IPOIC CID 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., 1960Lipoic Acid: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84007-5 1. Lipoic Acid-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.
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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 lipoic acid. 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 LIPOIC ACID .............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lipoic Acid .................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 24 The National Library of Medicine: PubMed ................................................................................ 25 CHAPTER 2. NUTRITION AND LIPOIC ACID .................................................................................... 45 Overview...................................................................................................................................... 45 Finding Nutrition Studies on Lipoic Acid................................................................................... 45 Federal Resources on Nutrition ................................................................................................... 52 Additional Web Resources ........................................................................................................... 53 CHAPTER 3. ALTERNATIVE MEDICINE AND LIPOIC ACID.............................................................. 55 Overview...................................................................................................................................... 55 National Center for Complementary and Alternative Medicine.................................................. 55 Additional Web Resources ........................................................................................................... 61 General References ....................................................................................................................... 64 CHAPTER 4. DISSERTATIONS ON LIPOIC ACID ............................................................................... 65 Overview...................................................................................................................................... 65 Dissertations on Lipoic Acid........................................................................................................ 65 Keeping Current .......................................................................................................................... 66 CHAPTER 5. CLINICAL TRIALS AND LIPOIC ACID .......................................................................... 67 Overview...................................................................................................................................... 67 Recent Trials on Lipoic Acid........................................................................................................ 67 Keeping Current on Clinical Trials ............................................................................................. 68 CHAPTER 6. PATENTS ON LIPOIC ACID .......................................................................................... 71 Overview...................................................................................................................................... 71 Patents on Lipoic Acid ................................................................................................................. 71 Patent Applications on Lipoic Acid ............................................................................................. 93 Keeping Current ........................................................................................................................ 124 CHAPTER 7. BOOKS ON LIPOIC ACID ............................................................................................ 127 Overview.................................................................................................................................... 127 Book Summaries: Online Booksellers......................................................................................... 127 Chapters on Lipoic Acid............................................................................................................. 128 CHAPTER 8. PERIODICALS AND NEWS ON LIPOIC ACID .............................................................. 131 Overview.................................................................................................................................... 131 News Services and Press Releases.............................................................................................. 131 Academic Periodicals covering Lipoic Acid ............................................................................... 133 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 137 Overview.................................................................................................................................... 137 NIH Guidelines.......................................................................................................................... 137 NIH Databases........................................................................................................................... 139 Other Commercial Databases..................................................................................................... 142 The Genome Project and Lipoic Acid ......................................................................................... 142 APPENDIX B. PATIENT RESOURCES ............................................................................................... 147 Overview.................................................................................................................................... 147 Patient Guideline Sources.......................................................................................................... 147 Finding Associations.................................................................................................................. 149 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 151 Overview.................................................................................................................................... 151 Preparation................................................................................................................................. 151
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Finding a Local Medical Library................................................................................................ 151 Medical Libraries in the U.S. and Canada ................................................................................. 151 ONLINE GLOSSARIES................................................................................................................ 157 Online Dictionary Directories ................................................................................................... 157 LIPOIC ACID DICTIONARY ..................................................................................................... 159 INDEX .............................................................................................................................................. 231
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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 lipoic acid 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 lipoic acid, 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 lipoic acid, 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 lipoic acid. 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 lipoic acid, 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 lipoic acid. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON LIPOIC ACID Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lipoic acid.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and lipoic acid, 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 “lipoic acid” (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: •
Alpha-Lipoic Acid: A Potential Role in Diabetes? Source: Dietitian's Edge. 2(1): 22-23. January-February 2001. Contact: Available from Dietitian's Edge. 70 Hilltop Road, 3rd Floor, Ramsey, NJ 07446. (201) 825-2552. Fax (201) 825-0553. E-mail:
[email protected]. Summary: This article examines the potential benefits of alpha lipoic acid in treating diabetes and its associated complications. Alpha lipoic acid is a nonessential vitamin like compound containing sulfur. Very small amounts are found in foods such as red meat, yeast, potatoes, and spinach. Dietary supplements contain doses ranging from 50 to 300 milligrams per pill or capsule. Supplemental alpha lipoic acid could theoretically benefit a condition such as diabetes by acting as an antioxidant limiting free radical damage, preventing glycation of proteins, or enhancing glucose uptake. Doses of alpha lipoic
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Lipoic Acid
acid up to 2,000 milligrams per day have been well tolerated with no serious adverse effects reported. Possible side effects include allergic skin reactions and possible hypoglycemia. There are no studies determining the safety of long term, daily supplementation in humans. The article reviews both animal and human studies investigating the effects of alpha lipoic acid. In vitro and animal studies suggest that alpha lipoic acid may play a beneficial role in conditions related to diabetes such as cataracts, glucose uptake, and oxidative stress. Small human studies also indicate that alpha lipoic acid supplementation may reduce markers of oxidative stress and improve glucose utilization. Evidence regarding the effect of alpha lipoic acid on diabetic neuropathy is mixed. The article recommends that dietitians inform their patients that there is some evidence that alpha lipoic acid is beneficial but that much more controlled research is needed. 12 references.
