzyme Q (CoQ) are present in vivo, and such antioxidant substances can also be intake with food. However, under specific circumstances such as ischemia, too much active oxygen is generated, which exceeds the biological protect system capacity to cause oxidative stress. Such active oxygen attacks the biological cell to destroy lipid, protein and RNA, DNA, and inhibits various enzymes to cause cancer, neurodegerative diseases and cardiovascular diseases and aging. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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7-Hydroxy chromones as potent antioxidants Inventor(s): Farrow, Thomas M.; (Denver, CO), Jia, Qi; (Superior, CO) Correspondence: SWANSON & BRATSCHUN L.L.C.; 1745 SHEA CENTER DRIVE; SUITE 330; HIGHLANDS RANCH; CO; 80129; US Patent Application Number: 20030207818 Date filed: May 3, 2002 Abstract: The present invention describes the identification and purification of 7hydroxychromes that exhibit potent antioxidant activity. In one embodiment the present invention includes a method for providing an antioxidant to a host in need thereof, comprising administering an effective amount of a 7-hydroxychrome or a mixture of 7-hydroxychromones. The present invention includes methods that are effective in inhibiting free radical and oxidation caused damage through the simultaneous suppression of free radical generation and the suppression of the production of reactive oxygen species (ROS). The present invention also includes methods for preventing and treating ROS mediated diseases and conditions and diseases and conditions associated with other oxidative processes. The method for preventing and treating ROS mediated diseases and conditions and diseases and conditions associated with other oxidative processes is comprised of administering to a host in need thereof an effective amount of a composition comprised of a 7hydroxychrome or a mixture of 7-hydroxychromones and a pharmaceutically acceptable carrier. Included in this invention is an improved method to isolate and purify 7hydroxychromones from plant sources. Excerpt(s): The present invention relates to the field of antioxidants. Specifically, this invention relates to the identification of a class of compounds, referred to herein as 7hydroxychromones, which have potent antioxidant activity. More specifically, this invention relates to a method for the prevention and treatment diseases and conditions associated with reactive oxygen species (ROS) damage and other oxidation processes by administration of one or more 7-hydroxychromones. Included in this invention is an improved method to isolate and purify 7-hydroxychromones from plant sources. Reactive oxygen species (ROS) are produced by normal physiological processes in the body and play a significant role in the flow energy and information in all the living systems. (Voeikov (2001) Riv. Biol. 94:237-258). ROS also perform critical functions related to intercellular induction of apoptosis (Bauer (2000) Anticancer Res. 20:41154139), inflammation processes and immune responses. ROS are also generated as byproducts of normal metabolic processes, from food additives, from environmental sources, such as ultraviolet radiation (Wenk et al. (2001) Curr. Probl. Dermatol. 29:83-94) and tobacco smoke (Stich et al. (1991) American Journal of Clinical Nutrition 53:298S304S), and from many other pollutants. Reactive oxygen species (ROS) include oxygen related free radicals, such as superoxide (O.sub.2.sup.-.), peroxyl (ROO.sup.-.), alkoxyl (RO.sup.-.), hydroxyl (HO.sup.-.), and nitric oxide (NO.sup.-.); and non-radical species, such as the singlet oxygen (.sup.1O.sub.2), hydrogen peroxide (H.sub.2O.sub.2) and hypochlorous acid (HOCl). If the processes that maintain oxidative homeostasis in the cell get out of balance, free radical levels become dangerous, as these are highly reactive, molecules that damage DNA, proteins and components on cell membranes, eventually leading to cellular damage throughout the body and contributing a primary role in the aging process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Aliphatic Polyester-Acrylic Blend Molding Composition Having Good Ductility and Weatherability Inventor(s): Arnould, Dominique Daniel; (Ossendrecht, NL), Hein, Christopher L.; (Evansville, IN), Honigfort, Paul; (Gaithersburg, MD), Pixton, Matthew R.; (Mt. Vernon, IN), Seyvet, Olivier; (Rennes, FR), Vollenberg, Peter H. Th.; (Evansville, IN) Correspondence: OPPEDAHL AND LARSON LLP; P O BOX 5068; DILLON; CO; 804355068; US Patent Application Number: 20030176541 Date filed: March 3, 2003 Abstract: A molding composition has a bulk resin component formed from: a) 5 to 93 percent by weight of cycloaliphatic polyester resin such as poly(1,4-cyclohexanedimethanol-1,4-dicarboxylate having a melt viscosity of at least 6000 poise; b) 5 to 93 percent by weight of an acrylate polymer or co-polymer; and c) 2 to 30 percent by weight of an impact modifier with a a shell comprising a repeating units derived from a C1-12 alkyl(meth)acrylate and a rubbery core having weatherability properties. The composition may further include a polycarbonate polymer or a styrene-acrylonitrile polymer as a phase compatabilizer as well as other conventional additives such as pigments, mineral fillers, antioxidants and the like. The composition has improved ductility, impact strength and weatherability. Excerpt(s): The present application claims the benefit of U.S. Provisional Application No. 60/361431, filed Mar. 1, 2002, the disclosure of which is incorporated herein by reference. The present invention relates to molding compositions based upon blends of thermoplastic polyester resin and thermoplastic polyacrylate resin binder materials. Molding compositions based upon thermoplastic polyacrylate binder materials such as polymethyl methacrylate (PMMA) have good hardness, gloss and weatherability. However they have poor ductility, are brittle and have limited solvent resistance. Molding compositions based upon thermoplastic cycloaliphatic polyester resin binder materials have good ductility, impact strength and weatherability properties at least in the case of cycloaliphatic polyesters which are substantially devoid of aromatic constituents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Antimicrobial lees Inventor(s): Shanbrom, Edward; (Santa Ana, CA) Correspondence: REED SMITH CROSBY HEAFEY LLP; 1901 AVENUE OF THE STARS, SUITE 700; LOS ANGELES; CA; 90067; US Patent Application Number: 20030198699 Date filed: April 9, 2003 Abstract: The lees or "dregs" produced during wine making are rich sources of antioxidants. Unexpectedly, these materials show significant antibacterial properties as well as antioxidant properties. The lees of red wine which consist of tannins and plant pigments precipitated around crystals of potassium tartarate can advantageously be used directly as a tonic or demulcent. The material can also be used topically for disinfecting the skin, etc. In addition, it is possible to use organic polymers to bind the

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pigments and/or solubilize them from the tartaric salt to facilitate their use or to make a relatively pure pigment/tannin component. Excerpt(s): The present application concerns natural products and more especially valuable materials that can be derived from the byproducts of vinification. Currently there is a growing concern on the part of the public that our modern diet of highly processed and refined foods is "missing some essential components" necessary for health and well-being. This "natural food" movement probably derives from at least two sources. First is the discovery of vitamins over the last three quarter's of a century, and the public realization that consumption of apparently adequate food can actually result in a serious deficiency syndrome. It is not hard to imagine that the already discovered vitamins, which are now added back to our refined foods, are but the tip of the iceberg. That is, many other vitamin-like substances may remain to be discovered meaning that our food is presently dangerously deficient in essential nutrients. Second is the realization that consumption of certain foods--in particular animal fats--seems to result in significant heart and vascular disease. Not only has the public come to learn that apparently complete foods are lacking a key ingredient, but the public has also learned that apparently innocuous and much favored foods are actually silent killers. The question in the public mind is "why did fatty foods suddenly become so deadly?" One answer is that fatty foods have always been harmful but that people didn't used to consume so much of them. Another answer is that lack of physical activity exacerbates the damage caused by fatty food--the American public certainly appears to have grown more sedentary as compared to Americans a century ago. However, the picture is convoluted by certain groups of people that appear to be immune to the dangers of fatty diets. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antioxidants for the stabilization of formulations comprising surfactants Inventor(s): Huglin, Dietmar; (Eimeldingen, DE), Kramer, Erich; (Basel, CH) Correspondence: CIBA SPECIALTY CHEMICALS CORPORATION; PATENT DEPARTMENT; 540 WHITE PLAINS RD; P O BOX 2005; TARRYTOWN; NY; 105919005; US Patent Application Number: 20030148916 Date filed: December 18, 2002 Abstract: The invention relates to cleaning compositions comprising(a.sub.1) a phenolic antioxidant of the formula (1) and/or (2); and/or(a.sub.2) an antioxidant of the formula (3); and(b) a surfactant comprising a long alkyl or alkenyl chain.The antioxidants used according to the invention have excellent reactivity, good stability to hydrolysis, particularly in an alkaline medium, and, because of their solubility, can be easily incorporated into the soap formulations. Excerpt(s): Solid and liquid soaps have been used for cleaning human skin for a long time. The stability of the soap composition is an important criterion for problem-free use or a long shelf life. It is known that free radical reactions adversely affect the stability of a soap composition. Free radicals initiate chain reactions which effect the decomposition of the long-chain hydrocarbon chains of the soaps, free acids or synthetic surfactants and the like in cleaning compositions. Such reactions can also bring about other negative effects, such as, for example, discoloration and rancidification. Degradation of the long hydrocarbon chains can be prevented in cleaning compositions by adding antioxidants,

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such as, for example, butylated hydroxytoluene (BHT), which either prevent the catalysis of certain free radical mechanisms or, as free radicals, terminate the free radical chain reaction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Aqueous formulations of parasiticides for skin applications Inventor(s): Dorn, Hubert; (Wuppertal, DE), Heukamp, Ulrich; (Kurten, DE), Sirinyan, Kirkor; (Bergisch Gladbach, DE) Correspondence: JEFFREY M. GREENMAN; VICE PRESIDENT, PATENTS AND LICENSING; BAYER CORPORATION; 400 MORGAN LANE; WEST HAVEN; CT; 06516; US Patent Application Number: 20030162773 Date filed: January 17, 2003 Abstract: The present invention relates to water-containing formulations for the dermal control of parasitic insects on animals, having the following compositiona) agonists or antagonists of the nicotinic acetylcholine receptors of insects in a concentration of from 1 to 20% by weight based on the overall weight of the formulation;b) water in a concentration of from 2.5 to 15% by weight;c) solvents from the group alcohols such as benzyl alcohol, tetrahydrofuryl alcohol or optionally substituted pyrrolidones in a concentration of at least 20% by weight based on the overall weight of the formulation;d) solvents from the group of the cyclic carbonates or lactones in a concentration of from 5 to up to 50% by weight based on the overall weight of the formulation;e) if desired, further auxiliaries from the group thickeners, spreading agents, colorants, antioxidants, propellants, preservatives, adhesives, emulsifiers, in a concentration of from 0.025 up to 10% by weight based on the overall weight of the formulation. Excerpt(s): The present invention relates to water-containing formulations for the dermal control of parasitic insects on animals by means of agonists or antagonists of the nicotinergic acetylcholine receptors of insects. Agonists or antagonists of the nicotinergic acetylcholine receptors of insects are known. They include the nicotinyl insecticides and especially the chloronicotinyl insecticides. Their use against fleas is known, for example, from WO 93/24002 and EP-A 682 869. This invention, accordingly, provides novel water-containing formulations for dermal application of agonists or antagonists of the nicotinergic acetylcholine receptors of insects which are suitable in particular for the dermal control of parasitic insects such as fleas, lice or flies on animals and which are distinguished by their excellent storage stability at low temperature (down to 30.degree. C.). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Cocoa extracts containing solvent-derived cocoa polyphenols from defatted cocoa beans Inventor(s): Buck, Margaret M.; (Morristown, NJ), Hammerstone, John F. JR.; (Nazareth, PA), Romanczyk, Leo J. JR.; (Hackettstown, NJ) Correspondence: CLIFFORD CHANCE US LLP; 200 PARK AVENUE; NEW YORK; NY; 10166; US Patent Application Number: 20030176493 Date filed: January 15, 2003 Abstract: Disclosed and claimed are cocoa extracts such as polyphenols or procyanidins, methods for preparing such extracts, as well as uses for them, especially as antineoplastic agents and antioxidants. Disclosed and claimed are antineoplastic compositions containing cocoa polyphenols or procyanidins and methods for treating patients employing the compositions. Additionally disclosed and claimed is a kit for treating a patient in need of treatment with an antineoplastic agent containing cocoa polyphenols or procyanidins as well as a lyophilized antineoplastic composition containing cocoa polyphenols or procyanidins. Further, disclosed and claimed is the use of the invention in antioxidant, preservative and topiosomerase-inhibiting compositions and methods. Excerpt(s): This invention relates to cocoa extracts such as polyphenols preferably polyphenols enriched with procyanidins. This invention also relates to methods for preparing such extracts, as well as to uses for them; for instance, as antineoplastic agents and antioxidants. Documents are cited in this disclosure with a full citation for each appearing in a References section at the end of the specification, preceding the claims. These documents pertain to the field of this invention; and, each document cited herein is hereby incorporated herein by reference. Polyphenols are an incredibly diverse group of compounds (Ferreira et al., 1992) which widely occur in a variety of plants, some of which enter into the food chain. In some cases they represent an important class of compounds for the human diet. Although some of the polyphenols are considered to be nonnutrative, interest in these compounds has arisen because of their possible beneficial effects on health. For instance, quercitin (a flavonoid) has been shown to possess anticarcinogenic activity in experimental animal studies (Deshner et al., 1991 and Kato et al., 1983). (+)-Catechin and (-)-epicatechin (flavan-3-ols) have been shown to inhibit Leukemia virus reverse transcriptase activity (Chu et al., 1992). Nobotanin (an oligomeric hydrolyzable tannin) has also been shown to possess anti-tumor activity (Okuda et al., 1992). Statistical reports have also shown that stomach cancer mortality is significantly lower in the tea producing districts of Japan. Epigallocatechin gallate has been reported to be the pharmacologically active material in green tea that inhibits mouse skin tumors (Okuda et al., 1992). Ellagic acid has also been shown to possess anticarcinogen activity in various animal tumor models (Bukharta et al., 1992). Lastly, proanthocyanidin oligomers have been patented by the Kikkoman Corporation for use as antimutageris. Indeed, the area of phenolic compounds in foods and their modulation of tumor development in experimental animal models has been recently presented at the 202nd National Meeting of The American Chemical Society (Ho et al., 1992; Huang et al., 1992). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Composite materials with improved phyllosilicate dispersion Inventor(s): Chaiko, David J.; (Naperville, IL) Correspondence: FOLEY & LARDNER; 150 EAST GILMAN STREET; P.O. BOX 1497; MADISON; WI; 53701-1497; US Patent Application Number: 20030176537 Date filed: March 18, 2002 Abstract: The present invention provides phyllosilicates edge modified with anionic surfactants, composite materials made from the edge modified phyllosilicates, and methods for making the same. In various embodiments the phyllosilicates are also surface-modified with hydrophilic lipophilic balance (HLB) modifying agents, polymeric hydrotropes, and antioxidants. The invention also provides blends of edge modified phyllosilicates and semicrystalline waxes. The composite materials are made by dispersing the edge modified phyllosilicates with polymers, particularly polyolefins and elastomers. Excerpt(s): This invention relates to phyllosilicates which have been modified to increase their dispersibility in polymers and methods for producing the same. More particularly, the present invention relates to mineral fillers which have been edge modified to improve their dispersibility in polymer matrices and methods for making composite materials using the mineral fillers. Mineral fillers are used extensively to enhance the performance of a wide range of thermoplastic and thermosetting polymers. Physical properties which are improved by fillers include stiffness, strength, impact and temperature resistance, improved dimensional stability, surface hardness and scratch resistance. Other properties improved with fillers include improved chemical resistance, electrical resistance, and flame retardancy. Mineral fillers can also be used to reduce the thermal expansion coefficient of thermoplastics and permeability to gases and liquids. The most commonly used mineral fillers in plastics are calcium carbonate, wollastonite, silica, and the phyllosilicates such as kaolin, talc, and mica. Talc is unique in that its surface is naturally hydrophobic and therefore compatible with olefinic polymers. On the other hand, calcium carbonate, silica, wollastonite and the other phyllosilicates are hydrophilic and must be surface treated in order to improve their dispersion and interaction with the polymer matrix. The surface treatment of hydrophilic phyllosilicates includes reaction of the basal surface of the mineral with organosilanes, modified oligomers and polymers containing anhydride functional groups, and a wide variety of surfactants. Maximum improvement in mechanical and barrier properties of polymers occurs with the use of well-dispersed platy minerals possessing high aspect ratios. and small particle sizes. The aspect ratios of platy minerals such as mica, talc and kaolin are typically in the range of 30 to 100. Since the late 1980's the focus of much research around the world has shifted from the traditional mineral fillers to the incorporation of fully exfoliated smectite clays, primarily montmorillonite with its extremely high aspect ratio, into a variety of thermoset and thermoplastic polymers. The aspect ratios of exfoliated smectite clays can range from 100 to 1,000 or more. The exfoliation and nanoscale dispersion of small amounts of smectite clays into polymers leads to composite materials with enhanced physical features, but with significant reductions in weight as compared to traditional mineral-filled polymers. Like the other hydrophilic phyllosilicates, the smectite clays must be surface-treated to render them compatible with olefinic polymers. The approach that has been most often used is based on the technology utilized for the last fifty years to make organoclays as Theological control agents in paints, inks, greases, etc. This approach utilizes quaternary amine-based surfactants to render the basal surface of the clay compatible with the polymer matrix.

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Various high-molecular-weight quaternary ammonium salts have been used such as dimethyl dihydrogenated tallow ammonium chloride, dimethyl benzyl hydrogenated tallow ammonium chloride, and methyl benzyl dihydrogenated tallow ammonium chloride. Other onium ions that have been used include the phosphonium and sulfonium groups. Surprisingly, this approach has not been very successful in promoting clay exfoliation in olefinic polymers such as polyethylene and polypropylene and their copolymers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Copper and optical fiber cable with improved filling material Inventor(s): Lichtenburg, Frederick T.; (Hartsdale, NY), Reyes-Gavilan, Jose L.; (Clifton, NJ) Correspondence: Patent Department; Ciba Specialty Chemicals Corporation; 540 White Plains Road; P.O. Box 2005; Tarrytown; NY; 10591-9005; US Patent Application Number: 20030142932 Date filed: October 29, 2002 Abstract: A copper and optical fiber filling material that comprises a hydrocarbon component, which is semisolid at use temperatures in combination with an antioxidant system comprising of (a) sulfur containing primary phenolic antioxidant; (b) a mixture of mono- and di-alkyl butyl/octyl diphenylamine; (c) an organic phosphite or phosphonite and (d) optionally one or more hindered phenol antioxidants exhibits excellent oxidative stability. Excerpt(s): This invention relates to copper and optical fiber cables having a filling material within their core, and more particularly to a filling material that exhibits excellent thermal oxidative stability. More particularly, this invention relates to copper and optical fiber cables having a core in which a composition of matter, which is greaselike and exhibits excellent thermal oxidative stability fills interstices in the core. In the cable industry, it is well known that changes in ambient conditions lead to differences in water vapor pressure between the inside and the outside of a plastic cable jacket. This generally operates to diffuse moisture in a unidirectional manner from the outside of the cable to the inside of the cable. Eventually, this will lead to an undesirably high moisture level inside the cable, especially if a plastic jacket is the only barrier to the ingress of the moisture. High levels of condensed moisture inside a cable sheath system may have a detrimental effect on the transmission characteristics of a metallic conductor cable. Furthermore, water may enter the cable because of damage to the cable, which compromises its integrity. For example, rodent attacks or mechanical impacts may cause openings in the sheath system of the cable to occur, allowing water to enter, and, if not controlled, to move longitudinally along the cable into splice closures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Cosmetic composition and methods of use Inventor(s): Anderson, Glen T.; (Cortlandt Manor, NY), Ptchelintsev, Dmitri; (Mahwah, NJ), Traudt, Michael; (Brookfield, CT) Correspondence: CHARLES N.J. RUGGIERO, ESQ.; OHLANDT, GREELEY, RUGGIERO & PERLE, L.L.P.; 10th FLOOR; ONE LANDMARK SQUARE; STAMFORD; CT; 06901-2682; US Patent Application Number: 20030180233 Date filed: February 18, 2003 Abstract: There are disclosed cosmetic compositions and methods for protection of keratinous tissue against environmental aggressors, such as smoke, smog and UV radiation. The compositions have as an essential antioxidant: (i) hesperetin, (ii) tetrahydrocurcumin, (iii) tetrahydrodemethoxycurcumin, or (iv) tetrahydrobisdemethoxycurcumin, or mixtures of thereof. The compositions are preferably in the form of oil in water emulsions and may optionally contain one or more emulsifiers, preservatives, thickeners, sunscreens, additional antioxidants, emollients, skin protectants, hair protectants, nail protectants and the like. Excerpt(s): The present invention relates to cosmetic, particularly skin care and treatment, compositions. More particularly, the present invention relates to emulsified cosmetic compositions having certain antioxidants. The antioxidants have been found highly effective in ameliorating or preventing damage to keratinous tissue, such as skin, hair and nails, caused by aggressive environmental substances, such as smoke and other atmospheric pollutants, as well as minimizing or relieving damage caused by ultraviolet radiation. Skin treatment compositions are extensively described in the art. Emulsified skin treatment compositions are disclosed in U.S. Pat. No. 5,093,109 to Mausner, which issued on Mar. 3, 1992. This patent provides an anti-aging composition comprising water, an anti-aging agent, a sunscreen, a preservative, a thickener, an antioxidant and an emulsifier. This patent discloses only "Tenox II", a product of Eastman Chemical Products, Inc., and ascorbyl palmitate as suitable antioxidants. U.S. Pat. No. 4,742,066 to Deckner et al., which issued on May 3, 1988, discloses a method for inhibiting the generation of free radicals in the skin. The method comprises applying a composition that may be in the form of an emulsion in which the free radical inhibitor may be ethoxyquin or "Trolox C". "Trolox C" is a product of Hoffmann-LaRoche. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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COSMETIC USE OF SELECTED POLYAMINO POLYMERS AS ANTIOXIDANTS Inventor(s): BOUSSOUIRA, BOUDIAF; (PARIS, FR), COLIN, CHRISTIAN; (PARIS, FR) Correspondence: FINNEGAN HENDERSON FARABOW; GARRETT & DUNNER; 1300 I STREET N W; WASHINGTON; DC; 200053315 Patent Application Number: 20030190335 Date filed: May 22, 1998 Abstract: Use of a polyamino polymer to inhibit the light-induced peroxidation of lipids, particularly inhibition of the photo-peroxidation of lipids induced by nanopigments. The invention also relates to the use of a polyamino polymer to inhibit the light-induced peroxidation of proteins. This property of polyamino polymers finds applications in particular in the cosmetics, pharmaceutical, veterinary and agrifood fields.

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Excerpt(s): Applicants reference herein the patent applications of BOUDIAF BOUSSOUIRA and DIDIER CANDAU for COMPOSITION COMPRISING A DIBENZOYLMETHANE DERIVATIVE AND A POLYAMINO POLYMER(Docket No. 05725.0304), and of BOUDIAF BOUSSOUIRA and DIDIER CANDAU for COMPOSITION COMPRISING A CINNAMIC ACID DERIVATIVE AND A POLYAMINO POLYMER (Docket No. 05725.0305), filed on even date herewith and incorporate the disclosures thereof specifically by reference herein. The present invention relates to the use of a polyamino polymer as an antioxidant. The invention relates in particular to the use of a polyamino polymer in order to inhibit the lightinduced peroxidation of lipids. This invention relates in particular to inhibition of the light-induced peroxidation of lipids of sebaceous origin (sebum), such as squalene, as well as to the light-induced peroxidation (or photo-peroxidation) of plant oils. The invention relates particularly to inhibition of the photo-peroxidation of lipids induced by nanopigments. The invention also relates to the use of a polyamino polymer in order to inhibit the light-induced peroxidation of proteins. This invention relates in particular to inhibition of the light-induced peroxidation of proteins of the skin, such as collagen, as well as to inhibition of the light-induced peroxidation (or photo-peroxidation) of proteins of animal or plant origin and derivatives thereof. This property of the polyamino polymers finds applications in particular in the cosmetic, pharmaceutical, veterinary and agrifood fields. It is known that lipids found at the surface of the skin, the scalp and the hair are permanently subjected to external attack and in particular to air, atmospheric pollutants, visible radiation and especially ultraviolet (UV) radiation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Dental care compositions Inventor(s): Lawlor, Thomas Mark; (Ashford, GB) 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: 20030198604 Date filed: April 25, 2003 Abstract: Disclosed are non volatile oral care compositions that comprise:i) from about 0.5% to about 60%, by weight, of a silicone resin;ii) from about 0.1% to about 30%, by weight, of a silicone gum;iii) from about 0.1% to about 95%, by weight, of a non volatile polysiloxane fluid which has a viscosity from about 1 cStk to about 1000 cStk; andiv) from about 0.01% to about 50%, by weight, of an oral care active selected from teeth colour modifying substances, anti-tartar agents, anti-plaque agents, fluoride ion sources, anti-microbial agents, nutrients, antioxidants, H-2 antagonists, analgesics, anti-viral agents, mucosally absorbed pharmacological agents and mixtures thereof.A second aspect of the present invention relates to the use of non volatile oral care silicone compositions in the oral cavity to treat the hard and soft tissue surfaces wherein the composition comprises:(i) from about 0.5% to about 60%, by weight, of a silicone resin;(ii) from about 0.1% to about 30%, by weight of a silicone gum;(iii) from about 0.1% to about 95%, by weight, of a non volatile polysiloxane fluid which has a viscosity from about 1 cStk to about 1000 cStk.Compositions of the present invention are useful for providing a substantive composition on the surfaces of the oral cavity which can provide prophylactic, therapeutic or cosmetic benefits.

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Excerpt(s): This application is a continuation of International Application PCT/US00/29384 with an international filing date of Oct. 25, 2000. The present invention relates to oral care compositions, which comprise a silicone resin, a silicone gum and a silicone fluid, and to the use of such oral care compositions to treat the hard and soft tissue surfaces of the oral cavity. More particularly, this invention relates to silicone oral care compositions which form a substantive film on the surface of the teeth or gums treating these surfaces and which are readily removed by brushing, rinsing or eating at the end of the treatment period. According to one aspect of this invention the compositions can also comprise an oral care active and as such can provide sustained delivery of this active to the tissues of the oral cavity. Compositions of the present invention are particularly useful for delivering of oral care actives, which either enhance the appearance of the teeth or provide therapeutic and/or prophylactic benefits. Many consumers have a good understanding of the prophylactic, therapeutic and cosmetic benefits of maintaining high standards in oral hygiene. These benefits include reduction in caries, plaque, gingivitis and tartar; treating hypersensitivity; freshening breath; whitening teeth and removing stains; remineralising teeth and the like. To date, a wide variety of oral care products are available which, over the short term, aid the maintenance of good oral hygiene by delivering various oral care substances or actives to the soft and hard tissues of the oral cavity. In general such products exist in the form that they are used by the consumer themselves either at-home or away from the home and/or are administered by dentists/hygienists as part of their professional routine of oral hygiene treatments. Specific examples of such products, particularly those for use by the consumer themselves, include dentifrices containing for example anti-caries actives and/or anti-bacterial plaque reducing actives; mouth washes containing breath freshening actives and/or anti-bacterial actives; and chewing gums containing tooth whitening actives. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Drechsleranol derivatives, processes for their preparation and their use Inventor(s): Eder, Claudia; (Hofheim, DE), Kurz, Michael; (Hofheim, DE), Toti, Luigi; (Hochheim, DE) Correspondence: ROSS J. OEHLER; AVENTIS PHARMACEUTICALS INC.; ROUTE 202-206; MAIL CODE: D303A; BRIDGEWATER; NJ; 08807; US Patent Application Number: 20030171427 Date filed: January 27, 2003 Abstract: The present invention provides novel drechsleranol compounds of formula (I) which are formed by the microorganism Drechslera australiensis, ST 003360, DSM 14093, or a fungus ST 004112, DSM 14524, during fermentation. A process for their preparation, pharmaceutical compositions containing said drechsleranols, their use for the treatment and/or prophylaxis of degenerative neuropathies, such as, Alzheimer's disease, or psychiatric disorders, such as depression, sleep disturbances or seasonally related affective disorders, and their use as chelating agents or antioxidants are also disclosed and claimed. 1 Excerpt(s): This application claims the benefit of German priority document number 10203557.1, filed Jan. 29, 2002, and U.S. Provisional Application No. 60/360,363, filed Feb. 28, 2002. The present invention relates to novel compounds called drechsleranols, which are formed by the microorganism Drechslera australiensis, ST 003360, DSM 14093, or a fungus ST 004112, DSM 14524, which has not been determined more closely

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taxonomically, during fermentation, a process for the preparation of these compounds, their use as pharmaceutical compositions, and their use for the treatment and/or prophylaxis of degenerative neuropathies, for example, Alzheimer's disease, or psychiatric disorders, such as depression, sleep disturbances or seasonally related affective disorders. Alzheimer's disease is a neuropsychiatric disorder which mainly occurs in elderly people. The disease is manifested by a multitude of symptoms which includes memory disorders, reduced perceptivity, orientation disorders, speech disorders, disorders of coordinated thought, etc. In Alzheimer's patients, characteristic neurohistological changes are found in the brain, such as, for example, deposits of "amyloid plaques" and also a degeneration of the neurofibrils in the nerve cells ("fibrillar bundles"). These neurohistological changes are characteristic, but nonspecific, since they also occur to a smaller extent in the normal aging process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Drugs, foods or drinks with the use of algae-derived physiologically active substances Inventor(s): Enoki, Tatsuji; (Otsu-shi, JP), Ikai, Katsushige; (Koka-gun, JP), Kato, Ikunoshin; (Uji-shi, JP), Koyama, Nobuto; (Uji-shi, JP), Nishiyama, Eiji; (Moriyama-shi, JP), Sagawa, Hiroaki; (Kusatsu-shi, JP), Sakai, Takeshi; (Hirosaki-shi, JP), Tominaga, Takanari; (Otsu-shi, JP), Yu, Fu-Gong; (Hirosaki-shi, JP) Correspondence: BROWDY AND NEIMARK, P.L.L.C.; SUITE 300; 624 NINTH STREET, N.W.; WASHINGTON; DC; 20001-5303; US Patent Application Number: 20030105029 Date filed: August 27, 2002 Abstract: Medicinal compositions for treating, ameliorating or preventing diseases with sensitivity to 3,6-anhydrogalactopyranose are represented by formula (I): 1These compositions include foods, drinks, cosmetics, etc. containing as the active ingredient at least one such compound, its aldehyde, its hydrate and 2-O-methylated derivatives thereof and soluble sugar compounds containing the above compound. These compounds show an apoptosis-inducing activity, carcinostatic activity and inhibitory activities on the production of active oxygen, lipid peroxide radicals and NO, which makes them useful also as the active ingredient of antioxidants and preservatives. Excerpt(s): The present invention relates to use of a physiologically active substance derived from algae. More specifically, it relates to a pharmaceutical composition, an antioxidant, a preservative composition for keeping freshness of foods and drinks, and a cosmetic composition which comprise the physiologically active substance as an active ingredient, as well as a functional food or drink which comprises the physiologically active substance. Furthermore, it relates to a saccharide for exhibiting the function. Recently, a mode of death of cells or tissues called as apoptosis (self-blasting or selfdestruction of cells) has been noticed. The apoptosis is a death which has been originally programmed in the genome of a cell and is different from necrosis which is a pathological cell death. Certain external or internal factors trigger the activation of a gene that programs the apoptosis to cause the biosynthesis of a programmed death protein. In some cases, a programmed death protein which has been present in a cell in its inactive form becomes activated. The active programmed death protein thus formed decomposes the cell to lead death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 185

