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

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

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

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Hypericin: 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: 0-497-00459-3 1. Hypericin-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 hypericin. 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 HYPERICIN ................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hypericin ...................................................................................... 4 E-Journals: PubMed Central ......................................................................................................... 8 The National Library of Medicine: PubMed .................................................................................. 9 CHAPTER 2. NUTRITION AND HYPERICIN ...................................................................................... 23 Overview...................................................................................................................................... 23 Finding Nutrition Studies on Hypericin ..................................................................................... 23 Federal Resources on Nutrition ................................................................................................... 27 Additional Web Resources ........................................................................................................... 28 CHAPTER 3. ALTERNATIVE MEDICINE AND HYPERICIN ................................................................ 29 Overview...................................................................................................................................... 29 National Center for Complementary and Alternative Medicine.................................................. 29 Additional Web Resources ........................................................................................................... 40 General References ....................................................................................................................... 42 CHAPTER 4. PATENTS ON HYPERICIN ............................................................................................. 43 Overview...................................................................................................................................... 43 Patents on Hypericin ................................................................................................................... 43 Patent Applications on Hypericin ............................................................................................... 52 Keeping Current .......................................................................................................................... 55 CHAPTER 5. BOOKS ON HYPERICIN ................................................................................................ 57 Overview...................................................................................................................................... 57 Book Summaries: Federal Agencies.............................................................................................. 57 Book Summaries: Online Booksellers........................................................................................... 58 CHAPTER 6. PERIODICALS AND NEWS ON HYPERICIN ................................................................... 59 Overview...................................................................................................................................... 59 News Services and Press Releases................................................................................................ 59 Academic Periodicals covering Hypericin.................................................................................... 60 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 65 Overview...................................................................................................................................... 65 NIH Guidelines............................................................................................................................ 65 NIH Databases............................................................................................................................. 67 Other Commercial Databases....................................................................................................... 69 APPENDIX B. PATIENT RESOURCES ................................................................................................. 71 Overview...................................................................................................................................... 71 Patient Guideline Sources............................................................................................................ 71 Finding Associations.................................................................................................................... 73 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 75 Overview...................................................................................................................................... 75 Preparation................................................................................................................................... 75 Finding a Local Medical Library.................................................................................................. 75 Medical Libraries in the U.S. and Canada ................................................................................... 75 ONLINE GLOSSARIES.................................................................................................................. 81 Online Dictionary Directories ..................................................................................................... 81 HYPERICIN DICTIONARY .......................................................................................................... 83 INDEX .............................................................................................................................................. 127

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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 hypericin 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 hypericin, 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 hypericin, 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 hypericin. 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 hypericin, 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 hypericin. 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 HYPERICIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hypericin.

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

Hypericin Update Source: Positively; Vol. 6, No. 9, Nov. 1993. Contact: Body Positive Houston, PO Box 66446, Houston, TX, 77266-6446, (713) 524-2374, http://www.bodypositivehouston.org. Summary: This article focuses on St. John's Wort, an herb which has been used for centuries in European folk medicine. St. John's Wort contains trace amounts of hypericin, a chemical substance believed to be the medically active component of the herb. Test tube experiments indicate that hypericin may have anti-HIV properties. In the laboratory, hypericin blocks viral budding. As a result, some people with HIV want to try hypericin as an anti-HIV treatment. According to this article, there is no evidence that St. John's Wort extracts help PWAs at all. There is no organized research program

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investigating this question. The article also warns that St. John's Wort has toxic properties, and its prolonged use may cause unwanted psychological effects.

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

Project Title: DRUG INTERACTIONS Principal Investigator & Institution: Rettie, Allan E.; Professor and Chair; Medicinal Chemistry; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-1983; Project End 31-JUL-2008 Summary: (provided by applicant): Metabolically-based drug-drug interactions are a major cause of morbidity and mortality in the therapeutic treatment of disease. Although significant advances have been made in our understanding of the etiology of such adverse drug reactions, quantitative prediction of these events at early stages of drug development and clinical use remains elusive. This Program Project Grant focuses on understanding the in vitro to in vivo relationships for drug-drug interactions involving the human cytochrome P450 family of enzymes and drug transporters. In the current proposal, we will investigate several emerging factors that complicate our ability to accurately predict changes in drug metabolizing enzyme and drug transporter activity that result from the co-administration of multiple interacting species; (i) nonhyperbolic kinetics and cooperative ligand binding to human P450s, (ii) sequential oxidative metabolism and the formation of metabolic-intermediate (MI) complexes, (iii) the variable contribution made by Type II binding to inhibitor Ki, (iv) the role(s) of drug transporters such as the human OCTs, MDRs and MRPs, and (v) the interplay of drugmetabolizing enzymes and drug transporters in drug interactions associated with induction mechanisms. In Project 1 we will synthesize novel high affinity inhibitors for human CYP2C enzymes and combine this with site-directed mutagenesis studies to enable construction of discriminating computational and structural models for the prediction of inhibitor Ki. In Project 2, we will explore the mechanistic basis for 'allosteric' kinetic behavior with CYP3A4, towards a variety of ligands including caffeine, acetaminophen, pyrene and hypericin using fluorescence and NMR-based

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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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approaches. In Project 3, we will explore reasons for the discrepancy between in vivo and in vitro Kis for the test compounds, itraconazole and fluvoxamine and develop new kinetic models for sequential metabolism and MI complex formation with macrolides and antidepressants. In Project 4 we will determine the molecular and genetic factors that influence, both in vivo and in vitro, the magnitude and spectrum of human P450 enzymes and drug transporters induced by the anti-HIV protease inhibitors, nelfinavir and ritonavir. Collectively, these studies should provide new conceptual and practical tools to achieve quantitative predictions of drug-drug interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FORMULATION DEPENDENT HELP INTERACTIONS WITH CHEMOTHERA* Principal Investigator & Institution: Kroll, David J.; Senior Research Pharmacologist; Research Triangle Institute Box 12194, 3040 Cornwallis Rd Research Triangle Park, Nc 277092194 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): As a result of our experience in cancer pharmacology, drug metabolism, and interest in therapeutic natural products (prescription drugs and dietary supplements), preliminary work was conducted to investigate potential pharmacodynamic and pharmacokinetic interactions between cytotoxic cancer chemotherapy and herbal supplements used commonly by cancer patients. For this R21 application, we propose that adverse actions attributed to herbal products derived from one specific plant may not necessarily hold true for other formulations manufactured from the same plant. This two-part pilot project will focus on the DNA topoisomerase II (topo II)-targeted anticancer agent etoposide (VP-16) and three of the most-widely used commercial formulations of St. John's wort (SJW), Hypericum perforatum. The antidepressant activity of SJW was originally attributed to the naphthodianthrone hypericin but recent data have more strongly implicated other components (including hyperforin and others). Regardless, most commercial SJW products are standardized to 0.3% hypericin. Hypericin is structurally similar to antitumor agents that target topo II, a nuclear enzyme required for DNA replication and chromosomal segregation during tumor cell proliferation. Preliminary studies revealed that hypericin bound to DNA but did not produce topo H-dependent DNA damage or activate the expression of DNA damage response genes as does etoposide (VP-16). Instead, hypericin inhibited topo II enzyme activity at a step prior that of anti-topo II chemotherapeutics resulting in potent, dose-dependent antagonism of the desired DNA damaging activity of etoposide and that of another topo II-targeted antitumor drug, amsacrine. Since cancer patients are often prescribed antidepressants or self-medicate with herbal products, we propose to investigate SJW extracts for similar effects on topo II activity in vitro and in cultured human tumor cells and determine whether these effects occur at physiologically achievable concentrations of individual components in the context of a complex extract. Our first hypothesis is that SJW extracts will act similar to pure hypericin and antagonize topo II- directed chemotherapeutics in vitro and in vivo; given that hypericin seems dispensible for antidepressant activity, depressed cancer patients might be directed safely toward hypericin-free SJW products. SJW extracts may also interact pharmacokinetically with cancer chemotherapeutics by inducing OR inhibiting CYP3A4 activity depending upon the duration of exposure and the SJW formulation used. CYP3A4 metabolizes etoposide as well as vincristine, vinblastine, irinotecan (CPT-11) and tamoxifen. Hyperforin appears to be the SJW component responsible for these effects but again, it may not be the antidepressant

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principle of the herb. Recent promotion of SJW formulations enriched for hyperforin raises concerns that certain SJW products may adversely compromise antitumor drug efficacy if CYP3A4 is induced by chronic SJW use. Therefore our second hypothesis is to test the formulation-dependence of SJW extracts in transcriptional activation via the primary CYP3A4 regulatory protein, pregnane X receptor (PXR), and in directly altering CYP3A4 content of cultured human hepatocytes. The research component central to this application is the RTI Natural Product Characterization Core (NPCC) whose analytical chemistry capabilities will determine the identity and concentrations of SJW constituent(s) responsible for any observed biological endpoints. These studies are designed in the interest of public health and the spirit that cancer patients should be steered away from harmful herbal products while being assured safe access to alternative formulations of the same herb. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF CYTOCHROME P450 ALLOSTERY Principal Investigator & Institution: Atkins, William M.; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Many drug-drug interactions are metabolic in origin, resulting from the activation or inhibition of Cytochrome P450 (CYP)-dependent drug clearance. A potential contribution to CYP-dependent drug interactions is the poorly characterized allostery that is widely observed in vitro, and also in vivo. This allostery includes nonhyperbolic steady state kinetic profiles for individual substrates (homotropic allostery), as well as alterations in the kinetic profiles of one drug by a second (heterotropic allostery). The molecular mechanisms leading to allostery are not defined, although several contrasting models have been proposed and include multiple ligand binding within a single fluid active site, multiple ligand binding within discrete subsites of this large active site, and ligand-dependent persistent protein conformational equilibria. Here, non-steady state kinetic methods will be exploited to challenge these models and to understand CYP allostery in the context of existing structural models for CYP3A4 and CYP2C9. The specific aims are: 1) to determine whether the elementary steps of ligand binding, ligand-dependent ferric spin state equilibrium, or ligand-dependent changes in gross protein conformation are differentially allosteric for the homotropic effects of testosterone, pyrene, and hypericin with CYP3A4; 2) to determine by paramagnetically shifted 1H-NMR spectra, the mechanism of allostery for the heterotropic effects between caffeine and acetaminophen or midazolam and alpha-naptho flavors with CYP3A4, and to initiate SAR-by-NMR to map ligand binding sites in uniformly deuterated, 15N-Phelabeled CYP3A4; 3) to monitor conformational dynamics of CYP3A4 via limited proteolysis/electrospray mass spectrometry as a function of ferric/ferrous redox state and ligand binding; 4) to map the CYP3A4/Cyt b5 binding surface via site-directed mutagenesis and catatylic turnover experiments, and determine whether specific interfacial residues contribute to Cyt b5-dependent allosteric effects. In addition, where possible, parallel experiments will be performed with CYPeryF, a soluble homolog for which X-ray crystallographic analysis is possible. In the long term, x-ray structures of [CYPeryF.ligand] complexes will be sought, via collaboration, in order to correlate allosteric effects with CYP structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: R21 PROJECT: ST. JOHN'S WORT VS. PLACEBO IN OCD Principal Investigator & Institution: Kobak, Kenneth A.; Senior Research Scientist; Dean Fdn for Health, Research & Educatn Research and Education Middleton, Wi 53562 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-JAN-2004 Summary: Obsessive compulsive disorder (OCD), a syndrome characterized by obsessions and compulsions, has a lifetime prevalence of 1-2%. Accumulating evidence in support of the serotonergic hypothesis on the etiology of OCD led to several serotonin reuptake inhibitors (SSRIs) being approved as a treatment for this disorder. However, even with adequate dose and duration non-response or partial response is the role. In addition, side effects with the SSRIs prompt the search for better tolerated compounds (e.g., drop-out rates in the multi-center trials of fluoxetine, fluvoxamine, sertraline, and paroxetine were 23%, 24%, 27%, and 20% respectively. There has been considerable worldwide interest in St. John's Wort (SJW) (Hypericum perforatum) as a treatment from mild to moderate depression. To date, there have been 23 randomized trials suggests SJW is more effective than placebo for the treatment of outpatients with mild to moderate depression. SJW is very well tolerated with mild side effects observed in only 2.5% of cases in a large drug monitoring study. SJW's mechanism of action is postulated by be via inhibition of the synaptosomal uptake of serotonin, and thus there is a suggestion that SJW may be effective for OCD. A recent 12- week open-label trial with 123 subjects with a fixed dose of 450 mg of hypericin twice daily found a significant change from baseline to endpoint, with a mean Y-BOCS change of 7.4 points (p=.002). Five of the 12 subjects previously failed to respond to a trial with an SSRI. The current study will be a 12-week, double-blind, placebo controlled parallel group study. The purpose of the study is to examine the efficacy and safety of SJW compared to placebo. Fifty subjects will be randomly assigned to SJW (Alterra bran, 450 mg, 1.35 hypericin) or matching placebo. This will be a fixed-dose design at 450 mg bid. An intent-to- treat analysis will be employed Subjects will be evaluated weekly for two weeks than bi-weekly thereafter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STANDARD EXTRACT PERFORATUM) (ST JOHNS WORT)

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(HYPERICUM

Principal Investigator & Institution: Gauthier, Jeff; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002 Summary: Hypericin is a common constituent of several plants belonging to the genus Hypericum. The most well-known of these species is Hypericum perforatum, which is more commonly known as St. John's Wort. Hypericum is registered and used in Germany as an anti-depressant, but it's use in the United States is limited to the nutritional supplement industry and physicians who practice natural medicine. Ongoing laboratory and animal studies are attempting to establish a chemical and/or biological link between the observed symptoms and hypericin activity in treating mild cases of depression. Imperative to these studies is the establishment of a strict protocol for the introduction of standards, on criteria for which will be 1H NMR data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES OF MECHANISM OF ACTION AND BIOAVAILABILITY Principal Investigator & Institution: Birt, Diane; Professor and Chair; Iowa State University Ames, Ia 500112207

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Timing: Fiscal Year 2002; Project Start 22-JUL-2002; Project End 31-MAY-2007 Summary: Aims: 1) Evaluation of the effects of Echinacea and Hypericum in animal models: non-specific and specific immune responses to herpes simplex-1 virus, inflammation and cell proliferation. 2) Explore the mechanisms of action of the above using cell culture systems 3) Evaluate the bioavailability of constituents of Hypericum (hypericin, pseudohypericin) and Echinacea (alkylamides, echinacoside). Researchers on this project include Diane Birt as the PI and 5 co-PI's (Susan Carpenter, Joan Cunnick, Suzanne Hendrich, Marian Kohut and Patricia Murphy). The bulk of the work will be done by two assistant scientists and one associate scientist. This project includes in vitro, in vivo and human studies. Facilities for this project are located in several buildings on the Iowa State University Campus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNTHESIS OF NOVEL ANTICANCER AGENTS Principal Investigator & Institution: Kozlowski, Marisa C.; Assistant Professor; Chemistry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 20-JUL-2004; Project End 30-JUN-2008 Summary: (provided by applicant): The potential for photodynamic cancer therapy with the perylenequinone and hypericin structural types is especially noteworthy given recent developments in this area. The proposed program focuses on synthesis of such complex natural products and their analogs by mimicking biological oxidative systems. Methods to form C-C bonds via oxidative C-H bond activation while establishing axial chirality will be developed using chiral oxidative catalysts. The possibility of selectivity in these transformations with respect to complex substrates is of significant synthetic potential. If such goals are realized, novel and unique synthetic strategies for the assembly of natural products can be envisioned. Routes to symmetric and dissymmetric chiral binaphthyl, perylenequinone, bisnaphthopyrone, bisanthraquinone, hypericin, and bisflavone natural products are presented. 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 “hypericin” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for hypericin in the PubMed Central database:

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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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Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation. by Lenard J, Rabson A, Vanderoef R.; 1993 Jan 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45619

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Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin. by Kerb R, Brockmoller J, Staffeldt B, Ploch M, Roots I.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163478

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Studies of the mechanisms of action of the antiretroviral agents hypericin and pseudohypericin. by Lavie G, Valentine F, Levin B, Mazur Y, Gallo G, Lavie D, Weiner D, Meruelo D.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297751

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Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. by Meruelo D, Lavie G, Lavie D.; 1988 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281723

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

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A comparative study on the photocytotoxicity of hypericin on A431 cells using three different assays. Author(s): Ugwu F, Vandenbogaerde AL, Merlevede WJ, de Witte PA. Source: Anticancer Res. 1998 March-April; 18(2A): 1181-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9615785

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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Hypericin

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A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy. Author(s): Lavie G, Kaplinsky C, Toren A, Aizman I, Meruelo D, Mazur Y, Mandel M. Source: British Journal of Cancer. 1999 February; 79(3-4): 423-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10027308

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Accumulation and photocytotoxicity of hypericin and analogs in two- and threedimensional cultures of transitional cell carcinoma cells. Author(s): Huygens A, Huyghe D, Bormans G, Verbruggen A, Kamuhabwa AR, Roskams T, de Witte PA. Source: Photochemistry and Photobiology. 2003 December; 78(6): 607-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14743871

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Antitumour activity of photosensitized hypericin on A431 cell xenografts. Author(s): Vandenbogaerde AL, Geboes KR, Cuveele JF, Agostinis PM, Merlevede WJ, De Witte PA. Source: Anticancer Res. 1996 July-August; 16(4A): 1619-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8712679

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Antiviral activities of hypericin. Author(s): Hudson JB, Lopez-Bazzocchi I, Towers GH. Source: Antiviral Research. 1991 February; 15(2): 101-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1650164