Federally Funded Research on Lipoic Acid The U.S. Government supports a variety of research studies relating to lipoic acid. 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 lipoic acid. 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 lipoic acid. The following is typical of the type of information found when searching the CRISP database for lipoic acid: •
Project Title: ALZHEIMER'S DISEASE IN DOWN SYNDROME: ANTIOXIDANT TRIAL Principal Investigator & Institution: Lott, Ira T.; Pediatrics; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The objective of this pilot clinical trial is to obtain information on the tolerability, safety, and efficacy of a high potency combinatorial supplement in the treatment of Alzheimer disease (AD) in Down syndrome (DS). Individuals with DS have an increased incidence of AD and evidence of oxidative stress in brain. The DS population is an excellent candidate for antioxidant intervention. The trial will conform to a double-blind, placebo-controlled, and repeated analysis of variance design. The supplement will consist two cellular antioxidants (vitamins E 900 IU/day and C 200 mg/day) and a mitochondrial antioxidant (alpha-lipoic acid 600 mg/day). The clinical diagnosis of AD in DS will be made by the investigators utilizing their previous experience with DSM-IV criteria for dementia in DS. There are three
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
specific aims: 1) to determine whether cognitive measures are improved by antioxidant supplementation. Outcome measures have been shown to have reliability and validity for DS. They comprise three informant scales (Dementia Rating Scale for Persons with Mental Retardation, Neuropsychology Behavior and Affect Profile, Vineland Adaptive Scales) and three direct assessments (Severe Impairment Battery, Brief Praxis Test, and the FULD-Object/Memory Test-modified); 2) to determine whether plasma biomarkers of lipid oxidative damage (malondialdehyde, isoprostanes), protein oxidative damage (carbonyl group formation), levels of beta-amyloid, and vitamin E levels will be altered in subjects receiving the diet; and 3) to determine the safety and tolerability of the antioxidant supplementation utilizing checklists for adverse events, clinical chemistries, and measures of medication compliance. All study measures will be obtained at baseline and at 6-month intervals for a total of 24 months of treatment. All study patients will be on an acetylcholinesterase inhibitor. Power analysis configured on the primary outcome measures supports a study group of 30 treated and 30 placebo randomized patients. Database management will facilitate analysis of the 24-month observations. The data from this study is intended to provide information relevant to the indications for a multicenter definitive clinical trial of antioxidants in DS. Since the process resulting in AD in DS is age dependent across the lifespan, a positive result from this pilot trial may have implications for utilizing high potency combinatorial antioxidants at earlier age epochs in DS. The pilot trial should also contribute information as to the possible role of antioxidants in the treatment or prevention of AD in the general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIOXIDANT FUNCTIONS OF LIPOIC ACID Principal Investigator & Institution: May, James M.; Associate Professor; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Lipoic acid has been promoted as an antioxidant effective in a variety of conditions in which there is oxidant damage to the vascular bed, including diabetes mellitus and atherosclerosis. An early manifestation of such damage is dysfunction of the vascular endothelium due to deficient generation or excessive destruction of nitric oxide. Whether lipoic acid can spare nitric oxide and thus lessen endothelial dysfunction is an unanswered question with important clinical implications. We have shown that cultured human endothelial cells take up lipoic acid and reduce it to dihydrolipoic acid. The latter protects the cells in a concentration dependent manner against both internal and external oxidant stresses, and this is associated with an increase in nitric oxide generation by the cells. In this proposal we seek to confirm these novel results, to clarify the mechanism by which they occur, and to determine whether they might be relevant to clinical atherosclerosis. In the first aim we will assess the antioxidant efficacy of lipoic acid in endothelial cells in culture. Oxidant stress will be initiated by agents with biological relevance for the cells, including H202 and minimally oxidized human low density lipoprotein (LDL). Cell protection by lipoic acid will be assessed using a fluorescence-based assay of intracellular oxidant stress, by measuring lipid peroxidation as F2-isoprostanes, and by assay of cellular antioxidants. In the second aim, we will determine whether and how these antioxidant effects of lipoic acid can explain its ability to enhance endothelial nitric oxide generation. We will focus on whether intracellular dihydrolipoic acid acts directly or through glutathione, whether it is synergistic with ascorbic acid, and whether it prevents or reverses impaired nitric oxide generation due to oxidized LDL. Showing that lipoic acid enhances endothelial nitric oxide generation and action will form the basis for a small double-blind, placebo-
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Lipoic Acid