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Elastomeric intumescent material Inventor(s): Abu-Isa, Ismat A.; (Rochester Hills, MI) Correspondence: VINCENT A. CICHOSZ; DELPHI TECHNOLOGIES, INC.; Legal Staff, Mail Code: 480-414-420; P.O. Box 5052; Troy; MI; 48007-5052; US Patent Application Number: 20030139492 Date filed: January 23, 2002 Abstract: A moldable elastomeric intumescent material comprises chlorinated polyethylene, plasticizers, phosphate based foaming agents, char forming materials, antioxidants, intumescent materials, flame retardant materials, and graphite and/or expandable graphite. A curing agent, and optionally a co-curing agent or an accelerator, may further be incorporated into the material to improve the rigidity of the material when it is exposed to fire. The composition also possesses enhanced intumescence and flame retardancy properties by the addition of graphite, and preferably expandable graphite, to the composition. Excerpt(s): This invention relates to fire protection materials, and, more particularly, to a moldable elastomeric intumescent composition. Various methods exist for the protection of persons and property against fire. Among these methods is the use of flame retardant materials, which generally comprise intumescent composite compounds that swell and form ceramic-like sponges when exposed to the high temperatures generally associated with fires. Typically, intumescent materials are incorporated into coatings or paints and are most often formed into mat-like structures that may be placed between a high fire risk apparatus and an apparatus or area for which fire protection is desired. Intumescent coatings are generally used on the wall surfaces of buildings, ships, aircraft, motor vehicles, or other vessels intended for human occupancy and which are susceptible to fires. The nature of the intumescent coating allows its thickness to be kept at a minimum until it is activated by high temperatures at which point the coating expands. Such intumescent coatings contain film-forming resins that, upon being subjected to high temperatures, undergo molecular changes that result in corresponding changes in physical properties such as a reduced ability to conduct heat. The intumescent coatings also contain ingredients that will react upon heating to generate gases and form an incombustible or low combustible residue, e.g., char. The expelled gases expand the residue or char into a foam having thermal insulating properties. In many instances a considerable portion of the char produced is a carbon material; the reaction product formed by the dehydration of a polyhydric substance such as a polyalcohol. The char forming reactions of the ingredients occur within the intumescent coating so that when the coating film is heated to beyond a specific elevated temperature, intumescent additives, such as polyhydric alcohol, ammonium hydrogen phosphate and hydrated magnesia, are decomposed, thereby generating water, carbon dioxide, ammonia, and/or other heat absorbing gases that do not readily support combustion. However, although intumescent coatings are readily available, their application to a surface requires a lengthy and complicated process. Often times, a primer is required to promote adhesion to the surface. In addition, the primer and/or intumescent coating require a substantial drying time, sometimes as long as many hours. When these primed intumescent coatings are exposed to fire and intumesce, the coatings transform into a weak sponge that cannot withstand raging drafts and thermal expansion forces that occur as a result of the fire. Oftentimes as a result, the intumescent coating provides only limited protection for a short period of time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Heat resistant organoclay Inventor(s): Kondo, Mitsuji; (Annaka-si, JP), Ohya, Mituru; (Annaka-si, JP), Onikata, Masanobu; (Gunma, JP) Correspondence: ARENT FOX KINTNER PLOTKIN & KAHN; 1050 CONNECTICUT AVENUE, N.W.; SUITE 400; WASHINGTON; DC; 20036; US Patent Application Number: 20030183809 Date filed: October 24, 2002 Abstract: A heat resisting organoclay which, when incorporated to plastic compounds at high processing temperature in excess of 150.degree. C., does not discolor the plastics, as well as a method of manufacture thereof, is provided. Antioxidant is intercalated between interlayers of the clay flakes to make a heat resistant organoclay. More specifically, antioxidant dissolved in a water-soluble organic solvent is added to a raw filter cake of organoclay for mixing. Alternatively, an aqueous solution of organic cations and antioxidants is added to a clay-water suspension. Then, they are mixed, filtered, dried and pulverized to produce a heat resistant organoclay. Excerpt(s): The present invention relates to an improved heat-resistant organoclay that does not discolor plastics even when the organoclay is incorporated to a plastic compound at an elevated processing temperature higher than approximately 150 degrees Celsius, and also to a method of manufacturing such an organoclay. As already known, an organoclay modifies physical properties such as viscosity, thixotropy, mechanical properties, barrier properties and so on, as its flakes are delaminated and dispersed in body of organic materials. Because of the performance of the organoclay, it has found applications in a wide range of field, including inks, greases, cosmetics, sealant and organic coatings as an agent for thickening and/or rheology controlling. In recent years, it has also been spotlighted as functional filler. It significantly improves mechanical properties of plastics, such as strength, elastic modulus and thermal deformation, as well as other properties such as inflammability, gas permeability and visible clarity when the flakes of the organoclay are delaminated and dispersed in as small a size as a nanometer unit in a variety of polymers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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LOW ASH LUBRICANT COMPOSITIONS CONTAINING OVERBASED MATERIALS AND MULTIPLE ANTIOXIDANTS

MULTIPLE

Inventor(s): Bardasz, Ewa A.; (Mentor, OH), Carrick, Virginia A.; (Chardon, OH), Ripple, David E.; (Kirtland, OH) Correspondence: The Lubrizol Corporation; 29400 Lakeland Boulevard; Wickliffe; OH; 44092-2298; US Patent Application Number: 20030134756 Date filed: May 28, 2002 Abstract: A low sulfate ash lubricating oil composition comprising an oil of lubricating viscosity, 0.1 to 3.0% of a calcium overbased acidic material, 0.1 to 2.0% of a magnesium overbased acidic material, and at least 0.5% of a combination of an alkylene-coupled hindered phenol antioxidant and an antioxidant other than an alkylene-coupled hindered phenol antioxidant, is particularly useful for lubricating stationary gas engines.

Patents 187

Excerpt(s): The present invention relates to lubricating oil compositions and concentrates therefore which provide low sulfated ash while maintaining high performance standards. There is continuous need for improving the performance characteristics of gasoline and diesel engines, stationary gas engines, and the lubricating oils used therein. For example, modern diesel engines are sometimes fitted with a particulate trap to minimize the amount of particulates which are emitted to the atmosphere as pollution. Such particulates may include soot from incomplete combustion but also include ash of various types, much of which is non-volatile metal compounds originating from metal-containing additives in the fuel or, especially, in the lubricant. Excessive ash buildup in particulate traps is a concern because certain types of metal-containing ash are not readily removed from the trap, thus making the regeneration and reuse of such traps difficult if not impossible. Likewise, stationary gas engines (typically large, heavy duty, stationary engines designed to run on natural gas and other like fuels) are facing changes. Trends in such engines include the development of smaller four-cycle, lean burning engines, for which low ash, high performance lubricants are important. Despite the drawbacks from the use of metal compounds in lubricants, additives, including metal-containing additives, have been used for many years and will likely continue to be used for many years in the future. This is because metal-containing additives perform essential functions in motor oils and other lubricants. Certain metal salts are detergents, which serve to neutralize acidic combustion products which make their way into motor oil. Others are dispersants or antiwear agents. To simply reduce or eliminate the amount of metal-containing additives from a motor oil would lead to failure of the oil in many industry-mandated performance tests. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Lubricating oil composition comprising borated and EC-treated succinimides and phenolic antioxidants Inventor(s): Kleijwegt, Peter; (Heinenoord, NL), Van Dam, Willem; (Novato, CA) Correspondence: Josetta I. Jones; ChevronTexaco Corporation; P.O. Box 6006; San Ramon; CA; 94583-0806; US Patent Application Number: 20030171224 Date filed: February 14, 2003 Abstract: An additive package comprising one or more borated dispersants, one or more EC-treated dispersants, and one or more phenolic antioxidants; a lubricating oil composition comprising said additive package; and a method of controlling bearing corrosion and valve train wear using said lubricating oil. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Application No. 60/357,028, filed Feb. 14, 2002. Lubricating oil deterioration and nitration is a problem with any lubricating oil when used in an engine. This problem is exacerbated in diesel engines that are equipped with exhaust gas recirculation systems that introduce NOx into the system because the level of NOx produced in such engines promotes oil nitration and deterioration. Elevated temperatures typically found in engines affect lubricating oil deterioration and increase the level of acid contamination. This problem is exacerbated in heavy-duty diesel engines equipped with exhaust gas recirculation systems because the operating temperatures for these engines are higher than other types of engines. The level of acid contamination is also higher than other types of engines. Higher operating temperatures and acid contamination may result in

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increased bearing corrosion. Lubricating engines with the lubricating oil of this invention resulted in improved bearing corrosion control in heavy-duty diesel engines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for assaying the antioxidant capacity of a sample Inventor(s): Hampsch-Woodill, Maureen; (Hyannis, MA), Huang, Dejian; (Randolph, MA), Ou, Boxin; (Stoughton, MA) Correspondence: IANDIORIO & TESKA; INTELLECTUAL PROPERTY LAW ATTORNEY; 260 BEAR HILL ROAD; WALTHAM; MA; 02451-1018; US Patent Application Number: 20030162297 Date filed: February 15, 2002 Abstract: A method of assaying the antioxidant capacity of a sample, the method including preparing an extraction solution including a solubility enhancing compound, adding the sample to the extraction solution, extracting the antioxidants present in the sample, adding a fluorescent probe to the extract, adding a free radical generator to the extract, detecting the fluorescence intensity decay of the probe in the presence of the sample over time, and calculating the antioxidant capacity of the sample based on the fluorescence intensity decay of the probe in the presence of the sample. Excerpt(s): This invention relates to an improved method for assaying the antioxidant capacity of a sample. Molecules are composed of atoms bonded together. This bonding process is accomplished by the sharing of electrons. When two atoms come together and their electrons pair up, a bond is created. Generally, only two electrons can exist in one bond. Paired electrons are quite stable and almost all electrons in the human body exist in a paired state. However, when a bond is broken, the electrons can either stay together or split up. If the electrons stay together, both electrons go to one of the atoms and none go to the other atom. In this case the molecular fragments are called ions, which are electrically charged and typically not harmful to humans or other animals. For example, sodium chloride, NaCl, can split up into a sodium cation (Na.sup.+) and a chloride anion (Cl.sup.-). But, if the electrons split up when a bond is broken, one electron will go to each atom, creating two molecules with unpaired electrons, called free radicals. The unpaired electrons of these free radicals are highly energetic and unstable and seek out other electrons with which to pair with. As a result, free radicals steal electrons from other molecules. The process of stealing electrons from other electron pairs is what makes free radicals dangerous because it causes oxidation, or loss of electrons, to the molecule it attacks, leaving an unstable, highly energetic molecule. Since most electrons exist in a paired state, free radicals often end up reacting with paired electrons and create still more free radicals. Only when a free radical pairs up with another free radical is the free radical terminated. Antioxidants, or free radical scavengers, function by offering easy electron targets for free radicals. In absorbing a free radical, antioxidants "trap", or de-energize and stabilize the lone free-radical electron and make it stable enough not be harmful. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 189

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Method for improving the paint adhesion of compatibilized polyphenylene etherpolyamide compositions Inventor(s): Gisbergen, Josephus Gerardus M. van; (Bergen op Zoom, NL), Ting, Sai-Pei; (Slingerlands, NY), van Bennekom, Antoinette C. M.; (Hansweert, NL) Correspondence: CANTOR COLBURN, LLP; 55 GRIFFIN ROAD SOUTH; BLOOMFIELD; CT; 06002 Patent Application Number: 20030130406 Date filed: November 7, 2002 Abstract: Thermoplastic resin composition are provided that comprise a thermoplastic resin and an amount of antioxidant effective to increase the adhesion of paint to an article made from the composition. Also provided are methods to improve the paint adhesion of articles wherein the articles have been subjected to a temperature of at least about 330.degree. F. for period of at least about 10 minutes. In a preferred embodiment, the antioxidant, also known as a stabilizer, or mixture of stabilizers is selected from the group consisting of the phenolic antioxidants, the 3-arylbenzofuranones, the hindered amine stabilizers, the ultraviolet light absorbers, the alkaline metal salts of fatty acids, the hydrotalcites, the epoxydized soybean oils, the hydroxylamines, the tertiary amine oxides, thermal reaction products of tertiary amine oxides, the thiosynergists, and mixture containing at least one of the foregoing. Excerpt(s): This application is a continuation in part of application Ser. No. 09/635,041 filed on Aug. 4, 2000, which claims the benefit of U.S. Provisional Application No. 60/201,805, filed May 4, 2000, the entire contents of both patents are incorporated herein by reference. The invention relates to methods to increase the paint adhesion of an article made from compatibilized polyphenylene ether-polyamide resin blends. The invention also relates to the compositions and articles, e.g., automotive components, made from the compositions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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METHOD OF EXTRACTING ANTIOXIDANTS FROM LAMIACEAE SPECIES AND THE EXTRACT PRODUCTS THEREOF Inventor(s): BRINKHAUS, FRIEDHELM; (DES MOINES, IA), GREAVES, JOHN; (DES MOINES, IA), HAWORTH, JAMES; (DES MOINES, IA) Correspondence: DAVIS, BROWN, KOEHN, SHORS & ROBERTS, P.C.; THE FINANCIAL CENTER; 666 WALNUT STREET; SUITE 2500; DES MOINES; IA; 503093993; US Patent Application Number: 20030185916 Date filed: May 20, 1998 Abstract: An increase in specific antioxidant activity of extracts from rosemary (Rosemarinus officinalis) is obtained by the use of a blend of tetrafluoroethane and acetone in the extraction process. A blend of tetrafluoroethane, acetone and methanol improves total yield. A tetrafluoroethane and acetone blend has higher efficacy but comparatively lower yields. The methods yield a liquid and oily extract that is readily mixed with a liquid product such as soybean oil for addition to animal feeds and human food.

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Excerpt(s): The invention relates generally to a method for extracting antioxidants from and, more specifically, to an improved method of extracting antioxidants from species of the family Labiatae, in particular, rosemary (Rosemarinus officinalis), using tetrafluoroethane based solvent blends and which yields a liquid and oily extract that is readily mixed with an edible oil for addition to animal feeds and human food. Worldwide demand for natural antioxidants has been rising due to safety concerns about synthetic food and feed additives and the public perception that natural food and feed supplements provide certain health benefits. The most important natural antioxidants being exploited commercially today are tocopherols. Tocopherols have a potent ability to inhibit lipid peroxidation in vivo by trapping peroxy radicals (Burton, G. W., and K. U Ingold (1989), in Vitamin E: Biochemistry and Health Implications, edited by A. T. Diplock, L. J. Machlin, L. Packer and W. A. Pryor, The New York Academy of Sciences, New York, pp 7-22). Various herbal extracts for use as natural antioxidants are being explored. Possibilities include the extraction of rosemary or other botanical sources. Such new antioxidants may play a role in combating carcinogenesis as well as the aging process, and may be applicable in the nutraceutical industry. Among the various natural extracts available in the market are rosemary extracts, which are reported to be highly effective in retarding lipid oxidation and protecting living cells from the damaging oxidative stress (Chen, Q., H. Shi and C-T Ho (1992), "Effects of rosemary extracts and major constituents on lipid oxidation and soybean lipoxygenase activity", J Am Oil Chem Soc 69: 999-1002; Wong, J. W., K. Hashimoto and T. Shibamoto (1995), "Antioxidant activities of rosemary and sage extracts and vitamin E in a model meat system", J Agric Food Chem 43: 2707-2712). These extracts are described as being superior to vitamin E, a well-known natural antioxidant and food supplement, in many food model systems (Lolinge, J, (1983), Natural antioxidants in Allen, J. C. and R. J. Hamilton eds, Rancidity in Foods, Elsevier Applied Science, London, Chapter 6). However, opposite findings are also documented. Wong et al. (1995) revealed that vitamin E is more effective than rosemary extract in a cooked beef homogenate. Additionally, rosemary extract is shown to be a synergist of vitamin E in stabilizing or retarding oxidation in sardine oil and fish muscle (Fang, X. and S. Wanda (1993), "Enhancing the antioxidant effect of.alpha.-tocopherol with rosemary extract in inhibiting catalyzed oxidation caused by Fe.sup.2+ and hemoprotein", Food Res Int 26: 405-411; Wanda, S. and X. Fang (1992), "The synergistic antioxidant effect of rosemary extract and.alpha.-tocopherol in sardine oil model system and frozen-crushed fish meat", J Food Process Preserv 16: 263-274). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for identifying compounds as antioxidants Inventor(s): Crapo, James D.; (Cherry Hills Village, CO), Day, Brian J.; (Englewood, CO), Melov, Simon; (Atlanta, GA), Wallace, Douglas C.; (Atlanta, GA) Correspondence: GREENLEE WINNER AND SULLIVAN P C; 5370 MANHATTAN CIRCLE; SUITE 201; BOULDER; CO; 80303; US Patent Application Number: 20030167474 Date filed: November 9, 2001 Abstract: The present application describes methods for the testing of compounds of potential usefulness as therapeutic antioxidants and/or as therapeutic free radical scavengers. The animal model for testing such compounds is the Sod2CJE homozygous Manganese Superoxide Dismutase-deficient mouse. When pups of these mice are

Patents 191

treated with certain antioxidants, they survive past about 7 days of age, and later develop characteristic histological changes and characteristic neurobehavioral disorders. Those treated mice can be further treated with test compounds which may or may not cross the blood brain barrier, and the life span and physical and neurobehavioral characteristics of those mice provide information about the potential utility of the test compound as a therapeutic antioxidant. Phenotypes of the treated mice allow conclusions regarding targeted areas of the brain and thus, applications to particular disorders such as Parkinsonism. Excerpt(s): This application is a Continuation of U.S. application Ser. No. 09/454,126 filed Dec. 3, 1999, which is a Continuation of U.S. application Ser. No. 08/924,301 filed Sep. 5, 1997, which is a Continuation-in-Part of U.S. Provisional Patent Application Serial No. 60/024,702, filed Sep. 6, 1996. The field of the invention is the area of the testing of pharmaceuticals in animal model systems, particularly those pharmaceuticals of benefit in protecting a human or animal against oxidative damage. Oxygen is a critical element in biological systems, having roles including a terminal electron acceptor in oxidative phosphorylation, in dioxygenase reactions, in hydroxylation reactions, in reactions involving activation and/or inactivation of xenobiotics, including carcinogens and in normal animal host defense mechanisms. Despite the wide range of essential and desirable reactions in which oxygen plays a role, the generation of excess amounts of oxygen free radicals through cellular processes has deleterious effects on biological systems including, without limitation, membrane lipid peroxidation, oxidation of nucleic acids, oxidation of sulfhydryl bonds and other moieties which are sensitive to oxidative damage. It has also been theorized that the effects of aging are due, in part, to cumulative oxidative damage to cellular systems. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for preventing and treating loss of balance function due to oxidative stress Inventor(s): Kopke, Richard D.; (San Diego, CA) Correspondence: Counsel for Intellectual Property; Naval Medical Research Center; 503 Robert Grant Avenue; Silver Spring; MD; 20910-7500; US Patent Application Number: 20030191064 Date filed: March 31, 2003 Abstract: The present invention provides methods for preventing and treating loss of, or impairments to, the sense of balance. Specifically, the invention provides methods for preserving the sensory hair cells and neurons of the inner ear vestibular apparatus by preventing or reducing the damaging effects of oxidative stress by administering an effective amount of the following therapeutic agents: antioxidants; compounds utilized by inner ear cells for synthesis of glutathione; antioxidant enzyme inducers; trophic factors; mitochondrial biogenesis factors; and combinations thereof. Excerpt(s): This application is a continuation-in-part application of U.S. application Ser. No. 09/766,625 filed Jan. 23, 2001 (the entirety of which is incorporated herein by reference for all purposes) which claims benefit of Non-Provisional application Ser. No. 09/126,707, now U.S. Pat. No. 6,177,434 filed Jul. 31, 1998 (the entirety of which is incorporated herein by reference for all purposes) which claims benefit of provisional application No. 60/069,761 filed Dec. 16, 1997 (the entirety of which is incorporated herein by reference for all purposes). The present invention relates generally to methods and composition for preventing and treating loss of, or impairments to, the sense of

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balance. More specifically, the invention provides methods and composition for preserving the sensory hair cells and neurons of the inner ear vestibular apparatus by preventing or reducing the damaging effects of oxidative stress by administering an effective amount of certain therapeutic agents to a subject at risk for or experiencing loss of balance or injury to the inner ear balance organ. Balance dysfunction is a common disorder affecting as many as 40 million people in the United States per year. Dizziness is one of the most frequent complaints causing a patient to seek medical care (See Palaniappan R., Balance Disorders in Adults: An Overview, Hosp. Med. Vol., (2002) 63(5):278-81). Balance problems are a frequent cause of falls among the elderly and such falls are a common cause of death in this population (See Bloem B., Steijns J., and SmitsEngelsman B., An Update on Falls, Curr. Opin. in Neurol., (2003) 16(1):15-26). At this time, medical treatment for balance disorders consists of supportive therapy, treatment of symptoms, and surgical or medical ablation of the injured ear where dizziness symptoms are relieved by cutting the balance nerve or completely destroying the balance tissue. Currently, there is no clinically proven medical approach for balance disorders that is aimed at preventing or reversing injury to the inner ear balance system (See Brandt T., Management of Vestibular Disorders, J. Neurol. (2000) 247(7):491-9). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for the treatment of skin disorders Inventor(s): Rosenbloom, Richard A.; (Elkins Park, PA) Correspondence: KNOBLE & YOSHIDA; EIGHT PENN CENTER; SUITE 1350, 1628 JOHN F KENNEDY BLVD; PHILADELPHIA; PA; 19103; US Patent Application Number: 20030105031 Date filed: October 24, 2002 Abstract: Methods for the reduction, treatment or partial prevention of reactive and inflammatory dermatoses, including eczema and psoriasis, are provided. The methods comprise administering a composition that includes one or more flavonoids and is optionally formulated in a pharmaceutically acceptable carrier. Also provided are methods of facilitating the healing of wounds, and of cleansing, beautifying, and improving the cosmetic appearance of the skin. Further optional ingredients may be added to the composition used in the present invention, such as non-flavonoid antioxidants, and one or more compounds that regulate cell differentiation and/or cell proliferation. The composition may be administered as a topical composition. Excerpt(s): The present application is a continuation-in-part of U.S. application Ser. No. 10/132,642, filed on Apr. 25, 2002, which is a continuation-in-part of U.S. application Ser. No. 10/045,790, filed on Jan. 14, 2002, which is a continuation-in-part of U.S. application Ser. No. 09/993,003, filed on Nov. 6, 2001, each of which is incorporated herein by reference in its entirety. The present invention relates to compositions and methods for treating skin disorders including reactive and inflammatory dermatoses such as eczema and psoriasis, to compositions and methods for treating wounds, and to compositions and methods for improving the cosmetic appearance of the skin. Reactive and inflammatory dermatoses are non-contagious disorders of the skin whose causes, when known, are usually related to allergic or other immune reactions. These disorders may take the form of mild irritation; however, in more severe cases, reactive and inflammatory dermatoses may be extremely painful, disfiguring, and debilitating conditions.

Patents 193

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Methods of preparing improved water-soluble extracts containing antioxidants and uses thereof Inventor(s): Bailey, David T.; (Boulder, CO), Nichols, Rebecca L.; (Broomfield, CO), Richheimer, Steven L.; (Westminster, CO) Correspondence: Steven C. Petersen; Hogan & Hartson, LLP; Suite 1500; 1200 17th Street; Denver; CO; 80202; US Patent Application Number: 20030138537 Date filed: December 19, 2001 Abstract: The present invention provides an improved process for preparing a watersoluble extract containing one or more naturally occurring antioxidants (from plant materials from the Labiatae family. The process produces an extract that is essentially odorless, flavorless and colorless when used at a concentration between about 5 and 1000 ppm. Excerpt(s): The invention provides a process for the production of improved watersoluble plant extracts having neutral flavor, odor, and color when used at the recommended dosage levels for use as antioxidants and as flavor stabilizers and/or enhancers. Antioxidants serve in a number of important commercial applications, especially as ingredients in food products susceptible to degeneration, in one form or another, due to oxidation. "Antioxidants" are defined by the Food and Drug Administration (21 CFR.sctn. 170.3) as "substances used to preserve food by retarding deterioration, rancidity, or discoloration due to oxidation." Commercial applications include use in processed meat and poultry, salad dressings, beverages, seasonings, snacks, nuts, soup bases, edible fats and oils, natural foods, pet foods and packaging. In addition to foods, antioxidants have been used to prevent oxidation in various cosmetic and toiletry products and in medicinal or pharmaceutical preparations. The primary purpose in each of these applications is to prevent deterioration of desirable product characteristics by inhibiting oxidation. More recently, antioxidants in food sources and dietary supplements have received attention for their potential to prevent or delay the onset of certain cancers and other chronic health conditions including heart disease, cataracts and aging. The theory is that, by preventing oxidation, these materials inhibit the formation of oxygen containing free radicals that are believed to play a significant role in initiation of these conditions and other chronic disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel antioxidant, nucleic acid constructs encoding same, pharmaceutical compositions containing same and use of same for reducing oxidative-stress Inventor(s): Levy, Andrew P.; (Kiryat Shmuel, IL) Correspondence: G.E. EHRLICH (1995) LTD.; c/o ANTHONY CASTORINA; SUITE 207; 2001 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20030113830 Date filed: July 11, 2001

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Abstract: Novel haptoglobin derived antioxidants, nucleic acid constructs encoding same, pharmaceutical compositions containing the novel antioxidant or the nucleic acid constructs, and methods of relieving oxidative stress by administration of the antioxidants, the nucleic acid constructs encoding same or the pharmaceutical composition containing same to a subject in need thereof are disclosed. Excerpt(s): It was recently found in multiple independent studies [5-8] (and Levy A P, Hochberg I, Jablonski K, et al. manuscript submitted for publication) of over 1000 individuals from Israel, Belgium and the United States that the haptoglobin phenotype is a predictor of the risk of developing both microvascular and macrovascular complications of diabetes. Specifically, diabetic individuals with the haptoglobin 1-1 phenotype were shown to be remarkably resistant to the development of diabetic retinopathy, diabetic nephropathy, and cardiovascular disease [5-8]. Moreover, it was found that there was a graded effect evident with regard to risk and the number of haptoglobin 2 alleles [7,8]. For example, in a prospective study of incident cardiovascular disease, it was found that individuals homozygous for the haptoglobin 2 allele had a 5 fold increase in the risk of cardiovascular disease compared to individuals homozygous for the haptoglobin 1 allele, while heterozygotes were found to have an intermediate risk (Levy A P, Hochberg I, Jablonski K, et al. manuscript submitted for publication). Further details in this respect are disclosed in U.S. Pat. No. 6,251,608; U.S. patent application Ser. Nos. 09/688,121; and 09/815,016 and in PCT Application Nos. IL00/00359; IL01/00368; and IL01/00369, which are incorporated by reference as if fully set forth herein. An increase in oxidative stress has been proposed to play a crucial role in the development of diabetic vascular complications [9-10]. Accordingly, differences in the genetically endowed antioxidant status may confer increased or decreased susceptibility to the development of these diabetic vascular complications. A key site of action of haptoglobin in neutralizing the oxidative capacity of hemoglobin is the extravascular space, particularly after endothelial injury. Haptoglobin 1-1 and 2-2 clearly differ in their ability to sieve into the extravascular compartment across the endothelial cell barrier [2]. Since this difference in sieving is possibly a reflection of the profound differences in the size of haptoglobin 1-1 dimers and haptoglobin 2-2 cyclic polymers it was sought to identify a minimal haptoglobin peptide with preserves antioxidant function and which would have an improved ability to penetrate into the extravascular space, assuming that such a minimal haptoglobin peptide, if isolateable, would serve to augment the anti-oxidative capabilities in vivo in subjects in need thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel lipoic acid heterocyclic or benzene derivatives, preparation and use thereof as medicines Inventor(s): Auguet, Michel; (Palaiseau, FR), Harnett, Jeremiah; (Gif-Sur-Yvette, FR) Correspondence: Bierman Muserlian & Lucas; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030105107 Date filed: September 10, 2002 Abstract: A subject of the invention is new heterocyclic or benzenic derivatives comprising a lateral chain derived from lipoic acid, which have an inhibitory activity on NO-synthase enzymes producing nitrogen monoxide NO and/or are agents allowing the regeneration of antioxidants or entities trapping the reactive oxygen species (ROS) and which intervene in a more general manner in the redox status of thiol groups. A

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subject of the invention is also their preparation methods, the pharmaceutical preparations containing them and their use for therapeutic purposes, in particular their use as inhibitors of NO-synthases and/or as agents which intervene in a more general manner in the redox status of thiol groups. Excerpt(s): A subject of the present invention is new heterocyclic or benzenic derivatives comprising a lateral chain derived from lipoic acid, which have an inhibitory activity on NO-synthase enzymes producing nitrogen monoxide NO and/or are agents which allow the regeneration of antioxidants or entities which trap the reactive oxygen species (ROS) and which intervene in a more general fashion in the redox status of thiol groups. These antioxidants or entities which trap the reactive oxygen species can be of natural origin, such as for example vitamin E or glutathione, or of synthetic origin such as certain products which trap the ROS or products having both an inhibitory activity on NO-synthase enzymes and an activity which traps the ROS. Examples of such products of synthetic origin can in particular be found in the PCT Patent Applications WO 96/09653, WO 98/42696 and WO 98/58934. Therefore, the invention relates in particular to the derivatives corresponding to general formula (I) defined below, their preparation processes, the pharmaceutical preparations containing them and their use for therapeutic purposes, in particular their use as NO-synthase inhibitors and/or as agents which allow the regeneration of antioxidants or entities which trap the ROS's and which intervene in a more general fashion in the redox status of thiol groups. cardiovascular and cerebrovascular disorders including for example atherosclerosis, migraine, arterial hypertension, septic shock, ischemic or hemorragic cardiac or cerebral infarctions, ischemias and thromboses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Polyethylene composition and method for making shaped objects from same Inventor(s): Berghe, Pascal Vanden; (Limal, BE), Plume, Denis; (Brussels, BE) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C.; FOURTH FLOOR; 1755 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20030105198 Date filed: December 18, 2002 Abstract: The invention concerns a polyethylene based composition comprising 0.05 to 0.5 wt. % of at least a saturated fatty acid amide containing 8 to 30 carbon atoms, 0 to 0.1 wt. % of an auxiliary lubricant selected among fatty acids, fatty acid esters, fatty acid salts, monounsaturated fatty acid amides, polyols containing at least 4 carbon atoms, monoalcohol or polyalcohol monoethers, glycerol esters, paraffins, polysiloxanes, fluorinated polymers and mixtures thereof, and 0 to 5 wt. % of one or more additives selected among the antioxidants, anti-acids, anti-UV stabilizers, colouring agents and antistatic agents. Excerpt(s): The invention relates to a composition based on polyethylene. It also relates to a method for producing shaped items, in particular a method for producing screw caps for bottles from this composition. It is generally known that caps for bottles can be produced from polyethylene. To optimize slip properties and to facilitate unscrewing of the cap, incorporating a lubricant into the polyethylene is also known. U.S. Pat. No. 5,948,846 describes the use of a composition comprising 13-docosenamide as a lubricant for producing caps. However, that composition has the disadvantage of causing a bad odor and bad flavor in foodstuffs stored in contact with caps based on that composition.