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Antiviral activity of the photoactive plant pigment hypericin. Author(s): Lopez-Bazzocchi I, Hudson JB, Towers GH. Source: Photochemistry and Photobiology. 1991 July; 54(1): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1658826

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Apoptotic and anti-apoptotic signaling pathways induced by photodynamic therapy with hypericin. Author(s): Agostinis P, Assefa Z, Vantieghem A, Vandenheede JR, Merlevede W, De Witte P. Source: Advances in Enzyme Regulation. 2000; 40: 157-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10828351

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Binding, uptake, and transport of hypericin by Caco-2 cell monolayers. Author(s): Sattler S, Schaefer U, Schneider W, Hoelzl J, Lehr CM. Source: Journal of Pharmaceutical Sciences. 1997 October; 86(10): 1120-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9344168

Studies

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Biodistribution and photodynamic therapy with hypericin in a human NPC murine tumor model. Author(s): Du HY, Bay BH, Olivo M. Source: International Journal of Oncology. 2003 May; 22(5): 1019-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684667

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Bio-distribution and subcellular localization of Hypericin and its role in PDT induced apoptosis in cancer cells. Author(s): Ali SM, Olivo M. Source: International Journal of Oncology. 2002 September; 21(3): 531-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12168096

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Cellular photodestruction induced by hypericin in AY-27 rat bladder carcinoma cells. Author(s): Kamuhabwa AR, Agostinis PM, D'Hallewin MA, Baert L, de Witte PA. Source: Photochemistry and Photobiology. 2001 August; 74(2): 126-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547545

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Comparison of hexamethylhypericin and tetrabromohypericin to hypericin for their in vivo efficacy as PDT tools. Author(s): Delaey E, Zupko I, Chen B, Derycke A, van Laar F, De Vos D, De Witte P. Source: International Journal of Oncology. 2003 August; 23(2): 519-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851704

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Cytotoxicity and antiproliferative effect of hypericin and derivatives after photosensitization. Author(s): Vandenbogaerde AL, Delaey EM, Vantieghem AM, Himpens BE, Merlevede WJ, de Witte PA. Source: Photochemistry and Photobiology. 1998 January; 67(1): 119-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9477769

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Determination of hyperforin, hypericin, and pseudohypericin in human plasma using high-performance liquid chromatography analysis with fluorescence and ultraviolet detection. Author(s): Bauer S, Stormer E, Graubaum HJ, Roots I. Source: J Chromatogr B Biomed Sci Appl. 2001 December 5; 765(1): 29-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11817306

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Differential cytotoxic effects induced after photosensitization by hypericin. Author(s): Vandenbogaerde AL, Cuveele JF, Proot P, Himpens BE, Merlevede WJ, de Witte PA. Source: Journal of Photochemistry and Photobiology. B, Biology. 1997 April; 38(2-3): 13642. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9203374

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Hypericin

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Effect of hypericin on confocal imaging of Ca2+ signaling in cultured human retinal pigment epithelium. Author(s): Gao Q, Hui Y, Wang Y, Wang L. Source: Yan Ke Xue Bao. 2001 September; 17(3): 148-53, 157. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567741

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Effects of anthralin and hypericin on growth factor signalling and cell proliferation in vitro. Author(s): Richter A, Davies DE. Source: Biochemical Pharmacology. 1995 December 22; 50(12): 2039-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8849331

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Effects of photodynamic therapy with hypericin in mice bearing highly invasive solid tumors. Author(s): Blank M, Lavie G, Mandel M, Keisari Y. Source: Oncology Research. 2000; 12(9-10): 409-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11697819

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Enhancement of radiosensitivity in human malignant glioma cells by hypericin in vitro. Author(s): Zhang W, Anker L, Law RE, Hinton DR, Gopalakrishna R, Pu Q, Gundimeda U, Weiss MH, Couldwell WT. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 1996 May; 2(5): 843-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9816239

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Fluorescence detection of flat bladder carcinoma in situ after intravesical instillation of hypericin. Author(s): D'Hallewin MA, De Witte PA, Waelkens E, Merlevede W, Baert L. Source: The Journal of Urology. 2000 August; 164(2): 349-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10893582

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Growth inhibition and apoptosis in human neuroblastoma SK-N-SH cells induced by hypericin, a potent inhibitor of protein kinase C. Author(s): Zhang W, Lawa RE, Hintona DR, Su Y, Couldwell WT. Source: Cancer Letters. 1995 September 4; 96(1): 31-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7553605

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Hypericin activated by an incoherent light source has photodynamic effects on esophageal cancer cells. Author(s): Hopfner M, Maaser K, Theiss A, Lenz M, Sutter AP, Kashtan H, von Lampe B, Riecken EO, Zeitz M, Scherubl H. Source: International Journal of Colorectal Disease. 2003 May; 18(3): 239-47. Epub 2002 November 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673490

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Hypericin and photodynamic therapy decreases human pancreatic cancer in vitro and in vivo. Author(s): Liu CD, Kwan D, Saxton RE, McFadden DW. Source: The Journal of Surgical Research. 2000 September; 93(1): 137-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10945955

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Hypericin as an inactivator of infectious viruses in blood components. Author(s): Lavie G, Mazur Y, Lavie D, Prince AM, Pascual D, Liebes L, Levin B, Meruelo D. Source: Transfusion. 1995 May; 35(5): 392-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7740610

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Hypericin in phototherapy. Author(s): Koren H, Schenk GM, Jindra RH, Alth G, Ebermann R, Kubin A, Koderhold G, Kreitner M. Source: Journal of Photochemistry and Photobiology. B, Biology. 1996 November; 36(2): 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9002247

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Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells. Author(s): Ali SM, Chee SK, Yuen GY, Olivo M. Source: International Journal of Molecular Medicine. 2002 June; 9(6): 601-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12011977

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Hypericin induces both differentiation and apoptosis in human promyelocytic leukemia HL-60 cells. Author(s): Lee KT, Kim JI, Rho YS, Chang SG, Jung JC, Park JH, Park HJ, Miyamoto K. Source: Biological & Pharmaceutical Bulletin. 1999 December; 22(12): 1271-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10746153

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Hypericin

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Hypericin photosensitization of tumor and metastatic cell lines of human prostate. Author(s): Colasanti A, Kisslinger A, Liuzzi R, Quarto M, Riccio P, Roberti G, Tramontano D, Villani F. Source: Journal of Photochemistry and Photobiology. B, Biology. 2000 February; 54(2-3): 103-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10836538

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Hypericin uptake in rabbits and nude mice transplanted with human squamous cell carcinomas: study of a new sensitizer for laser phototherapy. Author(s): Chung PS, Saxton RE, Paiva MB, Rhee CK, Soudant J, Mathey A, Foote C, Castro DJ. Source: The Laryngoscope. 1994 December; 104(12): 1471-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7990636

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Hypericin: a new laser phototargeting agent for human cancer cells. Author(s): VanderWerf QM, Saxton RE, Chang A, Horton D, Paiva MB, Anderson J, Foote C, Soudant J, Mathey A, Castro DJ. Source: The Laryngoscope. 1996 April; 106(4): 479-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8614225

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Hypericin: a potential antiglioma therapy. Author(s): Couldwell WT, Gopalakrishna R, Hinton DR, He S, Weiss MH, Law RE, Apuzzo ML, Law RE. Source: Neurosurgery. 1994 October; 35(4): 705-9; Discussion 709-10. Erratum In: Neurosurgery 1994 November; 35(5): 993. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7808614

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Hypericin: an answer for safer blood? Author(s): Kuhn D. Source: Common Factor. 1995 April; (No 10): 36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11362353

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Hypericin-based fluorescence diagnosis of bladder carcinoma. Author(s): D'Hallewin MA, Kamuhabwa AR, Roskams T, De Witte PA, Baert L. Source: Bju International. 2002 May; 89(7): 760-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966641

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Hypericin-induced apoptosis of human malignant glioma cells is light-dependent, independent of bcl-2 expression, and does not require wild-type p53. Author(s): Weller M, Trepel M, Grimmel C, Schabet M, Bremen D, Krajewski S, Reed JC. Source: Neurological Research. 1997 October; 19(5): 459-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9329022

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Hypericin-induced photosensitization of HeLa cells leads to apoptosis or necrosis. Involvement of cytochrome c and procaspase-3 activation in the mechanism of apoptosis. Author(s): Vantieghem A, Assefa Z, Vandenabeele P, Declercq W, Courtois S, Vandenheede JR, Merlevede W, de Witte P, Agostinis P. Source: Febs Letters. 1998 November 27; 440(1-2): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9862416

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Hypericin-induced phototoxicity of human leukemic cell line HL-60 is potentiated by omeprazole, an inhibitor of H+K+-ATPase and 5'-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger. Author(s): Mirossay L, Mirossay A, Kocisova E, Radvakova I, Miskovsky P, Mojzis J. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 1999; 48(2): 135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10534017

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Hypericin-mediated photodynamic therapy induces lipid peroxidation and necrosis in nasopharyngeal cancer. Author(s): Du HY, Olivo M, Tan BK, Bay BH. Source: International Journal of Oncology. 2003 November; 23(5): 1401-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532982

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Hypocrellins and Hypericin induced apoptosis in human tumor cells: a possible role of hydrogen peroxide. Author(s): Ali SM, Chee SK, Yuen GY, Olivo M. Source: International Journal of Molecular Medicine. 2002 May; 9(5): 461-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11956650

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In vitro and in vivo activation of hypericin with the incoherent light source PDT 1200 SOA (520-750 nm) and with solar simulated radiation (290-2500 nm). Author(s): Schempp CM, Simon-Haarhaus B, Heine A, Schopf E, Simon JC. Source: Photodermatology, Photoimmunology & Photomedicine. 1999 February; 15(1): 13-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9990663

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In vitro and in vivo evaluation of hypericin for photodynamic therapy of equine sarcoids. Author(s): Martens A, de Moor A, Waelkens E, Merlevede W, De Witte P. Source: Veterinary Journal (London, England : 1997). 2000 January; 159(1): 77-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10640414

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Hypericin

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In vitro study of the photocytotoxicity of some hypericin analogs on different cell lines. Author(s): Delaey EM, Obermueller R, Zupko I, De Vos D, Falk H, de Witte PA. Source: Photochemistry and Photobiology. 2001 August; 74(2): 164-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547550

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Induction of differentiation of the human histocytic lymphoma cell line U-937 by hypericin. Author(s): Kim JI, Park JH, Park HJ, Choi SK, Lee KT. Source: Arch Pharm Res. 1998 February; 21(1): 41-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9875513

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Influence of structure of human, rat, and bovine serum albumins on binding properties of photoactive drug hypericin. Author(s): Hritz J, Kascakova S, Ulicny J, Miskovsky P. Source: Biopolymers. 2002; 67(4-5): 251-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12012440

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Inhibition of c-erbB-2 expression an activity in human ovarian carcinoma cells by hypericin. Author(s): Hwang MS, Yum YN, Joo JH, Kim S, Lee KK, Gee SW, Kang HI, Kim OH. Source: Anticancer Res. 2001 July-August; 21(4A): 2649-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11724334

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Inhibition of epidermal growth factor receptor tyrosine kinase activity by hypericin. Author(s): de Witte P, Agostinis P, Van Lint J, Merlevede W, Vandenheede JR. Source: Biochemical Pharmacology. 1993 December 3; 46(11): 1929-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8267642

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Inhibition of human malignant glioma cell motility and invasion in vitro by hypericin, a potent protein kinase C inhibitor. Author(s): Zhang W, Law RE, Hinton DR, Couldwell WT. Source: Cancer Letters. 1997 November 25; 120(1): 31-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9570383

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Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent. Author(s): Nishiuchi T, Utsumi T, Kanno T, Takehara Y, Kobuchi H, Yoshioka T, Horton AA, Yasuda T, Utsumi K. Source: Archives of Biochemistry and Biophysics. 1995 November 10; 323(2): 335-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7487096

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Interaction of hypericin with serum albumins: surface-enhanced Raman spectroscopy, resonance Raman spectroscopy and molecular modeling study. Author(s): Miskovsky P, Hritz J, Sanchez-Cortes S, Fabriciova G, Ulicny J, Chinsky L. Source: Photochemistry and Photobiology. 2001 August; 74(2): 172-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547551

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Light-induced photoactivation of hypericin affects the energy metabolism of human glioma cells by inhibiting hexokinase bound to mitochondria. Author(s): Miccoli L, Beurdeley-Thomas A, De Pinieux G, Sureau F, Oudard S, Dutrillaux B, Poupon MF. Source: Cancer Research. 1998 December 15; 58(24): 5777-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9865736

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Light-induced photoactivation of hypericin inhibits cellular growth in pituitary adenoma cell line AtT20/D16v-F2 (hypericin inhibits cellular growth of AtT20/D16vF2). Author(s): Marekova M, Vavrova J, Vokurkova D, Cerman J. Source: Acta Medica (Hradec Kralove). 2001; 44(1): 7-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11367893

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Macro-microscopic fluorescence of human bladder cancer using hypericin fluorescence cystoscopy and laser confocal microscopy. Author(s): Olivo M, Lau W, Manivasager V, Tan PH, Soo KC, Cheng C. Source: International Journal of Oncology. 2003 October; 23(4): 983-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963977

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Malignant glioma sensitivity to radiotherapy, high-dose tamoxifen, and hypericin: corroborating clinical response in vitro: case report. Author(s): Zhang W, Hinton DR, Surnock AA, Couldwell WT. Source: Neurosurgery. 1996 March; 38(3): 587-90; Discussion 590-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8837815

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Molecular aspects of photodynamic therapy: low energy pre-sensitization of hypericin-loaded human endometrial carcinoma cells enhances photo-tolerance, alters gene expression and affects the cell cycle. Author(s): Varriale L, Coppola E, Quarto M, Veneziani BM, Palumbo G. Source: Febs Letters. 2002 February 13; 512(1-3): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11852097

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Hypericin

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Novel photodynamic diagnosis of bladder cancer: ex vivo fluorescence cytology using hypericin. Author(s): Olivo M, Lau W, Manivasager V, Bhuvaneswari R, Wei Z, Soo KC, Cheng C, Tan PH. Source: International Journal of Oncology. 2003 December; 23(6): 1501-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612919

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Over-expression of Bcl-2 does not protect cells from hypericin photo-induced mitochondrial membrane depolarization, but delays subsequent events in the apoptotic pathway. Author(s): Chaloupka R, Petit PX, Israel N, Sureau F. Source: Febs Letters. 1999 December 3; 462(3): 295-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622714

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Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Author(s): Gulick RM, McAuliffe V, Holden-Wiltse J, Crumpacker C, Liebes L, Stein DS, Meehan P, Hussey S, Forcht J, Valentine FT. Source: Annals of Internal Medicine. 1999 March 16; 130(6): 510-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075619

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Photoactivated hypericin is an anti-proliferative agent that induces a high rate of apoptotic death of normal, transformed, and malignant T lymphocytes: implications for the treatment of cutaneous lymphoproliferative and inflammatory disorders. Author(s): Fox FE, Niu Z, Tobia A, Rook AH. Source: The Journal of Investigative Dermatology. 1998 August; 111(2): 327-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9699738

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Photo-activation of hypericin with low doses of light promotes apparent photoresistance in human histiocytic lymphoma U937 cells. Author(s): Paba V, Quarto M, Varriale L, Crescenzi E, Palumbo G. Source: Journal of Photochemistry and Photobiology. B, Biology. 2001 July; 60(2-3): 8796. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11470563

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Photobleaching of hypericin bound to human serum albumin, cultured adenocarcinoma cells and nude mice skin. Author(s): Uzdensky AB, Iani V, Ma LW, Moan J. Source: Photochemistry and Photobiology. 2002 September; 76(3): 320-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12403454

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Photocytotoxicity of hypericin in normoxic and hypoxic conditions. Author(s): Delaey E, Vandenbogaerde A, Merlevede W, de Witte P. Source: Journal of Photochemistry and Photobiology. B, Biology. 2000 June; 56(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11073312

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Photodynamic activity of hypericin in human urinary bladder carcinoma cells. Author(s): Kamuhabwa AR, Agostinis P, D'Hallewin MA, Kasran A, de Witte PA. Source: Anticancer Res. 2000 July-August; 20(4): 2579-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10953329

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Photodynamic effects of hypericin on lipid peroxidation and antioxidant status in melanoma cells. Author(s): Hadjur C, Richard MJ, Parat MO, Jardon P, Favier A. Source: Photochemistry and Photobiology. 1996 August; 64(2): 375-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8760577

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Photodynamic inactivation of infectivity of human immunodeficiency virus and other enveloped viruses using hypericin and rose bengal: inhibition of fusion and syncytia formation. Author(s): Lenard J, Rabson A, Vanderoef R. Source: Proceedings of the National Academy of Sciences of the United States of America. 1993 January 1; 90(1): 158-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7678335

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Photodynamic therapy of transitional cell carcinoma multicellular tumor spheroids with hypericin. Author(s): Kamuhabwa AA, Huygens A, De Witte PA. Source: International Journal of Oncology. 2003 November; 23(5): 1445-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532989

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Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin. Author(s): Alecu M, Ursaciuc C, Halalau F, Coman G, Merlevede W, Waelkens E, de Witte P. Source: Anticancer Res. 1998 November-December; 18(6B): 4651-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9891535

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Photodynamically induced cytotoxicity of hypericin dye on human fibroblast cell line MRC5. Author(s): Hadjur C, Richard MJ, Parat MO, Favier A, Jardon P. Source: Journal of Photochemistry and Photobiology. B, Biology. 1995 February; 27(2): 139-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7714674