controlled clinical trial of its ability to reverse nitric oxide-dependent endothelial dysfunction (aim 3). Subjects with increased oxidant stress due to hypercholesterolemia will be studied before and after taking lipoic acid or placebo for 8 weeks with regard to changes in plasma and urinary F2-isoprostanes and flow-mediated brachial artery dilation. Despite the widespread use of lipoic acid, these studies are necessary to establish the biological basis and rationale for the clinical use of the agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSEMBLY AND FUNCTION OF BIOLOGICAL IRON-SULFUR CLUSTERS Principal Investigator & Institution: Johnson, Michael K.; Distinguished Research Professor of Chem; Chemistry; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2004 Summary: (Adapted from applicant's abstract) Iron-sulfur clusters are present in more than 120 different types of enzymes or proteins and constitute one of the most ancient, ubiquitous and structurally diverse classes of biological prosthetic groups. Although their primary role lies in mediating biological electron transport, iron-sulfur centers are known to constitute the active sites of numerous enzymes and to have important structural and regulatory roles. However, the functional diversity of biological ironsulfur clusters has yet to be fully defined, and the mechanism of cluster biosynthesis, which is central to cellular iron homeostasis and the regulatory roles of iron-sulfur clusters, is still poorly understood. The long-term goal of this project is a molecular-level understanding of cluster biosynthesis and of the newly emerging roles of biological iron-sulfur clusters in disulfide reduction, initiating radical reactions in Sadenosylmethionine-dependent enzymes, and providing the sulfur for biosynthesis of biotin and lipoic acid. Ultimately this will lead to enhanced understanding of iron homeostasis and human diseases related to iron overload and defects or inhibition of respiratory chain enzymes. The approach involves using molecular biology techniques to effect large scale expression and/or site-specific changes in the target enzymes and proteins, biochemical and enzymatic assays, and the application of biophysical spectroscopic techniques (electron paramagnetic resonance, absorption, magnetic circular dichroism, resonance, absorption, magnetic circular dichroism, resonance Raman, Mossbauer and mass spectrometry) that can probe the nature and detailed properties of iron or iron-sulfur centers during catalytic cycling or cluster biosynthesis. The specific systems to be investigated include the proteins involved with nitrogenfixation-specific and general iron-sulfur cluster biosynthesis in Azotobacter vinelandii, biotin synthase from Escherichia coli and ferredoxin:thioredoxin reductase from chloroplasts. The objectives are to establish the mechanism of NifU/NifS- and IscU/IscS-mediated iron-sulfur cluster biosynthesis, determine the role of the ironsulfur cluster in ferredoxin:thioredoxin reductase in mediating reductive cleavage of the active-site disulfide, characterize the cluster transformation that is responsible for providing the sulfur for biotin biosynthesis, determine the mechanism of iron-sulfur cluster-mediated reductive cleavage of S-adenosylmethionine in biotin synthase, and develop an in vitro catalytic system for biotin biosynthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CER ON CAM ANTIOXIDANT THERAPIES (CERCAT) Principal Investigator & Institution: Frei, Balz B.; Professor and Endowed Chair; None; Oregon State University Corvallis, or 973391086
Studies
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Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-MAY-2008 Summary: This Program Project is based in the Linus Pauling Institute, an emerging international leader in research and education on micronutrients and antioxidants, and one of a few centers in the US to focus entirely on health promotion and disease prevention by dietary and CAM approaches. The Center of Excellence for Research on Complementary and Alternative Medicine (CAM) Antioxidant Therapies (CERCAT) will investigate two specific categories of CAM antioxidants: (i) Antioxidants that modulate the cellular redox environment and, thus, cell signaling and transcriptional activation, e.g. by affecting critical thiols with a low pKa or upregulating endogenous antioxidant systems. The CAM antioxidants to be investigated from this category are dithiol compounds (e.g. alpha-Iipoic acid) and metal chelators (e.g. EDTA and desferrioxamine). (ii) Highly conjugated or aromatic compounds that inhibit tyrosine nitration by peroxynitrite and other reactive nitrogen species. The principal antioxidant to be examined in this category is uric acid. Using cell culture studies and relevant animal models, CERCAT will determine the molecular and cellular mechanisms of action of these CAM antioxidants, and their safety and efficacy in treating amyotrophic lateral sclerosis (ALS) and cardiovascular diseases (CVD) and reversing the loss of cellular resistance to stress that occurs with aging. These goals of CERCAT are buttressed by NCCAM's "increased emphasis on studies of the mechanism underlying CAM approaches" and its "FY 2003 Research Priorities" of "studies of the biology of EDTA chelation therapy in animal models of CVD" and "neurodegenerative disorders using in vitro studies and animal models." CERCAT's research goals will be accomplished through three highly interactiveprojects: 1) "Metal chelators and thiols in endothelial function, and CVD" (Balz Frei); 2) "Lower vulnerability to toxins in aging by treatment with lipoic acid" (Tory Hagen); and 3) "CAM antioxidants and ALS" (Joseph Beckman). Center Investigators will be aided by an Administrative Core, which handles budgetary, reporting, and external advisory needs. In summary, CERCAT will investigate the efficacy of CAM antioxidants in ALS, CVD and aging, and provide the essential knowledge about the underlying mechanisms, dose-response effects, and relevant biological targets to advance these CAM therapies to human trials; equally important, the studies will test for untoward effects that might discourage CAM antioxidant therapies from proceeding to human studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL MODULATION
OF
RETROVIRUS
CNS
DISEASE
BY
REDOX
Principal Investigator & Institution: Wong, Paul K.; Professor; Carcinogenesis; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 18-JUN-2002; Project End 31-MAY-2006 Summary: The retrovirus tsl, a mutant of Moloney murine leukemia virus, like HIV infection in human, causes a progressive neuroimmunodegenerative (NID) syndrome in mice. Infection in the central nervous system by tsl results in neuronal loss with gliosis and spongiform lesions. Since glial cells but not neurons are infected with the virus, the neuropathogenic mechanism of tsl, like those of HIV, are most likely indirect. We previously demonstrated that accumulation of tsl precursor envelope proteins occurs in the endoplasmic reticulum (ER) of tsl infected astrocytes. This accumulation is accompanied by cell death in tsl-infected astrocytes. We also observed intracellular calcium accumulation and activation of NFkappaB in both astrocytes and neurons m the area of lesions in the CNS of tsl- infected mice. We therefore hypothesize that the excessive accumulation of tsl precursor envelope proteins in the astrocytic ER activates