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That problem has been solved by adding a quantity of a particular zeolite to the compositions to act as a flavor and odor trap. A composition has now been discovered that does not suffer from the disadvantages cited above, without the need for a flavor and odor trap such as a zeolite, and which provides good slip properties. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Preparation antioxidants enriched functional food products from sugar cane and beet Inventor(s): Chou, Chung Chi; (South Huntington, NY) Correspondence: Chung Chi Chou; 103A Pidgeon Hill Rd.; South Huntington; NY; 11746; US Patent Application Number: 20030198694 Date filed: April 22, 2002 Abstract: Functional food products with excellent antioxidative strength have been prepared from natural sugar cane and beet. The processes used include one or more of the following: Clarification, Crystallization, Chromatographic separation process, Adsorption on/Desorption from adsorbents, Ion exchange resin decolorization and regeneration, and Ultra-Nano membrane filtration. The antioxidative capacities of the products are quantified in term of ORAC (Oxygen Radical Absorbance Capacity) unit as per analytical method developed at the Agricultural Research Services of the U.S. Department of agriculture. Excerpt(s): (4) Richard Riffer, non-sugar and sugar refining, chapter 36, Handbook of Sugar Refining (2000), edited by Chung Chi Chou, published by John Wily & Sons, Inc. New York. (10) Yukie Nagai, Takco Mizutani, Hiroshi Iwabe, Saiichi Araki, and Mamoru Suzuki Physiological function of sugar cane extracts. Technical proceeding of Sugar Technologists, Inc. 2001. (12) Frank G. Carpenter, chapter 17, decolorization, Cane sugar handbook 11.sup.th edition by James C. P. Chen, published by John Wiley and sons, 1985. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for extracting polyphenolic antioxidants from purine-containing plants Inventor(s): Hoving, Hendrik Derk; (Maastricht, NL), Kattenberg, Hans Robert; (Krommenie, NL), Starmans, Dick Antonius Johannes; (Wageningen, NL) Correspondence: STERNE, KESSLER, GOLDSTEIN & FOX PLLC; 1100 NEW YORK AVENUE, N.W.; WASHINGTON; DC; 20005; US Patent Application Number: 20030211184 Date filed: June 9, 2003 Abstract: The present invention is directed to a process for isolating polyphenolic antioxidants from purine-containing plant material, comprising the steps of: (a) extracting the plant material with a hydroxylic extracting liquid preferably at low temperature; (b) selectively adsorbing the extract obtained in step (a), preferably at low temperature; and (c) desorbing the adsorbed material with a hydroxylic desorbing liquid, preferably at relatively high temperature. The process is especially suitable for producing cocoa antioxidants for use in pharmaceutical, cosmetic and nutritional compositions.

Patents 197

Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/890,664, which is the National Stage of International Application No. PCT/US00/02411, filed Feb. 2, 2000, which is incorporated herein by reference. The present invention relates to a process for producing polyphenolic anti-oxidants with low purine content, from cocoa and other purine-containing plant materials. The invention also relates to an antioxidant composition obtainable using this process. The invention further relates to a nutritional, pharmaceutical or cosmetic antioxidant composition. Polyphenolic antioxidants from plant materials derived from cocoa, coffee, tea, and other theobroma species are interesting as they are assumed to be active in preventing cancer, coronary and cardiovascular disease and strokes, and in delaying aging processes. These antioxidants are usually water-soluble and comprise compounds of the chroman type, such as catechin and epicatechin (the stereoisomeric 2-(3,4-dihydroxyphenyl)-3,5,7trihydroxychromans), and oligomerised structures including procyanidin. However, these plant materials also contain purines such as caffeine (1,3,7-trimethyl-2,6purinedione or 1,3,7-trimethylxanthine) and theobromine (3,7-dimethyl-2,6-purinedione or 3,7-dimethylxanthine), and these components are usually undesired in antioxidant compositions because of their stimulating properties. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Product and process for stabilizing aloe vera gel Inventor(s): Maughan, Rex G.; (Paradise Valley, AZ), Phan, Banh Van; (Garland, TX), Poore, Roger A.; (Rockwall, TX) Correspondence: SCOTT T. GRIGGS; 12900 PRESTON ROAD; SUITE 1200, LB-15; DALLAS; TX; 75230; US Patent Application Number: 20030190380 Date filed: April 4, 2002 Abstract: A product and process for stabilizing Aloe vera gel is disclosed. The process includes the steps of rapidly heating the Aloe vera gel to a temperature in the range of from about 35.degree. C. to about 80.degree. C., adding to the heated Aloe vera gel one or more stabilizing antioxidants, and rapidly cooling the heated Aloe vera gel to a temperature in the range of from about 20.degree. C. to about 30.degree. C. The stabilizing antioxidants may be a tocotrienol/tocopherol blend, rosmarinic acid, polyphenols, or any combination thereof. Excerpt(s): This invention relates to the processing of Aloe vera gel, and more particularly to a product and controlled temperature process in which antioxidants and other stabilizing agents are used to stabilize the Aloe vera gel. Aloe vera is a tropical or subtropical plant of the lily (Liliaceae) family that has leaves growing in a spiral rosette pattern around a central stem. The leaves of the Aloe vera plant contain a viscous but essentially clear gel given structural rigidity by hair-like connective fibers that run therethrough. Freshly excised from the plant, Aloe vera gel has been used for centuries by those living where the plant naturally grows as a health and beauty aid. For example, Aloe vera is a traditional anti-inflammatory topical ointment used to combat the inflammation and pain caused by jelly fish stings, insect bites, sunburn and the like. Aloe vera soothes and cools the inflamed skin, numbs the pain associated with the inflammation and prevents itching. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Reduction inhibitory agent for active oxygen eliminating activity Inventor(s): Fukuda, Shigeharu; (Okayama, JP), Kubota, Michio; (Okayama, JP), Miyake, Toshio; (Okayama, JP), Oku, Kazuyuki; (Okayama, JP) Correspondence: BROWDY AND NEIMARK, P.L.L.C.; 624 Ninth Street, N.W.; Washington; DC; 20001-5303; US Patent Application Number: 20030108593 Date filed: November 20, 2002 Abstract: A reduction inhibitory agent for active oxygen eliminating activity which comprises cyclotetrasaccharide, i.e., cyclo{.fwdarw.6}-.alpha.-D-glucopyr- anosyl(1.fwdarw.3)-.alpha.-D-glucopyranosyl-(1.fwdarw.6)-.alpha.-D-glucopyranosyl(1.fwdarw.3)-.alpha.-D-glucopyranosyl-(1.fwdarw.), as an effective ingredient, a method for inhibiting the reduction of active oxygen eliminating activity which comprises incorporating either cyclotetrasaccharide or the reduction inhibitory agent into plant edible products and/or plant antioxidants, and a composition where the reduction of active oxygen eliminating activity of the plant edible products and/or plant antioxidants has been satisfactorily inhibited by the method. Excerpt(s): The present invention relates to an agent which inhibits reduction of active oxygen eliminating activity, uses of the same, and a method for inhibiting reduction of active oxygen eliminating activity. More particularly, the present invention relates to an agent for inhibiting reduction of active oxygen eliminating activity which comprises cyclo{.fwdarw.6}-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosyl(1.fwdarw.6)-.alpha.-D-glucopyranosyl-(1.fwdarw.3)-.alpha.-D-glucopyranosyl(1.fwdarw.), hereinafter abbreviated as "cyclotetrasaccharide", represented by Chemical Formula 1 as an effective ingredient, a method for inhibiting the reduction of plant active oxygen eliminating activity characterized in that it comprises the steps of incorporating either cyclotetrasaccharide or the inhibitory agent in the presence of an aqueous medium, and a composition which comprises a plant edible substance and/or a plant antioxidant where the reduction of active oxygen eliminating activity has been inhibited by the above method. It is well known that edible plant substances such as vegetables, mushrooms, and seaweeds are important for living bodies as sources of functional ingredients such as vitamins, minerals, and edible fibers, and are essential food materials for the growth of living bodies. Recently, interest has been focused on the active oxygen eliminating activity of these edible plants with respect to the maintenance and promotion of health, the prevention of aging and geriatric disease, and the inhibition of carcinogenesis. Mechanisms for the causes of aging of living bodies and related diseases thereof such as cancers, arteriosclerosis, liver cirrhosis, myocardial infarction, cerebral apoplexy, cataracts, Parkinson's disease, rheumatism, and Alzheimer's dementia are still unknown in many aspects. However, there are some consideration that these incurable diseases may relate to active oxygen molecules such as superoxide which is an oxygen molecule having an unpaired electron and relatively high reactivity, and derivatives thereof including hydroxyradical and hydrogen peroxide. It is believed that these molecules oxidize intracellular target molecules such as membrane lipids, proteins, and DNAs to induce oxygen-related defects and cause aging of living bodies and related diseases thereof. Enzymes capable of eliminating active oxygen such as superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6), and antioxidants such as L-ascorbic acid and.alpha.-tocopherol exist in living cells, so that the concentration of intracellular active oxygen is generally kept at a remarkably low level. However, irradiation from a relatively-large amount of ultraviolet rays, radiations, and magnetic waves, excessive physical exercise, great mental stress, and aging form

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active oxygen in an amount that cannot be eliminated by the active oxygen eliminating activity of living bodies. This results in an accumulation of compounds oxidized by the excessive amount of active oxygen which causes the aforesaid oxygen-related defects. To improve the problem, for example, Japanese Patent Kokai Nos. 168,435/93 and 143,466/96 proposed methods which comprise supplementing living bodies with active oxygen eliminating activity to maintain and promote health of living bodies by using a relatively-high active oxygen eliminating activity of edible plants. It was confirmed that, even if such edible plants were used, processing techniques such as squeeze, extraction, heating, and drying, or additional storage conditions for the edible plants might lower the inherent active oxygen eliminating activity of the plants or even extinguish this activity completely. It is desired to establish a novel method for inhibiting the reduction of active oxygen eliminating activity without causing serious side effects in living bodies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Rubber compositions and method for decreasing the tangent delta value Inventor(s): Greene, Peter K.; (Goshen, CT), Hannon, Martin J.; (Bethany, CT), Hong, Sung W.; (Cheshire, CT) Correspondence: Michael E. Carmen; DILWORTH & BARRESE, LLP; 333 Earle Ovington Blvd.; Uniondale; NY; 11553; US Patent Application Number: 20030119960 Date filed: September 4, 2001 Abstract: A rubber composition is disclosed wherein the rubber composition contains at least (a) a rubber component; (b) a silica filler; (c) a coupling agent; and (d) a cureenhancing amount of at least one polyalkylene oxide having a weight average molecular weight less than 200. The compositions may also include suitable amounts of other ingredients such as carbon black, antiozonants, antioxidants, etc. Excerpt(s): This invention relates generally to rubber compositions and a method for decreasing the tangent delta value (i.e., hysteresis) and improving the cure rate of the rubber compositions. The rubber compositions are particularly useful for tire tread applications in vehicles, e.g., passenger automobiles and trucks. The tire treads of modem tires must meet performance standards which require a broad range of desirable properties. Generally, three types of performance standards are important in tread compounds. They include good wear resistance, good traction and low rolling resistance. Major tire manufacturers have developed tire tread compounds which provide lower rolling resistance for improved fuel economy and better skid/traction for a safer ride. Thus, rubber compositions suitable for, e.g., tire treads, should exhibit not only desirable strength and elongation, particularly at high temperatures, but also good cracking resistance, good abrasion resistance, desirable skid resistance and low tangent delta values at low frequencies for desirable rolling resistance of the resulting treads. Additionally, a high complex dynamic modulus is necessary for maneuverability and steering control. Presently, silica has been added to rubber compositions as a filler to replace some or substantially all of the carbon black filler to improve these properties, e.g., lower rolling resistance. Although more costly than carbon black, the advantages of silica include, for example, improved wet traction, low rolling resistance, etc., with reduced fuel consumption. Indeed, as compared to carbon black, there tends to be a lack of, or at least an insufficient degree of, physical and/or chemical bonding between the silica particles and the rubber to enable the silica to become a reinforcing filler for the

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rubber thereby giving less strength to the rubber. Therefore a silica filler system requires the use of coupling agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Skin cream stimulating the surface bloodstream Inventor(s): Passi, Siro; (Rome, IT) Correspondence: YOUNG & THOMPSON; 745 SOUTH 23RD STREET 2ND FLOOR; ARLINGTON; VA; 22202 Patent Application Number: 20030108510 Date filed: November 1, 2002 Abstract: A formulation of a skin cream based on the synergical combination of three particular active principles--escin, bufemin and rutin--whose pharmacological action stimulating the venous and arterial branchings of the peripheral bloodstream and the perivasal tissues is further increased both by the presence of antioxidants and inhibitors of histidine decarboxylase and the high concentration in soya lecithin (3%) and sebumsimilar oil (2-10 %) causing the active principles to penetrate the skin where the three active principles should perform their action. Said cream finds therapeutical application in the treatment of cellulitis and disorders connected to the inefficiency of the surface bloodstream, phlebopathy, phlebothrombosis, surface periphlebitis, sense of heaviness, fatigue and weariness of limbs, spasms, tumefaction and edema of inflammatory origin, ecchymosis and hematoma, and chilblains. Excerpt(s): The present invention relates to cosmetics and more particularly a formulation for topical administering to stimulate the surface bloodstream and to eliminate disorders connected to its inefficiency, particularly the formation of cellulitis. The disclosed formulation is based upon the synergical combination of three particular active principles, i.e. escin, bufenin, and rutin, whose pharmacological action stimulating the venous and arterial branchings of the peripheral bloodstream and the perivasal tissues is further increased both by the presence of antioxidants and inhibitors of histidine decarboxylase and high concentration in soya lecithin (3%) and sebumsimilar oil (2-10%) causing the active principles to penetrate the skin where the three active principles should perform their action. Bufenin is a peripheral vasodilator acting by a.beta.-adrenergic stimulation and having a direct action to arteriae and arteriolae of the skin and skeletal muscles. Therefore, it is particularly active in the treatment of peripheral vascular diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stabilized oral pharmaceutical composition Inventor(s): Bauer, Juliane M.; (Portage, MI), Brugger, Andrew M.; (Libertyville, IL), Forbes, James C.; (Glenview, IL), Gao, Ping; (Portage, MI), Guido, Jane E.; (Vicksburg, MI), Hassan, Fred; (Peapack, NJ), Huang, Tiehua; (Kalamazoo, MI), Karim, Aziz; (Skokie, IL), Robins, Russell H.; (Portage, MI) Correspondence: Pharmacia Corporation; Patent Department; 800 N. Lindbergh Boulevard-04E; St. Louis; MO; 63167; US Patent Application Number: 20030105144 Date filed: April 9, 2002 Abstract: An orally deliverable pharmaceutical composition is provided comprising an aminosulfonyl-comprising drug, for example a selective cyclooxygenase-2 inhibitory drug such as celecoxib, and a solvent liquid comprising a polyethylene glycol and one or more free radical-scavenging antioxidants. At least a substantial part of the drug is in dissolved form in the solvent liquid. The composition has rapid-onset properties and is useful in treatment of cyclooxygenase-2 mediated conditions and disorders. Excerpt(s): This application claims priority of U.S. provisional patent application Serial No. 60/284,589 filed on Apr. 17, 2001, and of U.S. provisional patent application Serial No. 60/357,959 filed on Feb. 19, 2002. The present invention relates to orally deliverable pharmaceutical compositions that comprise a drug of low water solubility, more particularly to such compositions where the drug is in dissolved form. A need for formulated compositions of selective COX-2 inhibitory drugs, particularly rapid-onset compositions of such drugs, exists. Rapid-onset drug delivery systems can provide many benefits over conventional dosage forms. Generally, rapid-onset preparations provide a more immediate therapeutic effect than standard dosage forms. For example, in the treatment of acute pain, for example in headache or migraine, rapid-onset dosage forms are useful to provide fast pain relief. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stabilizing compositions for lubricating oils Inventor(s): Holt, Alan; (Manchester, GB), Mulqueen, Gerard; (Cheshire, GB) Correspondence: Thomas Q Henry; Woodard Emhardt Naughton Moriarty & McNett; Bank One Tower Suite 3700; 111 Monument Circle; Indianapolis; IN; 46204; US Patent Application Number: 20030171227 Date filed: November 5, 2002 Abstract: Stabilising compositions for lubricant base stocks and lubricant formulations are composed of a mixture of (a) at least one aromatic aminic amine antioxidant optionally blended with at least one hindered phenolic antioxidant and (b) at least one neutral organo phosphate or phosphite, optionally blended with at least one acid organo phosphate or phosphite. These stabilising composition mixtures are characterised by their stabilising capacity which is considerably higher than that of either the single antioxidants or the single phosphate or phosphite additives. These stabilising compositions can be used in all fields where the single components of the mixtures are generally used and where deterioration due to oxidation processes takes place. Excerpt(s): This invention relates to stabilising compositions for lubricant base stocks and lubricant formulations. We have unexpectedly found that mixtures of certain

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aromatic aminic antioxidants, optionally in admixture with certain hindered phenol antioxidants, when mixed with certain organo phosphate esters and organo phosphite esters offer unique synergy and improved performance in terms of stability when used within lubricant base stocks and lubricant formulations. By lubricant base stocks is meant lubricants such as mineral and synthetic base oils chosen from Group I, Group II, Group III, Group IV and Group V base stocks as classified by the American Petroleum Institute, as well as natural and synthetic esters including polyol esters, more particularly, but not limited to automotive oils, circulatory oils, gear oils, greases, hydraulic fluids, turbine fluids and metal working fluids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Stable surgical irrigating solutions Inventor(s): Doshi, Uday; (Fort Worth, TX), Liao, John C.; (Fort Worth, TX), Shah, Mandar V.; (Arlington, TX) Correspondence: ALCON RESEARCH, LTD.; R&D COUNSEL, Q-148; 6201 SOUTH FREEWAY; FORT WORTH; TX; 76134-2099; US Patent Application Number: 20030138499 Date filed: January 10, 2003 Abstract: Improved stability surgical irrigating solutions and methods of use are disclosed. The compositions comprise bifunctional compounds (i.e., compounds comprising antioxidant and antiinflammatory moieties) and physiological antioxidants to stabilize the bifunctional compounds. The compounds are useful in preventing and treating inflammatory and other disorders incident to surgery. Excerpt(s): The present invention is directed to the provision of improved stability surgical irrigating solutions comprising particular bifunctional compounds. More specifically, the present invention is directed to stable surgical irrigating solutions containing a bifunctional compound (i.e., a compound comprised of antioxidant and anti-inflammatory moieties) and an amount of physiological antioxidant (e.g., ascorbate) to stabilize the bifunctional compound. The present invention is also directed to various methods of using the compositions of the present invention, including the treatment of ocular inflammation associated with ophthalmic disease and ophthalmic surgery. Ocular surgery can result in various post-surgical complications to the eye. Such complications may include: 1) loss of vascular blood barrier function; 2) neutrophil accumulation; 3) tissue edema including conjunctiva swelling, conjuctiva congestion and corneal haze; 4) cataract formation; 5) cellular proliferative disorders including neovascularizations, fibrosis and posterior capsule opacification; and 6) loss of membrane integrity including decrease in docosahexanenoic acid levels in membrane phospholipids. Many of these complications are further potentiated in diabetic patients who are at risk for many ocular pathologies. Refractive surgery typically involves the modification of the cornea in myopic patients to correct the focus of light on the retina. Examples of such surgeries include radial keratotomy (radial slices in the cornea), photorefractive keratotomy (laser ablation of the epitheilial and stromal layers of the cornea), LASIK (slicing a cornea flap and removing part of the stromal layer followed by the replacement of the flap), as well as procedures involving the insertion of corneal rings or phakic intraocular lens ("IOL"). During these and other corneal surgeries the cornea is typically bathed with a surgical irrigating solution. Due to the traumatic insult of such procedures, however, various inflammatory events or other tissue or cellular complications may arise.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Storage-stable compositions of glycerol monoalkyl ethers Inventor(s): Beilfuss, Wolfgang; (Hamburg, DE), Gradtke, Ralf; (Tornesch, DE) Correspondence: Air Liquide; Intellectual Property Department; Suite 1800; 2700 Post Oak Boulevard; Houston; TX; 77056; US Patent Application Number: 20030149097 Date filed: December 9, 2002 Abstract: The present invention relates to compositions which comprise a combinationa) of one or more glycerol monoalkyl ether(s) of the general formulaR--O--CH.sub.2-CHOH--CH.sub.2OHin which R is a branched or unbranched C.sub.3-C.sub.18-alkyl group, where the alkyl group can be substituted by one or more hydroxyl and/or C.sub.1-C.sub.4-alkoxy group(s) and/or the alkyl chain can be interrupted by up to four oxygen atoms, withb) an antioxidant or two or more antioxidants as stabilizer(s),the simultaneous presence of phosphocholines and phosphocholine derivatives being excluded. Excerpt(s): The present invention relates to compositions comprising glycerol monoalkyl ethers for use in cosmetic and pharmaceutical preparations and in technical products. These compositions have in particular good long-term storage stability and comprise at least one glycerol monoalkyl ether and at least one antioxidant as stabilizer. Of the two substitution-isomeric glycerol monoalkyl ethers (2-alkoxy-1,3-propanediols and 3alkoxy-1,2-propanediols), the present invention relates in particular to the 3-alkoxy-1,2propanediols. The invention further relates to concentrates and working solutions. The compositions according to the invention, i.e. in particular the concentrates and working solutions, are added to pharmaceutical and cosmetic preparations and technical products. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Synthetic catalytic free radical scavengers usefuyl as antioxidants for prevention and therapy of disease Inventor(s): Doctrow, Susan Robin; (Arlington, MA), Malfroy-Camine, Bernard; (Arlington, MA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030216371 Date filed: May 30, 2003 Abstract: The invention provides antioxidant salen-metal complexes, compositions of such antioxidant salen-metal complexes having superoxide activity, catalase activity, and/or peroxidase activity, compositions of salen-metal complexes in a form suitable for pharmaceutical administration to treat or prevent a disease associated with cell or tissue damage produced by free radicals such as superoxide, and cosmetic and free radical quenching formulations of salen metal compounds. Excerpt(s): The invention provides antioxidant compositions, including pharmaceutical compositions, of synthetic catalytic small molecule antioxidants and free radical

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scavengers for therapy and prophylaxis of disease and prevention of oxyradicalmediated oxidation, methods for using the small molecule antioxidants in prevention and treatment of pathological conditions, methods for using the small molecule antioxidants as preservatives and oxyradical quenching agents in hydrocarbons, methods for using the small molecule antioxidants for targeted protection of tissues and/or cell types during cancer chemotherapy, and methods for using the small molecule antioxidants to prevent toxicologic damage to individuals exposed to irritating oxidants or other sources of oxidative damage, particularly oxygen-derived oxidative species such as superoxide radical. The compositions and methods of the invention are also used for preventing oxidative damage in human transplant organs and for inhibiting reoxygenation injury following reperfusion of ischemic tissues. The compositions and methods of the invention are also useful for chemoprevention of chemical carcinogenesis and alteration of drug metabolism involving epoxide or free oxygen radical intermediates. Molecular oxygen is an essential nutrient for nonfacultative aerobic organisms, including, of course, humans. Oxygen is used in many important ways, namely, as the terminal electronic acceptor in oxidative phosphorylation, in many dioxygenase reactions, including the synthesis of prostaglandins and of vitamin A from carotenoids, in a host of hydroxylase reactions, including the formation and modification of steroid hormones, and in both the activation and the inactivation of xenobiotics, including carcinogens. The extensive P450 system uses molecular oxygen in a host of important cellular reactions. In a similar vein, nature employs free radicals in a large variety of enzymic reactions. Excessive concentrations of various forms of oxygen and of free radicals can have serious adverse effects on living systems, including the peroxidation of membrane lipids, the hydroxylation of nucleic acid bases, and the oxidation of sulfhydryl groups and of other sensitive moieties in proteins. If uncontrolled, mutations and cellular death result. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Tarnish inhibiting formula and tarnish inhibiting articles using same Inventor(s): Kubik, Donald A.; (Dickenson, ND), Lyublinski, Efim Ya.; (Mayfield Heights, OH), Nygaard, Barbara A.; (Circle Pines, MN), Varshal, Boris G.; (Lynn, MA) Correspondence: Alfred D. Lobo; LOBO & CO., L.P.A.; 933 The Leader Building; 526 Superior Avenue, E.; Cleveland; OH; 44114-1902; US Patent Application Number: 20030207974 Date filed: June 3, 2003 Abstract: The present invention relates to tarnish inhibiting formulas. More particularly, in one embodiment the present invention relates to tarnish inhibiting formulas which comprise a mixture of: (i) at least one carrier; (ii) at least one strong alkali compound; and (iii) at least one compound which yields an insoluble compound. These mixtures can further include one or more additional additives such as antioxidants, corrosion inhibitors, etc. In yet another embodiment, the tarnish inhibiting formulas (and in some cases corrosion inhibiting as well) according to the present invention can be placed in a suitable polymer film and/or polymer article. Excerpt(s): In commerce and industry today, the useful life of corrodible items may be extended and/or preserved by providing corrosion inhibitors which protect the corrodible items from the adverse effects of its ambient environment. Among the common indications of corrosion manifested in useful metallic articles are oxidation, pitting, tarnishing, mottling, or discoloration of the surfaces of these items. These

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manifestations occur in metallic articles, particularly when exposed to oxygen, in either gaseous or liquid phase. Additionally, sulfides and/or chlorides (or chlorine) may cause corrosion or tarnishing problems as well. Inasmuch as both oxygen and water, including water vapor, occur normally and are available in nature, it is normally necessary to take precautions against tarnishing and/or corrosion when packaging metallic items for shipment or storage, or when subjecting such items to normal use. Metals which are frequently found to be susceptible to tarnish and/or corrosion under normal atmospheric and ambient conditions include, but are not limited to, iron, copper, brass, aluminum, silver, and alloys of these metals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Tin or tin alloy plating bath, tin salt solution and acid or complexing agent solution for preparing or controlling and making up the plating bath, and electrical and electric components prepared by the use of the plating bath Inventor(s): Obata, Keigo; (Akashi-shi, JP), Tsuji, Kiyotaka; (Kobe-shi, JP), Uchida, Ei; (Kobe-shi, JP), Yoshimoto, Masakazu; (Akashi-shi, JP) Correspondence: AKIN GUMP STRAUSS HAUER & FELD L.L.P.; ONE COMMERCE SQUARE; 2005 MARKET STREET, SUITE 2200; PHILADELPHIA; PA; 19103-7013; US Patent Application Number: 20030150743 Date filed: September 20, 2002 Abstract: There are provided a tin or tin-base alloy plating bath having significantly improved solderability, a tin salt solution and an acid or complexing agent solution for preparing or controlling and making up the plating bath, as well as electrical and electric components prepared by the use of the plating bath.The plating bath is a tin plating bath or a plating bath of an alloy of tin and one or more metals selected from the following group (I): copper, zinc, silver, indium, gold and bismuth, which bath comprises, as essential components, at least the following components (A) to (D):(A) 5 to 200 g/L of divalent tin ions,(B) one or more acids or complexing agents which form a water-soluble salt or complex with the divalent tin ions, the total amount of the acid(s) or complexing agent(s) being at least stoichiometrically equivalent to the divalent tin ions,(C) one or more metals selected from elements of Groups IB to VB of the fourth to sixth periods of the periodic table of the elements excluding tin, mercury, thallium and elements included in the group (I), the total concentration of the metal(s) being 20 to 2,000 ppm based on tin, and(D) 1 mg/L to 10 g/L of one or more antioxidants. Excerpt(s): The present invention relates to a plating technique, particularly to a plating bath for obtaining tin and/or tin alloy deposits which exhibit good solderability, a tin salt, acid or complexing agent solution used for preparing, controlling and making up the bath or for adjusting a concentration of the bath, and electrical and electric components prepared by the use of the plating bath. In order to prevent environmental pollution caused by lead eluted from tin-lead solders used in electrical and electric components, a number of studies have been made on lead-free solders (soldering materials). In corporation with these studies, for the plated films to which these soldering materials were applied, studies have been also made to replace the conventionally widely used tin-lead alloy plated film with an alternate lead-free film. Although a plated film of gold, silver, palladium or the like has also been studied as the alternate film, it is believed that a main plated film will be a tin plated film or a tin alloy plated film. Mainly, in the last several years, as an alternate for the tin-lead alloy plating, a number of reports have been made or patent applications have been submitted with

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respect to lead-free tin alloy plating (so-called lead-free plating), such as tin-copper, tinzinc, tin-silver, tin-indium and tin-bismuth alloy plating. However, the tin-lead alloy plated film is an alloy which is extremely suitable for soldering and, in fact, it is a current situation that lead-free plated films having solderability comparable to that of the tin-lead alloy plated film have not been obtained yet in the so-called lead-free plated films. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Ultra-stable composition comprising moringa oil and its derivatives and uses thereof Inventor(s): Brown, James H.; (Scottsdale, AZ), Kleiman, Robert; (Sun Lakes, AZ) Correspondence: The Halvorson Law Firm; Ste 1; 405 W. Southern Ave.; Tempe; AZ; 85282; US Patent Application Number: 20030198629 Date filed: April 8, 2003 Abstract: Compositions comprising long-chain organic molecules obtained from natural oils, particularly plant, bean, seed and nut oils, and their derivatives can be provided with increased oxygen stability by their combination with mixtures of particular classes of antioxidants, particularly combinations of at least one synthetic free-radical terminating antioxidant. The stabilization combination is particularly effective in combination with long-chain oils having less than 5% methylene interrupted unsaturation. The long-chain oil may comprise a natural oil or wax. The long-chain oil may have a percent methylene interrupted unsaturation of less than 5%, less than 3%, or less than 1%. The emollient composition may have at least one supplemental additive, which is a reducing agent present in an amount of from 0.01 to 5% or more by weight of said long-chain oil and the free-radical terminating antioxidant is present in an amount of from 0.01 to 5% by weight of said long-chain oil. The composition preferably has the long-chain oil selected from the class consisting of Macadamia oil and its derivatives, Moringa oil and its derivatives, Babassu oil and its derivatives, and Meadowfoam and its derivatives, High Oleic Sunflower, and having a percentage methylene interrupted unsaturation of less than 5. Excerpt(s): This application is a continuation-in-part of co-pending application Ser. No. 09/964,988, which was filed on Sep. 25, 2001, which was a continuation-in-part of copending application Ser. No. 09/917,091, which was filed on Jul. 27, 2001 and issued as U.S. Pat. No. 6,528,075 on Mar. 4, 2003. The present invention relates to ultra-stable long chain oils, particularly long chain oils used in conjunction with cosmetic and pharmaceutical products that are externally applied to patients. The present invention particularly relates to the provision of oxidatively ultra-stable emollients produced when free-radical terminating antioxidants are added to natural oils and waxes, and their derivatives, having a percentage of methylene unsaturation less than 5%. Emollients are materials that are applied to the skin of subjects to produce softness or smoothness. They have been used for centuries in both cosmetic and pharmaceutical products. The original emollients were extracts or directly concentrated materials from plants or animals, while modern emollients also include partially synthetic (derivatives of natural products) or completely synthetic materials. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Unique compositions having utility in rubber applications Inventor(s): Files, Edmee; (Floyds Knobs, IN), Hofer, Thomas; (Louisville, KY) Correspondence: ARMSTRONG,WESTERMAN & HATTORI, LLP; 1725 K STREET, NW; SUITE 1000; WASHINGTON; DC; 20006; US Patent Application Number: 20030158299 Date filed: February 21, 2002 Abstract: A composition including 8-hydroxyquinaldine and an N-acyl taurate is useful in compounding elastomer compositions. Compositions are described containing elastomers such as rubbers, metal oxides, plasticizers, fillers, antioxidants and curing agents. Rubber compositions of the invention have utility in a wide variety of applications. Excerpt(s): The present invention relates to compositions comprising 8hydroxyquinaldine and N-acyl taurates, particularly to compositions further comprising a polymer, and more particularly to compositions where the polymer is a rubber. Here, the acyl group may be generally any hydrocarbon or substituted hydrocarbon group. Generally, in the N-acyl taurate, the acyl group will have in the range of 8 to 20 carbon atoms. In formula (1), this would correspond to R.sup.1 having 7 to 19 carbon atoms. In the above formula, group R.sup.2 may be hydrogen or an alkyl group containing 1 to 20 carbon atoms. If group R.sup.2 is an alkyl group, the N-acyl taurate is, more specifically, an N-acyl-N-alkyl taurate. Generally, the N-acyl taurate will be provided in the composition in the form of a salt, for example, a metal salt, such as the sodium salt. However, the N-acyl taurate may conceivably be provided in the acid form (N-acyl taurine). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of bioquinones for producing cosmetic or dermatological preparations for treating the hair and scalp Inventor(s): Hoppe, Udo; (Heidmuhlen, DE), Pollet, Dieter; (Hamburg, DE), Sauermann, Gerhard; (Weimersdorf, DE) Correspondence: NIXON & VANDERHYE, PC; 1100 N GLEBE ROAD; 8TH FLOOR; ARLINGTON; VA; 22201-4714; US Patent Application Number: 20030180277 Date filed: January 28, 2003 Abstract: The invention relates to the use of one or more compounds from the bioquinone group for producing cosmetic or dermatological preparations for treating the scalp and the hair, in order to prolong the anagen phase and/or to treat and prevent seborrhoeic outbreaks, optionally with the additional use of one or more compounds from the group formed by carnitine, arginine, succinic acid, folic acid, conjugated fatty acids and their respective derivatives, in addition to antioxidants. Excerpt(s): The subject of the invention is the use of bioquinones for producing cosmetic or dermatological preparations for treating the hair and the scalp, which bring about a prolongation of the anagenic phase of the hair growth cycle, or are also effective against dandruff. It is known that hair growth corresponds to a cycle. Papillary hair is the name given to hair in the growth period, which is also known as the anagenic phase or anagen phase. In this phase the hair is anchored with its papilla in the skin. Approximately 80%