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Photophysics of hypericin and hypocrellin A in complex with subcellular components: interactions with human serum albumin. Author(s): Das K, Smirnov AV, Wen J, Miskovsky P, Petrich JW. Source: Photochemistry and Photobiology. 1999 June; 69(6): 633-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10378001

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Photosensitization of aqueous model systems by hypericin. Author(s): Senthil V, Longworth JW, Ghiron CA, Grossweiner LI. Source: Biochimica Et Biophysica Acta. 1992 January 23; 1115(3): 192-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1739734

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Strategies for evaluation of enveloped virus inactivation in red cell concentrates using hypericin. Author(s): Prince AM, Pascual D, Meruelo D, Liebes L, Mazur Y, Dubovi E, Mandel M, Lavie G. Source: Photochemistry and Photobiology. 2000 February; 71(2): 188-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10687393

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Subcellular distribution of hypericin in human cancer cells. Author(s): Miskovsky P, Sureau F, Chinsky L, Turpin PY. Source: Photochemistry and Photobiology. 1995 September; 62(3): 546-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8570710

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The activation of the c-Jun N-terminal kinase and p38 mitogen-activated protein kinase signaling pathways protects HeLa cells from apoptosis following photodynamic therapy with hypericin. Author(s): Assefa Z, Vantieghem A, Declercq W, Vandenabeele P, Vandenheede JR, Merlevede W, de Witte P, Agostinis P. Source: The Journal of Biological Chemistry. 1999 March 26; 274(13): 8788-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10085120

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The chemical and biological properties of hypericin--a compound with a broad spectrum of biological activities. Author(s): Lavie G, Mazur Y, Lavie D, Meruelo D. Source: Medicinal Research Reviews. 1995 March; 15(2): 111-9. Review. Erratum In: Med Res Rev 1995 May; 15(3): 259. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7739292

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Transferrin-mediated targeting of hypericin embedded in sterically stabilized PEGliposomes. Author(s): Derycke AS, De Witte PA. Source: International Journal of Oncology. 2002 January; 20(1): 181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743662

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Tumor cell toxicity of hypericin and related analogs. Author(s): Wills NJ, Park J, Wen J, Kesavan S, Kraus GA, Petrich JW, Carpenter S. Source: Photochemistry and Photobiology. 2001 August; 74(2): 216-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547558

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Tumor-specific and photodependent cytotoxicity of hypericin in the human LNCaP prostate tumor model. Author(s): Xie X, Hudson JB, Guns ES. Source: Photochemistry and Photobiology. 2001 August; 74(2): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547559

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Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. Author(s): Hendrickx N, Volanti C, Moens U, Seternes OM, de Witte P, Vandenheede JR, Piette J, Agostinis P. Source: The Journal of Biological Chemistry. 2003 December 26; 278(52): 52231-9. Epub 2003 October 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557269

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

Finding Nutrition Studies on Hypericin 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 “hypericin” (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 information is typical of that found when using the “Full IBIDS Database” to search for “hypericin” (or a synonym): •

Confluence dependent resistance to photo-activated hypericin in HeLa cells. Author(s): Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, K.U. Leuven, B-3000 Leuven, Belgium. Source: Delaey, E M Vandenbogaerde, A L Agostinis, P De Witte, P A Int-J-Oncol. 1999 April; 14(4): 759-63 1019-6439

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Determining hyperforin and hypericin content in eight brands of St. John's wort. Author(s): School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089-9121, USA. Source: de los Reyes, Gerlie C Koda, Robert T Am-J-Health-Syst-Pharm. 2002 March 15; 59(6): 545-7 1079-2082

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Effect of acetazolamide on hypericin photocytotoxicity. Source: Solar, P. Cavarga, I. Hofmanova, J. Cekanova Figurova, M. Miskovsky, P. Brezani, P. Hrckova, G. Kozubik, A. Fedorocko, P. Planta-med. Stuttgart : Georg Thieme Verlag,. July 2002. volume 68 (7) page 658-660. 0032-0943

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In vitro binding studies with two hypericum perforatum extracts--hyperforin, hypericin and biapigenin--on 5-HT6, 5-HT7, GABA(A)/benzodiazepine, sigma, NPYY1/Y2 receptors and dopamine transporters. Author(s): Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy. Source: Gobbi, M Moia, M Pirona, L Morizzoni, P Mennini, T Pharmacopsychiatry. 2001 July; 34 Suppl 1: S45-8 0176-3679

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In vivo photodynamic activity of hypericin in transitional cell carcinoma bladder tumors. Author(s): Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, B-3000 Leuven, Belgium. Source: Zupko, I Kamuhabwa, A R D'Hallewin, M A Baert, L De Witte, P A Int-J-Oncol. 2001 May; 18(5): 1099-105 1019-6439

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Induction of apoptosis by Hypericin through activation of caspase-3 in human carcinoma cells. Author(s): Department of Medical Sciences, National Cancer Centre, 11 Hospital Drive, Singapore 169610. [email protected] Source: Ali, S M Olivo, M Yuen, G Y Chee, S K Int-J-Mol-Med. 2001 November; 8(5): 52130 1107-3756

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Intracellular localisation of hypericin in human glioblastoma and carcinoma cell lines. Author(s): Department of Biophysics and Biocybernetics, Rostov State University, 194/1 Stachky Ave, Rostov-on-Don 344090, Russia. [email protected] Source: Uzdensky, A B Ma, L W Iani, V Hjortland, G O Steen, H B Moan, J Lasers-MedSci. 2001; 16(4): 276-83 0268-8921

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Intratumoral hypericin and KTP laser therapy for transplanted squamous cell carcinoma. Author(s): Department of Otolaryngology--Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Korea. Source: Chung, P S Rhee, C K Kim, K H Paek, W Chung, J Paiva, M B Eshraghi, A A Castro, D J Saxton, R E Laryngoscope. 2000 August; 110(8): 1312-6 0023-852X

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Investigation of the absorption of hypericin into the skin of hairless mice. Author(s): Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Belgium. Source: Kamuhabwa, A R Geboes, K R de Witte, P A J-Pharm-Pharmacol. 2000 May; 52(5): 487-94 0022-3573

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Jasmonic acid-induced hypericin production in cell suspension cultures of Hypericum perforatum L. (St. John's wort). Author(s): Department of Horticulture and Landscape Architecture, Colorado State University, Fort Collins 80523-1173, USA. Source: Walker, Travis S Pal Bais, Harsh Vivanco, Jorge M Phytochemistry. 2002 June; 60(3): 289-93 0031-9422

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Long-term effects of St. John's wort and hypericin on monoamine levels in rat hypothalamus and hippocampus. Author(s): Institute of Pharmacology and Toxicology, Domagkstrasse 12, 48149 Muenster, Germany. [email protected] Source: Butterweck, Veronika Bockers, Tobias Korte, Brigitte Wittkowski, Werner Winterhoff, Hilke Brain-Res. 2002 March 15; 930(1-2): 21-9 0006-8993

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Metabolic reaction and pathway for hypericin degradation by action of fungi. Author(s): Faculty of Natural Sciences, Kragujevac (Yugoslavia). Department of Chemistry Source: Solujic, S. Sukdolak, S. Krstic, Lj. Mikrobiologija (Yugoslavia). (1997). volume 34(2) page 89-98. bacteria fungi antimicrobials biodegradation 0581-1538

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Modulation of the phototoxic effect of hypericin in human leukemia CEM cell line by N-ethylmaleimide, amiloride and omeprazole. Author(s): Department of Pharmacology, Medical Faculty, P.J. Safarik University, Tr. SNP 1, 040 66 Kosice, Slovak [email protected] Source: Mirossay, A Mirossay, L Sarissky, M Papp, P Mojzis, J Physiol-Res. 2002; 51(6): 641-4 0862-8408

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Pharmacokinetics of hypericin and pseudohypericin after oral intake of the hypericum perforatum extract LI 160 in healthy volunteers. Author(s): Institut fur Klinische Pharmakologie, Universitatsklinikum Charite Berlin, Germany. Source: Staffeldt, B Kerb, R Brockmoller, J Ploch, M Roots, I J-Geriatr-Psychiatry-Neurol. 1994 October; 7 Suppl 1S47-53 0891-9887

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Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment. Author(s): Institute of Pharmacology and Toxicology, Munster, Germany. [email protected] Source: Butterweck, V Korte, B Winterhoff, H Pharmacopsychiatry. 2001 July; 34 Suppl 1: S2-7 0176-3679

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Phosphorylation of Bcl-2 in G2/M phase-arrested cells following photodynamic therapy with hypericin involves a CDK1-mediated signal and delays the onset of apoptosis. Author(s): Division of Biochemistry, Faculty of Medicine, Catholic University of Leuven, B-3000 Leuven, Belgium. Source: Vantieghem, A Xu, Y Assefa, Z Piette, J Vandenheede, J R Merlevede, W De Witte, P A Agostinis, P J-Biol-Chem. 2002 October 4; 277(40): 37718-31 0021-9258

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Photochemical effects and hypericin photosensitized processes in collagen. Author(s): National Technical University of Athens, Department of Electrical Engineering and Computing, Greece. Source: Yova, D Hovhannisyan, V Theodossiou, T J-Biomed-Opt. 2001 January; 6(1): 52-7 1083-3668

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Photodynamic therapy with hypericin in a mouse P388 tumor model: vascular effects determine the efficacy. Author(s): Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Van Evenstraat 4, B3000 Leuven, Belgium. Source: Chen, B Zupko, I de Witte, P A Int-J-Oncol. 2001 April; 18(4): 737-42 1019-6439

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Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates. Author(s): Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. Source: Fox, E Murphy, R F McCully, C L Adamson, P C Cancer-Chemother-Pharmacol. 2001; 47(1): 41-4 0344-5704

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Potentiation of hypericin and hypocrellin-induced phototoxicity by omeprazole. Author(s): Department of Pharmacology, Medical Faculty, P. J. Safarik University, Kosice, Slovak Republic. Source: Mirossay, A Mirossay, L Tothova, J Miskovsky, P Onderkova, H Mojzis, J Phytomedicine. 1999 November; 6(5): 311-7 0944-7113

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Sequence specific interaction of the antiretrovirally active drug hypericin with 5'ATGGCAGGATAT3' oligonucleotide: a resonance Raman spectroscopy study. Author(s): Department of Biophysics, P.J. Safarik University Jesenna 5, Kosice, Slovak Republic. Source: Kocisova, E Chinsky, L Miskovsky, P J-Biomol-Struct-Dyn. 1998 June; 15(6): 1147-54 0739-1102

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Simultaneous determination of hypericin and hyperforin in human plasma and serum using liquid-liquid extraction, high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry. Author(s): Institute of Analytical Chemistry and Radiochemistry, Leopold-Franzens University, Innrain 52a, 6020, Innsbruck, Austria. Source: Pirker, R Huck, C W Bonn, G K J-Chromatogr-B-Analyt-Technol-Biomed-LifeSci. 2002 September 25; 777(1-2): 147-53 1570-0232

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Solubility of hypericin in methanol and methanol-pyridine. Author(s): Department of Applied BioSciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH), Zurich, Switzerland. Source: Wirz, A Meier, B Sticher, O Pharmazie. 2002 August; 57(8): 543-5 0031-7144

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Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test. Author(s): Institute of Pharmaceutical Biology and Phytochemistry, Westfalische Wilhelms-Universitat, Munster, Germany. Source: Butterweck, V Petereit, F Winterhoff, H Nahrstedt, A Planta-Med. 1998 May; 64(4): 291-4 0032-0943

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Synergistic effect of photodynamic therapy with hypericin in combination with hyperthermia on loss of clonogenicity of RIF-1 cells. Author(s): Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium. Source: Chen, B Xu, Y Agostinis, P De Witte, P A Int-J-Oncol. 2001 June; 18(6): 1279-85 1019-6439

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The antidepressant hypericin inhibits progression of experimental proliferative vitreoretinopathy. Author(s): Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. Source: Tahara, Y R Sakamoto, T R Oshima, Y R Ishibashi, T R Inomata, H R Murata, T R Hinton, D R Ryan, S J Curr-Eye-Res. 1999 October; 19(4): 323-9 0271-3683

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The uptake, location and fluorescence of hypericin in bovine intact lens. Author(s): Istituto di Biofisica CNR, Pisa, Italy. Source: Sgarbossa, A Angelini, N Gioffre, D Youssef, T Lenci, F Roberts, J E Curr-EyeRes. 2000 August; 21(2): 597-601 0271-3683

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Variations in hypericin concentrations in Hypericum perforatum L. and commercial products. Source: Constantine, G.H. Karchesy, J. Pharm-biol. Lisse, the Netherlands : Swets & Zeitlinger, c1998-. December 1998. volume 36 (5) page 365-367. 1388-0209

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Wavelength-dependent properties of photodynamic therapy using hypericin in vitro and in an animal model. Author(s): Department of Human Microbiology, Sackler School of Medicine, Tel Aviv University, Israel. Source: Blank, M Kostenich, G Lavie, G Kimel, S Keisari, Y Orenstein, A PhotochemPhotobiol. 2002 September; 76(3): 335-40 0031-8655

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

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

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

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

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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/

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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/

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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

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

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

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

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

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

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

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

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

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to hypericin 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 “hypericin” (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 hypericin: •

Absorbance data of hypericin and pseudohypericin used as reference compounds for medicinal plant analysis. Author(s): Wirz A, Meier B, Sticher O. Source: Pharmazie. 2001 January; 56(1): 52-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11210670

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An in vitro and hydroponic growing system for hypericin, pseudohypericin, and hyperforin production of St. John's wort (Hypericum perforatum CV new stem). Author(s): Murch SJ, Rupasinghe HP, Saxena PK. Source: Planta Medica. 2002 December; 68(12): 1108-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494339

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Analysis of the hypericin and pseudohypericin content of commercially available St John's Wort preparations. Author(s): Draves AH, Walker SE.

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Source: Can J Clin Pharmacol. 2003 Fall; 10(3): 114-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506510 •

Antagonist effect of pseudohypericin at CRF1 receptors. Author(s): Simmen U, Bobirnac I, Ullmer C, Lubbert H, Berger Buter K, Schaffner W, Schoeffter P. Source: European Journal of Pharmacology. 2003 January 5; 458(3): 251-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504780

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Biochemical activities of extracts from Hypericum perforatum L. 5th communication: dopamine-beta-hydroxylase-product quantification by HPLC and inhibition by hypericins and flavonoids. Author(s): Denke A, Schempp H, Weiser D, Elstner EF. Source: Arzneimittel-Forschung. 2000 May; 50(5): 415-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10858868

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Catalytic inhibition of human DNA topoisomerase IIalpha by hypericin, a naphthodianthrone from St. John's wort (Hypericum perforatum). Author(s): Peebles KA, Baker RK, Kurz EU, Schneider BJ, Kroll DJ. Source: Biochemical Pharmacology. 2001 October 15; 62(8): 1059-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11597574

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Comparison of German St. John's wort products according to hyperforin and total hypericin content. Author(s): Wurglics M, Westerhoff K, Kaunzinger A, Wilke A, Baumeister A, Dressman J, Schubert-Zsilavecz M. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2001 July-August; 41(4): 560-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486982

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Confluence dependent resistance to photo-activated hypericin in HeLa cells. Author(s): Delaey EM, Vandenbogaerde AL, Agostinis P, De Witte PA. Source: International Journal of Oncology. 1999 April; 14(4): 759-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10087326

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Cytotoxic activity of Hypericum perforatum L. on K562 erythroleukemic cells: differential effects between methanolic extract and hypericin. Author(s): Roscetti G, Franzese O, Comandini A, Bonmassar E. Source: Phytotherapy Research : Ptr. 2004 January; 18(1): 66-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750204

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Detection of hypericins in the “red glands” of Hypericum elodes by ESI-MS/MS. Author(s): Piovan A, Filippini R, Caniato R, Borsarini A, Bini Maleci L, Cappelletti EM.

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Source: Phytochemistry. 2004 February; 65(4): 411-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759533 •

Determination of hypericin and pseudohypericin in pharmaceutical preparations by liquid chromatography with fluorescence detection. Author(s): Draves AH, Walker SE. Source: J Chromatogr B Biomed Sci Appl. 2000 November 10; 749(1): 57-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11129079

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Determination of hypericin content in Hypericum triquetrifolium Turra (Hypericaceae) growing wild in Jordan. Author(s): Alali F, Tawaha K, Al-Eleimat T. Source: Natural Product Research. 2004 April; 18(2): 147-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984088

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Determination of hypericin in plasma by high-performance liquid chromatography. Author(s): Chi JD, Franklin M. Source: J Chromatogr B Biomed Sci Appl. 1999 March 5; 724(1): 195-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10202973

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Determining hyperforin and hypericin content in eight brands of St. John's wort. Author(s): de los Reyes GC, Koda RT. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 March 15; 59(6): 545-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11908248

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Development of a simple, rapid and reproducible HPLC assay for the simultaneous determination of hypericins and stabilized hyperforin in commercial St. John's wort preparations. Author(s): de los Reyes GC, Koda RT. Source: Journal of Pharmaceutical and Biomedical Analysis. 2001 December; 26(5-6): 959-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600308

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Effect of acetazolamide on hypericin photocytotoxicity. Author(s): Solar P, Cavarga I, Hofmanova J, Cekanova-Figurova M, Miskovsky P, Brezani P, Hrckova G, Kozubik A, Fedorocko P. Source: Planta Medica. 2002 July; 68(7): 658-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12143007

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Effect of light on hypericins contents in fresh flowering top parts and in an extract of St. John's Wort (Hypericum perforatum). Author(s): Poutaraud A, Di Gregorio F, Tin VC, Girardin P.