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Lipoic Acid
ER overload response resulting in excessive Ca2+ release that uncouples mitochondria causing release of toxic reactive oxygen species (ROS). In the CNS of tsl-infected mice there is a significant reduction of cysteine levels. A consequence of cysteine deficiency is the decrease in intracellular glutathione, which provides the major antioxidant defense in cells. This together with our recent finding that tsl decreases catalase levels in infected astrocytes and CNS suggests that the defense against oxidative stress in astrocytes and in the CNS is deficient. The oxidative damaged astrocytes may fail to support the developing neurons, and the release of ROS from astrocytes may also result in damage to neuronal membrane. Both of these effects could in turn result in neuronal death. Glutathione precursor N-acetyl cysteine, or peroxisome proliferator that activate production of catalase, have been shown to ameliorate both the tsl-induced astrocytic death in vitro and to prolong the latency period of tsl-induced neurodegeneration in vivo. Based on these preliminary observations we therefore propose here to: 1) Determine whether tsl induces thiol deficiency and oxidative damage in astrocytes in culture and in the CNS, 2) Elucidate the mechanisms underlying tsl-mediated thiol deficiency and redox stress in astrocytes and neurons in culture and in the CNS, and 3) Determine whether (a) NAC, (b) alpha-lipoic acid/dihydrolipoic acid, (c) peroxisome proliferators, such as PBA, that generate catalase, and (d) other antioxidants, e.g. Oxothiazolidine-4-carboxylate (OTC), either alone or in combination, can prevent or ameliorate tsl-induced astrocyte damage and neurodegeneration in the CNS. This project is focused on a well-characterized animal model. It addresses questions critical to our understanding of thiol deficiency and oxidative stress in retroviral-induced encephalopathy. It also provides a therapeutic rationale for controlling retroviralinduced neurodegeneration Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DELAYING MITOCHONDRIAL DECAY WITH CARNITINE AND LIPOATE Principal Investigator & Institution: Ames, Bruce N.; Professor; Children's Hospital & Res Ctr at Oakland Research Center at Oakland Oakland, Ca 94609 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2002 Summary: The aging of the U.S. population represents an unprecedented challenge, which demands advances in basic and applied research- the proposed studies include both. Evidence continues to accumulate that mitochondria and reactive oxygen species are central to aging. Mitochondria are responsible for the bulk of ATP generation, oxygen consumption, and cellular oxygen radical generation, and are required for calcium homeostasis as well as essential biosynthetic pathways. They are involved in the control and execution of apoptosis, whose malfunction leads to degenerative disorders. The centrality of mitochondria, and their exposure to oxidative stress, have focused attention of their age-related decay, which includes: declines in respiratory and enzymatic activities, decreased membrane potential, increased oxidant generation, increased oxidative damage, alterations in membrane lipid profiles, and decreased transcriptional activity. What is not know, however, is whether mitochondrial decay itself is responsible for senescence at the physiological level, and whether it therefore principally determines the rate of aging and life span. On the applied front, the mitochondrial metabolite carnitine, administered as acetyl-L-carnitine (ALCAR), has been shown to antagonize mitochondrial dysfunction during pathological states and in aging, reversing some age-related changes. It has recently been administered in clinical trials as a treatment for Alzheimer's disease. The proposed studies will employ ALCAR and a second mitochondrial metabolite-the antioxidant lipoic acid-as pharmacological
Studies
9
tools for basic and applied research. Preliminary studies have shown that short-term dietary supplementation of rats with ALCAR/lipoate reverses age-related mitochondrial decay in liver cells, and that both components of the mixture are required for optimal effects. The proposed experiments will 1) further characterize the ALCAR/lipoate mitochondrial intervention, in order to validate its effectiveness in other tissues and at lower doses; 2) use in vivo mitochondrial intervention with ALCAR/lipoate as a tool to ask the central outstanding question outlined above ("does mitochondrial decay determine physiological decline?"); and 3) assess the long-term effect of ALCAR/lipoate on senescence/vitality and life span, in order both to test the hypothesis that mitochondrial decay determines life-span, and as a model for intervention in human age-related disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF ALPHA TOCOPHEROL AND ALPHA LIPOATE ON LDL OXIDATION Principal Investigator & Institution: Jialal, Ishwarlal; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001 Summary: The overall hypothesis is to examine the effect of alpha lipoic acid alone and in combination with alpha tocopherol on plasma and LDL oxidation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: EVALUATION OF ANTIOXIDANT SUPPL IN FOCAL CNS ISCHEMIA Principal Investigator & Institution: Clark, Wayne M.; Neurology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Stroke is a major cause of death and disability in the United States. Evidence suggests that even if blood flow is initially restored additional "reperfusion injury" processes can occur that can potentiate brain injury and reduce existing blood flow. Some of the mediators of this "reperfusion injury" appear to be due to an inflammatory responsive involving free radical generation, activated leukocytes, and platelet activated factor. Various commercially available "antioxidant supplements" appear to produce clinical benefit in several diseases. These supplements including Ginkgo biloba extract (EGb) and alpha lipoic acid (LA) have multitude of biologic effects including reducing free radical generation, inhibiting PAF and leukocyte activation (inhibit NFalphaB), and improving cerebral blood flow. Antioxidants have shown benefits in multiple disease models