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of head hair is in the anagen phase for approximately 3 to 5 years. In a subsequent transitional phase (catagen phase) the hair migrates for approximately 2 weeks to the epidermis and remains there for approximately 3 to 4 months in a resting stage (telogen phase) until it finally falls out. Hair loss over and above the norm is generally regarded as a serious cosmetic disorder, as are other hair growth disorders. Many agents have therefore already been proposed for the treatment of hair loss and balding, as well as hair growth agents which are intended to achieve or encourage hair growth. 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 antioxidants, 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 “antioxidants” (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 antioxidants. You can also use this procedure to view pending patent applications concerning antioxidants. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON ANTIOXIDANTS Overview This chapter provides bibliographic book references relating to antioxidants. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on antioxidants 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 “antioxidants” (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 antioxidants: •

101 Nutrition Tips for People with Diabetes Source: Alexandria, VA: American Diabetes Association. 1999. 122 p. 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: $14.95 plus shipping and handling. ISBN: 1580400280. Order number 482801. Summary: This book answers 101 of the most commonly asked questions about diabetes and nutrition. Questions in chapter one provide general information about nutrition, including the types of foods people who have diabetes need to eat to maintain good control, the difference between the Diabetes Food Pyramid and the U.S. Department of Agriculture Food Pyramid, and the use of carbohydrate counting in meal planning. Chapter two addresses nutrition issues as they relate to the use of oral agents and insulin. The next chapter focuses on nutrition issues relevant to children, such as

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refusing to eat and eating school lunches. This is followed by chapters that answer questions about fats, cholesterol, sugar, and sweetening agents. Chapter six provides information on food consumption before, during, and after exercise; the use of sports drinks; and weight training. The next chapter focuses on weight related issues such as body mass index, ideal body weight, weight loss, and weight loss drugs. This is followed by a chapter that answers questions about chromium, magnesium, vanadium, and folate supplements; antioxidants; and fenugreek. Chapter nine offers tips on shopping and meal planning. The next chapter addresses special situations, including treating low blood glucose, eating when sick, drinking alcohol, dining in restaurants, traveling, adjusting food and insulin for a swing shift schedule, preventing hypoglycemia, and using a nutritional supplement. Remaining chapters answer miscellaneous questions and list resources. The book concludes with an index. 17 tables. •

Coronary artery disease in women: What all physicians need to know Source: Philadelphia, PA: American College of Physicians: American Society of Internal Medicine. 1999. 615 pp. Contact: Available from American College of Physicians-American Society of Internal Medicine, 190 North Independence Mall West, Philadelphia, PA 19106. Telephone: (215) 351-2400 or (800) 523-1546 / fax: (215) 351- 2799 / e-mail: [email protected] / Web site: http://www.acponline.org. $43 for nonmembers, $32 for members; plus shipping and handling. Summary: This book for health care practitioners reviews all important aspects of coronary artery disease, with an emphasis on gender differences, age, and race. It contains five parts: the introduction, prevention, diagnosis, management, and conclusion. The section on prevention discusses smoking; diabetes and insulin resistance; the history and pharmacologic management of lipids/cholesterol; nutrition; hypertension; obesity; exercise as prevention; aspirin, antioxidants, and alcohol; and issues in hormone replacement therapy. The diagnosis section provides information on the differential diagnosis of chest pain, noninvasive testing techniques, and influence of gender in coronary angiography. Topics in the the section on management include angina pectoris, acute coronary syndromes, bypass grafting risks, angioplasty, congestive heart failure, psychosocial issues, and pharmacologic secondary prevention. The concluding section discusses future trends in treatment and research. Each chapter contains a summary and list of references. Numerous charts and graphs present statistical information. The book concludes with an index.

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The Anarchist AIDS Medical Formulary: A Guide to Guerrilla Immunology Contact: North Atlantic Books, PO Box 12327, Berkeley, CA, 94701-9998, (510) 559-8277. Summary: This monograph explores research in immunology and alternative therapies from the AIDS treatment underground, and takes a critical look at the response by the Government and medical establishment to the AIDS epidemic. It consists of a collection of essays adapted from Charles R. Caulfield's "HIV News" column in the San Francisco Sentinel. Caulfield, diagnosed with AIDS in 1983, contends that AIDS is survivable, with recovery possible through alternative healing and therapeutic strategies. Part I examines the politics and realities of AIDS treatment research. Part II discusses specific alternative AIDS treatments, focusing on theories, therapies, and resources. Among the therapies discussed are antioxidants, Acemannan, Dinitrochlorobenzene (DNCB), Chinese herbs, Germanium, vitamins A and C, and zinc.

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Living With the AIDS Virus: A Strategy for Long - Term Survival Contact: HK-Education, Incorporated, Education Division, PO Box 8207, Berkeley, CA, 94707. Summary: This monograph presents information about Acquired immunodeficiency syndrome (AIDS) and Human immunodeficiency virus (HIV) in order to outline a strategy for long-term survival of HIV-positive persons or Persons with AIDS (PWA's). The monograph holds that a realistic survival strategy calls for taking immediate steps to bring the virus under control; that each person needs to combine therapies, including antiviral drugs and alternative therapies; and that the longer HIV-positive persons survive, the better their chances of putting to use more effective therapies. The signs, symptoms, and progression of HIV disease, and its effect on the immune system, are discussed, and the roles of cytokines, antigens and antibodies, phagocytes, and T-cells are explained. The monograph describes other contributors and cofactors to AIDS and examines the prospects for a vaccine development. Azidothymidine (AZT) and other emerging antiviral drugs are described, along with the advantages and drawbacks of treatment. The alternative, or Now, therapies prescribed by this monograph involve substances found in the body, modified natural substances, synthetic substances with immune boosting potential, plant-derived substance, and other materials. Two separate sections of the monograph discuss phosphlipids and natural antioxidants and their roles in a survival strategy. In summary, this strategy is comprised of antiviral therapies, immune stimulators, nutrient therapies, phosphlipids, and antioxidants, as well as lifestyle changes.

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Foods That Harm, Foods That Heal: An A-Z Guide to Safe and Healthy Eating Source: Pleasantville, NY: Reader's Digest. 1997. 400 p. Contact: Available from Customer Service, Reader's Digest. Pleasantville, NY 10570. (800) 846-2100. PRICE: $30.00. ISBN: 0895779129. Summary: This nutrition reference book features more than 400 photographs and illustrations with more than 400 A to Z entries on a vast range of foods and health concerns, include caffeine, cancer, diabetes, fast food, garlic, heart disease, influenza, osteoporosis, pregnancy, sexually transmitted diseases, and vegetarianism. The book is designed to provide families with information to help understand the close links between foods and wellness. Each food entry provides at-a-glance information on its nutrients (or lack of) and its benefits and drawbacks. Each ailment is accompanied by a list of foods and beverages that are considered safe, and what foods or beverages should be cut down or avoided altogether. Personalized case studies help to illustrate various topics. There are special features on eating during different life stages, from infancy to old age, as well as such issues as genetically altered foods, irradiation, pesticides, and pollution. Other topics include how to cook foods to achieve maximum nutritional benefits; which dietary supplements really work; tips on exercising, storing food, and reading food labels; an instructive analysis of the most popular diet regimens; and controversial foods and additives such as eggs, nitrites, bran, cheese, milk, fat, wine, and alcohol. A glossary defines unfamiliar or technical terms; there is also a listing of organizations that can provide further information and resources. Topics specifically related to digestive diseases include allergic reactions to food, anorexia nervosa, antioxidants, appetite loss, basic food groups, carbohydrates, celiac disease, childhood and adolescent nutrition, cholesterol, constipation, convenience foods, Crohn's disease, diarrhea, dieting and weight control, digestive and malabsorption disorders, diverticulitis, fats, fiber, food poisoning, gastritis, gastroenteritis, gout, hiatal hernia,

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indigestion and heartburn, intolerance to milk and other foods, irritable bowel syndrome, malnutrition, medicine-food interactions, minerals, obesity, organic and health foods, preparation and storage of food, restaurants and eating out, smoking and diet, sports nutrition, supplements, traveler's health, ulcers, vitamins, and worms and other parasites. •

Ulcer Disease: Investigation and Basis for Therapy Source: New York, NY: Marcel Dekker, Inc. 1991. 528 p. Contact: Available from Marcel Dekker, Inc. P.O. Box 5005, Monticello, NY 12701-5185. (800) 228-1160 or (212) 696-9000. Fax (914) 796-1772. E-mail: [email protected]. PRICE: $195.00. ISBN: 0824782267. Summary: This textbook gives medical researchers and practicing clinicians a review of the origins, presentations, therapies, and human investigation of ulcer disease. Topics include the pathophysiology of peptic ulcer; epidemiology; biological rhythms in gastrointestinal function and processes; the clinical presentation of ulcer disease; nonsteroidal anti-inflammatory drug gastropathy; hemorrhage from gastric or duodenal ulceration; antacid therapy; H2-receptor antagonists; omeprazole; prostaglandins; sucralfate; antioxidants; endoscopic therapy of peptic ulcer disease; surgical treatment; statistical methods in trials of anti-ulcer drugs; clinical research organizations; pharmaceutical industry perspectives; and cost-effectiveness in the treatment of peptic ulcer disease. Each chapter includes numerous tables, figures and references; a subject index concludes the volume.

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 “antioxidants” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “antioxidants” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “antioxidants” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Advances in Oil and Fats, Antioxidants, and Oilseed By-Products (The Proceedings of the World Conference on Oilseed and Edible Oils processiNg, Vol 2) by S. S. Koseoglu (Editor), et al (1998); ISBN: 0935315845; http://www.amazon.com/exec/obidos/ASIN/0935315845/icongroupinterna

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Alpha Lipoic Acid Breakthrough: The Superb Antioxidant That May Slow Aging, Repair Liver Damage, and Reduce the Risk of Cancer, Heart Disease, and Diabetes by Burt Berkson, et al (1998); ISBN: 0761514570; http://www.amazon.com/exec/obidos/ASIN/0761514570/icongroupinterna

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Alpha Lipoic Acid: Nature's Ultimate Antioxidant by Allan E. Sosin, et al (1998); ISBN: 157566366X; http://www.amazon.com/exec/obidos/ASIN/157566366X/icongroupinterna

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Alpha Lipoic Acid: Nuture's Supreme Antioxidant by Rita Elkins (1998); ISBN: 1580540198; http://www.amazon.com/exec/obidos/ASIN/1580540198/icongroupinterna

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Antioxidant Adaptation: Its Role in Free Radical Pathology by Stephen A. Levine, Parris M. Kidd (1986); ISBN: 0961463007; http://www.amazon.com/exec/obidos/ASIN/0961463007/icongroupinterna

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Antioxidant Cookbook by Cory M.D. SerVaas (1995); ISBN: 0785275118; http://www.amazon.com/exec/obidos/ASIN/0785275118/icongroupinterna

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Antioxidant Food Supplements in Human Health by Lester Packer (Editor), et al (1999); ISBN: 0125435908; http://www.amazon.com/exec/obidos/ASIN/0125435908/icongroupinterna

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Antioxidant Methodology: In Vivo and in Vitro Concepts by Okezie I. Aruoma (Editor), Susan L. Cuppett (Editor) (1997); ISBN: 0935315799; http://www.amazon.com/exec/obidos/ASIN/0935315799/icongroupinterna

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Antioxidant Nutrients and Immune Functions (Advances in Experimental Medicine and Biology, 262) by Adrianne Bendich, et al; ISBN: 0306433966; http://www.amazon.com/exec/obidos/ASIN/0306433966/icongroupinterna

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Antioxidant Nutrition: Nature's Protectors Against Aging, Cancer and Degenerative Diseases by Rita Greer, Robert Woodward (Contributor) (1996); ISBN: 0285632760; http://www.amazon.com/exec/obidos/ASIN/0285632760/icongroupinterna

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Antioxidant Power: 366 Delicious Recipes for Great Health and Long Life by Dolores Riccio; ISBN: 0452277280; http://www.amazon.com/exec/obidos/ASIN/0452277280/icongroupinterna

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Antioxidant Vitamins and Health: Cardiovascular Disease, Cancer, Cataracts, and Aging by Claude Fernand Bourgeois (2003); ISBN: 0966428668; http://www.amazon.com/exec/obidos/ASIN/0966428668/icongroupinterna

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Antioxidants (Woodland Health Series) by Remi Cooper (1997); ISBN: 1885670524; http://www.amazon.com/exec/obidos/ASIN/1885670524/icongroupinterna

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Antioxidants : recent developments by Maurice William Ranney; ISBN: 081550747X; http://www.amazon.com/exec/obidos/ASIN/081550747X/icongroupinterna

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Antioxidants : syntheses and applications by J. C. Johnson; ISBN: 0815505620; http://www.amazon.com/exec/obidos/ASIN/0815505620/icongroupinterna

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Antioxidants Against Cancer by Ralph W. Moss; ISBN: 1881025284; http://www.amazon.com/exec/obidos/ASIN/1881025284/icongroupinterna

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Antioxidants and Cardiovascular Disease by Jean-Claude Tardif (Editor), Martial G. Bourassa (Editor); ISBN: 079236564X; http://www.amazon.com/exec/obidos/ASIN/079236564X/icongroupinterna

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Antioxidants and Exercise by Jan Karlsson, Jan Karisson (1997); ISBN: 0873228960; http://www.amazon.com/exec/obidos/ASIN/0873228960/icongroupinterna

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Antioxidants in Muscle Foods : Nutritional Strategies to Improve Quality by Eric A. Decker (Author), et al (2000); ISBN: 0471314544; http://www.amazon.com/exec/obidos/ASIN/0471314544/icongroupinterna

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Antioxidants in Therapy and Preventive Medicine (Advances in Experimental Medicine and Biology, 264) by Society for Free Radical Research Winter Meeting on

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Free Radicals in M, et al; ISBN: 0306434075; http://www.amazon.com/exec/obidos/ASIN/0306434075/icongroupinterna •

Antioxidants, the Real Story (Progressive Health Series) by Michael Colgan (1999); ISBN: 1896817114; http://www.amazon.com/exec/obidos/ASIN/1896817114/icongroupinterna

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Antioxidants: A Health Revolution: All You Need to Know about Antioxidants by Carolyn Lister (2003); ISBN: 047810832X; http://www.amazon.com/exec/obidos/ASIN/047810832X/icongroupinterna

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Antioxidants: In Science, Technology, Medicine & Nutrition by Gerald Scott (1997); ISBN: 1898563314; http://www.amazon.com/exec/obidos/ASIN/1898563314/icongroupinterna

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Antioxidants: Vitamins C and E for Health by Lester Packer (Editor), Kim Fahner (2003); ISBN: 1893997294; http://www.amazon.com/exec/obidos/ASIN/1893997294/icongroupinterna

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Antioxidants: Vitamins C and E for Health by Robert Youngston, et al (1999); ISBN: 0859698084; http://www.amazon.com/exec/obidos/ASIN/0859698084/icongroupinterna

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Atmospheric Oxidation and Antioxidants by Gerald Scott; ISBN: 0444896171; http://www.amazon.com/exec/obidos/ASIN/0444896171/icongroupinterna

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Biological Oxidants and Antioxidants: Molecular Mechanisms and Health Effects by Lester Packer (Editor), Augustine S.H. Ong (Editor) (1998); ISBN: 0935315918; http://www.amazon.com/exec/obidos/ASIN/0935315918/icongroupinterna

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Biotic Type Antioxidants: The Prospective Search Area for Novel Chemical Drugs by E. A. Parfenov, G. E. Zaikov (2000); ISBN: 9067643084; http://www.amazon.com/exec/obidos/ASIN/9067643084/icongroupinterna

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C.L.A.: The Essential Nutrient for Cutting Cancer Risk, Reducing Body Fat, and Providing Antioxidant Properties (Woodland Health Series) by Lane Williams, Woodland Publishing (1999); ISBN: 1580540082; http://www.amazon.com/exec/obidos/ASIN/1580540082/icongroupinterna

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Cellular Antioxidant Defense Mechanisms by Ching Kuang Chow (Editor) (1988); ISBN: 0849369185; http://www.amazon.com/exec/obidos/ASIN/0849369185/icongroupinterna

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Chinese Markets for Antioxidant [DOWNLOAD: PDF] by Asia Market Information & Development Company (Author); ISBN: B000063U9H; http://www.amazon.com/exec/obidos/ASIN/B000063U9H/icongroupinterna

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Cholesterol Cures: From Almonds and Antioxidants to Garlic, Golf, Wine and Yogurt325 Quick and Easy Ways to Lower Cholesterol and Live Longer by Richard Trubo, et al (1996); ISBN: 0875963994; http://www.amazon.com/exec/obidos/ASIN/0875963994/icongroupinterna

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Development of a Test Method for the Determination of the Hydroperoxide Potential and Antioxidant Effectiveness in Jet Fuels During (C R C Report (Coordinating Research Council), No 614) (1998); ISBN: 9999888674; http://www.amazon.com/exec/obidos/ASIN/9999888674/icongroupinterna

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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

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(Dietary Reference Intakes) by Institute Of Medicine; ISBN: 0309069351; http://www.amazon.com/exec/obidos/ASIN/0309069351/icongroupinterna •

Dietary Reference Intakes: Proposed Definition and Plan for Review of Dietary Antioxidants and Related Compounds (Compass Series) by Institute of Medicine Committee (Editor), Institute of Medicine (1999); ISBN: 0309061873; http://www.amazon.com/exec/obidos/ASIN/0309061873/icongroupinterna

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Dr. Earl Mindell's Complete Guide to Natural Cures: How to Heal Yourself and Prevent Disease With the Proven Power of Nature's Medicines, Vitamins, Antioxidants, Trace Minerals, Herbs, Fiber, and by Earl Mindell, Virginia Hopkins (2001); ISBN: 0130327034; http://www.amazon.com/exec/obidos/ASIN/0130327034/icongroupinterna

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Eat Away Illness: How to Age-Proof Your Body With Antioxidant Foods by Carlson Wade, Carolyn Wade; ISBN: 0132248093; http://www.amazon.com/exec/obidos/ASIN/0132248093/icongroupinterna

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Every Person's Guide to Antioxidants by John R. Smythies (1998); ISBN: 0813525756; http://www.amazon.com/exec/obidos/ASIN/0813525756/icongroupinterna

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Food Antioxidants: Technological, Toxicological, and Health Perspectives (Food Science and Technology, 71) by D. L. Madhavi (Editor), et al (1996); ISBN: 082479351X; http://www.amazon.com/exec/obidos/ASIN/082479351X/icongroupinterna

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Free Radicals in Diagnostic Medicine: A Systems Approach to Laboratory Technology, Clinical Correlations, and Antioxidant Therapy (Advances in Experimental Medicine and Biology, 366) by D. Armstrong (Editor), International Symposium on Free Radicals in Diagnostic Medicine 1993 (Editor) (1995); ISBN: 0306449811; http://www.amazon.com/exec/obidos/ASIN/0306449811/icongroupinterna

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Free Radicals, Antioxidants, Aging and Disease by Joseph A. Knight (1999); ISBN: 1890883182; http://www.amazon.com/exec/obidos/ASIN/1890883182/icongroupinterna

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Ginkgo Biloba: Therapeutic and Antioxidant Properties of the "Tree of Health" (Keats Good Herb Guide) by Frank Murray; ISBN: 0879837705; http://www.amazon.com/exec/obidos/ASIN/0879837705/icongroupinterna

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Glutathione: The Ultimate Antioxidant by Alan H. Pressman, Sheila Buff (Contributor); ISBN: 0312964323; http://www.amazon.com/exec/obidos/ASIN/0312964323/icongroupinterna

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Green Tea: Antioxidant Power to Fight Disease (Good Health Guides) by Debasis Bagchi (1999); ISBN: 0879839341; http://www.amazon.com/exec/obidos/ASIN/0879839341/icongroupinterna

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Green Tea: Antioxidants in a Cup (Storey Country Wisdom Bulletin, A-255) by Diana Rosen (2000); ISBN: 1580173020; http://www.amazon.com/exec/obidos/ASIN/1580173020/icongroupinterna

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Handbook of Oxidants and Antioxidants in Exercise by Chandan K. Sen (Editor), et al; ISBN: 0444826505; http://www.amazon.com/exec/obidos/ASIN/0444826505/icongroupinterna

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Jiaogulan: China's "Immortality Herb"--Unlocking the Secrets of Nature's Powerful Adaptogen and Antioxidant by Michael Blumert, Jialiu Liu (1999); ISBN: 1887089160; http://www.amazon.com/exec/obidos/ASIN/1887089160/icongroupinterna

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Lipid-Soluble Antioxidants: Biochemistry and Clinical Applications (Molecular and Cell Biology Updates) by A. S. H. Ong, L. Packer (1992); ISBN: 0817626670; http://www.amazon.com/exec/obidos/ASIN/0817626670/icongroupinterna

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Lipoic Acid: The Metabolic Antioxidant by Richard A. Passwater, Don R. Bensen (Editor); ISBN: 0879837209; http://www.amazon.com/exec/obidos/ASIN/0879837209/icongroupinterna

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Live Longer Live Healthier: The Power of Pycnogenol: The Practical Handbook of Antioxidants by Hasnain Walji (1996); ISBN: 0934252637; http://www.amazon.com/exec/obidos/ASIN/0934252637/icongroupinterna

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Maximize Your Health-Span With Antioxidants: The Baby-Boomer's Guide by Carmia Borek (1995); ISBN: 9995200759; http://www.amazon.com/exec/obidos/ASIN/9995200759/icongroupinterna

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Milk Thistle: A Remarkable Flavonoid Antioxidant and Liver Protectant (Woodland Health Ser) by Woodland Publishing Staff, Woodland Publishing (1999); ISBN: 1885670249; http://www.amazon.com/exec/obidos/ASIN/1885670249/icongroupinterna

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Natural Antioxidants and Anticarcinogens in Nutrition, Health and Disease (Special Publication (Royal Society of Chemistry (Great Britain))) by J.T. Kumpulainen (Editor), J.T. Salonen (Editor) (1999); ISBN: 085404793X; http://www.amazon.com/exec/obidos/ASIN/085404793X/icongroupinterna

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Natural Antioxidants and Food Quality in Atherosclerosis and Cancer Prevention (Rsc Special Publications, 181) by J, T. Kumpulainen, J. T. Salonen (1996); ISBN: 0854047212; http://www.amazon.com/exec/obidos/ASIN/0854047212/icongroupinterna

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Natural Antioxidants in Avian Nutrition and Reproduction by Surai (Editor) (2003); ISBN: 1897676956; http://www.amazon.com/exec/obidos/ASIN/1897676956/icongroupinterna

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Natural Antioxidants in Human Health and Disease by Balz Frei (Editor), Balz Grei (1994); ISBN: 0122669754; http://www.amazon.com/exec/obidos/ASIN/0122669754/icongroupinterna

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Natural Antioxidants: Chemistry, Health Effects, and Applications by Fereidoon Shahidi (Editor) (1997); ISBN: 0935315772; http://www.amazon.com/exec/obidos/ASIN/0935315772/icongroupinterna

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Naturally Occurring Antioxidants by Richard A. Larson; ISBN: 0873719573; http://www.amazon.com/exec/obidos/ASIN/0873719573/icongroupinterna

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Network Antioxidants by Lester Packer (1999); ISBN: 1893576019; http://www.amazon.com/exec/obidos/ASIN/1893576019/icongroupinterna

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Opc: The Miracle Antioxidant: How It Acts to Prevent Disease, Restore Health and Upgrade Quality of Life by Chris Kilham (1997); ISBN: 0879838426; http://www.amazon.com/exec/obidos/ASIN/0879838426/icongroupinterna

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Organosulfur Antioxidants in Hydrocarbon Oils (Sulfur Reports Series) by J. Robertson, D. N. Harpp; ISBN: 3718602962; http://www.amazon.com/exec/obidos/ASIN/3718602962/icongroupinterna

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Oxidants and Antioxidants in Cutaneous Biology (Current Problems in Dermatology, Vol. 29) by Jens Thiele (Editor), Peter Elsner (Editor) (2001); ISBN: 3805571321; http://www.amazon.com/exec/obidos/ASIN/3805571321/icongroupinterna

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Oxidants and Antioxidants: Ultrastructural and Molecular Biology Protocols by D. Armstrong (Editor); ISBN: 0896038513; http://www.amazon.com/exec/obidos/ASIN/0896038513/icongroupinterna

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Oxidants, Antioxidants, and Disease Prevention (Ilsi Europe Concise Monograph Series) by Lillian Langseth (1995); ISBN: 0944398529; http://www.amazon.com/exec/obidos/ASIN/0944398529/icongroupinterna

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Oxidative Stress and Antioxidant Defenses in Biology by Sami Ahmad (Editor), Sami Ajmad (1995); ISBN: 0412039710; http://www.amazon.com/exec/obidos/ASIN/0412039710/icongroupinterna

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Oxidative Stress and Antioxidant Protocols by Donald Armstrong (Editor) (2002); ISBN: 0896038505; http://www.amazon.com/exec/obidos/ASIN/0896038505/icongroupinterna

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Perspectives of Antioxidant Treatment of Emphysema With N-Acetyloysteine by V. Cichetti (Editor), et al (1986); ISBN: 3805545142; http://www.amazon.com/exec/obidos/ASIN/3805545142/icongroupinterna

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Phenolic Compounds in Foods and Their Effects on Health II: Antioxidants and Cancer Prevention (Acs Symposium, No. 507) by Mou-Tuan Huang (Editor), et al (1992); ISBN: 0841224765; http://www.amazon.com/exec/obidos/ASIN/0841224765/icongroupinterna

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Preventing Coronary Heart Disease: The Role of Antioxidants, Vegetables and Fruit by Tso (1997); ISBN: 0113220014; http://www.amazon.com/exec/obidos/ASIN/0113220014/icongroupinterna

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Proc. of the Intl. Meeting on Antioxidants, Inflammation, Cardiovascular and Opthalmic Diseases (Life Chemistry Reports Series) by Francisco Romero; ISBN: 3718656396; http://www.amazon.com/exec/obidos/ASIN/3718656396/icongroupinterna

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Proceedings of the International Symposium on Natural Antioxidants: Molecular Mechanisms and Health Effects by Lester Packer (Editor), et al (1996); ISBN: 0935315691; http://www.amazon.com/exec/obidos/ASIN/0935315691/icongroupinterna

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Pycnogenol Miracle Antioxidant (Woodland Health Series) by Rita Elkins, Louise Tenney (Editor) (1995); ISBN: 1885670095; http://www.amazon.com/exec/obidos/ASIN/1885670095/icongroupinterna

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Reverse the Aging Process Naturally: How to Build the Immune System With Antioxidants--The Super-Nutrients of the Nineties (The Gary Null Health Lib) by Gary Null, Martin Feldman (1993); ISBN: 0679745092; http://www.amazon.com/exec/obidos/ASIN/0679745092/icongroupinterna

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Simply Healthy: Over 250 Lowfat Recipes Rich in the Antioxidant Vitamins That Keep You Healthy by University of California at Berkeley, Lisa Koenig (Photographer) (1995); ISBN: 0929661281; http://www.amazon.com/exec/obidos/ASIN/0929661281/icongroupinterna

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Spices: Flavor Chemistry and Antioxidant Properties (Acs Symposium Series, 660) by Sara J. Risch (Editor), et al (1996); ISBN: 0841234957; http://www.amazon.com/exec/obidos/ASIN/0841234957/icongroupinterna

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Sports Nutrition Guide: Minerals, Vitamins & Antioxidants for Athletes by Michael Colgan (2002); ISBN: 0969527284; http://www.amazon.com/exec/obidos/ASIN/0969527284/icongroupinterna

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Studies on Effects of Antioxidants on Arterial Thrombosis and Endothelial Cell Injury: With Special Reference to Tocopherols and Apoa1 Milano (Comprehensive Summaries of Uppsala Dissertations, 936) by Dayuan Li (2000); ISBN: 9155447406; http://www.amazon.com/exec/obidos/ASIN/9155447406/icongroupinterna

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The Antioxidant Cookbook: A Nutritionist's Secret Strategy by Janet Weiner (Editor), Michael Weiner (1996); ISBN: 0912845139; http://www.amazon.com/exec/obidos/ASIN/0912845139/icongroupinterna

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The Antioxidant Pocket Counter by Gail Becker (1994); ISBN: 0812921437; http://www.amazon.com/exec/obidos/ASIN/0812921437/icongroupinterna

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The Antioxidant Pocket Counter: A Guide to the Essential Nutrients That Help Fight Cancer and Heart Disease by Gail, R.D. Becker (1994); ISBN: 0812924037; http://www.amazon.com/exec/obidos/ASIN/0812924037/icongroupinterna

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The Antioxidant Save-Your-Life Cookbook: 150 Nutritious and Delicious High-Fiber, Low-Fat Recipes to Protect Yourself Against the Damaging Effects of Free Radicals by Jane Kinderlehrer, Daniel A. Kinderlehrer (2002); ISBN: 1557045011; http://www.amazon.com/exec/obidos/ASIN/1557045011/icongroupinterna

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The ANTIOXIDANT VITAMIN COUNTER by Annette B. Natow (Author) (1994); ISBN: 0671783203; http://www.amazon.com/exec/obidos/ASIN/0671783203/icongroupinterna

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The Antioxidants by Richard A. Passwater; ISBN: 087983787X; http://www.amazon.com/exec/obidos/ASIN/087983787X/icongroupinterna

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The Antioxidants (The Nutrition Superbook, Vol 1) by Jean Barilla (Editor); ISBN: 0879836717; http://www.amazon.com/exec/obidos/ASIN/0879836717/icongroupinterna

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The Great Antioxidant Lie by Heather MacLean Walters (2000); ISBN: 0964891344; http://www.amazon.com/exec/obidos/ASIN/0964891344/icongroupinterna

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The Great Grape and Fine Pine, OPC Antioxidant Extracts, 3rd Edition by Tonita d'Raye; ISBN: 1889887072; http://www.amazon.com/exec/obidos/ASIN/1889887072/icongroupinterna

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The Gsh Phenomenon: Nature's Most Powerful Antioxidant and Healing Agent Nditions by Alan H. Pressman, et al; ISBN: 0312151357; http://www.amazon.com/exec/obidos/ASIN/0312151357/icongroupinterna

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The Index of Antioxidants and Antiozonants: An International Guide to More Than 1500 Products by Trade Name, Chemical, Application, and Manufacturer (Index Series) by Michael Ash (Compiler), Irene Ash (Compiler) (1997); ISBN: 056607883X; http://www.amazon.com/exec/obidos/ASIN/056607883X/icongroupinterna

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The Miracle Foods Cookbook: Easy, Low-Cost Recipes and Menus With AntioxidantRich Vegetables and Fruits That Help You Lose Weight, Fight Disease, A by M. J. Smith; ISBN: 1565610563; http://www.amazon.com/exec/obidos/ASIN/1565610563/icongroupinterna

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The Miracle Nutrient Cookbook: 100 Delicious Antioxidant-Enriched Recipes and Menu Suggestions for Optimum Health by Tamara Holt, Maureen Callahan

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(Contributor) (1995); ISBN: 0684802384; http://www.amazon.com/exec/obidos/ASIN/0684802384/icongroupinterna •

The Natural Health Guide to Antioxidant: Using Vitamins and Other Supplements to Fight Disease, Boost Immunity, and Maintain Optimal Health by Nancy Pauline Bruning, Natural Health Magazine (Contributor) (1994); ISBN: 0553565796; http://www.amazon.com/exec/obidos/ASIN/0553565796/icongroupinterna

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The Potato Antioxidant: Alpha Lipoic Acid: A Health Learning Handbook by Beth M. Ley; ISBN: 0964270366; http://www.amazon.com/exec/obidos/ASIN/0964270366/icongroupinterna

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The Saturday Evening Post Antioxidant Cookbook by Cory, M.D. Servaas, et al; ISBN: 0785275096; http://www.amazon.com/exec/obidos/ASIN/0785275096/icongroupinterna

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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

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Therapeutic Uses of Antioxidants for Health Improvements: Index of New Information With Authors, Subjects, and Bibliography (The World's Best Research Books) by American Health Research Institute (1995); ISBN: 0788304682; http://www.amazon.com/exec/obidos/ASIN/0788304682/icongroupinterna

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Therapeutic Uses of Antioxidants for Health Improvements: Index of New Information With Authors, Subjects, and Bibliography (The World's Best Research Books) (1995); ISBN: 0788304690; http://www.amazon.com/exec/obidos/ASIN/0788304690/icongroupinterna

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Two M.D.'s and a Pharmacist Ask, "Are You Getting It 5 Times a Day?": Fruits and Vegetables: Enzymes, Antioxidants, and Fiber by Sydney H. Crackower, et al (1996); ISBN: 0934252351; http://www.amazon.com/exec/obidos/ASIN/0934252351/icongroupinterna

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Vitamin a in Health and Disease (Antioxidants in Health and Disease, Vol 1) by Rune Blomhoff (Editor); ISBN: 0824791207; http://www.amazon.com/exec/obidos/ASIN/0824791207/icongroupinterna

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Vitamin C: The Vital Antioxidant for Disease Prevention by Hasnain Walji; ISBN: 0722532261; http://www.amazon.com/exec/obidos/ASIN/0722532261/icongroupinterna

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Your Personal Nutritionist: Antioxidant Counter by Edward R. Blonz, et al; ISBN: 0451184882; http://www.amazon.com/exec/obidos/ASIN/0451184882/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 “antioxidants” (or synonyms) into the search box, and select “books only.”