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Source: Planta Medica. 2001 April; 67(3): 254-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345698 •

High-performance liquid chromatographic determination of the biologically active principle hypericin in phytotherapeutic vegetable extracts and alcoholic beverages. Author(s): Micali G, Lanuzza F, Curro P. Source: J Chromatogr A. 1996 April 19; 731(1-2): 336-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8646329

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Hyperforin a constituent of St John's wort (Hypericum perforatum L.) extract induces apoptosis by triggering activation of caspases and with hypericin synergistically exerts cytotoxicity towards human malignant cell lines. Author(s): Hostanska K, Reichling J, Bommer S, Weber M, Saller R. Source: European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. 2003 July; 56(1): 12132. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837490

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Hypericin and hypocrellin induced apoptosis in human mucosal carcinoma cells. Author(s): Ali SM, Chee SK, Yuen GY, Olivo M. Source: Journal of Photochemistry and Photobiology. B, Biology. 2001 December 1; 65(1): 59-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748006

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Hypericin and pseudohypericin in some Hypericum species. Author(s): Kitanov GM. Source: Biochemical Systematics and Ecology. 2001 February 1; 29(2): 171-178. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106845

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Hypericin and pseudohypericin specifically inhibit protein kinase C: possible relation to their antiretroviral activity. Author(s): Takahashi I, Nakanishi S, Kobayashi E, Nakano H, Suzuki K, Tamaoki T. Source: Biochemical and Biophysical Research Communications. 1989 December 29; 165(3): 1207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2558652

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Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans. Author(s): Brockmoller J, Reum T, Bauer S, Kerb R, Hubner WD, Roots I. Source: Pharmacopsychiatry. 1997 September; 30 Suppl 2: 94-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9342768

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Hypericin as a non-antioxidant inhibitor of NF-kappa B. Author(s): Bork PM, Bacher S, Schmitz ML, Kaspers U, Heinrich M. Source: Planta Medica. 1999 May; 65(4): 297-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10364831

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Hypericin as a potential phototherapeutic agent in superficial transitional cell carcinoma of the bladder. Author(s): Kamuhabwa A, Agostinis P, Ahmed B, Landuyt W, Van Cleynenbreugel B, Van Poppel H, De Witte P. Source: Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology. 2004 August; 3(8): 772-80. Epub 2004 April 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15295634

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Hypericin in cancer treatment: more light on the way. Author(s): Agostinis P, Vantieghem A, Merlevede W, de Witte PA. Source: The International Journal of Biochemistry & Cell Biology. 2002 March; 34(3): 22141. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11849990

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Hypericin levels in human serum and interstitial skin blister fluid after oral singledose and steady-state administration of Hypericum perforatum extract (St. John's wort). Author(s): Schempp CM, Winghofer B, Langheinrich M, Schopf E, Simon JC. Source: Skin Pharmacology and Applied Skin Physiology. 1999 September-October; 12(5): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10461100

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Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8. Author(s): Schempp CM, Simon-Haarhaus B, Termeer CC, Simon JC. Source: Febs Letters. 2001 March 23; 493(1): 26-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277999

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Hypericin--a new antiviral and antitumor photosensitizer: mechanism of action and interaction with biological macromolecules. Author(s): Miskovsky P. Source: Current Drug Targets. 2002 February; 3(1): 55-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11899265

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Hypocrellin and hypericin-induced phototoxicity of HL-60 cells: apoptosis or necrosis? Author(s): Mirossay A, Mojzis J, Tothova J, Hajikova M, Lackova A, Mirossay L.

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Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2000 December; 7(6): 471-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11194175 •

In vitro binding studies with two hypericum perforatum extracts--hyperforin, hypericin and biapigenin--on 5-HT6, 5-HT7, GABA(A)/benzodiazepine, sigma, NPYY1/Y2 receptors and dopamine transporters. Author(s): Gobbi M, Moia M, Pirona L, Morizzoni P, Mennini T. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S45-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518075

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In vitro transport and uptake of protohypericin and hypericin in the Caco-2 model. Author(s): Kamuhabwa AR, Augustijns P, de Witte PA. Source: International Journal of Pharmaceutics. 1999 October 15; 188(1): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10528085

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Induction of apoptosis by Hypericin through activation of caspase-3 in human carcinoma cells. Author(s): Ali SM, Olivo M, Yuen GY, Chee SK. Source: International Journal of Molecular Medicine. 2001 November; 8(5): 521-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11605021

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Induction of hypericins and hyperforins in Hypericum perforatum in response to damage by herbivores. Author(s): Sirvent TM, Krasnoff SB, Gibson DM. Source: Journal of Chemical Ecology. 2003 December; 29(12): 2667-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969354

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Inhibition of MAO and COMT by hypericum extracts and hypericin. Author(s): Thiede HM, Walper A. Source: Journal of Geriatric Psychiatry and Neurology. 1994 October; 7 Suppl 1: S54-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7857510

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Inhibition of monoamine oxidase by hypericin. Author(s): Suzuki O, Katsumata Y, Oya M, Bladt S, Wagner H. Source: Planta Medica. 1984 June; 50(3): 272-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6484033

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Intracellular localisation of hypericin in human glioblastoma and carcinoma cell lines. Author(s): Uzdensky AB, Ma LW, Iani V, Hjortland GO, Steen HB, Moan J.

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Source: Lasers in Medical Science. 2001; 16(4): 276-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702633 •

Jasmonic acid-induced hypericin production in cell suspension cultures of Hypericum perforatum L. (St. John's wort). Author(s): Walker TS, Pal Bais H, Vivanco JM. Source: Phytochemistry. 2002 June; 60(3): 289-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031448

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Long-term effects of St. John's wort and hypericin on monoamine levels in rat hypothalamus and hippocampus. Author(s): Butterweck V, Bockers T, Korte B, Wittkowski W, Winterhoff H. Source: Brain Research. 2002 March 15; 930(1-2): 21-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879791

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Modulation of the phototoxic effect of hypericin in human leukemia CEM cell line by N-ethylmaleimide, amiloride and omeprazole. Author(s): Mirossay A, Mirossay L, Sarissky M, Papp P, Mojzis J. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2002; 51(6): 641-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511190

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Molecular and biochemical characterization of an enzyme responsible for the formation of hypericin in St. John's wort (Hypericum perforatum L.). Author(s): Bais HP, Vepachedu R, Lawrence CB, Stermitz FR, Vivanco JM. Source: The Journal of Biological Chemistry. 2003 August 22; 278(34): 32413-22. Epub 2003 June 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799379

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Novel therapeutic and diagnostic applications of hypocrellins and hypericins. Author(s): Diwu Z. Source: Photochemistry and Photobiology. 1995 June; 61(6): 529-39. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7568399

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Pharmacokinetics of hypericin and pseudohypericin after oral intake of the hypericum perforatum extract LI 160 in healthy volunteers. Author(s): Staffeldt B, Kerb R, Brockmoller J, Ploch M, Roots I. Source: Journal of Geriatric Psychiatry and Neurology. 1994 October; 7 Suppl 1: S47-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7857509

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Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's wort plant, in patients with chronic hepatitis C virus infection.

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Author(s): Jacobson JM, Feinman L, Liebes L, Ostrow N, Koslowski V, Tobia A, Cabana BE, Lee D, Spritzler J, Prince AM. Source: Antimicrobial Agents and Chemotherapy. 2001 February; 45(2): 517-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11158749 •

Pharmacological and endocrine effects of Hypericum perforatum and hypericin after repeated treatment. Author(s): Butterweck V, Korte B, Winterhoff H. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S2-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11518068

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Phosphorylation of Bcl-2 in G2/M phase-arrested cells following photodynamic therapy with hypericin involves a CDK1-mediated signal and delays the onset of apoptosis. Author(s): Vantieghem A, Xu Y, Assefa Z, Piette J, Vandenheede JR, Merlevede W, De Witte PA, Agostinis P. Source: The Journal of Biological Chemistry. 2002 October 4; 277(40): 37718-31. Epub 2002 July 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12101183

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Photocytotoxic effect of pseudohypericin versus hypericin. Author(s): Vandenbogaerde AL, Kamuhabwa A, Delaey E, Himpens BE, Merlevede WJ, de Witte PA. Source: Journal of Photochemistry and Photobiology. B, Biology. 1998 September; 45(23): 87-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9868799

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Photocytotoxicity of protohypericin after photoconversion to hypericin. Author(s): Delaey EM, Kamuhabwa AR, Vandenbogaerde AL, de Witte PA. Source: Planta Medica. 1999 December; 65(8): 719-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10630113

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Photodynamic therapy of murine fibrosarcoma with topical and systemic administration of hypericin. Author(s): Cavarga I, Brezani P, Cekanova-Figurova M, Solar P, Fedorocko P, Miskovsky P. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2001 September; 8(5): 325-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11695874

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Photodynamic therapy with hypericin in a mouse P388 tumor model: vascular effects determine the efficacy. Author(s): Chen B, Zupko I, de Witte PA.

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Source: International Journal of Oncology. 2001 April; 18(4): 737-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11251168 •

Photodynamic therapy with hypericin induces vascular damage and apoptosis in the RIF-1 mouse tumor model. Author(s): Chen B, Roskams T, Xu Y, Agostinis P, de Witte PA. Source: International Journal of Cancer. Journal International Du Cancer. 2002 March 10; 98(2): 284-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857421

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Photooxidation of lens alpha-crystallin by hypericin (active ingredient in St. John's Wort). Author(s): Schey KL, Patat S, Chignell CF, Datillo M, Wang RH, Roberts JE. Source: Photochemistry and Photobiology. 2000 August; 72(2): 200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10946573

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Phototoxic and apoptosis-inducing capacity of pseudohypericin. Author(s): Schempp CM, Simon-Haarhaus B, Simon JC. Source: Planta Medica. 2002 February; 68(2): 171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11859473

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Plasma levels of hypericin in presence of procyanidin B2 and hyperoside: a pharmacokinetic study in rats. Author(s): Butterweck V, Lieflander-Wulf U, Winterhoff H, Nahrstedt A. Source: Planta Medica. 2003 March; 69(3): 189-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12677519

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Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates. Author(s): Fox E, Murphy RF, McCully CL, Adamson PC. Source: Cancer Chemotherapy and Pharmacology. 2001; 47(1): 41-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11221960

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Potentiation of hypericin and hypocrellin-induced phototoxicity by omeprazole. Author(s): Mirossay A, Mirossay L, Tothova J, Miskovsky P, Onderkova H, Mojzis J. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 1999 November; 6(5): 311-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11962536

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Potentiation of photodynamic therapy with hypericin by mitomycin C in the radiation-induced fibrosarcoma-1 mouse tumor model. Author(s): Chen B, Ahmed B, Landuyt W, Ni Y, Gaspar R, Roskams T, de Witte PA.

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Source: Photochemistry and Photobiology. 2003 September; 78(3): 278-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556315 •

Production of hypericin, pseudohypericin and flavonoids in cell cultures of various Hypericum species and their chemotypes. Author(s): Kartnig T, Gobel I, Heydel B. Source: Planta Medica. 1996 February; 62(1): 51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8720388

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Quantitative characterization of direct P-glycoprotein inhibition by St John's wort constituents hypericin and hyperforin. Author(s): Wang EJ, Barecki-Roach M, Johnson WW. Source: The Journal of Pharmacy and Pharmacology. 2004 January; 56(1): 123-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980009

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Screen of receptor and uptake-site activity of hypericin component of St. John's wort reveals sigma receptor binding. Author(s): Raffa RB. Source: Life Sciences. 1998; 62(16): Pl265-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9585174

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Seasonal variation in hypericin content of Hypericum perforatum L. (St. John's Wort). Author(s): Southwell IA, Bourke CA. Source: Phytochemistry. 2001 March; 56(5): 437-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11261576

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Separation of hypericins and hyperforins in extracts of Hypericum perforatum L. using non-aqueous capillary electrophoresis with reversed electro-osmotic flow. Author(s): Jensen AG, Hansen SH. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 January 1; 27(1-2): 16776. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682223

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Short term treatment with St. John's wort, hypericin or hyperforin fails to induce CYP450 isoforms in the Swiss Webster mouse. Author(s): Bray BJ, Brennan NJ, Perry NB, Menkes DB, Rosengren RJ. Source: Life Sciences. 2002 February 1; 70(11): 1325-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11883710

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Simultaneous determination of hypericin and hyperforin in human plasma and serum using liquid-liquid extraction, high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry. Author(s): Pirker R, Huck CW, Bonn GK.

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Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 September 25; 777(1-2): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12270208 •

Simultaneous determination of the predominant hyperforins and hypericins in St. John's Wort (Hypericum perforatum L.) by liquid chromatography. Author(s): Gray DE, Rottinghaus GE, Garrett HE, Pallardy SG, Gray DE, Rottinghaus GE, Garrett HE, Pallardy SG. Source: J Aoac Int. 2000 July-August; 83(4): 944-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10995119

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Single-dose and steady-state pharmacokinetics of hypericin and pseudohypericin. Author(s): Kerb R, Brockmoller J, Staffeldt B, Ploch M, Roots I. Source: Antimicrobial Agents and Chemotherapy. 1996 September; 40(9): 2087-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8878586

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Solubilized hypericin and pseudohypericin from Hypericum perforatum exert antidepressant activity in the forced swimming test. Author(s): Butterweck V, Petereit F, Winterhoff H, Nahrstedt A. Source: Planta Medica. 1998 May; 64(4): 291-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9619107

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St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats. Author(s): Butterweck V, Winterhoff H, Herkenham M. Source: Molecular Psychiatry. 2001 September; 6(5): 547-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11526469

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Step by step removal of hyperforin and hypericin: activity profile of different Hypericum preparations in behavioral models. Author(s): Butterweck V, Christoffel V, Nahrstedt A, Petereit F, Spengler B, Winterhoff H. Source: Life Sciences. 2003 June 20; 73(5): 627-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12770617

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Stimulation of the production of hypericins by mannan in Hypericum perforatum shoot cultures. Author(s): Kirakosyan A, Hayashi H, Inoue K, Charchoglyan A, Vardapetyan H. Source: Phytochemistry. 2000 February; 53(3): 345-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703055

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Synergistic effect of photodynamic therapy with hypericin in combination with hyperthermia on loss of clonogenicity of RIF-1 cells. Author(s): Chen B, Xu Y, Agostinis P, De Witte PA. Source: International Journal of Oncology. 2001 June; 18(6): 1279-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11351263

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The effect of quercetin on light-induced cytotoxicity of hypericin. Author(s): Mirossay A, Onderkova H, Mirossay L, Sarissky M, Mojzis J. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2001; 50(6): 635-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11829327

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The importance of light in the anti-HIV effect of hypericin. Author(s): Hudson JB, Harris L, Towers GH. Source: Antiviral Research. 1993 February; 20(2): 173-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8460933

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The separation of hypericine and pseudohypericine from Hypericum perforatum L. Author(s): Smelcerovic A, Laatsch H, Lepojevic Z, Djordjevic S. Source: Pharmazie. 2002 March; 57(3): 178-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11933846

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Therapeutic agents with dramatic antiretroviral activity and little toxicity at effective doses: aromatic polycyclic diones hypericin and pseudohypericin. Author(s): Meruelo D, Lavie G, Lavie D. Source: Proceedings of the National Academy of Sciences of the United States of America. 1988 July; 85(14): 5230-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2839837

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 hypericin; 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 Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com

•

Herbs and Supplements Hypericum Perforatum Source: Integrative Medicine Communications; www.drkoop.com Klamathweed Source: Integrative Medicine Communications; www.drkoop.com Proton Pump Inhibitors Source: Prima Communications, Inc.www.personalhealthzone.com St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Alternative names: Hypericum perforatum, Klamathweed Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html

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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. PATENTS ON HYPERICIN 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.8 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 “hypericin” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hypericin, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Hypericin By performing a patent search focusing on hypericin, 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

8Adapted

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

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on hypericin: •

Antiviral agents Inventor(s): Lavie; David (Rehovot, IL), Lavie; Gad (Tenafly, NJ), Mazur; Yehuda (Rehovot, IL), Meruelo; Daniel (Scarborough, NY) Assignee(s): New York University (New York City, NY), Yeda Research and Development Co. Ltd. (Rehovot, IL) Patent Number: 6,576,784 Date filed: May 27, 1993 Abstract: Novel antiviral (including antiretroviral) compounds are mono- or dicarboxylic acid esters of hypericin in which one or both of the methyl groups of hypericin are substituted by carboxylic acid ester groups of the formula COOR.sup.3 in which R.sup.3 is alkyl, the chain of which is optionally interrupted by one or more oxygen or sulphur atoms. R.sup.3 is preferably methyl, ethyl, propyl, butyl, 2methoxyethyl or 2-(2-methoxyethoxy)ethyl. The compounds may be formulated into pharmaceutical compositions and may be used in any manner which has previously been known for hypericin. Excerpt(s): The present invention relates to new antiviral compounds and compositions and, more particularly, to compounds which are carboxylic ester analogs of hypericin. The invention also relates to methods of use of such compounds and compositions. Hypericin, a constituent of plants of the genus Hypericum, has been obtained in pure form from plants (Brockman et al., Annalen 553:1 (1942)), and has also been totally synthesized (Brockman et al., Chem. Ber. 90:2480 (1957), U.S. Pat. No. 5,120,412, issued Jun. 9, 1992). Hypericin, both from plant origin and prepared by synthesis, has been found to be a potent inhibitor of DNA and RNA containing enveloped viruses, and particularly of Human Immunodeficiency Virus (HIV), the presumed causative agent of AIDS and other conditions. Web site: http://www.delphion.com/details?pn=US06576784__

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Antiviral compositions Inventor(s): Lavie; David (Rehovot, IL), Revel; Michel (Rehovot, IL), Rotman; Dalia (Rehovot, IL), Velde; Vincent V. (Brussels, BE) Assignee(s): Yeda Research and Development Company Ltd. (Rehovot, IL) Patent Number: 4,898,891 Date filed: August 7, 1987 Abstract: The invention relates to antiviral compositions of matter containing as active ingredient hypericin or pseudohypericin. The novel compositions are of special use in the treatment of, and alleviation of symptoms of various diseases caused by viruses such as vesicular stomatitis, influenza, herpes simplex, HSV-1 and HSV-2. The mode of activity seems to be by inhibition of RNA synthesis and interfering with virus replication. The pharmaceutical compositions can be applied by a variety of routes. Topical applications have proved to be effective against a variety of viral afflictions.