involving reperfusion injury but have yet to be fully evaluated in reperfusion injury related to stroke. This project will investigate the treatment potential and protective mechanisms of selected antioxidants using an animal model that closely approximates clinical stroke. The specific aims of the study are as follows: Aim 1: To confirm and characterize the neuroprotective efficacy of EGb in focal CNS ischemia, determine the effects of EGb on the inflammatory response and CBF, and evaluate safety interventions with other medications used in stroke. Aim 2: To confirm and characterize the neuroprotective efficacy of LA and dihydro lipoic (DHLA) in focal CNS ischemia and determine their effects on the inflammatory response and CBF. This study will use the middle cerebral artery filament occlusion (MCAO) model in the mouse and will utilize a combination of ischemic damage (lesion size) and neurologic functional measurements to determine efficacy. Potential mechanisms of efficacy for
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Lipoic Acid
each antioxidant will be assessed including effects on in vivo cerebral blood flow (laser doppler measurement of blood flow) and the inflammatory response (molecular and flow cytometry). The information obtained from this project will be critical in planning future clinical stroke trials involving these agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FISH OIL & ALPHA LIPOIC ACID IN MILD ALZHEIMER'S DISEASE Principal Investigator & Institution: Shinto, Lynne H.; Neurology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): The heterogeneous nature of the biological mechanisms associated with Alzheimer's disease (AD) pathology make therapies that can target multiple mechanisms of action rather than a single mechanism attractive candidates to delay or prevent disease progression. Oxidative stress has been highly implicated in Alzheimer's disease pathology and recent studies show there is also an association between an increase in inflammation and cholesterol (respectively), and AD pathology. Fish oil and alpha lipoic also have the ability to decrease oxidative stress, inflammation, and lipid levels, making them strong candidates as therapeutic agents in slowing the progression of Alzheimer's disease. These supplements also have few reported side effects. Based on their mechanisms of action, a combination of the two supplements has the potential to maximize the therapeutic benefit in delaying the progression in AD. The proposed study will be a pilot trial designed to collect preliminary data to aid in the design of a larger clinical trial powered to assess both treatments' effect on mechanisms associated with AD pathology and clinical markers of AD pathology. This pilot study is designed as a 3-arm, parallel group, double-blind placebo-controlled trial. Subjects >55 yrs. diagnosed with probable AD and having mild cognitive impairment will be randomized to one of three groups (13 subjects/group): 1. fish oil alone, 2. fish oil plus alpha lipoic acid, 3. placebo. The treatment intervention will be for 1-year. Our primary objective, Aim 1, is to assess the treatments' effect on oxidative stress by measuring urine F2-isoprotane levels. We will also collect preliminary data on the treatments' effect on plasma lipid levels and high-sensitivity Creactive protein. Our secondary objective, Aim 2, is to collect preliminary data on ADrelated clinical outcome measures which will include: the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinical Dementia Rating scale (CDR), Mini Mental State Examination (MMSE), Alzheimer's Disease Cooperative Study Activities of Daily Living Scale, SF-36, and Logical Memory I1.Our tertiary objective, Aim 3, is to assess treatment safety by a monthly monitoring of adverse events and laboratory tests (metabolic panel, including liver function tests and platelet function assay). Compliance of fish oil supplementation will be assessed by red blood cell membrane fatty acid analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLOBOID CELL LEUKODYSTROPHY Principal Investigator & Institution: Singh, Avtar K.; Pathology and Lab Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 12-APR-2001; Project End 31-MAR-2006 Summary: (Verbatim from the Applicant's Abstract) Globoid cell leukocystorophy (Krabbe's Disease) is an autosomal metqabolic disordear of beta-galactocerebrosidase deficiency with progressive pathognomonic accumulation of psychosine
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(galactosylsphingosine) which subsequently becomes a neuroinflammatory disease resulting in demyelination, olidogendrocyte loss and death. The objectives of the proposed studies are to elucidate the possible role of psychosine in neuroinflammatory response and in the mechanism of oligodendrocyte loss by using twitcher mice, a murine model of globoid cell leukodystrophy (GLD). Studies from our laboratory have demonstrated the psychosine potentiates the cytokine-induced induction of iNOS and also the psychosine when incubated with C6 glial cells in culture, induces apoptotic cell loss. Achievement of these goals will be facilitated by understanding the molecular mechanism of induction of inducible nitric oxide synthase (iNOS) and inflammatory cytokines (e.g. TNFalpha and IL-6) and psychosine-induced apoptotic loss of oligodendrocytes. Studies are also proposed to investigate the psychosine-induced electrophysiological alterations in brain cells/brain slices form twitcher mice. We also propose to test the efficacy of antioxidants (N-acetyl cysteine, alpha-lipoic acid) and the compounds that are known to block the induction of inflammatory cytokines (lovastatin, sodium phenylacetate) for halting/delaying the disease process in twitcher mice. The proposed studies will provide a better understanding of the disease process in GLD/twitcher mice and the demonstration of beneficial effects of the drugs in twitcher mice) may help in the identification of an ideal candidate drug for subsequent use in clinical trials involving GLD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE RESTORATION BY LIPOIC ACID IN AIDS Principal Investigator & Institution: Jariwalla, Raxit J.; California Institute for Medical Res 2260 Clove Dr San Jose, Ca 95128 Timing: Fiscal Year 2001; Project Start 20-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): AIDS is characterized by