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From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

A review of the technological efficacy of some antioxidants and synergists. Author: Joint FAO/WHO Expert Committee on Food Additives.; Year: 1975; Geneva, World Health Organization, 1972

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Antioxidants in foods and the treatment of human diseases Author: International Food Science Centre.; Year: 1990; [Lystrup] Denmark: International Food Science Centre, [1991]

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Cellular antioxidant defense mechanisms Author: Chow, Ching Kuang,; Year: 1989; Boca Raton, Fla.: CRC Press, c1988; ISBN: 0849369169 http://www.amazon.com/exec/obidos/ASIN/0849369169/icongroupinterna

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CRC handbook of free radicals and antioxidants in biomedicine Author: Miquel, Jaime.; Year: 1984; Boca Raton, Fla.: CRC Press, c1989; ISBN: 0849332680 http://www.amazon.com/exec/obidos/ASIN/0849332680/icongroupinterna

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Food antioxidants Author: Hudson, B. J. F.; Year: 1991; London; New York: Elsevier Applied Science; New York, NY, USA: Sole distributor in the USA and Canada, Elsevier Science Pub. Co., c1990; ISBN: 1851664408 http://www.amazon.com/exec/obidos/ASIN/1851664408/icongroupinterna

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Lipid-soluble antioxidants: biochemistry and clinical applications Author: Ong, Augustine S. H.; Year: 1994; Basel; Boston: Birkhäuser, c1992; ISBN: 3764326670 http://www.amazon.com/exec/obidos/ASIN/3764326670/icongroupinterna

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Oxidative stress: oxidants and antioxidants Author: Sies, H. (Helmut),; Year: 1993; London; San Diego: Academic Press, c1991; ISBN: 0126427623 http://www.amazon.com/exec/obidos/ASIN/0126427623/icongroupinterna

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Oxygen radicals: proceedings of the 5th International Congress on Oxygen Radicals: active oxygen, lipid peroxides, and antioxidants, Kyoto, 17-21 November 1991 Author: Yagi, Kunio.; Year: 1990; Amsterdam; New York: Excerpta Medica, 1992; ISBN: 0444894853 http://www.amazon.com/exec/obidos/ASIN/0444894853/icongroupinterna

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The role of anti-oxidants in diabetes mellitus: oxygen radicals and anti-oxidants in diabetes = Stellenwert von Antioxidantien beim Diabetes mellitus: Sauerstoffradikale und Antioxidantien beim Diabetes Author: Gries, F. A. (F. Arnold); Year: 1990; Frankfurt Am Main: pmi Verlagsgruppe, c1993; ISBN: 3891192576

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Toxicological evaluation of some food additives including anticaking agents, antimicrobials, antioxidants, emulsifiers and thickening agents Author: Joint FAO/WHO Expert Committee on Food Additives.; Year: 1980; Geneva: World Health Organization, 1974; ISBN: 9241660058 http://www.amazon.com/exec/obidos/ASIN/9241660058/icongroupinterna

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.

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Chapters on Antioxidants In order to find chapters that specifically relate to antioxidants, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and antioxidants 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 “antioxidants” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on antioxidants: •

Antioxidants in Human Health and Disease Source: in McCormick, D.B., Bier, D.M., and Goodridge, A.G., eds. Annual Review of Nutrition. Palo Alto, CA: Annual Reviews Inc. 1996. Volume 16: 33-50. 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 article reviews current understanding of the role of antioxidants in human health and disease. Topics include why humans need antioxidants; reactive oxygen and nitrogen species; how radicals react; the toxicity of superoxide, hydrogen peroxide, and nitric oxide; antioxident defenses; antioxidants synthesized in the human body; dietary antioxidants; oxidative stress; and the role of diet in preventing oxidative stress and associated human disease. The author concludes with a brief consideration of the social and economic benefits of healthy dietary changes. 2 tables. 124 references.

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CHAPTER 8. MULTIMEDIA ON ANTIOXIDANTS Overview In this chapter, we show you how to keep current on multimedia sources of information on antioxidants. 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 antioxidants is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “antioxidants” 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 “antioxidants” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on antioxidants: •

Antioxidants and Atherogenesis Source: Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, 1992, 60 minutes. Contact: WIN, 1 WIN WAY, Bethesda, MD 20892-3665. Summary: In this lecture, Dr. Chait discusses the role of oxidation in atherogenesis, where antioxidants may fit in, current knowledge gaps, and a future research agenda. The search for forms of LDL cholesterol that bypass LDL regulators has revealed that oxidized LDL is the most likely candidate, and that it leads to thrombosis as well as lipid accumulation in atherogenesis. It seems to play a role in every stage of the athersclerotic process. Cardiovascular risk factors that increase the susceptibility of LDL to oxidation are cigarette smoking, diabetes, genetic factors, and polyunsaturated fatty acids. Questions that remain to be answered relate to in vivo mechanisms. Determining the efficacy of vitamin supplements requires large-scale, placebo-controlled clinical studies.

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In the interim, Dr. Chait recommends considering supplementary use of vitamins E and C, and beta carotene.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio 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 “Sound Recordings.” Type “antioxidants” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on antioxidants: •

1994 National Skills Building Conference: Session 6; AIDS, Medicine, Miracles Contact: HMR Duplications, 18 Gregory Place, Oakland, CA, 94619, (510) 482-8732. Summary: This series of cassettes contains the workshop on AIDS, medicine, and miracles, which discusses alternative ways that healing can occur in the lives of individuals. It describes the healing that occurs when humans come together. The first speaker, Russell Jaffee, discusses health-based approaches useful for HIV and AIDS. He tells the story of a Cambodian monk who came to stay in his apartment for what was initially expected to be a few days, but who stayed for 2 years, that comprises the basis for his belief in health-based versus disease-based interventions. He theorizes that an individual must have enough naturally-produced antioxidants to do battle with virallycaused oxidative stress. The next speaker is Laurel Lake, who discusses nutritional supplementation and micronutrient replacement for immunocompromised individuals. The lunch break, also recorded, consists of a hands-on learning experience in getting in touch with oneself. The remainder of the tapes is inaudible.

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CHAPTER 9. PERIODICALS AND NEWS ON ANTIOXIDANTS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover antioxidants.

News Services and Press Releases One of the simplest ways of tracking press releases on antioxidants 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 “antioxidants” (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 antioxidants. 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 “antioxidants” (or synonyms). The following was recently listed in this archive for antioxidants: •

Antioxidants play key role in estrogen-deficiency bone loss Source: Reuters Medical News Date: September 19, 2003

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Eating dark chocolate raises antioxidant levels Source: Reuters Medical News Date: August 27, 2003

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Antioxidants may have role in HIV-related lipoatrophy Source: Reuters Industry Breifing Date: August 21, 2003

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Antioxidants don't prevent cancer in male smokers Source: Reuters Health eLine Date: July 22, 2003

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Antioxidant supplements do not prevent cancer in male smokers Source: Reuters Industry Breifing Date: July 22, 2003

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Antioxidants don't cut heart disease risk: study Source: Reuters Health eLine Date: June 13, 2003

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Antioxidants counter alcohol brain damage in rats Source: Reuters Health eLine Date: June 03, 2003

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Novel antioxidants have therapeutic potential in HIV dementia Source: Reuters Medical News Date: February 19, 2003

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Antioxidant supplements could ease asthma symptoms Source: Reuters Health eLine Date: February 17, 2003

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Antioxidant can protect kidneys during heart test Source: Reuters Health eLine Date: February 06, 2003

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Berries provide good source of plant antioxidant Source: Reuters Medical News Date: February 05, 2003

•

Berries a good source of plant antioxidant Source: Reuters Health eLine Date: February 04, 2003

•

Antioxidant-amino acid mix shields blood vessels Source: Reuters Health eLine Date: January 22, 2003

•

Incara, Elan terminate option agreement for antioxidant compounds Source: Reuters Industry Breifing Date: January 15, 2003

•

Antioxidants may help patients after surgery Source: Reuters Health eLine Date: January 13, 2003

•

Some antioxidants higher, lower in hypertensives Source: Reuters Health eLine Date: January 03, 2003

•

Jury out on antioxidant, eye condition: study Source: Reuters Health eLine Date: December 16, 2002

Periodicals and News

•

Investigational antioxidant for HIV-related dementia safe, but benefits uncertain Source: Reuters Medical News Date: December 12, 2002

•

Bilirubin an essential, powerful antioxidant in mammalian cells Source: Reuters Medical News Date: November 26, 2002

•

Antioxidants missing in mouths with gum disease Source: Reuters Health eLine Date: November 26, 2002

•

WAVE trial: No cardioprotective benefits with HRT or antioxidants Source: Reuters Industry Breifing Date: November 20, 2002

•

Antioxidant limits contrast-induced nephrotoxicity in susceptible patients Source: Reuters Industry Breifing Date: November 11, 2002

•

Total dietary antioxidant potential associated with reduced risk of gastric cancer Source: Reuters Medical News Date: November 01, 2002

•

Antioxidant may slow Parkinson's progress Source: Reuters Health eLine Date: October 14, 2002

•

Antioxidant may slow functional decline in Parkinson's disease Source: Reuters Medical News Date: October 14, 2002

•

Antioxidant gene therapy curbs restenosis after vascular manipulation in animals Source: Reuters Industry Breifing Date: September 16, 2002

•

Women could need antioxidants more than men Source: Reuters Health eLine Date: September 02, 2002

•

Antioxidant vitamins may be helpful in diabetic ketoacidosis treatment Source: Reuters Medical News Date: August 29, 2002

•

Honey shown to boost antioxidants in blood Source: Reuters Health eLine Date: August 19, 2002

•

Statins may benefit cardiac function through antioxidant action Source: Reuters Industry Breifing Date: August 16, 2002

•

Dietary antioxidants may reduce risk of Alzheimer's disease Source: Reuters Industry Breifing Date: June 25, 2002

•

Antioxidants may delay Alzheimer's disease onset Source: Reuters Health eLine Date: June 25, 2002

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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 “antioxidants” (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 “antioxidants” (or synonyms). If you know the name of a company that is relevant to antioxidants, 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 “antioxidants” (or synonyms).

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

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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 “antioxidants” (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 antioxidants: •

A Vote for Oats Source: University of California, Berkeley, Wellness Letter. 17(2):3. November 2000. Contact: Health Letter Associates. P.O. Box 412, Prince Street Station, New York, NY 10012-0007. www.wellnessletter.com. Summary: Oats are a whole grain rich in soluble fiber. In 1997, the Food and Drug Administration (FDA) allowed the labels on oat products to state that they, along with a diet low in saturated fat and cholesterol, "may reduce the risk of heart disease." Aside from lowering blood cholesterol, oats may also help control blood sugar, improve insulin sensitivity, and lower blood pressure. Oats also contain phytochemicals and antioxidants that may reduce the risk of heart disease. The article recommends reading labels when buying oat products and suggests looking for those with at least 2 or 3 grams of fiber per serving.

•

Navy Patent Holds Promise for Noise-Induced Hearing Loss Source: ASHA Leader. 6(7): 1, 13. April 17, 2001. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 8970157. Website: www.asha.org. Summary: The United States Navy recently received a patent for a technique that can prevent or reduce hearing loss after a damaging noise exposure. This brief article describes the technique, which uses a microcatheter (a tiny tube) inserted into the ear to deliver drugs, such as antioxidants, to rescue the cochlear hair cells fundamental to sound detection. This technique is not a cure for cumulative hearing loss, but can be used as an intervention after an exposure to a high level of noise. The article briefly explains how noise exposure damages the cochlear hair cells, and how drug therapy can interrupt that process. The author also reports on animal studies that were used to support this technique. The article concludes with a web site that readers can consult for additional information (www.onr.navy.mil/onr/newsrel/nr980731.htm).

•

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

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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.' •

Drugs in Development Source: Research and Practice. 5(3): 2-3. Fall 1997. Contact: Alzheimer's Association. 919 North Michigan Avenue, Suite 1000, Chicago, IL 60611-1676. (800) 272-3900. (312) 335-8700. FAX: (312) 335-1110. Internet: www.alz.org. PRICE: Free. Summary: This newsletter article highlights the status of new treatments under investigation for the treatment of Alzheimer's disease (AD). It discusses the types of drugs that currently are being studied and summarizes some of the initial findings about the effects of antioxidants such as vitamin E or selegiline, non-steroidal antiinflammatory drugs, and estrogen. It includes a chart summarizing current research into drugs that may improve the cognitive symptoms of AD. The chart includes the names of 22 drugs being studied and brief descriptions of the mechanisms of action, trial sponsors, and phase of development.

Academic Periodicals covering Antioxidants Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to antioxidants. In addition to these sources, you can search for articles covering antioxidants 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.”

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APPENDICES

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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 Institute12: •

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/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 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:14 •

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

13

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). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

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 “antioxidants” 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 “antioxidants” (or synonyms) into the “For these words:” box. The following is a sample result: •

Anti - Oxidants (General Information) Contact: AIDS Project Los Angeles, 3550 Wilshire Blvd Ste 300, Los Angeles, CA, 900102404, (213) 201-1600, http://www.apla.org. Summary: A compilation of information about antioxidants, this report describes the functions, characteristics, and possible therapeutic and preventative uses of these compounds. Free radicals, byproducts of cellular metabolism, are especially dangerous to HIV-infected people and antioxidants can absorb and neutralize these byproducts. A list of factors which deplete antioxidants including cigarette smoke, oxidants like acetaminophen, and halocarbons like bromobenzene is given. The essential characteristics of the well-known, non-enzyme antioxidants like vitamins E and C, and beta-carotene are discussed, especially their immunity-boosting effects. Additionally, enzyme antioxidants are examined with their mineral cofactors like zinc, copper, and iron. The nutrient, Coenzyme Q10 (CoQ), which is needed to produce energy in every cell, is detailed because like other antioxidants it boosts antibody levels. However, CoQ levels seem to correlate to severity of AIDS symptoms. Other antioxidants looked at include N-Acetyl-L-cysteine (NAC) and glutathione, which inhibit HIV replication in vitro.

•

Free Radicals in HIV Progression Pycnogenol Reverses Their Effects: A Preliminary Report Contact: Keep Hope Alive, PO Box 270041, West Allis, WI, 53227, (262) 548-4344, http://www.keephope.net. Summary: In this report, the author proposes that free radicals produced by HIV because of its unique molecular structure cause the most cellular damage in AIDS, and that Pycnogenol, a natural flavinoid, can reverse much of this damage. A list of 10 cellular effects of free radicals, and a description of the composition of several free radicals including superoxide and hydroxyl are provided. The author discusses other antioxidants and free radical scavengers such as Beta-carotene and vitamin A, and contrasts their actions to that of Pycnogenol. Preliminary case reports of three HIVpositive persons taking Pycnogenol with success are presented. One individual lists

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twelve health benefits in 10 days including increased energy and normal sleep patterns. A saturation dosage seems necessary, and a precaution about possible increased pain initially is noted. Further information sources are given. •

Progress Report on Alzheimer's Disease 2000: Taking the Next Steps Source: Bethesda, MD: National Institute on Aging. 2000. 62 p. Contact: Available from Alzheimer's Disease Education and Referral (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. Order number: Z-164. NIH Publication Number: 00-4859. Summary: This annual report highlights recent research into Alzheimer's disease (AD) supported by the National Institute on Aging and eight other branches of the National Institutes of Health. The report first reviews the characteristics, causes, diagnosis and treatment of AD. Research advances include: etiology involving amyloid, presenilins, apoptosis, apolipoproteins, and protein aggregation; early diagnosis; drug treatments such as estrogen, anti-inflammatories, antioxidants, and neurotrophic factors; caregiver support; and research infrastructure. The report also reviews areas for future research. Sidebars throughout the report cover issues such as brain structure, AD and Parkinson's disease, and the AD Clinical Trials Database. 114 references.

•

HIV Treatment Strategy, Part III: Drug Information for People Living With AIDS Contact: Carl Vogel Center, 1012 14th St NW Ste 707, Washington, DC, 20005, (202) 6380750. Summary: This paper provides prescriptive drug treatment information for Persons With AIDS (PWA's). It is important for HIV-positive individuals to talk to a physician about a complete antiviral, immunomodulatory, and prophylactic drug program. Antivirals/antibiotics include AZT, ddc, and/or ddi; Combination of the three is thought to increase overall effectiveness. D4T either alone or with ddi looks promising. Many physicians include acyclovir to prevent HIV activation by herpes viruses. Some physicians recommend IV Compound Q for individuals with CD-4's over 100. Doxycycline is used as an anti-mycoplasma agent, Peptide-T seems most useful for neuropathy and cognitive dysfunction problems. Bitter melon is being tried with CD-4 increases is also looking promising. Some immune modulators include: Antioxidants, antabuse/disulfiram, coenzyme Q10, DNCB, glutathione, isoprinosine, naltrexone, pentoxifylline/trental, recombinant gp 160 vaccine, and thymus derivatives. Pap smears and vaginal exams should be conducted regularly for women. Extra nutrients for women should be implemented.

The NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. 15 16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

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).

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Type “antioxidants” (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 103726 265 462 52 3 104508

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “antioxidants” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 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 staff.21 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.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

The HSTAT URL is http://hstat.nlm.nih.gov/.

19

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. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21

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. 22 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.

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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/.

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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 antioxidants 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 antioxidants. 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 antioxidants. 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 “antioxidants”:

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•

Guides on antioxidants Antioxidants http://www.nlm.nih.gov/medlineplus/antioxidants.html

•

Other guides Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Cancer Alternative Therapy http://www.nlm.nih.gov/medlineplus/canceralternativetherapy.html Dietary Fiber http://www.nlm.nih.gov/medlineplus/dietaryfiber.html Macular Degeneration http://www.nlm.nih.gov/medlineplus/maculardegeneration.html

Within the health topic page dedicated to antioxidants, the following was listed: •

General/Overviews Antioxidant Vitamins Source: American Heart Association http://www.americanheart.org/presenter.jhtml?identifier=4452

•

Specific Conditions/Aspects Anti-Aging Therapies: Youth in a Bottle? Source: Mayo Clinic http://www.mayoclinic.com/invoke.cfm?id=HQ00233 Coenzyme Q-10 Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00606 JAMA Patient Page: How Much Vitamin C Do You Need? Source: American Medical Association http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZFJ0QSJAC&s ub_cat=379 Selenium Source: National Institutes of Health, Office of Dietary Supplements http://www.cc.nih.gov/ccc/supplements/selen.html Tea and Cancer Prevention Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/tea Vitamin E Source: National Institutes of Health, Office of Dietary Supplements http://www.cc.nih.gov/ccc/supplements/vite.html

Patient Resources

•

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From the National Institutes of Health Study of Menopausal Women with Heart Disease Finds No Benefit, Potential for Harm from Hormone Therapy and Antioxidant Vitamins Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/nov2002/nhlbi-19.htm Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease Source: National Institute of Neurological Disorders and Stroke http://www.nih.gov/news/pr/oct2002/ninds-14.htm

•

Organizations Food and Nutrition Information Center Source: National Agricultural Library http://www.nal.usda.gov/fnic/ Office of Dietary Supplements Source: National Institutes of Health, Office of Dietary Supplements http://dietary-supplements.info.nih.gov/

•

Research Antioxidant Vitamins and Zinc Reduce Risk of Vision Loss From Age-Related Macular Degeneration Source: National Eye Institute http://www.nih.gov/news/pr/oct2001/nei-12.htm Antioxidants and Cancer Prevention Source: National Cancer Institute http://www.cancer.gov/newscenter/pressreleases/antioxidants Antioxidants and Cancer: The Jury's Still Out Source: American Cancer Society http://www.cancer.org/docroot/NWS/content/NWS_2_1x_Antioxidants_and_Ca ncer_The_Jurys_Still_Out.asp Study of Menopausal Women with Heart Disease Finds No Benefit, Potential for Harm from Hormone Therapy and Antioxidant Vitamins Source: National Heart, Lung, and Blood Institute http://www.nih.gov/news/pr/nov2002/nhlbi-19.htm Study Suggests Coenzyme Q10 Slows Functional Decline in Parkinson's Disease Source: National Institute of Neurological Disorders and Stroke http://www.nih.gov/news/pr/oct2002/ninds-14.htm USDA-NCC Carotenoid Database for U.S. Foods-1998 Source: Dept. of Agriculture http://www.nal.usda.gov/fnic/foodcomp/Data/car98/car98.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

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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 antioxidants. 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: •

What About Antioxidants? Contact: AIDS Committee of Toronto, 399 Church St 4th Fl, Toronto, (416) 340-2437, http://www.actoronto.org. Summary: This brochure, in a question-and-answer format, advises HIV-positive people about eating foods containing antioxidants and taking food supplements that contain them. 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

•

Vitamin A and Carotenoids Summary: Answers basic questions about the antioxidant vitamin A, 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=6442 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

Patient Resources

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ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to antioxidants. 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

•

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 antioxidants. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with antioxidants. 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 antioxidants. 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.

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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 “antioxidants” (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 “antioxidants”. Type the following hyperlink into your 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 “antioxidants” (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 “antioxidants” (or a synonym) into the search box, and click “Submit Query.”

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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.23

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

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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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)24: •

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/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

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/

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•

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/

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•

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/

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•

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

253

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).

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

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ANTIOXIDANTS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Ablation: The removal of an organ by surgery. [NIH] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] 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] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] 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] Acid Rain: Acidic water usually pH 2.5 to 4.5, which poisons the ecosystem and adversely affects plants, fishes, and mammals. It is caused by industrial pollutants, mainly sulfur oxides and nitrogen oxides, emitted into the atmosphere and returning to earth in the form of acidic rain water. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the

256 Antioxidants

alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] 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] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [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] 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] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [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] Adolescent Nutrition: Nutrition of children aged 13-18 years. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] 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

Dictionary 257

carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] 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] 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] 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] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]

Aldehyde Reductase: An enzyme that catalyzes reversibly the oxidation of an aldose to an alditol. It possesses broad specificity for many aldoses. EC 1.1.1.21. [NIH] 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]

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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 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [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] Allergens: Antigen-type substances (hypersensitivity, immediate). [NIH]

that

produce

immediate

hypersensitivity

Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allo: A female hormone. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [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] 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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [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]

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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] 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] Aminosalicylic Acids: A group of 2-hydroxybenzoic acids that can be substituted by amino groups at any of the 3-, 4-, 5-, or 6-positions. [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] Ammonium Chloride: An acidifying agent that is used as an expectorant and a diuretic. [NIH]

Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [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] 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 inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a,

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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] 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] 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] 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] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] 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] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or

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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] 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-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

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] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU]

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Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antithrombins: An endogenous family of proteins belonging to the serpin superfamily that neutralizes the action of thrombin. Six naturally occuring antithrombins have been identified and are designated by Roman numerals I to VI. Of these, Antithrombin I and antithrombin III appear to be of major importance. [NIH] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] 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 associated with tumor growth. [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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argon: A noble gas with the atomic symbol Ar, atomic number 18, and atomic weight 39.948. It is used in fluorescent tubes and wherever an inert atmosphere is desired and nitrogen cannot be used. [NIH]

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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] Arteriolar: Pertaining to or resembling arterioles. [EU] 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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [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 considered an antioxidant. [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] Astringent: Causing contraction, usually locally after topical application. [EU] 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] Atopic: Pertaining to an atopen or to atopy; allergic. [EU]

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Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] 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, or hormonal changes. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [NIH] Azoospermia: Absence of spermatozoa in the semen, or failure of formation of spermatozoa. [EU]

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 Physiology: Physiological processes and activities of bacteria. [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 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] 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 donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] 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] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

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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] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Berylliosis: A lung disease caused by exposure to metallic beryllium or its soluble salts. [NIH]

Beryllium: An element with the atomic symbol Be, atomic number 4, and atomic weight 9.01218. Short exposure to this element can lead to a type of poisoning known as berylliosis. [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] 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] Bile Acids: Acids made by the liver that work with bile to break down fats. [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 agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] 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] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [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] Biological Transport: The movement of materials (including biochemical substances and

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drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [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 Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [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 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] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral

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capillaries and the brain tissue. [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 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] 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] 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 Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [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] 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] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

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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] Butylated Hydroxytoluene: Antioxidant used in foods, cosmetics, petroleum products, etc. It may inhibit some neoplasms and facilitate others. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [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 Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [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] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH]

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Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] 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] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [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] Carboxy: Cannabinoid. [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]

Carcinostatic: Pertaining to slowing or stopping the growth of cancer. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [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 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

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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] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] 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] Catechol: A chemical originally isolated from a type of mimosa tree. Catechol is used as an astringent, an antiseptic, and in photography, electroplating, and making other chemicals. It can also be man-made. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [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] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] 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] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called

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nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] 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 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 Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [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]

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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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] 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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervical intraepithelial neoplasia: CIN. A general term for the growth of abnormal cells on the surface of the cervix. Numbers from 1 to 3 may be used to describe how much of the cervix contains abnormal cells. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chamomile: Common name for several daisy-like species native to Europe and Western Asia, now naturalized in the United States and Australia. The dried flower-heads of two species, Anthemis nobilis (Chamaemelum nobile) and Matricaria recutita, have specific use as herbs. They are administered as tea, extracts, tinctures, or ointments. Chamomile contains choline, coumarins, cyanogenic glycosides, flavonoids, salicylate derivatives, tannins, and volatile oils. [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]

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Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body. [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] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chilblains: Recurrent localized itching, swelling and painful erythema on the fingers, toes or ears, produced by exposure to cold. It is also called pernio. [NIH] Chlorides: Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. [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] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [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]

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Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] 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 Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] 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] 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 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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [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

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molecules. [NIH] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Coagulants: Exogenous substances used to promote blood coagulation. The endogenous blood coagulation factors are considered to be coagulants only when administered as drugs. [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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [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] 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.