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Excerpt(s): The invention relates to pharmaceutical compositions of matter which contain as active ingredient hypericin or pseudohypericin. The compositions are effective in inhibiting viral replication and thus bring about the gradual destruction of the virus. The compositions are of value in systemic as well as topical application. They can be used effectively against vesicular stomatitis virus, influenza virus, herpes simplex HSV-1, HSV-2 and others. The active ingredient can be isolated from the perennial plant Hypericum triquetrifolium Turra (or Hypericum crispum L.). There are provided antiviral pharmaceutical compositions which contain as active ingredient hypericin or pseudohypericin. The compositions are effective in interfering with the development and replication of viruses in mammals, including humans, inducing their destruction, without any appreciable toxicity to the mammal. In order to display their activity, the compounds have to be in direct contact with the virus. The estimation of the antiviral activity is based on protection of cells by the compounds from destruction by the virus, previously put in contact with low concentrations of the compounds tested. Web site: http://www.delphion.com/details?pn=US04898891__ •

Apocynum venetum extract for use as antidepressant Inventor(s): Butterweck; Veronika (Muenster, DE), Nishibe; Sansei (Hokkaido, JP), Sasaki; Tsutomu (Chiba, JP), Seo; Shujiro (Chiba, JP) Assignee(s): Tokiwa Phytochemical Co., Ltd. (Sakura, JP) Patent Number: 6,737,085 Date filed: November 1, 2001 Abstract: The present invention provides (1) an Apocynum extract containing not less than 4% of flavonoid compounds and is free of hypericin and hyperforin, (2) an antidepressant composition (in the form of a food, dietary supplement or medicine) containing the Apocynum extract, and (3) a method for treating depression using the Apocynum extract. Excerpt(s): The present invention relates to novel Apocynum extracts, antidepressant compositions containing the Apocynum extracts in the form of foods, dietary supplements, medicines and the like, and methods for treating depression using the Apocynum extracts. The etiology of depression has been extensively discussed by many works, but has not been sufficiently explained yet. Various factors seem to be involved in the etiology and complicated with each other. Possible factors include biological factors such as neurochemical and genetic findings as well as situational or psychosociological factors such as previous personality or life stress. Clinical features of depression include depressive state, anhedonia (the inability to enjoy themselves), psychomotor inhibition, incoherence of thought/cognition, anxiety and agitation, physical (autonomic) symptoms, etc. Web site: http://www.delphion.com/details?pn=US06737085__

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Compounds and therapy for resisting memory loss in humans Inventor(s): Altman; David A. (1165 Suffield, Birmingham, MI 48009) Assignee(s): none reported Patent Number: 6,159,986 Date filed: November 2, 1999 Abstract: Therapies and compounds for the inhibition of memory loss. In one embodiment, a combination of Huperzine A and hypericin is employed. Excerpt(s): The present invention relates generally to the inhibition of memory impairment, and more particularly to compounds and therapies for the treatment of persons with Alzheimer's disease or other diseases affecting memory to help minimize the effects of memory impairment. In recent years there has been a growing interest in the use of over the so counter supplements to help improve physical health and emotional well-being. Though not intended to diagnose, treat, cure or prevent any disease, so-called "home" or "natural" remedies have become popular substitutes for prescription drugs and other regulated substances. By way of illustration, symptoms of depression and other cognitive functions are believed to be alleviated by the administration of St. John's Wort. Mental alertness and improved memory is believed to be improved through such supplements as Huperzine A (which has been noted in the art as an inhibitor of acetylcholinesterase). Web site: http://www.delphion.com/details?pn=US06159986__

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Medication for treatment of viral disease based on active agents of plant hypericum (St. John's Wort) and method of production of the medication Inventor(s): Elten; Holger (Oldendorf, DE), Steinbeck-Klose; Annemarie (Bonn, DE) Assignee(s): Dreluso Pharmazeutika Dr. Elten & Sohn GmbH (Oldendorf, DE) Patent Number: 6,245,362 Date filed: June 17, 1998 Abstract: A medication for treatment of disease caused by virus, and particularly retrovirus, and a method of production of the medication are based on use of the active agents, polycyclic diones (hypericin, pseudohypericin and/or salts thereof), of the plant Hypericum (St. John's Wort) with other components occurring in the plant wherein the concentration of polycyclic diones is between 0.05% and 50% whereby a therapeutic antiretroviral effect is attained while undesirable side effects are largely avoided. Excerpt(s): The invention relates to a medication for treatment of a disease caused by a virus, particularly a retrovirus, based on the active agents of the plant Hypericum (St. John's Wort) and to a method of production of the medication. The plant St. John's Wort as well as its applicability as a pharmaceutical were already known to people of antiquity. Most of the approximately 370 species of this plant worldwide comprise the red pigment hypericin, a naphthodianthrone derivative having a molecular weight of 504.43 and the empirical formula C.sub.30 H.sub.16 O.sub.8. In addition to hypericin, a number of structural analogs was identified which have been described in the literature as pseudohypericin, protohypericin, protopseudohypericin, cyclopseudohypericin, isohypericin, Kielcortin etc., so-called polycyclic diones. Other components of the plant are, for example, the flavonoid quertecine as well as other bioflavonoids and flavonoid glycosides, vegetable acids such as chlorogenic and coffeic acid, hyperforin--a

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phloroglucine derivative--tanning agents, flower pigments as well as cyanidin chloride and xantophyll, anthraquinone, xanthone derivatives, distilled oils such as terpineol, resin-like substances, fats and waxes. It has recently been found that polycyclic diones (hypericin, pseudohypericin and/or salts thereof) in highly pure form have antiviral efficacy. In particular, an inhibiting effect on retrovirus can be observed in vitro (cf. EP 0 332 697 B1); this applies also with respect to the human immunodeficiency virus (HIV) which in humans causes the acquired immune deficiency syndrome (AIDS). Hypericin or pseudohypericin were herein used in highly pure form. In order to obtain this form, the extract from the plant Hypericum was treated until nearly pure hypericin/pseudohypericin was obtained. Alternatively, highly pure hypericin was produced synthetically. The medications suggested in this connection comprised nearly pure hypericin/pseudohypericin (or pharmaceutically efficacious salts thereof) as the sole active agent, and, in addition, pharmacologically known solvents and carrier substances suitable in known manner for various forms of administration and dosages. Web site: http://www.delphion.com/details?pn=US06245362__ •

Method for delivery of nucleic acids to cells using hypericin polyamine complexes Inventor(s): Lavie; Gad (Rehovot, IL), Prince; Alfred M. (Pound Ridge, NY) Assignee(s): New York Blood Center (New York, NY), New York University (New York, NY) Patent Number: 5,824,654 Date filed: September 2, 1994 Abstract: The invention provides improved methods for delivery of nucleic acids to cells, which comprise forming ternary complexes between a hydrophobic, membranebinding anion such as hypericin; a polycation such as polylysine; and a nucleic acid such as DNA; and contacting cells with the tenary complexes. Also provided are pharmaceutical formulations comprising these ternary complexes and a pharmaceutically acceptable carrier or diluent. The methods and compositions find use in mediating DNA uptake into cells, including gene therapy applications. Excerpt(s): This invention pertains to improved methods for delivery of nucleic acids to cells, which methods can be applied to gene therapy. Advances in the understanding of the molecular basis of disease have led to the development of methods to treat diseases by introducing foreign DNA into affected cells. The foreign DNA may act by interfering with the expression of deleterious genes, whether they are host genes, or genes of viruses or other invading microorganisms. For example, timely interference with the expression of certain viral early genes by administration of antisense DNA to infected cells in culture can forestall their interaction with cellular tumor suppressor genes; in this manner, oncogenic transformation caused by the virus can be inhibited (Pietenpol et al., 1990, Cell 61:777-785). Another example is the long-term treatment of human immunodeficiency virus-infected cells with antisense oligonucleotides. In this case, the antisense oligonucleotides hybridize to viral mRNA molecules and directly inhibit translation of viral proteins (Lisziewicz et al., 1993, Proc. Natl. Acad. Sci. USA 90:38603864). Another approach involves the introduction into a cell of catalytic RNAs ("ribozymes"), which contain autocleavage domains and can selectively hydrolyze and inactivate RNA targets, whether host-derived or foreign (Foster et al, 1987, Cell 49:211220; Rossi et al., 1991, Pharmacol. Ther., 50:245-254. Alternatively, the introduced DNA may act positively, by supplying alternative or supplemental genes whose expression counteracts the pathological condition. For example, introduction of the adenosine

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deaminase gene can overcome immunodeficiency, or introduction of the cystic fibrosis transmembrane receptor (CFTR) gene into cystic fibrosis respiratory epithelial cells improves bronchial mucous fluidity and facilitates mucous removal and alveolar function. Web site: http://www.delphion.com/details?pn=US05824654__ •

Method of treating papilloma virus infection using hypericin Inventor(s): Lavie; Gad (Tenafly, NJ), Meruelo; Daniel (Scarborough, NY) Assignee(s): New York University (New York, NY) Patent Number: 5,506,271 Date filed: August 10, 1993 Abstract: A method for treating a papilloma virus infection comprising topically administering hypericin which is effective to inhibit the replication, growth and/or the infectivity of the virus. The papilloma viruses include those capable of causing benign warts or a malignancy such as human papilloma virus-1 (HPV-1), HPV-2, HPV-6, HPV11, HPV-16 and HPV-18. Excerpt(s): The invention, in the fields of virology, immunology and medicine, relates to a method for inactivating a pathogenic microorganism or virus and/or enhancing its immunogenicity by treating the microorganism or virus with a polycyclic aromatic hydrocarbon, preferably hypericin or an analog thereof. The invention also provides a method for producing a vaccine, comprising inactivating a microorganism or virus in a way which preserves and enhances its immunogenic properties using the method of the invention, vaccines produced by this method, and methods for vaccinating against a disease, comprising immunization with the vaccine of the present invention. Vaccination against bacterial or viral induced diseases is an old concept which dates back to Louis Pasteur. The first vital vaccine devised by Lister involved the inoculation of humans with cow pox virus (Vaccinia) to obtain immunity against the human pox virus (Variola). Since then, a wide variety of vaccines against numerous childhood diseases such as mumps, measles and German measles (Rubella), as well as against poliovirus and Hepatitis B virus have been developed and approved for use. The requirements for a vaccine against a disease-causing virus have been defined. Effective vaccine preparations must exhibit several properties described below. Web site: http://www.delphion.com/details?pn=US05506271__

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Methods and polycyclic aromatic compound containing compositions for treating Tcell-mediated diseases Inventor(s): Lavie; Gad (Tenafly, NJ), Meruelo; Daniel (Scarborough, NY) Assignee(s): New York University (New York, NY) Patent Number: 5,514,714 Date filed: March 30, 1993 Abstract: T cell-mediated diseases in mammals are treated using compositions comprising a polycyclic aromatic compound, preferably hypericin or pseudohypericin, and related compounds, including isomers, analogs, derivatives, salts, or ion pairs of hypericin or pseudohypericin. The above composition may be administered in

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combination with an immunosuppressive agent. Pharmaceutical compositions useful for treating a T cell-mediated disease comprise the above polycyclic aromatic compound, alone or in combination with an immunosuppressive agent. The compositions and methods are useful in treating diseases which include multiple sclerosis, myasthenia gravis, scleroderma, polymyositis, graft-versus-host disease, graft rejection, Graves disease, Addison's disease, autoimmune uveoretinitis, autoimmune thyroiditis, pemphigus vulgaris and rheumatoid arthritis. Psoriasis and systemic lups erythematosus. Also provided are methods for diminishing the expression of CD4 Molecules on the surface of a T lymphocyte, and for inducing multidrug resistance in a cell, comprising incubating the cell with an effective concentration of a polycyclic aromatic compound. Excerpt(s): This invention pertains to the administration of polycyclic aromatic compounds for the treatment of T cell-mediated diseases in mammals and compositions useful for treating T cell-mediated diseases. T cell-mediated diseases have been characterized by the induction of cytotoxic T-lymphocytes expressing the CD8 antigen on their cell surface and/or helper T cells expressing the CD4 antigen on their cell surface. These diseases, non-limiting examples being graft-versus-host diseaser graft rejection, and autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, Graves diseases Addison's diseases polymyositis, insulin dependent diabetes, primary biliary cirrhosis, systemic Lupus erythematosus, psoriasis, scleroderma, represent a large number of host immune system disorders. Graft-versus-host disease may occur when cells of the immune system such as stem cells or lymphocytes are transplanted into an allogeneic host, such as one genetically different at the major histocompatibility complex, which encodes cell surface antigens that give rise to strong immunological reactions. Transplants of cells of the immune system are made for treating certain forms of leukemia, aplastic anemia, and various immunodeficiency diseases. In order to prevent rejection of the foreign cells, the host is typically immunosuppressed, as with irradiation and/or immunosuppressive drugs. The transplanted immunocompetent cells recognize the host as foreign and mount an immune response directed against the host. In humans, the clinical manifestations of this graft-versus-host disease include fever, rash, anorexia, nausea, vomiting and watery or bloody diarrhea, weight loss and death. Web site: http://www.delphion.com/details?pn=US05514714__ •

Neuroprotective composition for the prevention and/or treatment of nervous and behavioural alterations due to anxiety states or depression, comprising acetyl-Lcarnitine and hypericin Inventor(s): Cavazza; Claudio (Rome, IT) Assignee(s): Sigma-Tau Healthscience S.p.A. (Pomezia, IT) Patent Number: 6,346,282 Date filed: December 26, 2000 Abstract: This invention relates to a composition of acetyl-L-carnitine in combination with hypericin and/or Hypericum extract (Hypericum perforatum L. (St. John's Wort)) in synergistically effective amounts. The composition is effective at treating a nervous alteration due to an anxiety state, irritability, or depression. Excerpt(s): The present invention relates to a composition for the prevention and/or treatment of nervous and behavioural alterations due to anxiety states or depression.

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Accordingly the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in. (b) 1,3,4,6,8,13-hexahydroxy-10,11dimethylphenanthro[1,10,9,8-opqra]perylene- 7,14-dione (hypericin) or Hypericum extract (Hypericum perforatum L., "Saint-John's-wort") comprising at least 0.3% by weight of hypericin. Web site: http://www.delphion.com/details?pn=US06346282__ •

Photoactivated hypericin and the use thereof Inventor(s): Fox; Floyd Eliot (Bellmawr, NJ), Rook; Alain H. (Wynnewood, PA), Tobia; Alfonso J. (Doylestown, PA) Assignee(s): The Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 6,001,882 Date filed: July 3, 1997 Abstract: The invention provides methods of using photoactivated hypericin compounds which, when photoactivated using visible or UV-A light, are useful for treating numerous diseases and disorders in mammals. The compounds of the invention are useful for inhibiting the proliferation and accumulation of mammalian leukocytes and for inducing apoptosis in mammalian leukocytes. Excerpt(s): The field of the invention is inhibition of normal and pathological cell growth, proliferation, and accumulation. Recently, increasing attention has been devoted to photodynamic therapy (PDT) because of the discovery that many photosensitizer compounds, either naturally occurring or synthesized, exhibit remarkable anti-cancer and antiviral activities (Diwu et al., 1994, Pharmacol. Ther. 63:135). Several studies have shown that benign hyperproliferative and hypervascular conditions such as psoriasis can be improved by photosensitization with porphyrins (Levy, 1994, Sem. Oncol. 21(6 Suppl. 15):4-10). Selective sensitization of psoriatic tissue using porphyrins has been demonstrated as an effective treatment for psoriasis and the efficacy of the treatment method may be related to the increased vascularity of psoriatic plaques (Stringer et al., 1996, J. Invest. Dermatol. 107:76-81). Another report using systemic tin-protoporphyrin in combination with long wavelength ultraviolet light suggests that this combination effects amelioration of psoriasis in psoriatic patients (Calzavara-Pinton et al., 1996, J. Photochem. Photobiol. B-Biol. 36:225-231). Web site: http://www.delphion.com/details?pn=US06001882__

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Preparation of hypericin Inventor(s): Bock; Harald (Berlin, DE), Lavie; David (Rehovot, IL), Mazur; Yehuda (Rehovot, IL) Assignee(s): Yeda Research and Development Co. Ltd. (Rehovot, IL) Patent Number: 5,120,412 Date filed: November 9, 1990

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Abstract: A process for preparing hypericin comprises oxidative dimerization of emodin anthrone and conversion of the intermediate protohypericin to hypericin by irradiation with visible light. Excerpt(s): Hypericin is a constituent of plants belonging to the genus Hypericum. It was isolated from this natural source in a chemically pure state by H. Brockmann et al. (Ann. 1942, 553, 1). Hypericin always appears in nature accompanied by the chemically related compound pseudo-hypericin. Hypericin has gained interest in the last few years by virtue of the discovery of its anti-viral and anti-retroviral activity (cf., inter alia, European Patent Application No. 0 256 452 and G. Lavie et al., Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 596). Hypericin is now considered as a potentially effective drug against a number of diseases caused by the above-mentioned viruses. The isolation of hypericin from Hypericum plants is not feasible on a larger scale, because it requires a lengthy procedure involving extraction with large volumes of solvents and cumbersome chromatographic separations on silica gel columns. The main difficulty in obtaining hypericin in a pure state from the plant material resides in its separation from the accompanying pseudohypericin. This necessitates the aforementioned chromatography with the elution of a large number of fractions, only a few of which contain the pure desired material. The yield of hypericin from the plants is very low, not more than 0.3%, based on the dry plant material. Web site: http://www.delphion.com/details?pn=US05120412__ •