infection with HIV which leads to collapse of the immune system. Although highly active antiretroviral therapy (HAART) has contributed significantly to lowering morbidity and mortality from AIDS, antiretroviral drugs do not fully restore the immune system and patients often fail multi-drug treatment. Hence, there is a need for alternative/complementary medicine (CAM) that can restore an immune system ravaged by HIV/AIDS. To address this need, investigators have formed a multidisciplinary collaboration to evaluate and demonstrate utility of natural immune-based modulators in ethnically diverse patients with HIV/AIDS. The long-term goal of this proposal is to develop a CAM therapy to facilitate immune reconstitution and HIV eradication following cessation of antiretroviral treatment or concurrent with continued antiretroviral treatment. It is based on the premise of a widespread deficiency of glutathione (GSH), vital to lymphocyte function, in patients with HIV/AIDS. The proposed project will study the immunomodulatory and antiretroviral effects of a dietary antioxidant, alpha-lipoic acid (ALA), which is known to efficiently boost systemic GSH. In this amended placebocontrolled study, 42 HIV-infected adults unresponsive to HAART (i.e. those with persistent CD4+ count 10,000 copies/cc) will be randomized into two arms, treatment and control, of 21 patients each. The treatment group will be given 300 mg ALA thrice daily for 6 months and the control group will receive inert placebo. Studies performed at baseline, bimonthly and at 6 months will include estimation of CD4+ count, HIV RNA, T-cell reactivity in vitro and whole blood GSH level. Significance of changes from baseline parameters will be analyzed by unpaired t-tests. The proposed research will show whether GSH augmentation by ALA increases CD4+ cell number and T cell function and reduces viral load in subjects unresponsive to antiretroviral therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Lipoic Acid
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Project Title: INTERVENTIONS THAT RETARD MAMMALIAN AGING Principal Investigator & Institution: Harrison, David E.; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Aging-associated debilitation is a primary source of human misery. Healthy life spans in mammalian models can be increased by dietary and genetic means; however, no effective intervention applicable to humans has yet been validated in mammals. Human trials for "anti-aging" treatments are unlikely to proceed without such validation, which is the purpose of this RFA. The following aims are designed to definitively identify effective anti-aging interventions and to rule out those that are ineffective. Aim 1: To verify that potential anti-aging interventions produce their expected biological effects. For anti-inflammatory agents (corticosterone, ibuprofin, celecoxib), insulin sensitizing agents (CL316,243, rosiglitazone), agents that promote mitochondrial function or suppress oxidative damage (R-alpha lipoic acid, Lcarnitine), and for multi-functional phytochemicals, the following will be determined: doses and modes of administration that produce biological effects, both short and long term, without toxicity or a decrease in food consumption. Aim 2: To test the hypotheses that potential anti-aging interventions in these three categories actually retard aging in biological systems and increase life spans. Noninvasive, longitudinal measures are made of growth, immune cells, insulin/glucose, collagen, healing and urine. Because aging is multifactorial, combinations of interventions proven in Aim 1 also will be tested. Aim 3: To confirm and augment the conclusions regarding interventions successful in the first phase of the program. Whether interventions that increase maximum life span also retard expression of aging in the following biological systems will be tested: Neurobehavorial/sensory, mitochondrial, gene expression and protein modification, followed by detailed histopathological analyses. Results in these systems may suggest mechanisms by which the interventions retard aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIPOIC MITOCHONDRIA
ACID
SYNTHESIS
AND
ATTACHMENT
IN
Principal Investigator & Institution: Cronan, John E.; Professor and Head; Mrc Dunn Human Nutrition Unit Welcome Trust/Mrc Bldg - Hills Rd Cambridge, Timing: Fiscal Year 2003; Project Start 19-AUG-2003; Project End 18-AUG-2004 Summary: (provided by applicant): Lipoic acid plays a vital role in aerobic energy metabolism in mammals, plants, and bacteria. Despite its metabolic importance the enzymes responsible for the synthesis and covalent attachment of this enzyme cofactor remain poorly understood. A number of recent advances in our knowledge of these processes has occurred in bacterial systems. Given these data and the fact that mitochondria are derived from endosymbiotic bacteria, it seems likely that the bacterial pathways are conserved in mammalian mitochondria, the cellular compartment where the lipoic acid-modified proteins reside. This proposal is to examine mammalian mitochondrial lipoic acid metabolism and test if the proteins involved function as do those in bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIPOIC ATHEROSCLEROSIS
ACID,
ENDOTHELIAL
ACTIVATION
13
AND
Principal Investigator & Institution: Zhang, Weijian; None; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) This project is based upon the hypothesis that the cellular redox status plays a critical role in preventing vascular cell dysfunction that is related to the initiation and progression of atherosclerosis. Oxidative stress has been implicated as an etiologic factor in atherosclerosis and its clinical manifestations, and therefore, antioxidants may have anti-atherogenic properties and may reduce the morbidity and mortality from coronary heart disease. Since endothelial activation is one of the initiating events in atherosclerosis and has been related to oxidative stress through specific redox sensitive processes, intracellular antioxidants may affect the response of endothelial cells to oxidative stress or inflammatory cytokines, and be of therapeutic potential in pathologies related to endothelial dysfunction. Previous studies have evaluated the effects of the antioxidant lipoic acid (LA) on vascular redox sensitive processes in cultured cells in vitro; however, little is known about