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Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] 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]

Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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]

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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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] 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] 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] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] 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]

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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] Constrict: Tighten; narrow. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [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] 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] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [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] 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] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [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 Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [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]

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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [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] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] 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] Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [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 whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor 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] Cruciferous vegetables: A family of vegetables that includes kale, collard greens, broccoli, cauliflower, cabbage, brussels sprouts, and turnip. These vegetables contain substances that may protect against cancer. [NIH] Crystalluria: The excretion of crystals in the urine, producing renal irritation. [EU]

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Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [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] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] 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] 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] 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

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buffalo. [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] 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] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroascorbic Acid: The reversibly oxidized form of ascorbic acid. It is the lactone of 2,3diketogulonic acid and has antiscorbutic activity in man on oral ingestion. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Demulcent: Soothing; bland; allaying the irritation of inflamed or abraded surfaces. [EU] 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] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH]

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Dentures: An appliance used as an artificial or prosthetic replacement for missing teeth and adjacent tissues. It does not include crowns, dental abutments, nor artificial teeth. [NIH] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU] 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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] 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 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] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] DHEA: Dehydroepiandrosterone. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [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] 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] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the

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abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [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] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilate: Relax; expand. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphenylamine: In humans it may be irritating to mucous membranes. Methemoglobinemia has been produced experimentally. In veterinary use, it is one of active ingredients in topical agents for prevention and treatment of screwworm infestation. An indicator in tests for nitrate poisoning. [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] 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] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [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

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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 to designate a position on the dental arch farther from the median line of the jaw. [EU] Disulfiram: A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [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] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [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] 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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [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] Dosimetry: All the methods either of measuring directly, or of measuring indirectly and computing, absorbed dose, absorbed dose rate, exposure, exposure rate, dose equivalent, and the science associated with these methods. [NIH]

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Douche: A procedure in which water or a medicated solution is used to clean the vagina and cervix. [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 Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the 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] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [NIH]

Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] 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] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Ecchymosis: Extravasation of blood into the skin, resulting in a nonelevated, rounded or irregular, blue or purplish patch, larger than a petechia. [NIH] Ecosystem: A dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. [NIH] Ectopia Lentis: Congenital displacement of the lens resulting from defective zonule formation. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] 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] Elasticity: Resistance and recovery from distortion of shape. [NIH]

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Elastin: The protein that gives flexibility to tissues. [NIH] Elastomers: A generic term for all substances having the properties of natural, reclaimed, vulcanized, or synthetic rubber, in that they stretch under tension, have a high tensile strength, retract rapidly, and recover their original dimensions fully. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [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] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroretinogram: The electrical effect recorded from the surface of the eyeball and originated by a pulse of light. [NIH] 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] 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] 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 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] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH]

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Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [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] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [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-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] Enhancer: Transcriptional element in the virus genome. [NIH]

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Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Enterochromaffin Cells: Group of basal granular cells of the gut whose granules stain readily with silver and chromium salts. The cells secrete serotonin, substance P, and enkephalins. There are three types: gastric (antral mucosa), duodenal, and intestinal. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] 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, 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] 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] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] 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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH]

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Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escin: Saponin occurring in the seed of the horse chestnut tree. Inhibits edema formation and decreases vascular fragility. [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] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [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]

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] Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide. [NIH] Ethionine: 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms. [NIH] Ethoxyquin: Antioxidant; also a post-harvest dip to prevent scald on apples and pears. [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] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] 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 Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory

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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 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] Exfoliation: A falling off in scales or layers. [EU] 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] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]

Expiration: The act of breathing out, or expelling air from the lungs. [EU] 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] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Faecal: Pertaining to or of the nature of feces. [EU] 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] 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]

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Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [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] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Flatus: Gas passed through the rectum. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Fleas: Parasitic, blood-sucking, wingless insects comprising the order Siphonaptera. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH]

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Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [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] Follicular Atresia: The degeneration and resorption of an ovarian follicle before it reaches maturity and ruptures. [NIH] Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods. [NIH]

Food Chain: The sequence of transfers of matter and energy from organism to organism in the form of food. Food chains intertwine locally into a food web because most organisms consume more than one type of animal or plant. Plants, which convert solar energy to food by photosynthesis, are the primary food source. In a predator chain, a plant-eating animal is eaten by a larger animal. In a parasite chain, a smaller organism consumes part of a larger host and may itself be parasitized by smaller organisms. In a saprophytic chain, microorganisms live on dead organic matter. [NIH] Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [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] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH]

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Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries. [NIH] Freeze-dried: A method used to dry substances, such as food, to make them last longer. The substance is frozen and then dried in a vacuum. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [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] 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] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Oryzanol: The frequency of activity bursts ranging from 20 to 90 hertz, this term is used in analogy with a range of high-frequency X-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [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] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU]

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Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [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] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU]

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Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [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] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [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] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [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]

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]

Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic radicals as well as epoxides and arene oxides to glutathione. Addition takes place at the sulfur atom. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. EC 2.5.1.18. [NIH] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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]

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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] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [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] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] 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] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] 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] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [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] 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] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Graphite: An allotropic form of carbon that is used in pencils, as a lubricant, and in matches and explosives. It is obtained by mining and its dust can cause lung irritation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses

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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 Disorders: Deviations from the average values for a specific age and sex in any or all of the following: height, weight, skeletal proportions, osseous development, or maturation of features. Included here are both acceleration and retardation of growth. [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] 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]

Hair Cells: Mechanoreceptors located in the organ of Corti that are sensitive to auditory stimuli and in the vestibular apparatus that are sensitive to movement of the head. In each case the accessory sensory structures are arranged so that appropriate stimuli cause movement of the hair-like projections (stereocilia and kinocilia) which relay the information centrally in the nervous system. [NIH] 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] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [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 Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [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] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and

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lymphoma. Also called hematologic cancers. [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] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [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 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 A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [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] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary

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mutations are passed on from parents to offspring. Also called germline mutation. [NIH] 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]

Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [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]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [NIH] Hiatal Hernia: A small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. Causes heartburn from stomach acid flowing back up through the opening. [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] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histidine Decarboxylase: An enzyme that catalyzes the decarboxylation of histidine to histamine and carbon dioxide. It requires pyridoxal phosphate in animal tissues, but not in microorganisms. EC 4.1.1.22. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogenate: A suspension of animal tissue that is ground in the all-glass "homogenizer" described by Potter and Elvehjem in 1936. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] 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] 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

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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 papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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 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] Hydroxybenzoic Acids: Benzoic acid substituted by one or more hydroxy groups in any position on the benzene ring. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylamines: Organic compounds that contain the (-NH2OH) radical. [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] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH]

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Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperoxaluria: Excretion of an excessive amount of oxalate in the urine. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [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 the number of cells. [NIH] Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [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] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypochlorous Acid: HClO. An oxyacid of chlorine containing monovalent chlorine that acts as an oxidizing or reducing agent. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] 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] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH]

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Immune response: The activity of the immune system against foreign substances (antigens). [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 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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] 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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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] 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] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] 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] Infancy: The period of complete dependency prior to the acquisition of competence in

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walking, talking, and self-feeding. [NIH] 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] 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]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] 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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [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] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inhalation Exposure: The exposure to potentially harmful chemical, physical, or biological agents by inhaling them. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [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] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [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]

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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] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] 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] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intraocular: Within the eye. [EU] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]

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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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [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, 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] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainic Acid: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose. [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]

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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] Keratotomy: A surgical incision (cut) of the cornea. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [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] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to indomethacin. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity. [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [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] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactation: The period of the secretion of milk. [EU] 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] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

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]

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Lethal: Deadly, fatal. [EU] 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] 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] Levothyroxine: Levo isomer of the thyroid hormone thyroxine. It is used for replacement therapy in reduced or absent thyroid function. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH] Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligation: Application of a ligature to tie a vessel or strangulate a part. [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] 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 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] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU]

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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] 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] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [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 Neoplasms: Tumors or cancer of the liver. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobsters: Large marine decapod crustaceans of the family Homaridae, commonly used for food. [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] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [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 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

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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] Lubricants: Oily or slippery substances. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Luteal Phase: The period of the menstrual cycle that begins with ovulation and ends with menstruation. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] 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] 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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and 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] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive

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material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mannans: Polysaccharides consisting of mannose units. [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]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] 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] 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] Melanosomes: Melanin-containing organelles found in melanocytes and melanophores. [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] 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] Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] 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

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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] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [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] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] 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] Methacrylate: A vinyl monomer. [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 functions. It is a chelating agent for heavy metals. [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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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

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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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] 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] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] 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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molasses: The syrup remaining after sugar is crystallized out of sugar cane or sugar beet juice. It is also used in animal feed, and in a fermented form, is used to make industrial ethyl alcohol and alcoholic beverages. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU]

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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] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monounsaturated fat: An unsaturated fat that is found primarily in plant foods, including olive and canola oils. [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] Motor Neurons: Neurons which activate muscle cells. [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] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [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]

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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] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Myalgia: Pain in a muscle or muscles. [EU] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] 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] 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]

Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] 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]

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Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] N-acetyl: Analgesic agent. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [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 Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [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] Neonatal: Pertaining to the first four weeks after birth. [EU] 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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH]

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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 tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [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] Neurofibrils: The delicate interlacing threads, formed by aggregations of neurofilaments and neurotubules, coursing through the cytoplasm of the body of a neuron and extending from one dendrite into another or into the axon. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] 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] 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] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotoxin: A substance that is poisonous to nerve tissue. [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]

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Neutrophil: A type of white blood cell. [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] 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 tobacco smoke. [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] Nitrogen Oxides: Inorganic oxides that contain nitrogen. [NIH] Nonmelanoma skin cancer: Skin cancer that arises in basal cells or squamous cells but not in melanocytes (pigment-producing cells of the skin). [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] 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] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage,

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and processing. [NIH] Occupational Health: The promotion and maintenance of physical and mental health in the work environment. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] 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] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [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 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] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [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; lysomomes; plastids; and vacuoles. [NIH] Organoselenium Compounds: Organic compounds which contain selenium as an integral part of the molecule. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a

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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] 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] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [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] 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]

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 Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [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

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bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Compounds: Inorganic compounds that contain oxygen as an integral part of the molecule. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [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] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Papilla: A small nipple-shaped elevation. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU]

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Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] 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] Pathologies: The study of abnormality, especially the study of diseases. [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]

Peak flow: The maximum amount of air breathed out; the power needed to produce this amount. [EU] Pelvic: Pertaining to the pelvis. [EU] 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] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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]

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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 Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [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 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] 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] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petechia: A pinpoint, nonraised, perfectly round, purplish red spot caused by intradermal or submucous haemorrhage. [EU] 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] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [NIH]

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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] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [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 between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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] 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

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of disease or abnormality. [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. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Picornavirus: Any of a group of tiny RNA-containing viruses including the enteroviruses and rhinoviruses. [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] Pink eye: Acute contagious conjunctivitis. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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] 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] Plasticizers: Materials incorporated mechanically in plastics (usually PVC) to increase flexibility, workability or distensibility; due to the non-chemical inclusion, plasticizers leach out from the plastic and are found in body fluids and the general environment. [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] Platelet Aggregation: The attachment of platelets to one another. This clumping together

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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] 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]

Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [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] Polyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours. [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 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] Polymethyl Methacrylate: Polymerized methyl methacrylate monomers which are used as sheets, moulding, extrusion powders, surface coating resins, emulsion polymers, fibers, inks, and films (From International Labor Organization, 1983). This material is also used in tooth implants, bone cements, and hard corneal contact lenses. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU]

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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] 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 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] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH] Potentiate: 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH]

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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] Prenatal: Existing or occurring before birth, with reference to the fetus. [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 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] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [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] 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] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [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] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [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] Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific

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affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits. [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). 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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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]

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Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [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] 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-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [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]

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-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [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] Pruritic: Pertaining to or characterized by pruritus. [EU] 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] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] 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]

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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 Circulation: The circulation of blood through 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 Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [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] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyridones: Pyridine derivatives with one or more keto groups on the ring. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyridoxal Phosphate: 3-Hydroxy-2-methyl-5-((phosphonooxy)methyl)-4pyridinecarboxaldehyde. An enzyme co-factor vitamin. [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] Quiescent: Marked by a state of inactivity or repose. [EU] 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] Radial Keratotomy: Commonly referred to as RK; a surgical procedure designed to correct myopia (nearsightedness) by flattening the cornea using radial cuts. [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.

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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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] 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] 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] 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]

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Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [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] 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 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] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [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] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Personnel: Those individuals engaged in research. [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] Respirable: Dust particles smaller than 0. 005 mm, which are deposited in the respiratory region of the lungs. [NIH] 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] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any

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of its parts. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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] 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] Retinal pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [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] 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] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [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] 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]

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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] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rickettsia: A genus of gram-negative, aerobic, rod-shaped bacteria often surrounded by a protein microcapsular layer and slime layer. The natural cycle of its organisms generally involves a vertebrate and an invertebrate host. Species of the genus are the etiological agents of human diseases, such as typhus. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [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] 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] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [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] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH]

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Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [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] 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] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [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] 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] 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] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [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] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and

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opening into the vestibule by five openings. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] 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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [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] 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] 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] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Ships: Large vessels propelled by power or sail used for transportation on rivers, seas, oceans, or other navigable waters. Boats are smaller vessels propelled by oars, paddles, sail, or power; they may or may not have a deck. [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]

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 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

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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] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [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] Skin Pigmentation: Coloration of the skin. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [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]

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] Social Problems: Situations affecting a significant number of people, that are believed to be sources of difficulty or threaten the stability of the community, and that require programs of amelioration. [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]

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Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [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] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [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] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] 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] Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by 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] Speech Disorders: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sperm Motility: Ability of the spermatozoon to move by flagellate swimming. [NIH] Sperm Transport: Passive transport or active migration of spermatozoa from the testes through the male genital system as well as within the female genital system. [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] Spermatozoon: The mature male germ cell. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH]

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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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] 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] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] 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] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] 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] 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] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH]

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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] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [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] Subcapsular: Situated below a capsule. [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] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [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] Succinic Anhydrides: A subclass of anhydrides with the general structure of dihydrofurandione. They can be substituted on any carbon atom. They modify and inhibit proteins and enzymes and are used in the acylation of amino- and hydroxyl groups. [NIH] Succinimides: A subclass of imides with the general structure of pyrrolidinedione. They are prepared by the distillation of ammonium succinate. They are sweet-tasting compounds that are used as chemical intermediates and plant growth stimulants. [NIH] Sucralfate: A basic aluminum complex of sulfated sucrose. It is advocated in the therapy of peptic, duodenal, and prepyloric ulcers, gastritis, reflux esophagitis, and other gastrointestinal irritations. It acts primarily at the ulcer site, where it has cytoprotective, pepsinostatic, antacid, and bile acid-binding properties. The drug is only slightly absorbed by the digestive mucosa, which explains the absence of systemic effects and toxicity. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by

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means of a tube and a device that acts on negative pressure. [NIH] Sulfides: Chemical groups containing the covalent sulfur bonds -S-. The sulfur atom can be bound to inorganic or organic moieties. [NIH] Sulfites: Inorganic salts of sulfurous acid. [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] Sulfur Oxides: Inorganic oxides of sulfur. [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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [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]

Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [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

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in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergist: A medicament which supplements the action of another. [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] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Talc: A native magnesium silicate. [NIH] Tartar: A mass of calcium and magnesium salts deposited around the teeth and upon artificial dentures. [NIH] 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] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogenicity: The power to cause abnormal development. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testicular: Pertaining to a testis. [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] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [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] Theca Cells: The connective tissue cells of the ovarian follicle. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart

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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] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (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] 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]

Thromboses: The formation or presence of a blood clot within a blood vessel during life. [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] 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

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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] Tome: A zone produced by a number of irregular spaces contained in the outermost layer of denture of the root of a tooth. [NIH] 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] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] 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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicologic: Pertaining to toxicology. [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] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Traction: The act of pulling. [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] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [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] 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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a

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protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [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] Triolein: (Z)-9-Octadecenoic acid 1,2,3-propanetriyl ester. [NIH] Trophic: Of or pertaining to nutrition. [EU] 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] 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 model: A type of animal model which can be 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] 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 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] 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]

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Tunicamycin: An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms. [NIH] 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] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [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]

Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [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] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH]

Dictionary 347

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Urolithiasis: Stones in the urinary system. [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] 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] 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] 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 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 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] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] 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] Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [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] 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] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU]

348 Antioxidants

Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] 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] 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] 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 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] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Wetting Agents: A surfactant that renders a surface wettable by water or enhances the spreading of water over the surface; used in foods and cosmetics; important in contrast media; also with contact lenses, dentures, and some prostheses. Synonyms: humectants; hydrating agents. [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]

Dictionary 349

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [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] Zinc Oxide: A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock. [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]

351

INDEX A Abdomen, 255, 266, 267, 288, 304, 308, 320, 322, 339 Abdominal, 107, 255, 283, 294, 301, 304, 305, 311, 320, 322, 333, 346 Abdominal Pain, 255, 294, 305, 346 Ablation, 192, 202, 255 Abrasion, 160, 199, 255 Acatalasia, 255, 270 Acceptor, 155, 165, 191, 204, 255, 307, 319, 344 Acetaldehyde, 255, 284 Acetaminophen, 102, 236, 255 Acetone, 189, 255, 306 Acetylcholine, 177, 255, 273, 274, 289, 317 Acetylcholinesterase, 9, 255 Acetylcysteine, 20, 42, 255 Acid Rain, 146, 147, 255 Acidosis, 255, 282 Acrylonitrile, 175, 256, 334 Actin, 53, 56, 256, 313, 315 Acute renal, 256, 298 Acyclovir, 237, 256 Acyl, 49, 207, 256, 289, 310 Acylation, 256, 340 Adaptability, 256, 271 Adaptation, 8, 38, 213, 256, 324 Adduct, 57, 78, 256 Adenine, 256, 330 Adenosine, 256, 268, 301, 323, 343 Adhesives, 142, 157, 158, 171, 177, 256, 267 Adjustment, 5, 256 Adjuvant, 52, 256, 294 Adolescent Nutrition, 211, 256 Adrenal Cortex, 256, 279, 289, 327 Adrenergic, 15, 117, 200, 256, 284, 288, 341 Adverse Effect, 41, 135, 143, 165, 204, 256, 336 Aerobic, 25, 146, 159, 165, 204, 256, 312, 319, 334, 346 Aerobic Metabolism, 25, 256, 257, 319 Aerobic Respiration, 256, 319 Aerosol, 257, 341 Affinity, 48, 154, 257, 263, 307, 316, 328, 337 Agar, 257, 324 Age of Onset, 257, 346 Agonist, 257, 284, 305, 315, 317

Airway, 32, 34, 38, 52, 68, 257 Albumin, 71, 257, 319, 324 Aldehyde Dehydrogenase, 257, 284 Aldehyde Reductase, 8, 257 Aldehydes, 8, 257, 349 Aldose Reductase Inhibitor, 49, 257 Alertness, 258, 268 Alfalfa, 258, 348 Algorithms, 258, 266 Alimentary, 258, 320, 321 Alkaline, 157, 160, 162, 163, 176, 189, 256, 258, 259, 268, 320, 323 Alkaloid, 258, 317, 342 Alkylating Agents, 12, 258 Alleles, 194, 258, 299 Allergens, 52, 258 Allergic Rhinitis, 38, 258 Allo, 258, 296 Allopurinol, 47, 258 Allylamine, 258, 259 Aloe, 197, 258 Alpha Particles, 258, 330 Alternative medicine, 228, 258 Aluminum, 205, 258, 340 Alveoli, 258, 330, 347 Ameliorated, 31, 37, 258 Ameliorating, 181, 184, 258 Amenorrhea, 258, 260, 325 Amine, 157, 172, 179, 189, 201, 259, 299 Amino Acid Sequence, 259, 261, 294 Aminosalicylic Acids, 85, 88, 259 Ammonia, 185, 259 Ammonium Chloride, 180, 259 Amnestic, 259, 310 Amplification, 54, 259 Ampulla, 259, 287 Amyloid, 9, 16, 71, 184, 237, 259 Anaerobic, 25, 259, 314 Anaesthesia, 259, 302 Anal, 50, 259 Analgesic, 255, 259, 315 Analog, 256, 259, 327 Analogous, 259, 325, 344 Analysis of Variance, 9, 259 Anaphylatoxins, 259, 276 Anatomical, 260, 278, 302, 335 Anemia, 115, 171, 260, 268, 292, 322 Anesthesia, 257, 260, 287

352 Antioxidants

Angina, 108, 210, 260 Angina Pectoris, 210, 260 Angiography, 136, 260 Angioplasty, 153, 210, 260, 314 Anhydrides, 163, 260, 340 Animal model, 16, 17, 19, 20, 28, 30, 33, 41, 44, 47, 56, 61, 62, 162, 178, 190, 191, 260, 345 Animal Welfare, 60, 260 Anionic, 179, 260 Anions, 257, 260, 305, 341 Annealing, 260, 325 Anorexia, 108, 211, 260, 294, 346 Anorexia Nervosa, 108, 211, 260 Anovulation, 260, 325 Antagonism, 260, 268, 343 Anterior Cerebral Artery, 260, 272 Anthracycline, 32, 260 Antibacterial, 175, 260, 338 Antibiotic, 260, 261, 338, 346 Antibodies, 44, 153, 211, 261, 262, 288, 297, 302, 309, 324 Antibody, 236, 257, 261, 276, 297, 299, 301, 302, 303, 305, 313, 330, 331, 338, 349 Anticarcinogenic, 162, 178, 261 Anticoagulant, 8, 261, 328 Antifungal, 261, 291 Antigen, 15, 46, 52, 59, 257, 258, 261, 262, 276, 281, 288, 299, 301, 302, 303 Antigen-Antibody Complex, 261, 276 Antigen-presenting cell, 261, 281 Anti-infective, 261, 292, 300, 304, 337 Anti-Infective Agents, 261, 292 Anti-Inflammatory Agents, 18, 31, 261, 263, 271, 279, 306 Antimetabolite, 256, 261, 282, 289 Antimicrobial, 146, 147, 157, 158, 175, 261, 282 Antineoplastic, 32, 161, 162, 178, 258, 261, 279 Antineoplastic Agents, 161, 162, 178, 258, 261, 279 Antipyretic, 255, 261 Antiseptic, 255, 262, 270, 349 Antiserum, 59, 262 Antithrombins, 153, 262 Antithrombotic, 28, 262, 328 Antiviral, 211, 237, 255, 256, 262, 282, 289, 346 Anus, 259, 262, 264, 267 Apolipoproteins, 42, 237, 262, 308

Aqueous, 34, 142, 156, 163, 169, 171, 172, 177, 186, 198, 262, 264, 280, 286, 300, 306, 308 Arachidonate 12-Lipoxygenase, 262, 308 Arachidonate 15-Lipoxygenase, 262, 308 Arachidonate Lipoxygenases, 262, 308 Arachidonic Acid, 40, 49, 132, 262, 307, 328 Arginine, 152, 207, 259, 262, 317 Argon, 135, 262 Aromatic, 17, 52, 157, 175, 201, 202, 263, 295, 323, 340 Arterial, 53, 153, 195, 200, 218, 258, 263, 267, 272, 273, 301, 304, 329, 342 Arteries, 53, 168, 263, 266, 272, 278, 301, 305, 308, 311, 314, 330, 343, 346 Arteriolar, 53, 263, 267 Arterioles, 53, 263, 266, 269, 311, 314, 347 Arteriolosclerosis, 263 Arteriosclerosis, 108, 137, 138, 198, 263, 314 Arteriovenous, 263, 272, 312 Ascorbic Acid, 5, 11, 20, 34, 40, 51, 65, 80, 90, 198, 263, 281, 300, 319 Aspirin, 75, 137, 210, 263 Assay, 22, 40, 49, 51, 57, 62, 86, 88, 151, 263, 346 Astringent, 263, 270, 349 Astrocytes, 19, 51, 263, 295, 313, 316 Asymptomatic, 255, 263, 320 Ataxia, 37, 76, 81, 263, 342 Atherogenic, 45, 139, 263 Atopic, 22, 70, 263 Atresia, 11, 264 Atrophy, 23, 264, 316 Auditory, 18, 60, 264, 297 Autodigestion, 264, 320 Autoimmune disease, 158, 264, 313 Autonomic, 255, 264, 317, 322 Autopsy, 7, 264 Azoospermia, 148, 264 B Bacterial Physiology, 256, 264 Bactericidal, 264, 289, 346 Bacteriophage, 264, 324, 344 Bacterium, 56, 264, 277, 298 Basal cells, 264, 317 Basal Ganglia, 43, 263, 264, 301 Basal Ganglia Diseases, 263, 264, 301 Base, 150, 151, 163, 201, 205, 221, 256, 264, 280, 281, 292, 294, 305, 322, 323, 342, 346 Base Sequence, 264, 280, 292, 294

Index 353

Basement Membrane, 264, 290 Basophil, 264, 299 Benign, 108, 263, 264, 297, 315, 320, 331, 348 Benzene, 194, 265, 300, 305 Benzo(a)pyrene, 14, 265 Benzyl Alcohol, 177, 265 Berylliosis, 265 Beryllium, 86, 88, 265 Beta carotene, 4, 5, 224, 265 Beta Rays, 265, 286 Beta-pleated, 259, 265 Bilateral, 265, 325 Bile, 265, 293, 308, 339, 340, 342 Bile Acids, 265, 339, 342 Biliary, 265, 268, 320 Biliary Tract, 265, 268, 320 Bilirubin, 227, 257, 265 Binding agent, 155, 265 Bioavailable, 41, 58, 265 Biogenesis, 191, 265 Biological therapy, 265, 297 Biological Transport, 265, 283 Biomarkers, 7, 9, 21, 23, 25, 43, 45, 52, 57, 74, 132, 266 Biopsy, 266, 321 Biosynthesis, 171, 184, 262, 266, 280, 308, 336 Biotechnology, 50, 61, 68, 158, 220, 228, 235, 266 Biotic, 157, 158, 214, 266, 346 Biotransformation, 266 Bismuth, 205, 206, 266 Bladder, 266, 308, 313, 316, 328, 332, 333, 346, 347 Blastocyst, 266, 324 Bloating, 266, 302, 305 Blood Cell Count, 266, 322 Blood Coagulation, 10, 266, 268, 275, 343 Blood Coagulation Factors, 266, 275 Blood Glucose, 4, 10, 210, 266, 298, 304 Blood pressure, 7, 169, 229, 266, 269, 301, 313, 322, 330, 337 Blood-Brain Barrier, 20, 266, 307 Body Fluids, 266, 267, 268, 285, 324, 337, 345 Body Mass Index, 4, 50, 210, 267 Bone Cements, 267, 325 Bone Marrow, 154, 265, 267, 297, 302, 309, 313, 337, 340 Bowel, 41, 77, 112, 154, 259, 267, 283, 303, 304, 306, 316, 322, 339, 346

Bowel Movement, 267, 283, 339 Brachial, 153, 267 Brachytherapy, 267, 304, 305, 330, 349 Bradykinin, 267, 317, 324 Brain Ischemia, 267, 272 Brain Stem, 267, 272 Branch, 62, 251, 267, 309, 321, 329, 338, 343 Breakdown, 267, 271, 282, 283, 293, 318 Bronchi, 267, 288, 290, 343 Bronchial, 267, 299, 343 Bronchioles, 258, 267, 330 Bronchiolitis, 46, 267 Bronchitis, 32, 109, 267, 274 Bronchoalveolar Lavage, 52, 267 Buffers, 148, 267 Burns, 109, 146, 168, 169, 268 Burns, Electric, 268 Butylated Hydroxytoluene, 177, 268 Butyric Acid, 268, 289 Bypass, 210, 223, 268, 314 C Cadmium, 32, 107, 268 Cadmium Poisoning, 268 Caffeine, 26, 31, 152, 167, 197, 211, 268, 330 Calcification, 27, 263, 268 Calcium, 29, 47, 54, 61, 156, 179, 186, 267, 268, 276, 311, 314, 319, 329, 336, 342 Calcium Carbonate, 179, 267, 268 Calcium Oxalate, 61, 268, 319 Calculi, 268, 296 Callus, 101, 268 Calmodulin, 54, 268 Candidiasis, 269, 291 Capillary, 267, 269, 270, 334, 347 Capillary Fragility, 269, 270, 334 Capsid, 59, 269 Capsules, 269, 284, 291, 294 Carbohydrate, 85, 87, 144, 149, 209, 269, 279, 295, 296, 317, 326, 336 Carbon Dioxide, 185, 269, 280, 281, 293, 299, 324, 332, 347 Carboxy, 172, 269, 305 Carcinogen, 51, 256, 265, 269 Carcinogenesis, 12, 14, 30, 35, 51, 57, 77, 106, 165, 190, 198, 204, 269, 273 Carcinogenic, 8, 258, 265, 269, 303, 318, 327, 339, 346 Carcinoma, 76, 269 Carcinostatic, 184, 269 Cardiac arrest, 13, 269 Cardiomyopathy, 32, 269

354 Antioxidants

Cardiotoxicity, 32, 269 Cardiovascular disease, 10, 17, 23, 54, 70, 137, 139, 158, 169, 173, 194, 197, 269 Cardiovascular System, 28, 47, 153, 269 Carnitine, 24, 207, 269 Carotene, 5, 31, 50, 51, 118, 129, 137, 145, 236, 265, 269, 333 Carotenoids, 5, 14, 43, 44, 50, 84, 106, 119, 144, 145, 159, 165, 204, 214, 244, 265, 270 Case report, 236, 270 Caspase, 13, 270 Catalase, 18, 19, 28, 49, 50, 58, 159, 165, 173, 198, 203, 255, 270 Cataract, 31, 202, 270 Catechin, 162, 178, 197, 270 Catechol, 30, 77, 270 Catecholamine, 270, 284 Catheterization, 260, 270, 314 Cathode, 265, 270, 286 Cations, 186, 270, 305 Caudal, 270, 283, 301, 326 Causal, 38, 43, 270, 304 Causality, 41, 270 Cause of Death, 7, 13, 23, 28, 58, 192, 270 Caustic, 270, 337 Cecum, 270, 306 Celecoxib, 201, 270 Celiac Disease, 211, 271 Cell Count, 18, 37, 271 Cell Cycle, 13, 25, 271, 274, 329 Cell Death, 29, 32, 35, 36, 38, 44, 64, 66, 103, 184, 262, 271, 315 Cell Degranulation, 60, 271 Cell Differentiation, 192, 271, 336 Cell Division, 264, 271, 297, 310, 312, 324, 327, 335 Cell Extracts, 52, 271 Cell membrane, 32, 35, 154, 174, 266, 271, 282, 290, 323 Cell proliferation, 12, 35, 57, 192, 263, 271, 318, 336 Cell Respiration, 256, 257, 271, 312, 319, 332 Cell Size, 271, 291 Cell Survival, 271, 297 Cellobiose, 271 Cellular metabolism, 236, 271 Cellulitis, 200, 271 Cellulose, 152, 155, 271, 293, 324 Central Nervous System, 43, 255, 265, 268, 272, 293, 295, 297, 307, 313, 318, 336, 343

Central Nervous System Infections, 272, 297 Centrifugation, 272, 312 Cerebellar, 15, 263, 272, 331, 345 Cerebellum, 272, 331 Cerebral Arteries, 272, 312 Cerebral Infarction, 195, 272 Cerebrovascular, 138, 195, 264, 269, 272, 342 Cerebrovascular Disorders, 138, 195, 272, 342 Cerebrum, 272, 342 Cervical, 11, 109, 148, 154, 272 Cervical intraepithelial neoplasia, 11, 272 Cervix, 272, 285, 332 Chamomile, 25, 272 Character, 260, 272, 281, 295 Chelating Agents, 86, 88, 183, 273 Chelation, 17, 116, 273 Chelation Therapy, 17, 116, 273 Chemokines, 46, 273 Chemoprevention, 17, 24, 79, 165, 204, 273 Chemopreventive, 51, 57, 65, 273 Chemotactic Factors, 273, 276 Chemotherapy, 81, 120, 145, 148, 165, 204, 273 Chest Pain, 210, 273 Chilblains, 200, 273 Chlorides, 205, 273 Chlorine, 205, 273, 301 Chlorophyll, 120, 273, 280, 293 Chloroplasts, 273, 280 Cholesterol Esters, 273, 308 Choline, 255, 272, 273 Cholinergic, 274, 317 Choroid, 274, 333 Chromatin, 262, 274, 288, 338 Chromium, 91, 104, 210, 274, 288 Chromosomal, 105, 154, 259, 274, 333 Chromosome, 274, 277, 297, 307, 335, 345, 346 Chronic Disease, 22, 68, 274 Chronic Fatigue Syndrome, 105, 274 Chronic Obstructive Pulmonary Disease, 41, 77, 80, 104, 109, 274 Chronic renal, 274, 325, 346 Chylomicrons, 274, 308 CIS, 55, 62, 274, 333 Cisplatin, 14, 91, 274 Citrus, 263, 274 Clear cell carcinoma, 274, 282 Clinical Medicine, 104, 274, 327