St. John's wort composition Inventor(s): Ghosal; Shibnath (Varanasi, IN) Assignee(s): Indian Herbs Research & Supply Company Ltd. (IN), Natreon Inc. (Highland Park, NJ) Patent Number: 6,224,906 Date filed: August 31, 1999 Abstract: A composition of St. John's Wort, in the form of a stable, free-flowing, powder, having effective antidepressant properties, characterized by having essentially no hypericin therein. Excerpt(s): This invention relates to St. John's wort compositions, and, more particularly, to such compositions in the form of a stable, free-flowing powder having effective antidepressant properties, characterized by having essentially no hypericin therein, and pharmaceutical and nutritional use formulations thereof. St. John's wort is the common name for the plants Hypericum perforatum and Hypericum augustifolia; however, Hypericum augustifolia is rarely used in commercial products. Accordingly, the term as used herein refers to Hypericum perforatum, as its whole fresh or dried plant, and compositions and use formulations derived therefrom. St. John's wort has been used externally to treat wounds, muscle aches and burns, and, internally, for relieving psychogenic disturbances, including depressive states, sleep disorders, anxiety and/or nervous excitement, particularly those associated with menopause. An advantage of treatment of certain cases of depression with St. John's wort is that it is rarely accompanied by sexual dysfunction, as with many prescription antidepressants. However, the art does not fully understand what chemical or chemicals in St. John's wort are responsible for its anti-depressant effect. Web site: http://www.delphion.com/details?pn=US06224906__

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Patent Applications on Hypericin As of December 2000, U.S. patent applications are open to public viewing.9 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 hypericin: •

Helianthrone derivatives as anti-cancer agents Inventor(s): Lavie, Gad; (Rehovot, IL), Mazur, Yehuda; (Tel Aviv, IL) Correspondence: Winston & Strawn; Patent Department; 1400 L Street, N.W.; Washington; DC; 20005-3502; US Patent Application Number: 20030105357 Date filed: July 30, 2002 Abstract: Hypericin, helianthrone and derivatives thereof of general formula (I) 1wherein the dotted line between positions 11 and 12 represent an optional C11-C12 bond; R is independently selected from the group consisting of hydroxy, C.sub.1C.sub.10 alkoxy, NH--C.sub.1-C.sub.10 alkyl, and NH-hydroxy(C.sub.1-C.sub.10)alkyl; R' is independently selected from the group consisting of hydroxy and C.sub.1-C.sub.10 alkoxy; R" is independently selected from the group consisting of hydrogen, hydroxy, C.sub.1-C.sub.10 alkoxy, NH--C.sub.1-C.sub.10 alkyl, and NH-hydroxy(C.sub.1C.sub.10)alkyl; and R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently selected from the group consisting of hydrogen, hydroxy, chloro, bromo, C.sub.1-C.sub.10 alkyl, C.sub.1-C.sub.10 alkoxy, and C.sub.1-C.sub.10 alkoxycarbonyl, provided that R" is not hydrogen when there is a C11-C12 bond, are useful as inhibitors of angiogenesis and can be used to prevent formation of metastases and restenosis and for the treatment of angiogenesis-associated ophthalmologic disorders. In addition, the helianthrones of formula (I) can be used for the treatment of tumors in the absence of light irradiation. New compounds include those of formula I which are other than hypericin and known hypericin derivatives and there is either a C11-C12 bond or at least one R" is other than hydrogen. Excerpt(s): This application is a continuation of the U.S. National Stage designation of International Application PCT/IL01/00091, filed Jan. 31, 2001, the entire content of which is expressly incorporated herein by reference thereto, which is a continuation-inpart of application Ser. No 09/496,296 filed Jan. 31, 2000, now U.S. Pat. No. 6,229,048. The present invention relates to the therapeutic use of polycyclic dianthraquinones such as hyperycins and helianthrones as inhibitors of angiogenesis, and to the use of some of them, particularly of 1,3,4,6-tetrahydroxy-helianthrone and derivatives thereof, as anticancer agents in the absence of light irradiation. The discovery of the signal transduction pathways that activate cell proliferation in response to interactions between growth factors and corresponding cellular receptors, triggered an extensive search for inhibitors that can interfere with this cascade in malignancies where malignant cells undergo uncontrolled proliferation. The chemical signals in this cascade have been identified as phosphorylation of proteins either on tyrosine residues, catalyzed by a group of enzymes collectively termed protein tyrosine kinases (PTK), or on serine/threonine residues by protein kinases A, B, and C. Protein kinase C (PKC) is also an important cellular signal transducer that contains a catalytic domain which phosphorylates substrates and a regulatory domain which controls its activity. Polyhydroxylated

9

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

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flavones such as genistein and quercetin were identified as inhibitors of the phosphorylation kinases (Losiewicz et al., 1994). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

HYPERICIN AND HYPERICUM EXTRACT: SPECIFIC T-TYPE CALCIUM CHANNEL BLOCKER, AND THEIR USE AS T-TYPE CALCIUM CHANNEL TARGETED THERAPEUTICS Inventor(s): LING, LEI; (EDMONTON, CA), PANG, PETER K. T.; (EDMONTON, CA), SHAN, JACQUELINE J.; (EDMONTON, CA), WU, XI-CHEN; (EDMONTON, CA) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 1425 K Street, N.W.; Suite 800; Washington; DC; 20005; US Patent Application Number: 20030207940 Date filed: January 11, 2000 Abstract: Hypericin has been shown to specifically inhibited T-type calcium channel activity. Hypericum extract containing hypericin also inhibited T-type calcium channel activity. Moreover, other chemicals in Hypericum extract showed a synergistic effect to hypericin. In view of this, hypericin or hypericin-containing Hypericum extract can be used as T-channel blockers. Hypericum extract, extract of other species of the Hypericum genus, extract of other plants containing hypericin, hypericin, hypericin derivatives, hypericin analogs, such as pseudohypericin, and other hypericum extract constituents can be used as therapeutics targeted at T-type calcium channels for treatment of diseases associated with T-channel abnormality. Methods for administering hypericin and hypericum extract are disclosed. Excerpt(s): This application is a continuation-in-part of International Application PCT/US99/14132, filed Jul. 9, 1999, and designating the United States, the disclosure of which is incorporated by reference. This invention relates to Hypericum perforatum, extracts of Hypericum perforatum, compounds found in Hypericum perforatum, e.g. hypericin, and the derivatives and analogs of hypericin. One aspect of the present invention is the discovery that Hypericum perforatum (referred to as Hypericum herein after unless otherwise indicated), Hypericum extracts, certain compounds in Hypericum, including hypericin, pseudohypericin, hyperforin, ashyperforin, quercetin, quercitrin, isoquercitrin, hyperoside, rutin, amentoflavone and hyperin, hypericin derivatives and hypericin analogs can be used as therapeutics targeted at T-type calcium channels in various biological systems, such as cardiovascular system, central nervous system and endocrine system, to treat diseases treatable with T-type calcium blocking agents. The diseases treatable with T-type calcium blocking agents include depression, chronic heart failure, congestive heartfailure, ischaemc condition, arrhythmia, angina pectoris, hypertension, hypo- and hyperinsulinemia, diabete mellitus, hyperaldosteronemia, epilepsy, migraine headache, brain aging or neurodegenerative related diseases, such as Alzheimer's disease, and preterm labor. Hypericin is one of the chemical constituents from a perennial herbaceous plant, Hypericum perforatum or St. John's Wort. Hypericum is known to have medicinal properties since ancient times and it is widely used in phytotheraphy. Hypericum has been widely researched for its antidepressant and anti-viral properties. In addition to these properties, Hypericum has historically been used for a variety of neurological conditions, including anxiety, insomnia due to restlessness, irritability, neuralgia, trigeminal neuralgia, neuroses, migraine headaches, fibrositis, dyspepsia, and sciatica. Hypericum contains several compounds of biological interest, including

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naphthodianthrones, e.g. hypericin and pseudohypericin, phloroglucinols, e.g. hyperforin and ashyperforin, and a broad spectrum of flavonoids which are considered to be primarily responsible for Hypericum's activity. However, the lack of a clearly definable pharmacologic mechanism of Hypericum and its chemical components cause the failure of identifying the constituents most responsible for Hypericum's activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method and preparation for the preventing and/or treating vascular disorders and secondary disorders associated therewith Inventor(s): Hageman, Robert Johan Joseph; (Waddinxveen, NL), Kiliaan, Amanda Johanne; (Wageningen, NL) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20020040058 Date filed: July 9, 2001 Abstract: The present invention relates to a method for the prevention and/or treatment of vascular disorders and/or secondary disorders associated therewith, such as depression. The method according to the invention comprises the oral administration of a preparation which contains at least the following fractions:a) long chain polyunsaturated fatty acids;b) at least two different phospholipids selected from the group consisting of phosphatidylserine, phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine andc) one or more compounds which are a factor in methionine metabolism, which compounds are selected from the group consisting of folate, vitamin B12, vitamin B6, magnesium and zinc or equivalents thereof.The invention also relates to a preparation for oral dosage comprising:at least 120 mg of long chain polyunsaturated fatty acids;at least 200 mg phospholipids;at least 200.mu.g folate; andat least 0.1 mg hypericin and/or at least 100 mg extract of Withania somnifera. Excerpt(s): The present invention relates to a method for the prevention and/or treatment of vascular disorders and secondary disorders associated therewith, such as depression. The invention is also concerned with a preparation that can be used in the prevention and/or treatment of the aforementioned disorders. 3. the tunica adventitia which is composed of loosely woven collagen fibers, which are infiltrated by tiny lymphatic and blood vessels. The endothelial cells in the tunica intima are in direct contact with blood and have a barrier function for the underlying tissue. This barrier function includes selective transport of components from blood to the underlying tissue and vice versa, and protection of the underlying tissue. Endothelial cells get easily damaged due to a wide variety of causes like mechanic forces or interaction with stressor components such as classic anaphylatoxins, and components that may occur in the blood, such as homocysteine or components that result from treatment with certain types of drugs (e.g. chemotherapeutics). Vascular permeability can further be increased by a wide variety of humoral- and cell-derived mediators. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with hypericin, 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 “hypericin” (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 hypericin. You can also use this procedure to view pending patent applications concerning hypericin. 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 5. BOOKS ON HYPERICIN Overview This chapter provides bibliographic book references relating to hypericin. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hypericin 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 “hypericin” (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 hypericin: •

AIDS/HIV and Opportunistic Infection Update: National Lesbian and Gay Health Conference : New Orleans, LA: July 26, 1991 Contact: Encore Cassettes, PO Box 231340, San Diego, CA, 92194, (619) 596-8402. Summary: This sound recording of proceedings from the 1991 National Gay and Lesbian Health Conference features a joint presentation on recent research developments for the treatment of the Human immunodeficiency virus (HIV), Acquired immunodeficiency syndrome (AIDS), and its opportunistic infections. The presentation begins with a discussion of the cell cycle, viral replication, and the methods that are being developed to disrupt this process. The action and status of the nucleoside analogs (AZT, ddI, and ddC) are summarized. The discussion that follows examines new areas of research: Reverse transcriptase inhibitors; HIV proteases; TAT inhibitors; and hypericin (St. John's wort). Oral bioavailability is addressed. Recent advances on the decreased susceptibility to AZT and combination dose-ranging pharmacokinetic studies are presented. Recent developments in vaccine research and clinical trials are

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summarized. The presentation continues with a discussion of animal models, vectors, subunits, and inactivated whole virus with application to vaccine development. The presentation concludes with an update on clinical trials and opportunistic infections.

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

Signaling Pathways in the Control of Apoptosis by UVB or Hypericin (Acta Biomedica Lovaniensia 208) by Zerihun Assefta Tereffe; ISBN: 9058670023; http://www.amazon.com/exec/obidos/ASIN/9058670023/icongroupinterna

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CHAPTER 6. PERIODICALS AND NEWS ON HYPERICIN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hypericin.

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

Successful preliminary results using hypericin for treatment of glioblastoma reported Source: Reuters Medical News Date: October 29, 1998

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

Academic Periodicals covering Hypericin Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hypericin. In addition to

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61

these sources, you can search for articles covering hypericin 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 Institute10: •

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/

10

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.11 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:12 •

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

11

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). 12 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 NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hypericin” (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 483 2 147 17 0 649

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “hypericin” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 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.19 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.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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. 20 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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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 hypericin 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 hypericin. 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 hypericin. 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 “hypericin”:

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Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Herbal Medicine http://www.nlm.nih.gov/medlineplus/herbalmedicine.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on hypericin. 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: •

Hypericin Contact: Seattle Treatment Education Project, 1123 E John St, Seattle, WA, 98102, (206) 329-4857, http://www.thebody.com/step/steppage.html. Summary: This fact sheet reports on hypericin, a chemical extract from the St. John's wort plant and related species. The fact sheet tells how hypericin works as an antiviral and reports on several studies conducted in various countries worldwide, including both laboratory and human trials. Side effects, including phototoxicity, are discussed, as are sources for purchasing hypericin. The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to hypericin. 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.

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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 hypericin. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hypericin. 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 hypericin. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “hypericin” (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

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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 “hypericin”. 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 “hypericin” (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 “hypericin” (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.21

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

21

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)22: •

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/

22

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

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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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

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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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HYPERICIN 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] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [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] 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] 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] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]

Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [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]

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Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] 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] 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] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allogeneic: Taken from different individuals of the same species. [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] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]

Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric

Dictionary 85

acid, that have no relation to proteins. Abbreviated AA. [EU] 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] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amsacrine: N-(4-(9-Acridinylamino)-3-methoxyphenyl)methanesulfonamide. Aminoacridine derivative that is a potent intercalating antineoplastic agent. It is effective in the treatment of acute leukemias and malignant lymphomas, but has poor activity in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy protocols. It produces consistent but acceptable myelosuppression and cardiotoxic effects. [NIH] 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] 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] 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, 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] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [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] 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

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supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthralin: An anti-inflammatory anthracene derivative used for the treatment of dermatoses, especially psoriasis. It may cause folliculitis. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] 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] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] 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] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [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

Dictionary 87

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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [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] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Attenuated: Strain with weakened or reduced virulence. [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] 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] 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] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located

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in the basal regions of the cerebral hemispheres. [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] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the 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 duct: A tube through which bile passes in and out of the liver. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biodegradation: The series of processes by which living organisms degrade pollutant chemicals, organic wastes, pesticides, and implantable materials. [NIH] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [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] 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] Bladder: The organ that stores urine. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found

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in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] 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] 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] 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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] 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] 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 Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH]

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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] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Carcinoma in Situ: A malignant tumor that has not yet invaded the basement membrane of the epithelial cell of origin and has not spread to other tissues. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiotoxic: Having a poisonous or deleterious effect upon the heart. [EU] Cardiovascular: Having to do with the heart and blood vessels. [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 hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [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] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cauda Equina: The lower part of the spinal cord consisting of the lumbar, sacral, and coccygeal nerve roots. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell 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

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metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] 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] Chemotherapeutics: Noun plural but singular or plural in constructions : chemotherapy. [EU]

Chemotherapy: Treatment with anticancer drugs. [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] 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] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH]

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Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [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] 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] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [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] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [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] Colloidal: Of the nature of a colloid. [EU] 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,

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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] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] 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] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [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]

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Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [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] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [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] 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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until

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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] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] 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] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydroxy: AMPA/Kainate antagonist. [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] 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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Diuresis: Increased excretion of urine. [EU] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] 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] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when

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the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [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] Dyspepsia: Impaired digestion, especially after eating. [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] Elastin: The protein that gives flexibility to tissues. [NIH] 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]

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] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic

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endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] 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] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH]

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Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [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]

Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibrositis: Aching, soreness or stiffness of muscles; often caused by inexpedient work postures. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] 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] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an

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antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [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] Folliculitis: Inflammation of follicles, primarily hair follicles. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [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] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] 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] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [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] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug

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sensitivity, particularly for leukemia. [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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] 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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [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] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] 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] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal

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products. [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] 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] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU]

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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 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] Heterotropic: Of organisms that cannot live without an external source of organic food. [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] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] 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] 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] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] 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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU]

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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] Hypericum: Genus of perennial plants in the family Clusiaceae (Hypericaceae). Herbal and homeopathic preparations are used for depression, neuralgias, and a variety of other conditions. Contains flavonoids, glycosides, mucilage, tannins, and volatile oils (oils, essential). [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypervascular: Having a large number of blood vessels. [NIH] Hypnotic: A drug that acts to induce sleep. [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] Hypoxic: Having too little oxygen. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]

Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] 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] 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]

Immunogenic: Producing immunity; evoking an immune response. [EU] 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] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It

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may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] 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] 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]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Instillation: . [EU] 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] 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] 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,

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implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intracellular: Inside a cell. [NIH] Intravesical: Within the bladder. [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]

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] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [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] 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] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [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] Kinetic: Pertaining to or producing motion. [EU] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [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] 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] Life cycle: The successive stages through which an organism passes from fertilized ovum or

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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] Ligands: A RNA simulation method developed by the MIT. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] 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] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked glycosidically to one or more sugar moieties. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune response-

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associated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [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] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH]

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Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [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] 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] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [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] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH]

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Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of

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some cancer treatments. [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] 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] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] 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] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [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] 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] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [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] 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] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neuroses: Functional derangement due to disorders of the nervous system which does not

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affect the psychic personality of the patient. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] 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] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [EU] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH]

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Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] 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]

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] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [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] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous

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membranes or glandular ducts. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] 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] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perennial: Lasting through the year of for several years. [EU] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Perylene: Dibenz(de, kl)anthracene. Polycyclic hydrocarbon soil and water pollutant; also used as fluorescent lipid probe in cytochemistry of membranes and other lipid structures; derivatives may be carcinogenic. Synonyms: peri-dinaphthalene. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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

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function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [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] Phosphorylates: 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] Photoallergy: Sensitization of the skin to light usually due to the action of certain substances or drugs, may occur shortly after exposure to a substance or after a latent period of from days to months. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Photosensitization: The development of abnormally heightened reactivity of the skin to sunlight. [EU] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [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]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [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] 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 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] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous

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membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] 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] Polylysine: A peptide which is a homopolymer of lysine. [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] 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] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] 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] 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] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [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] 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] 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]

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Promyelocytic leukemia: A type of acute myeloid leukemia, a quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] 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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH]

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Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

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]

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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [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] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [NIH]

Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign

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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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] 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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [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] 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] 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] 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] 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]

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Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [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] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [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] 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]

Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Rose Bengal: A bright bluish pink compound that has been used as a dye, biological stain, and diagnostic aid. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Sciatica: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of sciatic neuropathy; radiculopathy (involving the L4, L5, S1 or S2 spinal nerve roots; often associated with intervertebral disk displacement); or lesions of the cauda equina. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] 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]

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Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] 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] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soft tissue sarcoma: A sarcoma that begins in the muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH]

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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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasmogenic: Capable of producing convulsions. [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] 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] 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] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH]

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Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Steady state: Dynamic equilibrium. [EU] 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] 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]

Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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] Substrate: A substance upon which an enzyme acts. [EU] 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] Superoxide: Derivative of molecular oxygen that can damage cells. [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] 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] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH]

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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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [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] 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]

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] Thyroiditis: Inflammation of the thyroid gland. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [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] 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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] 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

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(ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transitional cell carcinoma: A type of cancer that develops in the lining of the bladder, ureter, or renal pelvis. [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 protein. It occurs on the ribosome and is unidirectional. [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] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] 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 suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tunica Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] 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.