Index 355

Clinical trial, 6, 9, 24, 36, 42, 46, 59, 99, 101, 135, 139, 235, 274, 278, 331 Clone, 8, 274 Cloning, 64, 266, 274 Cluster Analysis, 23, 275 Coagulants, 157, 158, 275 Coagulation, 8, 10, 266, 275, 324, 343 Coal, 32, 265, 275 Cochlea, 18, 275, 303 Cochlear, 18, 38, 229, 275 Cod Liver Oil, 275, 286 Codon, 75, 275, 294 Coenzyme, 40, 120, 121, 173, 236, 237, 242, 243, 263, 275, 308 Cofactor, 12, 275, 329, 343 Cognition, 15, 275 Cohort Studies, 23, 50, 275 Colitis, 41, 116, 275, 305 Collagen, 182, 256, 264, 270, 275, 291, 294, 325, 327 Collapse, 153, 267, 275 Colloidal, 257, 276, 286, 322, 341 Colonoscopy, 30, 276 Colorectal, 30, 50, 110, 276 Colorectal Cancer, 50, 110, 276 Colostrum, 86, 89, 276 Combinatorial, 9, 276 Complement, 259, 276, 324 Complementary and alternative medicine, 99, 100, 130, 139, 276 Complementary medicine, 100, 276 Compress, 153, 276, 298 Computational Biology, 235, 277 Computed tomography, 277 Computerized axial tomography, 277 Computerized tomography, 45, 277 Concomitant, 39, 47, 59, 277 Conduction, 50, 277 Cones, 277, 333 Confounding, 27, 277 Congestion, 202, 277, 288 Congestive heart failure, 32, 46, 210, 277 Conjugated, 17, 151, 207, 277, 280, 314 Conjugation, 266, 277, 295 Conjunctiva, 202, 277, 303 Conjunctivitis, 277, 324 Connective Tissue, 263, 267, 271, 275, 277, 278, 291, 293, 294, 309, 311, 333, 340, 342 Connective Tissue Cells, 277, 278, 342 Consciousness, 259, 278, 281, 284, 333 Constipation, 211, 278, 305 Constrict, 54, 278

Constriction, 53, 278, 305, 347 Constriction, Pathologic, 278, 347 Consultation, 21, 278 Consumption, 23, 26, 28, 43, 79, 131, 145, 160, 176, 199, 210, 278, 282, 294, 317, 320 Contact dermatitis, 168, 169, 278 Contamination, 187, 278 Contraindications, ii, 278 Contrast Media, 278, 348 Control group, 7, 278 Convulsions, 278, 316 Convulsive, 171, 278 Coordination, 272, 273, 278, 313 Cornea, 202, 278, 306, 330, 335 Corneum, 278, 288 Coronary Angiography, 210, 278 Coronary Circulation, 260, 278 Coronary heart disease, 23, 27, 144, 145, 269, 278 Coronary Thrombosis, 279, 311, 314 Corpus, 279, 309, 327 Corpus Luteum, 279, 309, 327 Corrosion, 187, 188, 204, 279 Cortex, 263, 272, 279, 312, 331 Cortical, 36, 71, 279, 289, 342 Corticosteroid, 279, 339 Cortisol, 257, 279 Cortisone, 279, 282 Coumarins, 272, 279 Cranial, 272, 279, 297, 318, 322 Craniocerebral Trauma, 264, 279, 297, 342 Creatine, 45, 279 Creatinine, 279, 346 Criterion, 164, 176, 279 Crossing-over, 279, 331 Cruciferous vegetables, 80, 279 Crystalluria, 61, 279 Cultured cells, 53, 280 Curative, 280, 343 Cutaneous, 48, 51, 216, 269, 278, 280 Cyanobacteria, 14, 280 Cyclic, 28, 57, 146, 177, 194, 268, 280, 297, 317, 323, 326, 328, 343 Cystathionine beta-Synthase, 54, 280, 300 Cysteine, 19, 32, 49, 54, 64, 67, 71, 121, 126, 136, 155, 171, 236, 255, 273, 280, 341 Cystine, 280 Cytochrome, 280, 319 Cytokine, 33, 42, 280, 321 Cytoplasm, 47, 55, 154, 262, 271, 280, 288, 296, 313, 316, 334 Cytoprotection, 42, 280

356 Antioxidants

Cytoskeleton, 53, 56, 280 Cytotoxic, 35, 49, 103, 146, 280, 331, 337 Cytotoxicity, 12, 42, 49, 79, 102, 258, 274, 280 D Dairy Products, 50, 280, 334 Databases, Bibliographic, 235, 281 Decarboxylation, 281, 299 Decidua, 281, 324 Decubitus, 281, 337 Decubitus Ulcer, 281, 337 Defense Mechanisms, 191, 214, 220, 281 Degenerative, 17, 39, 51, 66, 145, 183, 184, 213, 281, 295, 298, 309, 333 Dehydration, 185, 281 Dehydroascorbic Acid, 20, 281 Deletion, 55, 262, 281, 294 Dementia, 3, 4, 9, 21, 43, 110, 115, 198, 226, 227, 281, 310 Demethylation, 171, 281 Demulcent, 175, 281 Denaturation, 281, 325 Dendrites, 281, 316 Dendritic, 46, 154, 281, 310 Dendritic cell, 46, 154, 281 Density, 26, 33, 69, 144, 149, 164, 267, 272, 281, 291, 308, 318, 325, 328, 338 Dentifrices, 183, 281 Dentists, 183, 281 Dentures, 282, 342, 348 Deoxyglucose, 37, 282 Depigmentation, 282, 348 Depolarization, 282, 337 Deprivation, 36, 48, 84, 87, 282 Dermal, 177, 282 Dermatitis, 110, 282, 285 DES, 146, 189, 259, 282 Detergents, 163, 187, 282, 337 Detoxification, 8, 55, 103, 159, 282 Deuterium, 282, 300 Developed Countries, 282, 292 Dexamethasone, 103, 282 DHEA, 121, 282 Diabetes Mellitus, 46, 110, 135, 220, 282, 295, 298 Diabetic Ketoacidosis, 227, 282 Diabetic Retinopathy, 194, 282, 323 Diagnostic procedure, 141, 228, 282 Dialyzer, 282, 298 Diaphragm, 282, 299 Diarrhea, 211, 283, 305 Diarrhoea, 283, 294

Diastolic, 283, 301 Diencephalon, 272, 283, 301, 342 Diffusion, 48, 164, 266, 283, 317 Digestion, 52, 258, 265, 267, 283, 285, 302, 304, 308, 321, 339 Digestive system, 140, 283, 294 Dihydrotestosterone, 283, 331 Dihydroxy, 283, 334 Dilatation, 260, 283, 327, 330, 347 Dilate, 153, 283 Dilated cardiomyopathy, 37, 283 Dimerization, 55, 64, 159, 283 Dimethyl, 180, 197, 283 Diphenylamine, 180, 283 Diploid, 283, 324 Direct, iii, 8, 9, 19, 37, 40, 44, 47, 200, 274, 283, 284, 331 Disease Progression, 44, 283 Disease Vectors, 283, 303 Disinfectant, 283, 289 Disparity, 38, 139, 283 Disposition, 25, 283 Dissociation, 257, 283, 305 Distal, 38, 284, 322, 329, 330 Disulfiram, 237, 284 Diuresis, 268, 284, 343 Diuretic, 259, 284, 338 Diverticula, 284 Diverticulitis, 211, 284 Diverticulum, 284 Dizziness, 192, 284 Domesticated, 284, 297 Dopamine, 43, 71, 284, 307, 313, 323 Dorsal, 50, 284, 326 Dorsum, 284 Dosage Forms, 201, 284, 322 Dose-dependent, 58, 284 Dosimetry, 34, 38, 284 Douche, 148, 285 Drug Delivery Systems, 201, 285 Drug Interactions, 285 Drug Resistance, 12, 285 Drug Tolerance, 285 Duct, 259, 270, 285, 290, 320, 334 Duodenal Ulcer, 212, 285 Duodenum, 265, 285, 287, 339 Dura mater, 285, 310, 320 Dyes, 153, 157, 158, 259, 285, 292, 322 Dyspepsia, 285, 302 Dysplasia, 30, 71, 109, 285 E Ecchymosis, 200, 285

Index 357

Ecosystem, 255, 285 Ectopia Lentis, 171, 285 Eczema, 192, 285 Edema, 135, 200, 202, 278, 282, 285, 289, 298, 314, 317, 346 Effector, 42, 255, 276, 285, 323 Effector cell, 42, 285 Efficacy, 7, 9, 17, 18, 20, 25, 26, 29, 31, 36, 37, 41, 55, 57, 139, 152, 189, 220, 223, 285 Elasticity, 263, 285 Elastin, 275, 286 Elastomers, 132, 166, 179, 207, 286 Electrocoagulation, 275, 286 Electrolysis, 260, 270, 286 Electrolyte, 148, 162, 279, 286, 326, 337, 346 Electrons, 48, 158, 188, 261, 264, 265, 270, 286, 305, 319, 330, 331 Electrophoresis, 52, 286 Electroplating, 270, 286 Electroretinogram, 136, 286 Elementary Particles, 286, 316, 329 Embolus, 286, 303, 304 Embryo, 14, 266, 271, 286, 291, 302, 325, 346 Emodin, 258, 286 Emollient, 161, 206, 286, 295, 318 Emphysema, 32, 110, 217, 274, 286 Emulsion, 181, 286, 325 Encapsulated, 152, 286 Encephalitis, 19, 286, 287, 310 Encephalitis, Viral, 286, 287 Encephalocele, 287, 316 Encephalopathy, 37, 287 Endarterectomy, 260, 287 Endemic, 287, 339 Endometrial, 287 Endometriosis, 30, 287 Endometrium, 281, 287, 310 Endoscope, 287 Endoscopic, 212, 276, 287 Endothelial cell, 26, 45, 53, 56, 154, 194, 266, 287, 343 Endothelium, 64, 287, 317 Endothelium-derived, 287, 317 Endotoxemia, 42, 287 Endotoxic, 287, 307 Endotoxin, 42, 287, 345 End-stage renal, 274, 287, 325 Energetic, 47, 188, 287 Energy Intake, 4, 287 Enhancer, 287, 333

Enkephalins, 288 Enterochromaffin Cells, 154, 288 Enterohepatic, 25, 288 Environmental Exposure, 33, 38, 43, 288 Environmental Health, 234, 236, 288 Enzymatic, 37, 47, 76, 157, 167, 170, 268, 270, 276, 288, 289, 299, 325, 333 Eosinophils, 271, 288, 296, 307 Epidemic, 59, 154, 210, 288, 339 Epidemiological, 14, 28, 43, 57, 132, 139, 144, 145, 288 Epidermal, 51, 288, 306, 310, 348 Epidermal Growth Factor, 51, 288 Epidermis, 208, 264, 278, 288, 300, 306, 327 Epigastric, 288, 320 Epinephrine, 256, 284, 288, 317, 346 Epithelial, 30, 31, 34, 38, 52, 60, 61, 64, 66, 68, 266, 281, 288, 320 Epithelial Cells, 30, 31, 34, 61, 64, 66, 68, 288 Epithelium, 31, 61, 264, 287, 288, 293, 305, 320 Epitopes, 44, 288 Erythema, 110, 146, 273, 278, 288, 341 Erythrocytes, 260, 266, 267, 289, 331 Escin, 200, 289 Esophageal, 79, 289 Esophagitis, 289, 340 Esophagus, 264, 283, 289, 294, 297, 323, 331, 339 Esterification, 145, 289 Estradiol, 57, 289 Estrogen, 30, 36, 57, 62, 77, 79, 225, 230, 237, 289, 327 Estrogen receptor, 36, 77, 289 Ethanol, 28, 70, 289, 291 Ether, 189, 203, 289 Ethidium, 289, 327 Ethionine, 289 Ethoxyquin, 8, 181, 289 Evacuation, 278, 289, 306 Evaluable patients, 24, 289 Excipient, 168, 169, 289 Excitation, 289, 291 Excitatory, 289, 295, 305, 316 Excitatory Amino Acid Agonists, 289, 305 Excitatory Amino Acids, 289, 316 Excitotoxicity, 36, 105, 290 Excrete, 290, 332 Exfoliation, 179, 290 Exocrine, 290, 320 Exocytosis, 271, 290, 299

358 Antioxidants

Exogenous, 18, 39, 41, 50, 104, 146, 266, 275, 285, 290, 295, 346 Expectorant, 259, 290 Expiration, 290, 332, 348 Extensor, 290, 329, 348 External-beam radiation, 290, 305, 330, 349 Extracellular, 8, 38, 45, 51, 56, 259, 263, 277, 290, 291, 312, 316, 337 Extracellular Matrix, 45, 277, 290, 291 Extracellular Space, 290 Extraction, 144, 147, 188, 189, 190, 199, 290 Extrapyramidal, 284, 290 Extravasation, 285, 290, 298 Extravascular, 194, 290 Eye Movements, 136, 290 F Faecal, 104, 283, 290 Family Planning, 235, 290 Fat, 21, 50, 144, 169, 211, 214, 218, 262, 265, 267, 268, 269, 276, 278, 279, 281, 286, 290, 306, 307, 313, 317, 318, 326, 333, 334, 335, 337, 341 Fatigue, 132, 200, 274, 290, 297 Fatty acids, 33, 40, 49, 67, 71, 170, 189, 195, 207, 257, 282, 290, 295, 296, 307, 308, 328, 337 Feces, 278, 290, 339 Femoral, 153, 290, 291 Femoral Artery, 153, 291 Femur, 290, 291 Fermentation, 167, 183, 184, 291, 292 Ferritin, 5, 291 Fetal Development, 291, 316 Fetus, 291, 324, 327, 346, 347 Fibrin, 8, 266, 291, 343 Fibrinogen, 45, 291, 324, 343 Fibroblasts, 58, 76, 278, 291 Fibrosis, 6, 110, 169, 202, 258, 291, 335 Filler, 160, 186, 199, 291 Filtration, 196, 291 Flatus, 291, 293 Flavoring Agents, 291, 292, 322 Fleas, 177, 291 Flow Cytometry, 29, 291 Fluconazole, 85, 88, 291 Fluorescence, 188, 289, 291, 292 Fluorescent Dyes, 291, 292 Flushing, 284, 292 Folate, 36, 155, 210, 292 Fold, 194, 292, 311 Folic Acid, 90, 155, 171, 207, 292

Follicles, 11, 292 Follicular Atresia, 11, 292 Food Additives, 174, 220, 292 Food Chain, 162, 178, 292 Food Coloring Agents, 292 Food Preservatives, 292 Forced Expiratory Volume, 41, 292 Forearm, 266, 292 Frameshift, 292, 346 Frameshift Mutation, 292, 346 Free Radical Scavengers, 165, 173, 188, 190, 203, 204, 236, 293 Freeze-dried, 157, 293 Friction, 163, 293 Frontal Lobe, 260, 272, 293 Fructose, 293, 296, 299 Fungi, 63, 158, 261, 277, 293, 297, 311, 312, 346, 349 Fungus, 183, 269, 293 G Gallate, 51, 162, 178, 293 Gallbladder, 76, 255, 265, 283, 293, 294, 308 Gamma Oryzanol, 161, 293 Ganglia, 7, 50, 255, 264, 293, 315, 322 Gas, 153, 186, 187, 259, 262, 269, 273, 283, 291, 293, 300, 302, 305, 314, 317, 340, 341, 347 Gas exchange, 293, 347 Gasoline, 187, 265, 293 Gastric, 79, 212, 227, 264, 269, 284, 288, 293, 297, 299, 300, 321 Gastric Juices, 293, 321 Gastric Mucosa, 293, 321 Gastrin, 293, 299 Gastritis, 79, 111, 211, 293, 340 Gastroenteritis, 211, 294 Gastroenterology, 6, 77, 294 Gastrointestinal, 6, 60, 77, 212, 267, 268, 288, 289, 294, 307, 336, 339, 340, 345 Gastrointestinal tract, 289, 294, 307, 336, 339, 345 Gelatin, 294, 296, 343 Gels, 169, 294 Gene, 8, 12, 14, 25, 29, 31, 36, 37, 39, 43, 45, 53, 55, 56, 57, 66, 71, 75, 77, 144, 145, 184, 220, 227, 258, 266, 294, 298, 318, 324, 333, 335 Gene Deletion, 39, 294 Gene Expression, 12, 25, 29, 31, 37, 53, 55, 56, 71, 144, 294 Generator, 188, 294

Index 359

Genetic Code, 294, 317 Genetic testing, 294, 325 Genetics, 29, 131, 277, 294 Genital, 31, 274, 294, 338 Genotype, 4, 26, 294, 323 Geriatric, 198, 294 Germ Cells, 30, 294, 310, 318, 319, 338, 342 Germline mutation, 294, 299 Gestation, 294, 324 Ginkgo biloba, 6, 25, 28, 123, 295 Ginseng, 122, 123, 127, 295 Gland, 256, 279, 295, 309, 320, 324, 328, 335, 339, 340, 343 Gliosis, 37, 295 Glucocorticoid, 31, 35, 55, 282, 295 Glucokinase, 295, 299 Glucose, 36, 49, 66, 73, 132, 257, 263, 266, 271, 274, 282, 295, 296, 298, 299, 303, 334, 338 Glucose Intolerance, 282, 295 Glucuronic Acid, 295, 298 Glucuronosyltransferase, 72, 295 Glutamate, 290, 295 Glutamic Acid, 292, 295, 327 Glutathione Peroxidase, 4, 18, 22, 24, 50, 146, 159, 295, 335 Glutathione Transferase, 159, 295 Gluten, 271, 295 Glycerol, 195, 203, 268, 295, 296, 323 Glycerophospholipids, 296, 323 Glycine, 296, 336 Glycols, 296, 300 Glycolysis, 8, 296 Glycoprotein, 154, 291, 296, 313, 343, 345 Glycoside, 296, 334 Glycosylation, 12, 296 Goats, 280, 296 Gonadal, 296, 339 Gonadotropin, 30, 296 Gout, 211, 296 Governing Board, 296, 326 Gp120, 154, 296 Graft, 26, 142, 153, 296, 300, 314 Grafting, 210, 296 Gram-negative, 280, 287, 296, 314, 334 Gram-Negative Bacteria, 280, 287, 296 Granulocytes, 264, 296, 337, 348 Graphite, 159, 185, 296 Grasses, 292, 296 Growth Disorders, 208, 297 Growth factors, 30, 58, 297, 318 Guanylate Cyclase, 28, 297, 317

Guinea Pigs, 38, 297 H Hair Cells, 191, 192, 229, 297 Hair follicles, 297, 348 Haploid, 297, 324 Haptens, 257, 297 Headache, 201, 268, 297, 303 Headache Disorders, 297 Health Promotion, 17, 297 Health Services, 84, 297 Heart attack, 167, 171, 269, 297 Heart failure, 23, 46, 47, 297 Heartburn, 212, 297, 299, 302 Hematologic malignancies, 32, 297 Hematoma, 200, 298 Heme, 8, 65, 75, 76, 265, 280, 298, 314, 320, 326 Hemodialysis, 73, 268, 282, 298 Hemodynamics, 13, 298 Hemoglobin, 70, 136, 194, 260, 266, 273, 289, 298, 326 Hemoglobin A, 273, 298, 326 Hemolytic, 70, 298 Hemorrhage, 212, 279, 286, 297, 298, 314, 340, 348 Hemorrhagic stroke, 23, 298 Heparin, 8, 298 Hepatic, 37, 42, 86, 89, 257, 298, 308, 313 Hepatitis, 42, 111, 116, 298 Hepatocyte, 102, 298 Hepatoma, 72, 81, 298 Hereditary, 54, 294, 296, 298, 316, 322 Hereditary mutation, 54, 294, 298 Heredity, 294, 299 Hernia, 55, 299 Herpes, 237, 256, 299 Herpes virus, 237, 299 Herpes Zoster, 299 Heterogeneity, 22, 257, 299 Heterotrophic, 293, 299 Heterozygotes, 194, 299 Hexokinase, 8, 299 Hiatal Hernia, 211, 299 Histamine, 75, 259, 299, 301 Histamine Release, 75, 259, 299 Histidine, 200, 299 Histidine Decarboxylase, 200, 299 Homeostasis, 15, 54, 174, 299 Homogenate, 190, 299 Homogeneous, 162, 263, 299, 323 Homologous, 59, 258, 279, 299, 329, 335, 341, 345

360 Antioxidants

Hormonal, 24, 30, 103, 264, 279, 299 Hormone Replacement Therapy, 210, 300 Horny layer, 288, 300 Host, 59, 63, 154, 165, 174, 191, 204, 264, 283, 292, 300, 302, 307, 333, 334, 348 Human papillomavirus, 63, 300 Hybrid, 274, 300 Hydrochloric Acid, 273, 300 Hydrogen, 28, 29, 32, 59, 62, 71, 158, 166, 170, 173, 174, 185, 198, 207, 221, 255, 256, 259, 264, 267, 269, 270, 281, 282, 295, 300, 307, 313, 316, 319, 329, 341 Hydrogen Peroxide, 28, 29, 32, 59, 62, 71, 159, 170, 173, 174, 198, 221, 270, 295, 300, 307, 341 Hydrolysis, 176, 255, 266, 271, 274, 300, 323, 326, 329 Hydrophilic, 86, 88, 179, 282, 300 Hydrophobic, 179, 282, 296, 300, 308 Hydroxides, 300 Hydroxybenzoic Acids, 259, 300 Hydroxyl Radical, 19, 32, 36, 300 Hydroxylamines, 189, 300 Hydroxylation, 165, 191, 204, 300 Hydroxylysine, 275, 300 Hydroxyproline, 275, 300 Hygienic, 300, 337 Hypercholesterolemia, 26, 112, 138, 300 Hyperglycemia, 10, 46, 300 Hyperhomocysteinemia, 280, 300 Hyperlipidemia, 69, 301 Hyperoxaluria, 61, 301 Hyperoxia, 15, 301 Hyperplasia, 58, 108, 301 Hypersecretion, 32, 301 Hypersensitivity, 55, 183, 258, 301, 307, 334 Hypersensitivity, Immediate, 258, 301 Hypertension, 27, 53, 54, 69, 82, 111, 112, 114, 195, 210, 263, 269, 297, 301, 346 Hypertrophy, 301 Hyperuricemia, 296, 301 Hypochlorous Acid, 174, 301 Hypoglycemia, 210, 301 Hypokinesia, 301, 320 Hypoplasia, 55, 301 Hypotension, 278, 284, 301 Hypothalamic, 30, 301 Hypothalamus, 283, 301, 324 Hypoxanthine, 301, 349 Hypoxia, 267, 272, 301, 342

I Id, 17, 89, 107, 242, 245, 250, 252, 301 Idiopathic, 70, 301 Ileostomy, 301, 315 Iliac Artery, 291, 301, 346 Immune function, 15, 301 Immune response, 46, 174, 256, 261, 264, 279, 297, 302, 340, 345, 348 Immune system, 60, 75, 169, 211, 261, 265, 285, 302, 307, 309, 313, 322, 347, 348 Immunity, 12, 48, 219, 236, 302, 318 Immunization, 65, 302, 327 Immunocompromised, 224, 302 Immunodeficiency, 73, 154, 211, 302 Immunodeficiency syndrome, 211, 302 Immunofluorescence, 59, 302 Immunogenic, 302, 307 Immunohistochemistry, 25, 302 Immunologic, 273, 302, 321, 331 Immunology, 56, 210, 256, 257, 292, 302 Immunosuppressant, 258, 302 Immunosuppressive, 12, 295, 302 Impairment, 9, 18, 33, 36, 263, 272, 302, 311 Implant radiation, 302, 304, 305, 330, 349 Incision, 302, 304, 306, 328, 333 Indicative, 212, 302, 321, 347 Indigestion, 212, 302 Indomethacin, 302, 306 Induction, 8, 12, 14, 19, 31, 46, 55, 58, 63, 65, 75, 154, 164, 174, 302, 327 Infancy, 211, 302 Infarction, 46, 113, 137, 267, 272, 298, 303, 332 Infertility, 112, 113, 148, 303 Infestation, 283, 303 Inflammatory bowel disease, 6, 41, 75, 303 Influenza, 59, 211, 303 Ingestion, 268, 281, 303, 311, 325 Inhalation, 33, 167, 257, 303, 325 Inhalation Exposure, 33, 303 Initiation, 53, 65, 193, 303, 327, 344 Inner ear, 37, 191, 192, 303 Inorganic, 170, 273, 274, 300, 303, 313, 317, 320, 341 Inotropic, 284, 303 Insecticides, 152, 157, 158, 177, 303, 322, 349 Insight, 7, 34, 35, 50, 58, 303 Insulator, 303, 313 Insulin, 23, 58, 74, 76, 209, 210, 229, 282, 303, 304, 306, 346

Index 361

Insulin-dependent diabetes mellitus, 303, 304 Insulin-like, 58, 304 Intensive Care, 53, 69, 304 Intensive Care Units, 53, 304 Intermittent, 304, 308 Internal Medicine, 34, 46, 53, 84, 86, 87, 89, 210, 294, 304 Internal radiation, 304, 305, 330, 349 Interstitial, 58, 267, 290, 304, 305, 349 Intervention Studies, 21, 304 Intestinal, 6, 25, 60, 75, 270, 271, 288, 304, 309 Intestine, 25, 267, 276, 288, 304, 306 Intoxication, 103, 304, 347, 349 Intracranial Embolism, 272, 304 Intracranial Embolism and Thrombosis, 272, 304 Intraepithelial, 304 Intraocular, 202, 304 Intraperitoneal, 36, 304 Intrinsic, 13, 31, 257, 264, 304 Invasive, 30, 302, 304 Involuntary, 264, 304, 314, 331, 338 Iodine, 155, 304 Ion Channels, 263, 304, 316, 341 Ionization, 33, 305 Ionizing, 14, 258, 288, 305, 309, 331, 346 Ions, 17, 29, 67, 180, 188, 205, 264, 267, 268, 273, 283, 286, 300, 305, 313, 329 Iris, 278, 305, 330 Irradiation, 75, 198, 211, 305, 349 Irritable Bowel Syndrome, 212, 305 Ischemia, 6, 13, 20, 29, 32, 86, 88, 106, 173, 264, 267, 281, 298, 305, 314, 316, 332 Ischemic stroke, 20, 23, 305 Isoenzyme, 299, 305 Isoflavones, 101, 128, 305 J Joint, 5, 42, 116, 142, 220, 229, 305, 341 K Kainic Acid, 105, 305 Kb, 234, 305 Keratin, 306, 335 Keratinocytes, 66, 306 Keratotomy, 202, 306 Keto, 8, 306, 330 Ketone Bodies, 255, 282, 306 Ketorolac, 85, 87, 306 Ketorolac Tromethamine, 85, 87, 306 Ketosis, 282, 306 Kidney stone, 61, 306, 319, 332, 346

Kinetic, 11, 133, 305, 306 L Labile, 276, 306 Labyrinth, 275, 303, 306, 335, 348 Lactation, 30, 276, 306, 327 Large Intestine, 25, 270, 276, 283, 304, 306, 331, 337 Latent, 154, 306 Laxative, 257, 286, 306, 338 Lens, 31, 135, 202, 270, 285, 306, 348 Lesion, 10, 12, 29, 153, 295, 306, 308, 346 Lethal, 31, 264, 307 Leukemia, 66, 112, 162, 178, 297, 307 Leukocytes, 28, 266, 267, 273, 288, 296, 302, 307, 313, 322, 345 Leukotrienes, 262, 307 Levodopa, 307, 335 Levothyroxine, 155, 307 Library Services, 250, 307 Lice, 177, 307 Lidocaine, 265, 307 Life cycle, 293, 307 Ligament, 307, 328 Ligation, 47, 307 Linkage, 41, 144, 271, 307 Lipid A, 37, 223, 307 Lipid Peroxides, 220, 307 Lipophilic, 86, 88, 179, 307 Lipopolysaccharides, 307, 308 Lipoprotein, 26, 33, 40, 69, 296, 308 Liposome, 169, 308 Lipoxygenase, 190, 262, 307, 308 Lithotripsy, 61, 308 Liver Cirrhosis, 112, 198, 308 Liver Neoplasms, 289, 308 Lobe, 260, 272, 308 Lobsters, 14, 308 Localization, 15, 31, 64, 75, 79, 302, 308 Localized, 24, 267, 273, 286, 298, 303, 308, 313, 324, 346 Locomotion, 308, 324 Longitudinal Studies, 21, 308 Long-Term Care, 21, 308 Loop, 25, 125, 299, 301, 308 Lovastatin, 19, 308 Low-density lipoprotein, 33, 308 Lubricants, 150, 152, 187, 202, 309, 322 Lumen, 60, 153, 309 Luteal Phase, 85, 87, 309 Lutein Cells, 309, 327 Lycopene, 31, 43, 59, 125, 145, 309 Lymph, 60, 154, 272, 287, 309, 340

362 Antioxidants

Lymph node, 60, 154, 272, 309 Lymphatic, 112, 287, 303, 309, 311, 337, 343 Lymphatic system, 309, 337, 343 Lymphocyte, 261, 309 Lymphoid, 261, 309 Lymphoma, 112, 298, 309 M Macrophage, 33, 52, 309 Macula, 14, 135, 309 Macula Lutea, 309 Macular Degeneration, 14, 72, 99, 112, 242, 243, 309 Malabsorption, 211, 271, 309 Malignant, 261, 263, 309, 315, 331 Malnutrition, 78, 136, 212, 257, 264, 309 Malondialdehyde, 9, 43, 151, 309 Mammary, 57, 276, 309 Mammogram, 268, 309, 311 Manifest, 46, 309 Man-made, 270, 309 Mannans, 293, 310 Meat, 50, 190, 193, 310, 334 Medial, 53, 263, 310 Mediate, 14, 34, 41, 144, 284, 310 Medicament, 310, 342 MEDLINE, 235, 310 Megaloblastic, 292, 310 Meiosis, 11, 310, 341, 346 Melanin, 63, 282, 305, 310, 323, 346 Melanocytes, 49, 310, 317 Melanosomes, 310 Membrane, 26, 34, 39, 40, 61, 165, 191, 196, 198, 202, 204, 255, 258, 263, 271, 273, 274, 276, 277, 282, 287, 290, 296, 304, 310, 313, 314, 315, 318, 319, 323, 326, 329, 333, 337, 345, 348 Membrane Fluidity, 26, 310 Memory, 5, 9, 27, 132, 184, 260, 281, 310 Memory Disorders, 184, 310 Meninges, 272, 279, 285, 310 Meningitis, 59, 113, 291, 310 Menopause, 113, 310, 326 Menstrual Cycle, 309, 310, 327 Menstruation, 258, 281, 309, 310, 318 Mental Disorders, 140, 301, 310, 327, 329 Mental Health, iv, 6, 140, 234, 238, 311, 318, 327, 329 Mental Retardation, 9, 171, 311 Mentors, 10, 311 Mercury, 85, 88, 205, 291, 311 Mesenchymal, 58, 288, 311

Mesenteric, 60, 311 Mesentery, 311, 322 Metabolic disorder, 296, 311 Metabolite, 25, 169, 266, 283, 308, 311 Metastasis, 311 Metastatic, 24, 311 Methacrylate, 311, 325 Methanol, 189, 311 Methionine, 36, 42, 54, 65, 66, 67, 126, 154, 155, 171, 283, 289, 311, 341 MI, 46, 185, 201, 253, 311 Microbe, 311, 344 Microbiology, 25, 56, 85, 88, 256, 311 Microcalcifications, 268, 311 Microcirculation, 308, 311 Micronutrients, 4, 17, 76, 312 Microorganism, 183, 275, 312, 348 Microscopy, 18, 59, 60, 264, 312 Microsomal, 144, 312 Middle Cerebral Artery, 20, 29, 312 Migration, 26, 166, 312, 316, 338 Milk Thistle, 126, 128, 216, 312, 337 Mitochondria, 23, 37, 39, 76, 173, 312, 314, 318 Mitochondrial Swelling, 312, 315 Mitogen-Activated Protein Kinase Kinases, 312 Mitogen-Activated Protein Kinases, 51, 312 Mitosis, 262, 312 Modification, 27, 45, 151, 165, 202, 204, 312 Molasses, 161, 312 Molecular Structure, 236, 313 Molecule, 29, 36, 47, 51, 59, 154, 159, 165, 188, 198, 203, 256, 260, 261, 264, 275, 276, 283, 285, 287, 289, 296, 300, 313, 318, 319, 320, 331, 336, 344 Monitor, 30, 279, 313, 317 Monoamine, 313, 335 Monoamine Oxidase, 313, 335 Monoclonal, 305, 313, 330, 349 Monocytes, 10, 307, 313 Mononuclear, 76, 104, 313, 345 Monounsaturated fat, 144, 195, 313 Morphological, 50, 57, 286, 293, 310, 313 Morphology, 32, 38, 59, 164, 270, 313 Motor Neurons, 48, 313 Mucolytic, 255, 267, 313 Mucosa, 38, 60, 271, 288, 293, 313, 315, 327, 340 Mucus, 32, 148, 290, 313, 346

Index 363

Multiple sclerosis, 19, 313 Muscle Contraction, 53, 313 Muscle Fibers, 313, 315 Mutagen, 265, 314 Mutagenesis, 30, 55, 79, 105, 314 Mutagenic, 258, 314, 346 Mutagenicity, 78, 314 Myalgia, 303, 314 Mycoplasma, 237, 272, 314 Myelin, 313, 314, 316 Myocardial infarction, 46, 198, 279, 311, 314 Myocardial Ischemia, 137, 260, 314 Myocardial Reperfusion, 314, 332 Myocardial Reperfusion Injury, 314, 332 Myocarditis, 59, 314 Myocardium, 47, 260, 311, 314 Myoglobin, 314, 326 Myopia, 314, 315, 330, 331 Myosin, 54, 313, 315 N N-acetyl, 19, 32, 49, 67, 126, 255, 315, 346 Naloxone, 315 Naltrexone, 237, 315 Narcotic, 255, 315 Nasal Cavity, 315 Nasal Mucosa, 38, 303, 315 Natural selection, 265, 315 Nausea, 284, 294, 302, 306, 315, 346 NCI, 1, 140, 233, 274, 315 Nearsightedness, 314, 315, 330 Necrosis, 67, 104, 184, 262, 272, 303, 311, 314, 315, 332, 336 Necrotizing Enterocolitis, 6, 315 Need, 3, 7, 30, 51, 52, 151, 161, 174, 178, 187, 194, 196, 201, 209, 210, 214, 221, 223, 227, 228, 236, 242, 246, 256, 274, 315 Neonatal, 36, 37, 38, 49, 84, 86, 87, 89, 315 Neoplasia, 30, 55, 315 Neoplasm, 315, 320, 345 Neoplastic, 12, 309, 315, 318 Nephropathy, 194, 315 Nervous System, 51, 171, 272, 297, 315, 316, 322, 341, 342 Neural, 39, 54, 171, 259, 287, 313, 316 Neural tube defects, 54, 171, 316 Neuroblastoma, 71, 78, 316 Neurodegenerative Diseases, 6, 37, 39, 86, 88, 158, 264, 316 Neurofibrils, 184, 316 Neurofilaments, 316 Neuroglia, 295, 316

Neurologic, 13, 29, 43, 287, 316 Neuromuscular, 255, 316, 346 Neuromuscular Junction, 255, 316 Neuronal, 16, 20, 36, 44, 67, 105, 316 Neurons, 15, 36, 43, 48, 51, 191, 192, 281, 289, 290, 293, 307, 313, 316, 317, 341 Neuropathy, 49, 59, 138, 237, 257, 316, 322 Neuroprotective Agents, 35, 316 Neurotoxicity, 44, 305, 316 Neurotoxin, 36, 316 Neutrons, 258, 305, 316, 330 Neutrophil, 42, 202, 317 Neutrophil Infiltration, 42, 317 Nicotine, 45, 317 Nitric Oxide, 19, 28, 45, 47, 48, 64, 66, 86, 89, 132, 174, 221, 317 Nitrogen Dioxide, 34, 317 Nitrogen Oxides, 255, 317 Nonmelanoma skin cancer, 51, 317 Norepinephrine, 256, 284, 317 Nuclear, 15, 35, 44, 55, 264, 277, 286, 310, 315, 317, 318 Nuclei, 258, 260, 277, 286, 312, 316, 317, 318, 329 Nucleic acid, 165, 191, 193, 194, 204, 264, 269, 289, 294, 301, 317, 327, 330 Nutritional Status, 12, 317 Nutritive Value, 292, 317 O Occupational Health, 33, 318 Ocular, 202, 318 Odour, 263, 318, 346 Ointments, 169, 272, 284, 318, 337, 349 Oligomenorrhea, 318, 325 Omega-3 fatty acid, 106, 318 Oncogenes, 30, 318, 329 Oncogenic, 11, 318 Oocytes, 11, 318 Opacity, 270, 281, 318 Ophthalmic, 202, 318 Opsin, 318, 333 Optic Disk, 282, 309, 318 Optic Nerve, 318, 320, 333, 335 Oral Health, 318 Oral Hygiene, 183, 318 Organ Culture, 318, 344 Organelles, 272, 280, 310, 313, 318 Organoselenium Compounds, 146, 318 Osmotic, 257, 312, 318 Osteoporosis, 211, 319 Ovalbumin, 52, 319 Ovarian Follicle, 279, 292, 319, 342

364 Antioxidants

Ovaries, 319, 325, 332 Ovary, 30, 58, 279, 289, 319, 325, 340 Ovulation, 11, 148, 152, 260, 309, 319 Ovum, 279, 281, 294, 307, 319, 327 Oxalate, 61, 301, 319 Oxalic Acid, 268, 319 Oxidation-Reduction, 266, 319 Oxidative metabolism, 44, 256, 257, 307, 319 Oxidative Phosphorylation, 165, 191, 204, 319 Oxides, 189, 207, 295, 317, 320, 341 Oxygen Compounds, 172, 173, 320 Oxygen Consumption, 24, 47, 320, 332 Oxygenase, 8, 65, 75, 76, 320 Oxygenation, 53, 298, 320 P Pachymeningitis, 310, 320 Palladium, 205, 320 Palliative, 320, 343 Pancreas, 30, 255, 266, 283, 294, 303, 320, 335, 345 Pancreatic, 50, 113, 269, 293, 320 Pancreatic cancer, 50, 320 Pancreatitis, 6, 30, 113, 132, 320 Papilla, 207, 320 Papilloma, 11, 320 Papillomavirus, 320 Parasite, 292, 320 Parasitic, 177, 291, 303, 307, 320, 334 Parenteral, 73, 287, 320 Parkinsonism, 16, 191, 307, 320 Paroxysmal, 260, 297, 321 Particle, 32, 52, 172, 179, 308, 310, 321, 338, 344 Parturition, 321, 327 Patch, 285, 321 Pathogenesis, 6, 14, 16, 33, 34, 38, 44, 45, 49, 56, 139, 321 Pathologic, 11, 40, 44, 57, 255, 262, 266, 278, 301, 321, 329, 332, 347 Pathologic Processes, 262, 321 Pathologies, 24, 47, 202, 321 Pathophysiology, 19, 26, 58, 212, 321 Patient Education, 244, 248, 250, 253, 321 Peak flow, 74, 321 Pelvic, 287, 321, 328 Pentoxifylline, 237, 321 Pepsin, 321 Pepsin A, 321 Peptic, 113, 212, 321, 340 Peptic Ulcer, 113, 212, 321

Peptide, 67, 71, 194, 237, 306, 321, 326, 328, 329 Perception, 190, 321, 335 Percutaneous, 61, 153, 308, 321 Perennial, 147, 321, 345 Perfusion, 293, 301, 321 Perineal, 321, 331 Peripheral blood, 200, 321 Peripheral Nervous System, 288, 316, 322, 340 Peripheral Neuropathy, 59, 322 Peripheral Vascular Disease, 113, 200, 322 Peritoneal, 30, 304, 322 Peritoneal Cavity, 304, 322 Peritoneum, 311, 322 Pernicious, 171, 310, 322 Pernicious anemia, 171, 322 Peroxidase, 159, 165, 173, 203, 262, 307, 322 Peroxide, 29, 32, 159, 184, 322 Pesticides, 43, 211, 303, 322 Petechia, 285, 322 Petrolatum, 286, 322 Petroleum, 157, 158, 202, 268, 293, 322 Phagocyte, 319, 322 Pharmaceutic Aids, 292, 322 Pharmaceutical Preparations, 106, 150, 169, 172, 193, 195, 203, 271, 289, 294, 322, 323 Pharmaceutical Solutions, 284, 323 Pharmacokinetic, 59, 323 Pharmacologic, 8, 210, 260, 323, 344 Pharynx, 303, 315, 323 Phenolphthalein, 286, 323 Phenotype, 48, 194, 294, 323 Phenyl, 168, 323 Phenylacetate, 19, 323 Phenylalanine, 321, 323, 346 Phosphodiesterase, 321, 323 Phospholipases, 323, 336 Phospholipids, 49, 202, 290, 308, 310, 323, 329 Phosphorous, 151, 323 Phosphorus, 150, 268, 323 Phosphorylated, 275, 312, 323 Phosphorylation, 51, 54, 55, 56, 67, 312, 323, 329 Photocoagulation, 275, 323 Photodynamic therapy, 323 Photosensitizer, 151, 323 Physical Examination, 135, 323

Index 365

Physiologic, 257, 266, 291, 301, 310, 312, 324, 328, 331, 332, 345 Physiology, 13, 53, 60, 72, 77, 84, 86, 87, 88, 104, 294, 324 Picornavirus, 59, 324 Pigment, 15, 66, 68, 161, 162, 176, 265, 273, 282, 309, 310, 314, 317, 324, 333 Pigmentation, 48, 324 Pilot study, 26, 324 Pink eye, 14, 324 Pitch, 159, 324 Pituitary Gland, 7, 279, 324 Placenta, 171, 289, 324, 327, 346 Plaque, 10, 45, 153, 182, 183, 260, 263, 324 Plasma cells, 261, 324 Plasma protein, 257, 324, 329 Plasticity, 15, 324 Plasticizers, 132, 185, 207, 324 Platelet Activation, 324, 337 Platelet Aggregation, 259, 317, 321, 324, 343 Platelets, 45, 262, 271, 317, 324, 325, 336, 343 Platinum, 274, 308, 320, 325 Poisoning, 110, 211, 265, 268, 273, 283, 294, 304, 311, 315, 325 Pollen, 325, 330 Polycystic, 58, 325 Polycystic Ovary Syndrome, 58, 325 Polyesters, 144, 175, 325 Polyethylene, 180, 185, 195, 201, 325 Polymerase, 25, 325, 327 Polymerase Chain Reaction, 25, 325 Polymers, 143, 164, 175, 179, 181, 182, 186, 194, 195, 325, 329, 340 Polymethyl Methacrylate, 175, 325 Polymorphic, 54, 325 Polymorphism, 43, 75, 133, 326 Polypeptide, 259, 275, 288, 291, 314, 321, 326, 327, 349 Polyposis, 276, 326 Polysaccharide, 84, 86, 261, 271, 326 Polyunsaturated fat, 223, 326, 343 Porphyrins, 18, 326 Posterior, 31, 202, 259, 263, 272, 274, 284, 305, 320, 326, 335 Postmenopausal, 26, 319, 326 Postnatal, 39, 53, 326, 339 Postoperative, 306, 326 Postsynaptic, 326, 336, 341 Potassium, 155, 175, 326, 337 Potassium hydroxide, 155, 326

Potentiate, 28, 326 Potentiation, 326, 337 Practice Guidelines, 238, 326 Precancerous, 273, 326 Precipitating Factors, 270, 297, 326 Preclinical, 58, 327 Precursor, 16, 155, 262, 265, 273, 284, 285, 288, 307, 317, 323, 327, 329, 345, 346 Prenatal, 55, 286, 327 Prevalence, 9, 46, 327 Prickle, 306, 327 Primary Prevention, 46, 137, 327 Prion, 37, 272, 327 Probe, 25, 60, 188, 327 Progesterone, 127, 152, 327, 339 Progression, 12, 14, 20, 30, 34, 37, 39, 41, 45, 133, 137, 138, 211, 236, 260, 327, 335, 345 Progressive, 15, 18, 37, 43, 46, 81, 214, 263, 271, 274, 281, 285, 297, 315, 316, 324, 327, 345 Projection, 281, 317, 318, 327, 331 Prolactin, 7, 327 Proline, 275, 300, 327 Promoter, 8, 55, 65, 327 Promotor, 327, 333 Prone, 18, 158, 327 Prophase, 318, 327, 341, 346 Prophylaxis, 165, 183, 184, 204, 327, 333 Propidium, 32, 327 Prospective study, 41, 101, 194, 328 Prostaglandin, 105, 170, 328, 343 Prostaglandins A, 49, 159, 165, 204, 302, 328 Prostaglandins D, 328 Prostate, 24, 81, 114, 134, 148, 169, 266, 328, 331, 332, 333, 345 Prostate gland, 148, 328 Prostatectomy, 24, 328, 331 Protease, 59, 328 Protein C, 52, 257, 259, 262, 264, 275, 291, 306, 308, 328 Protein Kinase C, 64, 312, 329 Protein Kinases, 12, 56, 312, 318, 329 Protein S, 220, 266, 294, 329, 334 Protein-Serine-Threonine Kinases, 312, 329 Proteolytic, 276, 291, 329 Prothrombin, 10, 329, 343 Protons, 258, 300, 305, 329, 330 Proto-Oncogenes, 318, 329 Protozoa, 277, 312, 329

366 Antioxidants

Proximal, 284, 315, 329 Pruritic, 285, 329 Psoriasis, 80, 192, 329, 333 Psychiatric, 183, 184, 310, 329 Psychiatry, 329, 347 Public Health, 23, 26, 37, 144, 238, 265, 329 Public Policy, 235, 330 Publishing, 61, 214, 216, 330 Pulmonary, 32, 34, 38, 41, 53, 55, 64, 114, 167, 266, 267, 273, 278, 293, 307, 330, 341, 347 Pulmonary Artery, 266, 330, 347 Pulmonary Circulation, 53, 330 Pulmonary Edema, 114, 273, 330 Pulmonary Emphysema, 167, 330 Pulmonary hypertension, 53, 55, 330 Pulse, 286, 313, 330 Pupil, 278, 330 Purines, 197, 264, 330, 336, 349 Pyridones, 169, 330 Pyridoxal, 155, 280, 299, 330 Pyridoxal Phosphate, 280, 299, 330 Q Quaternary, 179, 327, 330 Quercetin, 5, 17, 92, 330 Quiescent, 24, 330, 348 R Race, 4, 43, 169, 210, 312, 330 Radial Keratotomy, 202, 330 Radiation therapy, 290, 304, 305, 330, 349 Radical prostatectomy, 24, 331 Radioactive, 300, 302, 304, 305, 309, 317, 318, 330, 331, 349 Radiolabeled, 305, 330, 331, 349 Radiological, 321, 331 Radiopharmaceutical, 294, 331 Radiotherapy, 267, 305, 331, 349 Randomized, 6, 9, 21, 24, 43, 63, 101, 285, 331 Reagent, 54, 148, 273, 300, 319, 331 Receptor, 15, 16, 31, 45, 51, 53, 72, 154, 212, 256, 261, 284, 296, 305, 329, 331, 336 Recombinant, 237, 331 Recombination, 14, 277, 331 Rectum, 262, 267, 276, 283, 291, 293, 303, 306, 328, 331 Recurrence, 61, 273, 331 Red blood cells, 289, 298, 320, 331, 334, 337 Red Nucleus, 263, 331 Reductase, 8, 36, 49, 54, 64, 66, 67, 81, 91, 257, 308, 331

Refer, 1, 276, 284, 293, 295, 299, 308, 309, 316, 331, 347 Reflex, 290, 331 Reflux, 331, 340 Refraction, 314, 331, 338 Refractory, 159, 286, 332 Regeneration, 150, 187, 194, 195, 196, 332 Regimen, 148, 285, 332 Regurgitation, 297, 332 Reliability, 9, 40, 332 Remission, 331, 332 Renal pelvis, 306, 332 Renal tubular, 61, 332 Reperfusion, 13, 28, 32, 63, 85, 86, 87, 88, 89, 104, 165, 204, 314, 332 Reperfusion Injury, 28, 32, 63, 86, 89, 332 Reproductive cells, 294, 298, 332 Reproductive system, 328, 332 Research Personnel, 19, 332 Resorption, 292, 332 Respirable, 32, 332 Respiration, 44, 269, 313, 332, 333 Respiratory distress syndrome, 73, 332 Respiratory Physiology, 332, 347 Response Elements, 8, 333 Restoration, 314, 332, 333 Resuscitation, 13, 333 Retina, 14, 65, 105, 135, 145, 202, 274, 277, 282, 306, 309, 314, 316, 318, 333, 334, 348 Retinae, 309, 333 Retinal, 14, 15, 66, 68, 282, 283, 318, 333, 348 Retinal pigment epithelium, 14, 333 Retinoids, 333, 348 Retinol, 333 Retinopathy, 114, 257, 282, 333 Retropubic, 328, 331, 333 Retropubic prostatectomy, 331, 333 Retrovirus, 154, 333 Reversion, 14, 333, 346 Rheology, 186, 321, 333 Rheumatism, 198, 333, 334 Rheumatoid, 5, 63, 101, 114, 115, 229, 319, 334 Rheumatoid arthritis, 5, 63, 101, 229, 334 Ribosome, 334, 345 Rickettsia, 56, 65, 334 Rickettsiae, 56, 334 Rigidity, 43, 185, 197, 320, 324, 334 Risk factor, 21, 27, 30, 46, 223, 270, 300, 328, 334 Rod, 264, 287, 334

Index 367

Rodenticides, 322, 334 Rubber, 160, 166, 199, 207, 256, 286, 334 Rutin, 200, 330, 334 S Salicylate, 17, 272, 334 Salicylic, 63, 65, 67, 334 Saline, 267, 334 Salivary, 283, 320, 334, 340 Salivary glands, 283, 334 Saponins, 78, 334, 339 Saturated fat, 27, 144, 195, 229, 334 Schizoid, 335, 349 Schizophrenia, 106, 115, 310, 335, 349 Schizotypal Personality Disorder, 335, 349 Sclera, 274, 277, 335 Sclerosis, 17, 37, 48, 71, 169, 263, 313, 335 Screening, 24, 30, 50, 58, 106, 132, 136, 274, 335 Scrotum, 335, 342 Sebaceous, 182, 335, 348 Sebaceous gland, 335, 348 Sebum, 173, 182, 200, 335 Secretion, 11, 25, 279, 288, 299, 301, 304, 306, 313, 335 Secretory, 271, 335, 341 Secretory Vesicles, 271, 335 Sedentary, 7, 176, 335 Segregation, 331, 335 Selegiline, 6, 230, 335 Selenium, 3, 4, 24, 59, 92, 104, 105, 106, 152, 214, 242, 318, 335 Selenomethionine, 24, 335 Sella, 284, 324, 335 Semen, 264, 328, 335, 336 Semicircular canal, 303, 335 Seminal vesicles, 148, 336 Senescence, 10, 39, 336 Senile, 115, 319, 336 Sepsis, 7, 336 Septic, 7, 195, 336 Sequence Analysis, 59, 336 Sequencing, 59, 64, 325, 336 Sequester, 273, 336 Serine, 155, 280, 312, 329, 336 Serotonin, 288, 313, 336, 345 Serous, 276, 287, 336 Serum, 12, 22, 23, 27, 43, 79, 137, 144, 171, 257, 259, 262, 276, 296, 309, 336, 345 Sexually Transmitted Diseases, 115, 211, 336 Sharpness, 336, 348 Ships, 185, 336

Shock, 61, 76, 115, 195, 287, 308, 336, 345 Side effect, 32, 135, 199, 256, 265, 301, 336, 344 Signal Transduction, 15, 28, 49, 51, 56, 170, 336 Silymarin, 85, 88, 312, 337 Skeletal, 132, 134, 200, 297, 337, 338 Skeleton, 256, 291, 305, 328, 337 Skin Care, 181, 337 Skin Pigmentation, 48, 337 Skull, 279, 287, 316, 337, 342 Sludge, 150, 337 Small intestine, 270, 274, 285, 300, 304, 337 Smooth muscle, 53, 58, 258, 259, 268, 278, 299, 301, 337, 338, 340 Soaps, 176, 337 Social Problems, 49, 337 Sodium, 19, 76, 155, 188, 207, 267, 296, 337 Soft tissue, 182, 183, 267, 337 Solar radiation, 146, 337 Solid tumor, 32, 337 Solvent, 153, 157, 175, 178, 186, 190, 201, 255, 265, 289, 295, 311, 318, 323, 337 Somatic, 310, 312, 322, 338 Somatic cells, 310, 312, 338 Sorbitol, 49, 257, 299, 338 Sound wave, 277, 338 Soybean Oil, 189, 326, 338, 348 Spasm, 278, 338 Spastic, 305, 338 Spatial disorientation, 284, 338 Specialist, 245, 338 Specificity, 151, 257, 262, 338 Spectrophotometry, 55, 170, 338 Spectrum, 84, 87, 169, 338, 346 Speech Disorders, 184, 338 Sperm, 148, 274, 294, 298, 325, 332, 338, 342 Sperm Motility, 148, 338 Sperm Transport, 148, 338 Spermatozoa, 264, 335, 338 Spermatozoon, 338 Spina bifida, 316, 338 Spinal cord, 263, 267, 272, 273, 285, 310, 315, 316, 320, 322, 331, 339 Spinous, 288, 306, 339 Sporadic, 48, 316, 339 Squamous, 317, 339 Squamous cells, 317, 339 Stabilization, 14, 164, 176, 206, 339 Stabilizer, 157, 164, 189, 203, 339 Statistically significant, 5, 339

368 Antioxidants

Steel, 159, 160, 339, 347 Stem Cells, 154, 339, 346 Stent, 153, 339 Sterility, 303, 339 Steroid, 30, 31, 165, 204, 279, 334, 339 Steroid therapy, 31, 339 Stimulant, 167, 268, 299, 339 Stimulus, 285, 289, 304, 331, 339, 343 Stool, 305, 306, 339 Strand, 13, 102, 325, 339 Streptococcal, 70, 339 Streptococcus, 339 Stroke, 20, 23, 28, 35, 58, 69, 115, 140, 234, 243, 269, 298, 305, 316, 340 Stromal, 30, 202, 287, 340 Stromal Cells, 30, 340 Structure-Activity Relationship, 18, 340 Styrene, 175, 334, 340 Subacute, 303, 340 Subarachnoid, 297, 340 Subcapsular, 31, 340 Subclinical, 27, 303, 340 Subcutaneous, 271, 285, 320, 340 Submaxillary, 288, 340 Subspecies, 338, 340 Substance P, 149, 311, 335, 340 Substrate, 142, 143, 172, 340 Succinic Anhydrides, 163, 340 Succinimides, 187, 340 Sucralfate, 212, 340 Suction, 291, 340 Sulfides, 205, 341 Sulfites, 156, 341 Sulfur, 54, 150, 151, 180, 216, 255, 295, 311, 341 Sulfur Oxides, 255, 341 Sunburn, 115, 146, 197, 341 Supplementation, 9, 10, 39, 44, 45, 50, 79, 102, 104, 105, 106, 138, 139, 224, 341 Suppression, 63, 65, 66, 67, 174, 279, 341 Suppurative, 271, 341 Surfactant, 161, 176, 341, 348 Survival Rate, 46, 341 Suspensions, 169, 341 Sympathomimetic, 284, 288, 317, 341 Symphysis, 328, 341 Symptomatic, 320, 341 Synaptic, 317, 337, 341 Synaptic Transmission, 317, 341 Synergist, 168, 190, 342 Synergistic, 81, 134, 161, 164, 190, 327, 342

Systemic, 33, 44, 65, 72, 116, 266, 267, 269, 284, 288, 298, 303, 305, 330, 340, 342, 347, 349 Systolic, 5, 144, 301, 342 Systolic blood pressure, 5, 144, 342 T Talc, 31, 179, 342 Tartar, 182, 183, 342 Taurine, 105, 155, 207, 342 Telencephalon, 264, 342 Temporal, 12, 297, 309, 342 Teratogenic, 258, 342 Teratogenicity, 70, 342 Terminator, 275, 342 Testicles, 148, 335, 342 Testicular, 148, 342 Testis, 289, 342 Testosterone, 331, 342 Tetrahydrocannabinol, 63, 342 Thalamic, 263, 342 Thalamic Diseases, 263, 342 Theca Cells, 11, 309, 342 Theophylline, 330, 342 Therapeutics, 313, 343 Thermal, 163, 179, 180, 185, 186, 189, 283, 316, 325, 343 Thigh, 290, 291, 343 Threonine, 155, 312, 329, 336, 343 Threshold, 301, 343 Thrombin, 10, 262, 291, 325, 328, 329, 343 Thrombocytes, 325, 343 Thrombomodulin, 328, 343 Thromboses, 195, 343 Thrombosis, 10, 81, 153, 218, 223, 304, 329, 340, 343 Thromboxanes, 262, 343 Thrombus, 279, 303, 305, 314, 325, 343 Thymus, 129, 237, 302, 309, 343 Thyroid, 304, 307, 343, 346 Thyroid Gland, 343 Thyroxine, 155, 257, 307, 323, 343 Tin, 205, 322, 325, 343 Tissue Culture, 52, 343 Tome, 119, 344 Tomography, 344 Tonic, 175, 344 Tooth Preparation, 256, 344 Topical, 51, 161, 168, 169, 192, 197, 200, 263, 283, 289, 300, 322, 337, 344, 349 Torsion, 303, 344

Index 369

Toxicity, 33, 34, 47, 48, 59, 66, 74, 85, 86, 88, 107, 133, 221, 269, 285, 286, 311, 340, 344 Toxicokinetics, 344 Toxicologic, 165, 204, 344 Toxicology, 5, 39, 57, 75, 86, 88, 102, 104, 236, 344 Toxins, 8, 17, 49, 261, 286, 295, 303, 344 Trace element, 3, 274, 343, 344 Traction, 160, 199, 344 Transcriptase, 137, 154, 162, 178, 333, 344 Transcription Factors, 12, 64, 318, 333, 344 Transduction, 336, 344 Transfection, 55, 65, 266, 344 Transferases, 296, 344 Translation, 12, 344 Translational, 13, 54, 345 Translocate, 33, 345 Translocation, 55, 345 Transmitter, 255, 263, 284, 290, 304, 316, 317, 345 Transplantation, 63, 274, 302, 345 Transurethral, 328, 345 Transurethral Resection of Prostate, 328, 345 Trauma, 35, 38, 289, 315, 316, 320, 345 Trees, 66, 334, 345 Tremor, 320, 345 Triolein, 33, 345 Trophic, 48, 191, 345 Tryptophan, 62, 275, 336, 345 Tuberculosis, 72, 278, 334, 345 Tumor marker, 266, 345 Tumor model, 162, 178, 345 Tumor Necrosis Factor, 58, 71, 345 Tumor-derived, 49, 345 Tumour, 104, 345 Tunicamycin, 8, 346 Type 2 diabetes, 76, 78, 135, 346 Typhimurium, 100, 346 Tyrosine, 17, 48, 284, 346 U Ubiquinone, 159, 346 Ulcer, 212, 271, 281, 285, 321, 340, 346 Ulcerative colitis, 30, 303, 346 Ultraviolet Rays, 198, 346 Umbilical Arteries, 346 Umbilical Cord, 84, 87, 346 Umbilical cord blood, 84, 87, 346 Unconscious, 281, 301, 346 Univalent, 300, 319, 346 Uraemia, 320, 346

Ureter, 308, 332, 346 Urethra, 328, 345, 346, 347 Uric, 17, 34, 68, 159, 170, 258, 296, 301, 330, 346 Urinary, 5, 22, 148, 268, 328, 333, 347, 349 Urine, 22, 171, 266, 268, 279, 284, 288, 301, 306, 319, 332, 346, 347 Urolithiasis, 61, 347 Uterus, 272, 279, 281, 287, 310, 319, 327, 332, 347 V Vaccine, 65, 211, 237, 256, 345, 347 Vagina, 269, 272, 282, 285, 310, 332, 347 Vaginal, 148, 237, 347 Vanadium, 210, 347 Vascular Resistance, 53, 347 Vasculitis, 272, 320, 347 Vasoconstriction, 54, 288, 347 Vasodilation, 284, 347 Vasodilator, 200, 267, 284, 299, 314, 347 Vegetarianism, 211, 347 Vein, 7, 56, 65, 136, 165, 204, 263, 317, 346, 347 Venous, 171, 200, 263, 266, 272, 304, 329, 347 Venous blood, 266, 272, 347 Ventilation, 53, 347 Ventricle, 301, 330, 342, 347 Venules, 266, 269, 311, 347 Vesicular, 299, 312, 347 Vestibular, 191, 192, 297, 347 Vestibule, 275, 303, 336, 347, 348 Veterinary Medicine, 104, 235, 348 Villous, 271, 348 Viral, 59, 116, 154, 157, 158, 182, 224, 255, 269, 286, 287, 303, 318, 329, 333, 344, 348 Virulence, 59, 344, 348 Virus, 11, 59, 65, 73, 154, 162, 178, 211, 264, 269, 272, 287, 296, 300, 324, 344, 348 Viscosity, 162, 175, 182, 186, 255, 333, 348 Visual Acuity, 14, 135, 348 Vital Capacity, 292, 348 Vitamin A, 4, 35, 244, 333, 348 Vitamin E, 5, 10, 49, 68, 84, 90, 91, 169, 190, 214, 219, 229, 242, 244, 348 Vitiligo, 49, 80, 348 Vitreous Body, 333, 348 Vitreous Hemorrhage, 282, 348 Vitro, 11, 16, 17, 26, 31, 40, 45, 47, 51, 52, 55, 56, 57, 58, 59, 75, 81, 85, 87, 134, 213, 236, 298, 302, 325, 344, 348

370 Antioxidants

Vivo, 10, 11, 18, 20, 25, 26, 29, 40, 45, 52, 55, 57, 67, 100, 101, 104, 173, 190, 194, 213, 223, 298, 302, 307, 319, 343, 348 Vulgaris, 118, 129, 348 W Warts, 168, 169, 300, 348 Wetting Agents, 142, 171, 348 White blood cell, 261, 264, 276, 307, 309, 313, 317, 324, 348 Withdrawal, 36, 48, 349 X Xanthine, 47, 258, 349

Xanthine Oxidase, 47, 258, 349 Xenobiotics, 12, 55, 165, 191, 204, 349 Xenograft, 67, 260, 345, 349 X-ray, 14, 270, 277, 291, 293, 305, 309, 310, 314, 317, 330, 331, 339, 346, 349 X-ray therapy, 305, 349 Y Yeasts, 293, 323, 349 Z Zinc Oxide, 33, 349 Zymogen, 328, 349

Index 371

372 Antioxidants

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

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

Hepatitis A Vaccine: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Butternut Squash: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Facial Paralysis - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

Breast Augmentation - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Premenstrual Dysphoric Disorder - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Anagrelide: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Peanut Allergy: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Cauda Equina Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Magnesium Citrate: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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

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

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

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