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[NIH]

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] 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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] 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] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Proteins: Proteins found in any species of virus. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU]

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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] 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]

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] 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]

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INDEX A Abdomen, 83, 106, 112, 121, 122 Acantholysis, 83, 113 Acceptor, 83, 106, 112 Acetaminophen, 4, 6, 83 Acetylcholine, 83, 91, 111 Acetylcholinesterase, 46, 83 Acute leukemia, 83, 85 Acute myeloid leukemia, 83, 116 Adenine, 83, 117 Adenocarcinoma, 18, 83 Adenoma, 17, 83 Adenosine, 47, 83, 87, 89, 114 Adenosine Deaminase, 48, 83 Adrenergic, 83, 95, 97, 122, 124 Adverse Effect, 83, 120 Aerobic, 83, 84, 108, 112 Aerobic Metabolism, 84, 112 Aerobic Respiration, 84, 112 Affinity, 4, 84, 87 Agonist, 84, 95, 122 Agoraphobia, 84, 103, 112 Alertness, 46, 84, 89 Algorithms, 84, 88 Alkaline, 84, 85, 89 Allergen, 84, 120 Allogeneic, 49, 84, 100 Alpha Particles, 84, 117 Alternative medicine, 60, 84 Ambulatory Care, 84 Amino acid, 84, 86, 87, 95, 100, 103, 106, 108, 113, 115, 116, 119, 120, 122, 123, 124 Ammonia, 83, 85 Amnestic, 85, 99, 108 Amsacrine, 5, 85 Anaesthesia, 85, 104 Analgesic, 83, 85 Analog, 48, 85 Anaphylatoxins, 54, 85, 93 Anatomical, 85, 104, 108, 119 Anemia, 85, 99 Anesthesia, 85, 108 Angina, 53, 85 Angina Pectoris, 53, 85 Angiogenesis, 52, 85 Animal model, 8, 27, 58, 85 Anions, 85, 105, 120 Anorexia, 49, 85

Antagonism, 5, 85, 89 Anthralin, 12, 86 Antibacterial, 86, 121 Antibiotic, 86, 113, 121 Antibodies, 86, 101, 103, 106, 117 Antibody, 84, 86, 92, 93, 101, 102, 103, 104, 105, 107, 109, 117, 118, 120, 121, 126 Anticoagulant, 86, 116 Antifungal, 86, 105 Antigen, 49, 84, 86, 92, 102, 103, 104, 107, 108, 120 Anti-infective, 86, 102 Anti-inflammatory, 83, 86 Antineoplastic, 85, 86, 100, 115, 125 Antineoplastic Agents, 85, 86, 125 Antioxidant, 19, 33, 86 Antiproliferative, 11, 86 Antipyretic, 83, 86 Antiviral, 10, 33, 35, 40, 44, 45, 47, 50, 72, 86, 110 Anxiety, 45, 49, 51, 53, 86, 99, 111, 112 Anxiolytic, 86, 108 Aplastic anemia, 49, 86 Apoptosis, 10, 11, 12, 13, 14, 15, 20, 21, 24, 25, 32, 33, 34, 36, 37, 50, 58, 86, 90 Applicability, 46, 87 Aqueous, 20, 38, 87, 94, 102, 105 Arginine, 85, 87 Arrhythmia, 53, 87 Arterial, 87, 103, 116, 122 Arteries, 87, 89, 93, 108, 110 Arterioles, 87, 89, 90, 110 Aspergillosis, 87, 105 Assay, 31, 87 Astrocytes, 87, 108, 109 Astrocytoma, 87, 100 ATP, 87, 95, 100, 102, 114, 116, 124 Attenuated, 87, 125 Autoimmune disease, 87, 109 Autonomic, 45, 83, 87, 111, 121 B Bacteria, 25, 86, 87, 108, 119, 121, 123, 124, 125 Bacteriophage, 87, 124 Basal cell carcinoma, 19, 87 Basal cells, 87 Basal Ganglia, 87, 100 Basement Membrane, 88, 90

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Hypericin

Basophils, 88, 105 Benign, 48, 50, 83, 88, 101, 110, 112, 117, 126 Bile, 88, 102, 106, 115 Bile duct, 88, 115 Binding Sites, 6, 88 Bioavailability, 8, 57, 88 Biochemical, 12, 16, 30, 32, 35, 88, 98, 120 Biodegradation, 25, 88 Biological Factors, 45, 88 Biological therapy, 88, 101 Biosynthesis, 88, 116, 120 Biotechnology, 8, 9, 60, 67, 88 Bladder, 11, 12, 14, 17, 18, 19, 24, 33, 88, 94, 105, 109, 116, 118, 124, 125 Blastomycosis, 88, 105 Blister, 33, 88, 113 Blood Coagulation, 88, 89, 123 Blood Platelets, 88, 120 Blood pressure, 89, 103, 109 Blood vessel, 54, 85, 89, 90, 92, 97, 103, 106, 108, 120, 124, 125 Bone Marrow, 83, 86, 89, 99, 100, 103, 106, 109, 116, 121 Brachytherapy, 89, 104, 105, 117, 126 Bronchi, 89, 97 Bronchial, 48, 89, 102 Buccal, 89, 122 Burns, 51, 89 Burns, Electric, 89 C Caffeine, 4, 6, 89, 117 Calcium, 53, 89, 92 Calcium Channels, 53, 89 Camptothecin, 89, 105 Capillary, 38, 90, 119, 125 Capillary Fragility, 90, 119 Carbohydrates, 84, 90, 91, 112 Carcinogenic, 90, 111, 113 Carcinoma, 11, 12, 14, 16, 17, 19, 24, 32, 34, 90, 95 Carcinoma in Situ, 12, 90 Cardiac, 89, 90, 97, 108, 110 Cardiorespiratory, 90, 108 Cardiotoxic, 85, 90 Cardiovascular, 53, 89, 90, 120 Cardiovascular System, 53, 90 Carnitine, 49, 90 Carotene, 90, 118 Case report, 17, 90 Caspase, 24, 33, 34, 90 Catalytic Domain, 52, 90

Catecholamine, 90, 95 Cauda Equina, 90, 119 Caudal, 90, 95, 103, 115 Cell Cycle, 17, 57, 90, 98 Cell Death, 86, 90, 98, 110 Cell Division, 87, 90, 91, 98, 101, 108, 114, 120 Cell membrane, 89, 91, 94, 114 Cell motility, 16, 91 Cell proliferation, 5, 8, 12, 52, 91 Cell Respiration, 84, 91, 108, 112, 118 Cell Survival, 91, 101 Cellulose, 90, 91, 114 Central Nervous System, 53, 83, 89, 91, 100, 101, 108, 109, 120 Central Nervous System Infections, 91, 101 Cerebral, 88, 91, 97, 100, 117 Cerebral hemispheres, 88, 91, 100 Cerebrospinal, 26, 37, 91 Cerebrospinal fluid, 26, 37, 91 Character, 85, 91, 94 Chemotherapeutics, 5, 54, 91 Chemotherapy, 5, 36, 37, 39, 85, 91 Cholesterol, 88, 91, 107, 122 Choline, 83, 91 Choroid, 91, 118 Chromaffin System, 92, 96 Chromatin, 87, 92, 97 Chromosomal, 5, 92, 119 Chromosome, 92, 101, 120 Chronic, 6, 35, 53, 88, 92, 104, 113, 115, 116, 119, 122, 126 Circulatory system, 92, 96 Cirrhosis, 92, 115 CIS, 92, 118 Clinical trial, 4, 57, 67, 92, 96, 116, 118 Cloning, 88, 92 Cognition, 45, 92 Collagen, 26, 54, 84, 88, 92, 99, 114, 115 Colloidal, 92, 96, 120 Complement, 85, 92, 93, 107, 114, 120 Complement Activation, 85, 93 Complementary and alternative medicine, 29, 42, 93 Complementary medicine, 29, 93 Compulsions, 7, 93, 111 Computational Biology, 67, 93 Cones, 93, 118 Conjugated, 93, 94, 110 Conjunctiva, 93, 104, 124

129

Connective Tissue, 89, 92, 93, 98, 99, 106, 108, 119 Constitutional, 93, 109 Contraindications, ii, 93 Coordination, 93, 109 Coronary, 85, 93, 94, 108, 110 Coronary Circulation, 85, 94 Coronary Thrombosis, 94, 108, 110 Cranial, 94, 101, 110, 124 Craniocerebral Trauma, 94, 101 Curative, 94, 123 Cutaneous, 18, 88, 94, 114 Cyclic, 89, 94, 115 Cystoscopy, 17, 94 Cytochrome, 4, 6, 15, 94 Cytoplasm, 87, 88, 91, 94, 97, 109, 119 Cytotoxic, 5, 11, 30, 49, 94, 117, 118 Cytotoxicity, 11, 19, 21, 32, 40, 94 D Deamination, 94, 109 Degenerative, 94, 101 Deletion, 86, 94 Dentate Gyrus, 94, 102 Depolarization, 18, 94 DES, 85, 94 Deuterium, 95, 102 Diagnostic procedure, 43, 60, 95 Diarrhea, 49, 95 Diastolic, 95, 103 Diencephalon, 95, 103 Digestion, 88, 95, 96, 106, 122 Digestive tract, 95, 121 Dihydroxy, 95, 119 Dimerization, 51, 95 Dimethyl, 10, 15, 95 Diploid, 95, 114 Direct, iii, 38, 45, 54, 95, 118 Discrete, 6, 95 Dissociation, 84, 95 Diuresis, 89, 95 DNA Topoisomerase, 95, 100 Dopamine, 24, 30, 34, 95, 109, 111, 113 Dose-dependent, 5, 95 Double-blind, 7, 96 Drug Interactions, 4, 6, 96 Drug Monitoring, 7, 96 Drug Tolerance, 96, 123 Dyspepsia, 53, 96 E Efficacy, 6, 7, 11, 26, 36, 47, 50, 96 Elastin, 92, 96 Electrons, 86, 96, 105, 112, 117, 118

Electrophoresis, 38, 96 Embryo, 96, 104, 115 Emodin, 51, 96 Empirical, 46, 96 Endocardium, 96, 124 Endocrine Glands, 96 Endocrine System, 53, 96 Endogenous, 95, 96 Endometrial, 17, 96 Endometrium, 96 Endopeptidases, 96, 116 Endoscopic, 94, 97, 108 Endothelial cell, 54, 96, 97, 123, 124 Endothelium, 97, 124 Entorhinal Cortex, 97, 102 Environmental Health, 66, 68, 97 Enzymatic, 84, 89, 90, 93, 97, 102, 107, 118 Enzyme, 4, 5, 10, 35, 83, 89, 90, 95, 97, 99, 100, 102, 105, 109, 114, 116, 122, 123, 126 Eosinophils, 97, 105 Epidermal, 16, 97, 107, 126 Epidermal Growth Factor, 16, 97 Epidermis, 83, 87, 88, 97, 113 Epidermoid carcinoma, 97, 121 Epinephrine, 83, 95, 97, 111, 124 Epithelial, 48, 83, 90, 97, 101, 112 Epithelial Cells, 48, 97, 101 Epithelium, 88, 97 Erythrocytes, 85, 89, 97, 120 Esophageal, 13, 97 Esophagus, 95, 97, 113, 122 Estrogen, 97, 120, 122 Ethylmaleimide, 25, 35, 98 Etoposide, 5, 98 Exhaustion, 85, 98 Extensor, 98, 116 External-beam radiation, 98, 105, 117, 126 Extraction, 26, 38, 51, 98 Extrapyramidal, 95, 98 F Family Planning, 67, 98 Fat, 89, 90, 98, 106, 109, 115, 119, 120 Fatigue, 98, 101 Fibrosarcoma, 36, 37, 98 Fibrosis, 48, 98, 119 Fibrositis, 53, 98 Fixation, 98, 120 Fluorescence, 4, 11, 12, 14, 17, 18, 27, 31, 98 Fluoxetine, 7, 98 Fluvoxamine, 5, 7, 99 Folate, 54, 99

130

Hypericin

Folic Acid, 99 Folliculitis, 86, 99 Free Radicals, 86, 95, 99 Fungi, 25, 86, 87, 99, 108, 125, 126 G Gamma Rays, 99, 117, 118 Gas, 85, 99, 102 Gastric, 90, 97, 99, 102, 111 Gastric Acid, 99, 111 Gastrointestinal, 97, 99, 120 Gastrointestinal tract, 99, 120 Gelatin, 99, 100, 123 Gene, 17, 47, 88, 99, 106, 120 Gene Expression, 17, 99 Gene Therapy, 47, 99 Genetic Code, 100, 111 Genetics, 83, 100 Genistein, 53, 100 Gland, 92, 100, 106, 112, 116, 119, 122, 123 Glioblastoma, 24, 34, 59, 100 Glioma, 12, 14, 16, 17, 100 Glucokinase, 100, 102 Glucose, 91, 100, 101, 102, 104, 121 Glycerol, 100, 113 Glycerophospholipids, 100, 113 Glycine, 84, 100, 111, 120 Glycoprotein, 38, 100, 123, 124 Governing Board, 100, 115 Graft, 49, 100 Graft Rejection, 49, 100 Graft-versus-host disease, 49, 100 Gravis, 49, 100 Growth factors, 52, 101, 108 H Hair follicles, 99, 101, 126 Haploid, 101, 114 Haptens, 84, 101 Headache, 53, 89, 101, 104 Headache Disorders, 101 Heart failure, 53, 101 Heme, 94, 101, 110, 115 Hemoglobin, 85, 97, 101, 115 Hemoglobin A, 101, 115 Hemoglobinopathies, 99, 101 Hemorrhage, 94, 101 Hemostasis, 101, 120 Hepatitis, 35, 48, 72, 101 Hepatocytes, 6, 101 Heredity, 99, 100, 101 Herpes, 8, 44, 45, 102 Herpes Zoster, 102 Heterogeneity, 84, 102

Heterotrophic, 99, 102 Heterotropic, 6, 102 Hexokinase, 17, 102 Hippocampus, 25, 35, 94, 102, 122 Histamine, 85, 102 Histamine Release, 85, 102 Homologous, 99, 102, 120 Hormone, 94, 97, 102, 104, 107, 119, 123 Humoral, 54, 100, 102 Humour, 102 Hydrogen, 15, 52, 83, 90, 95, 102, 106, 109, 111, 112, 116 Hydrogen Peroxide, 15, 102, 106 Hydrolysis, 83, 102, 115 Hydrophobic, 47, 100, 102 Hydroxylysine, 92, 103 Hydroxyproline, 84, 92, 103 Hypersensitivity, 84, 103, 119, 120 Hypertension, 53, 101, 103 Hyperthermia, 27, 40, 103 Hypervascular, 50, 103 Hypnotic, 103, 108 Hypothalamus, 25, 35, 95, 103 Hypoxic, 19, 103 I Imipramine, 39, 103 Immune response, 8, 49, 86, 87, 100, 101, 103, 106, 120, 125 Immune Sera, 103 Immune system, 49, 88, 103, 104, 106, 109, 126 Immunization, 48, 103, 120 Immunodeficiency, 9, 19, 44, 47, 49, 57, 103 Immunodeficiency syndrome, 57, 103 Immunogenic, 48, 103 Immunologic, 103, 118 Immunology, 48, 84, 103 Immunosuppression, 103, 112 Immunosuppressive, 49, 104 Impairment, 46, 104 Implant radiation, 104, 105, 117, 126 In vitro, 4, 5, 6, 8, 12, 13, 15, 16, 17, 24, 27, 29, 34, 47, 99, 104 In vivo, 4, 5, 6, 8, 11, 13, 15, 24, 99, 104 Incision, 104, 105 Induction, 4, 16, 24, 34, 49, 104 Infarction, 94, 104, 108, 110 Infection, 35, 48, 57, 88, 103, 104, 106, 110, 112, 113, 119, 122, 126 Inflammation, 8, 86, 98, 99, 101, 102, 104, 107, 114, 119, 122, 123, 126

131

Influenza, 44, 45, 104 Inotropic, 95, 104 Insomnia, 53, 104 Instillation, 12, 104 Insulator, 104, 109 Insulin, 49, 104 Insulin-dependent diabetes mellitus, 104 Internal radiation, 104, 105, 117, 126 Interstitial, 33, 89, 105, 126 Intervertebral, 105, 117, 119 Intervertebral Disk Displacement, 105, 117, 119 Intracellular, 24, 34, 89, 104, 105, 107, 118, 119, 125 Intravesical, 12, 105 Intrinsic, 84, 88, 105 Invasive, 12, 105 Ionizing, 84, 105, 117 Ions, 89, 95, 102, 105 Irinotecan, 5, 105 Irradiation, 49, 51, 52, 105, 126 Isoenzyme, 102, 105 Itraconazole, 5, 105 K Kb, 66, 105 Kinetic, 4, 6, 105 L Laser therapy, 24, 105 Laxative, 96, 105, 121 Lens, 27, 37, 105 Lesion, 88, 105, 106 Leukemia, 25, 35, 49, 83, 100, 105 Leukocytes, 50, 88, 89, 97, 105, 109, 124 Life cycle, 99, 105 Ligament, 106, 116 Ligands, 4, 106 Lipid, 15, 19, 91, 100, 104, 106, 108, 109, 113 Lipid Peroxidation, 15, 19, 106 Liposomes, 21, 106 Liver, 83, 88, 90, 92, 99, 101, 102, 106, 109, 115 Localization, 11, 106 Localized, 98, 104, 106, 109, 114, 119 Locomotion, 106, 114 Lymph, 92, 97, 102, 106, 122 Lymph node, 106 Lymphatic, 54, 97, 104, 106, 108, 121, 123 Lymphatic system, 106, 121, 123 Lymphocyte, 49, 86, 104, 106, 107 Lymphoid, 86, 106 Lymphoma, 16, 18, 106

Lymphoproliferative, 18, 106 Lysine, 103, 106, 115 M Macrolides, 5, 106 Major Histocompatibility Complex, 49, 106 Malignancy, 48, 107 Malignant, 12, 14, 16, 17, 18, 32, 52, 83, 85, 86, 90, 100, 107, 110, 117 Malignant tumor, 90, 107 Mammary, 107, 122 Mastication, 107, 124 Mediate, 95, 107 Mediator, 107, 120 MEDLINE, 67, 107 Melanin, 107, 113, 124 Melanocytes, 107 Melanoma, 19, 107 Membrane, 18, 47, 87, 91, 93, 94, 106, 107, 109, 110, 111, 112, 114, 118 Membrane Lipids, 107, 114 Membrane Proteins, 106, 107 Memory, 46, 85, 107 Meninges, 91, 94, 107 Meningitis, 105, 107 Menopause, 51, 107 Menstruation, 107 Mental, iv, 4, 46, 66, 68, 92, 95, 98, 107, 108, 116, 117 Mental Health, iv, 4, 66, 68, 108, 117 Mesenchymal, 97, 108 Metabolite, 95, 108 Metastasis, 108 Metastatic, 14, 108 Methanol, 26, 108 Methionine, 54, 95, 108, 122 MI, 4, 46, 81, 108 Microbe, 108, 123 Microglia, 87, 108, 109 Microorganism, 48, 108, 126 Midazolam, 6, 108 Mitochondria, 17, 108 Mitochondrial Swelling, 108, 110 Mitosis, 87, 108 Mitotic, 98, 108, 125 Modeling, 17, 109 Molecular, 5, 6, 13, 15, 17, 34, 35, 39, 46, 47, 67, 69, 88, 93, 94, 106, 109, 118, 122, 123, 124 Molecule, 86, 88, 93, 95, 101, 102, 109, 112, 118, 123, 125 Monitor, 6, 109, 111

132

Hypericin

Monoamine, 25, 34, 35, 109, 124 Monoamine Oxidase, 34, 109, 124 Monoclonal, 105, 109, 117, 126 Monocytes, 105, 109 Mononuclear, 109, 124 Motility, 109, 120 Motion Sickness, 109, 110 Mucosa, 109, 122 Multidrug resistance, 49, 109 Multiple sclerosis, 49, 109 Mutagenesis, 4, 6, 109 Mutagens, 109 Myalgia, 104, 109 Myasthenia, 49, 109 Myelin, 109 Myelosuppression, 85, 109 Myocardial Ischemia, 85, 110 Myocardium, 85, 108, 110 Myoglobin, 110, 115 N Nasal Mucosa, 104, 110 Nausea, 49, 110, 112 Necrosis, 10, 15, 33, 86, 100, 104, 108, 110 Nelfinavir, 5, 110 Neoplasm, 110, 112 Neoplastic, 106, 110 Nerve, 83, 85, 90, 107, 109, 110, 117, 118, 119, 121, 124 Nervous System, 91, 107, 110, 111, 122, 124 Neural, 102, 108, 109, 110 Neuralgia, 53, 110 Neuroblastoma, 12, 110 Neurologic, 100, 110 Neuromuscular, 83, 110 Neuromuscular Junction, 83, 110 Neuronal, 89, 110 Neuropathy, 110, 119 Neurophysiology, 94, 110 Neurosecretory Systems, 96, 110 Neuroses, 53, 110 Neurotransmitter, 83, 84, 95, 100, 102, 111, 124 Neutrons, 84, 105, 111, 117 Neutrophil, 16, 111 Norepinephrine, 83, 95, 111 Nuclear, 5, 87, 89, 96, 99, 100, 110, 111 Nuclei, 84, 96, 99, 108, 111, 116 Nucleic acid, 47, 100, 109, 111, 117, 125 Nucleus, 87, 88, 92, 94, 95, 97, 99, 105, 109, 111, 116

O Obsession, 93, 111 Obsessive-Compulsive Disorder, 99, 111 Omeprazole, 15, 25, 26, 35, 37, 111 Oncogenic, 47, 111 Ophthalmologic, 52, 111 Ophthalmology, 27, 98, 111 Opportunistic Infections, 57, 112 Opsin, 112, 118, 119 Optic Chiasm, 103, 112 Osmosis, 112 Osmotic, 38, 108, 112, 120 Outpatient, 112 Oxidation, 83, 86, 94, 106, 112 Oxidative metabolism, 4, 84, 112 P Palate, 112, 122 Palliative, 112, 123 Pancreas, 104, 112 Pancreatic, 13, 90, 112 Pancreatic cancer, 13, 112 Panic, 99, 103, 112 Panic Disorder, 99, 103, 112 Papilloma, 48, 112 Parietal, 111, 113 Paroxetine, 7, 113 Paroxysmal, 85, 101, 113 Partial response, 7, 113 Particle, 113, 124, 125 Pathologic, 87, 93, 103, 113, 116 Pathologic Processes, 87, 113 Patient Education, 72, 76, 78, 81, 113 Pelvic, 113, 116 Pemphigus, 49, 83, 113 Penicillin, 86, 113 Peptide, 84, 96, 113, 115, 116 Perennial, 45, 53, 103, 113 Peripheral stem cells, 100, 113 Perylene, 50, 113 Pesticides, 88, 113 Pharmaceutical Preparations, 31, 91, 99, 113 Pharmacodynamic, 5, 113 Pharmacokinetic, 5, 37, 57, 113 Pharmacologic, 54, 85, 113, 123 Pharynx, 104, 113 Phenylalanine, 113, 124 Phospholipids, 54, 98, 107, 113 Phosphorus, 89, 114 Phosphorylates, 52, 114 Phosphorylation, 25, 36, 52, 114, 116 Photoallergy, 114

133

Photodynamic therapy, 10, 11, 12, 13, 15, 17, 19, 20, 21, 25, 26, 27, 36, 37, 40, 50, 114 Photosensitivity, 32, 114 Photosensitization, 11, 14, 15, 20, 50, 114 Photosensitizer, 33, 50, 114 Phototherapy, 13, 14, 114 Physiologic, 84, 88, 107, 114, 118 Pigment, 10, 46, 107, 110, 114, 118 Plants, 7, 44, 51, 53, 91, 96, 100, 103, 111, 114, 115, 119, 123 Plasma, 11, 26, 31, 37, 38, 86, 91, 99, 101, 114, 120 Plasma protein, 114, 120 Platelet Aggregation, 85, 114 Pneumonia, 93, 114 Podophyllotoxin, 98, 114 Poisoning, 110, 115 Pollen, 115, 117 Polylysine, 47, 115 Polypeptide, 84, 92, 97, 110, 115, 116, 126 Polysaccharide, 86, 91, 115 Polyunsaturated fat, 54, 115 Porphyrins, 50, 115 Posterior, 91, 112, 115, 119 Postnatal, 115, 122 Practice Guidelines, 68, 115 Precursor, 91, 95, 97, 111, 113, 115, 124 Prevalence, 7, 115 Primary Biliary Cirrhosis, 49, 115 Probe, 113, 115 Progression, 27, 85, 115 Progressive, 92, 96, 110, 115 Proline, 92, 103, 115 Promyelocytic leukemia, 13, 116 Prostate, 14, 21, 116 Protease, 5, 110, 116, 119 Protease Inhibitors, 5, 116 Protein C, 6, 87, 116 Protein Conformation, 6, 116 Protein Kinases, 52, 116 Protein S, 88, 100, 116, 119 Proteins, 52, 84, 86, 90, 91, 92, 107, 109, 113, 114, 116, 118, 120, 123, 125 Protein-Tyrosine Kinase, 100, 116 Protocol, 7, 116 Protons, 84, 102, 105, 116, 117 Protozoa, 108, 116, 125 Psoriasis, 49, 50, 86, 116 Psychic, 108, 111, 116, 117, 120 Psychogenic, 51, 116 Psychology, 93, 95, 116

Psychomotor, 45, 117 Public Health, 6, 68, 117 Public Policy, 67, 117 Publishing, 8, 117 Pulse, 109, 117 Purines, 117, 120 Pyrimidines, 117, 120 Q Quaternary, 116, 117 Quercetin, 40, 53, 117 R Radiation, 15, 37, 85, 98, 99, 103, 104, 105, 117, 126 Radiation therapy, 98, 105, 117, 126 Radiculopathy, 117, 119 Radioactive, 102, 104, 105, 111, 117, 126 Radioimmunotherapy, 117, 118 Radiolabeled, 105, 117, 126 Radiotherapy, 17, 89, 105, 117, 126 Randomized, 7, 96, 118 Reagent, 98, 118 Receptor, 6, 13, 16, 38, 48, 86, 95, 118, 120 Receptors, Serotonin, 118, 120 Recombination, 99, 118 Rectum, 95, 99, 116, 118 Refer, 1, 89, 92, 98, 99, 102, 106, 111, 117, 118, 123 Refraction, 118, 121 Regimen, 96, 118 Renal pelvis, 118, 124 Respiration, 109, 118 Retina, 91, 93, 105, 112, 118, 119 Retinal, 12, 112, 118, 119 Retinal pigment epithelium, 12, 118 Retinol, 118, 119 Retroviral vector, 99, 119 Retrovirus, 46, 119 Rheumatism, 119 Rheumatoid, 49, 119 Rheumatoid arthritis, 49, 119 Rhodopsin, 112, 118, 119 Ribose, 83, 119 Ribosome, 119, 124 Rickettsiae, 119, 125 Ritonavir, 5, 119 Rods, 118, 119 Rose Bengal, 9, 19, 119 Rutin, 53, 117, 119 S Salivary, 112, 119, 122 Sciatica, 53, 119 Scleroderma, 49, 119

134

Hypericin

Sclerosis, 109, 119 Screening, 92, 119 Sebaceous, 119, 126 Secretion, 97, 102, 104, 108, 111, 119, 120 Secretory, 111, 120 Sedative, 103, 108, 120 Segregation, 5, 118, 120 Seizures, 100, 113, 120 Selective estrogen receptor modulator, 120, 122 Semen, 116, 120 Semisynthetic, 89, 98, 120 Sensitization, 17, 50, 114, 120 Serine, 52, 96, 120 Serotonin, 7, 98, 99, 109, 111, 113, 118, 120, 124 Sertraline, 7, 120 Serum, 16, 17, 18, 20, 26, 33, 38, 85, 92, 93, 103, 120, 124 Serum Albumin, 16, 17, 18, 20, 120 Sex Characteristics, 120, 123 Side effect, 7, 46, 72, 83, 88, 109, 120, 123 Smooth muscle, 85, 89, 102, 120 Soft tissue, 89, 98, 120 Soft tissue sarcoma, 98, 120 Solid tumor, 12, 85, 121 Solvent, 100, 108, 112, 121 Somatic, 102, 108, 121 Sorbitol, 102, 121 Soybean Oil, 115, 121 Spasmogenic, 85, 121 Specialist, 73, 121 Species, 4, 7, 32, 38, 46, 53, 72, 83, 84, 97, 108, 109, 121, 122, 124, 125, 126 Specificity, 84, 89, 96, 121 Spectrum, 5, 20, 54, 108, 121 Spinal cord, 87, 90, 91, 107, 110, 117, 121 Spinal Nerve Roots, 117, 119, 121 Spleen, 106, 121 Squamous, 14, 19, 24, 97, 121, 122 Squamous cell carcinoma, 14, 19, 24, 97, 121 Squamous cells, 121, 122 Steady state, 6, 122 Stem Cells, 49, 113, 122 Stimulant, 89, 102, 122 Stomach, 95, 97, 99, 102, 110, 113, 121, 122 Stomatitis, 44, 45, 122 Stress, 45, 90, 110, 119, 122 Subacute, 104, 122 Subarachnoid, 101, 122 Subclinical, 104, 120, 122

Subiculum, 102, 122 Submaxillary, 97, 122 Subspecies, 121, 122 Substrate, 90, 122, 124 Sulfur, 108, 122 Superoxide, 16, 122 Sympathomimetic, 95, 97, 111, 122, 124 Symphysis, 116, 122 Synergistic, 27, 40, 53, 122 Systemic, 36, 45, 49, 50, 89, 97, 104, 105, 117, 119, 122, 124, 126 Systolic, 103, 122 T Tamoxifen, 5, 17, 120, 122 Temporal, 101, 102, 123 Testosterone, 6, 123 Therapeutics, 53, 109, 123 Threonine, 52, 120, 123 Threshold, 103, 123 Thrombin, 114, 116, 123 Thrombomodulin, 116, 123 Thymus, 103, 106, 123 Thyroid, 123, 124 Thyroid Gland, 123 Thyroiditis, 49, 123 Tolerance, 17, 123 Topical, 36, 44, 45, 102, 123 Topoisomerase inhibitors, 105, 123 Toxic, iv, 4, 94, 108, 110, 114, 123 Toxicity, 9, 21, 40, 45, 96, 123 Toxicology, 25, 68, 123 Toxin, 123 Transcriptase, 57, 119, 123 Transduction, 52, 124 Transfection, 88, 99, 124 Transfer Factor, 103, 124 Transitional cell carcinoma, 10, 19, 24, 33, 124 Translation, 47, 84, 124 Transmitter, 83, 87, 95, 107, 111, 124 Transplantation, 103, 106, 124 Trauma, 110, 124 Tricyclic, 103, 124 Trigeminal, 53, 124 Tryptophan, 92, 120, 124 Tumor Necrosis Factor, 33, 124 Tumor suppressor gene, 47, 124 Tunica, 54, 109, 124 Tunica Intima, 54, 124 Tyramine, 109, 124 Tyrosine, 16, 52, 95, 116, 124

135

U Ureter, 118, 124 Urethra, 116, 124, 125 Urinary, 19, 94, 125 Urine, 88, 95, 97, 118, 124, 125 Uterus, 96, 107, 125 V Vaccines, 48, 125 Vascular, 26, 36, 37, 54, 91, 97, 101, 104, 123, 125 Vasodilator, 95, 102, 125 Vector, 124, 125 Vein, 111, 125 Ventricle, 102, 103, 117, 122, 125 Venules, 89, 90, 125 Vesicular, 44, 45, 102, 125 Veterinary Medicine, 67, 125 Vinblastine, 5, 125 Vinca Alkaloids, 125 Vincristine, 5, 125 Viral, 3, 44, 45, 46, 47, 48, 51, 53, 57, 104, 111, 119, 124, 125, 126

Viral Proteins, 47, 125 Virulence, 87, 123, 125 Virus, 8, 9, 19, 20, 35, 44, 45, 46, 47, 48, 57, 87, 91, 119, 124, 125 Virus Replication, 44, 125 Vitreous, 105, 118, 125 Vitro, 5, 126 Vivo, 5, 18, 126 Vulgaris, 49, 83, 126 W Warts, 48, 115, 126 White blood cell, 86, 105, 106, 109, 111, 126 X Xenograft, 85, 126 X-ray, 6, 98, 99, 105, 111, 117, 118, 126 X-ray therapy, 105, 126 Y Yeasts, 99, 126 Z Zymogen, 116, 126

136

Hypericin

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