the role of LA in endothelial activation in vivo. Therefore, the overall objective of this project is to determine the role of LA in oxidative stress-induced endothelial activation and atherosclerosis in vivo. Specific aim 1 will determine the role of cellular LA in endothelial activation in mice challenged with cytokines or bacterial endotoxin lipopolysaccharide (LPS). In vivo oxidative stress will be monitored and the expression of adhesion molecules and monocyte chemoattractant protein-l (MCP-1) will be determined. Mechanisms for observations will be further addressed including gene regulation and nuclear factor-kappaBeta (NFkB) activation. Specific aim 2 will determine the role of LA in atherosclerotic lesion development in an ApoE knockout mouse model. Plasma cholesterol levels will be examined and atherosclerotic plaque areas will be quantified at the aortic origin. The work contained in this proposal will provide new insights into the effectiveness of LA treatment to inhibit the earliest stages of atherosclerotic lesion development and will be integrated in the long-term objectives to examine the potential of LA to lower coronary risk in humans by dietary supplementation. Taken together, the studies of this proposal will contribute to the understanding of the mechanisms by which cellular antioxidant status is important in the maintenance of vascular homeostasis and, thus, provide new targeted strategies for the prevention and treatment of atherosclerosis and other inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF ACTIVATION & CATALYSIS IN BIOTIN SYNTHASE Principal Investigator & Institution: Jarrett, Joseph T.; Biochemistry and Biophysics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Biotin is an essential protein cofactor used in carboxylation reactions central to human metabolism including enzymes involved in fatty acid biosynthesis, gluconeogenesis, and branched-chain amino acid catabolism. The terminal step in biotin biosynthesis involves the insertion of a sulfur atom between C6 and C9 of the precursor dethiobiotin, forming the biotin thioether ring. This insertion reaction is deceptively simple yet represents an impressive feat of enzymatic catalysis, requiring the enzyme break two saturated, inactivated CH bonds in dethiobiotin prior to sulfur insertion. This
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Lipoic Acid
reaction is catalyzed by the E. Coli BioB protein, a dimeric iron- sulfur protein, and requires the participation of adenosylmethionine (AdoMet) and reduced flavodoxin. The requirement for AdoMet and flavodoxin suggests that biotin synthase is a member of a family of enzymes that reductively cleave AdoMet to generate a 5' - deoxyadenosyl radical, which is then used to generate a protein radical or to directly abstract a hydrogen atom from the substrate. More generally, biotin synthase belongs to a class of enzymes that are able to generate and control carbon and/or sulfur radicals in order to carry out difficult biosynthetic transformations; these enzymes include the human enzymes ribonucleotide reductase and lipoic acid synthase. Several obstacles have hindered in depth studies of the mechanism of biotin thioether ring formation: (I) the sulfur- containing substrate for BioB is not known, (II) the redox requirements for thioether ring formation are not known, and (III) the role of AdoMet and flavodoxin in enzyme activation is not understood. Studies described in this proposal address these substrate, protein, and activation requirements for biotin thioether ring formation, and will lead to more detailed studies of the chemical mechanism of radical-mediated sulfur insertion. By integrating information from these studies our knowledge of other enzymes in the biotin biosynthetic pathway, reconstitution of essential components of this pathway may in the future provide a convenient and inexpensive source of biotin for nutritional, therapeutic, and industrial applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISTIC STUDIES OF LIPOIC ACID SYNTHASE Principal Investigator & Institution: Booker, Squire; Biochem and Molecular Biology; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Lipoic acid is an essential sulfur-containing cofactor of several multienzyme complexes that are involved in primary metabolism. It has been known for a number of years to be derived directly from octanoic acid, but the mechanism of sulfur insertion into the unactivated fatty acid has remained obscure. Recently, a gene has been cloned which appears to be the catalytic core of the enzymatic activity that is involved in the sulfur insertion reaction. Signature motifs within its deduced primary sequence and initial spectroscopic characterization of the protein collectively indicate that this "lipoic acid synthase" belongs to an emerging class of enzymes that contain iron-sulfur clusters, and that use S-adenosyl-L-methionine as a means of generating carbon-centered radical intermediates in enzymatic reactions. The roles of S-adenosyl-L-methionine and iron-sulfur clusters in this class of enzymes represent departures from the roles that they have traditionally been assigned in biochemical textbooks. Iron-sulfur clusters have traditionally been thought of as electron transfer agents or Lewis acid catalysts, while S-adenosyl-L-methionine is still considered to be mainly a cellular methylating agent. The experiments proposed herein seek to reveal the "new" molecular enzymology associated with these cofactors. Several experimental mechanisms are discussed, and experiments are proposed that will distinguish among them. Aside from the involvement of lipoic acid as a cofactor in enzyme complexes of energy metabolism, it is known to modulate glucose metabolism in patients with type II diabetes and to serve as a general cellular antioxidant, among many other things. There is significant evidence that lipoic acid can be endogenously synthesized in mammalian cells. Experiments outlined in this proposal will lay a foundation upon which studies to address whether the inability to synthesize lipoic acid endogenously can lead to a compromising of cellular function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MICROARRAYS FOR ALZHEIMER'S DISEASE MOUSE MODELS Principal Investigator & Institution: Reddy, Hemachandra Hemachandra.; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2004 Summary: (Revised Abstract) 23. Tools for Research on the Genetics and Proteomics of Aging. Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by impairment of cognitive functions and by beta amyloid plaques in cerebral cortex and hippocampus. Because of the challenges in identifying and obtaining presymptomatic human AD brains, we investigated an established amyloid precursor protein (APP) transgenic mice line (Tg2576) for gene expression profiles at ages long before (2 months), immediately before (5-6 months), and after (18 months) the appearance of amyloid plaque pathology and cognitive impairment. We employed cDNA microarray techniques and measured mRNA levels of the cerebral cortex in APP transgenic and wild-type mice at each time point for 11,400 genes. Our preliminary screening of gene expression in APP mice compared to age-matched wild-type mice revealed that at 2 months of age, up-regulated genes are associated mainly with mitochondrial energy metabolism and oxidative stress, and these same genes are progressively up-regulated in 5- and 18-month-old APP mice. We confirmed these results by Northern blot and real-time PCR analyses. Based on these preliminary results, we hypothesize that impairment of mitochondrial energy metabolism is an early cellular event in the progression of AD in APP mice. Currently, our laboratory is testing this hypothesis by treating APP mice and age-matched wild-type mice with mitochondrial antioxidants such as lipoic acid, melatonin and co-enzyme Q10 to determine whether mitochondrial antioxidants can rescue cognitive deficits, reduce mRNA expression, and compensate for biochemical enzymes in mitochondrial energy metabolism. Ultimately, successful agents may be used as clinical trials in AD patients. However, global screening of gene expression for routine detection of gene expression in APP mice after treatment with antioxidants is very expensive. To reduce the cost of global screening of mouse genes for mRNA expression, we propose to develop custom cDNA microarrays for AD transgenic mice. The objective of this research proposal is to develop custom cDNA microarrays for AD transgenic mice. In the present study, we propose to develop high-sensitivity, low-density mitochondrial, oxidative damage and inflammatory response related cDNA microarrays in mice. These custom cDNA microarrays will be instrumental in continuing our studies on the dysfunction of gene expression before and after treatment with mitochondrial antioxidants in APP mice. The outcome of this proposed investigation will be useful in screening several mitochondrial antioxidants in AD transgenic mouse models as pre-clinical trials of AD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MINORITY PREDOCTORAL FELLOWSHIP PROGRAM Principal Investigator & Institution: Nesbitt, Natasha M.; Biochem and Molecular Biology; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2001; Project Start 01-AUG-2001 Summary: Lipoic acid, 6,8,-thioctic acid, is a key component of many multienzyme complexes that are essential in primary metabolism. It is found in most prokaryotes and eukaryotes as well as plant and animal tissue. Because of its antioxidant properties, lipoic acid has been shown to prevent diabetic neuropathy and to successfully treat heavy metal poisoning. Although lipoic acid is a relatively simple cofactor in structure,
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Lipoic Acid
the mechanism by which it is biosynthesized is presently unknown. Recent studies from several laboratories indicate that the product of the lipA gene in E. coli (lipoic acid synthase or LAS) mediates insertion of two sulfur atoms into the 6 and 8 positions of octanoic acid. Characterization of the protein product of the lipA gene suggests that LAS is a member of an emerging class of enzymes that use AdoMet synergistically with ironsulfur clusters to initiate radical dependent enzymatic reactions, cleaving AdoMet to 5'deoxyadenosine and methionine in the process. Well- characterized members of this family include lysine 2,3-aminomutase, pyruvate-formate lyase activase, and anaerobic ribonucleotide reductase activase. The goal of the researched proposed herein is to show experimentally that AdoMet functions similarly in LAS. This will be carried out by determining whether AdoMet binds to LAS and by assessing whether tritium or deuterium is transferred to 5'- deoxyadenosine from various isotopically labeled forts of octanoic acid. Lastly, analogues of AdoMet with the potential to stabilize a radical at the 5'-carbon of 5'-deoxyadenosine will be used to establish the involvement of radical intermediates in the LAS reaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROSCIENCES ANTIOXIDANTS
TECHNOLOGY
DEVELOPMENT
FOR
Principal Investigator & Institution: Kumar, Dinender; Director; Brain Research Laboratories, Inc. (Brl) 115 Mill St Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: adapted from applicant's abstract): There is growing evidence that ROS may be implicated in aging and a variety of age-related human degenerative disorders. In this context, exogenous antioxidants are beginning to assume an unprecedented importance in the arsenal of therapeutic agents that are continuously being developed in order to combat age related diseases and the phenomenon of aging itself. These antioxidants are supposed to supplement and reinforce the natural defenses of the body and to protect it when the endogenous antioxidant levels are diminished as a result of disease or aging. The current problems in the in vitro assay of antioxidants are many and varied: (a) different laboratories use different species of ROS and different target molecules under different experimental conditions in formulating their assay systems; (b) there are no comparative studies to evaluate the reliability of one method over an other, (c) many have been mainly employed for investigating the mechanisms of action of specific oxygen free radicals and are not particularly relevant as procedures for the assay of antioxidants; (d) since many of the methods are not specifically designed for antioxidant assay, they have not been optimized taking into consideration the prooxidant or antioxidant properties of certain substances under different conditions; and (e) they often require expensive instrumentation and highly sophisticated technical skill to perform the analysis and to interpret the resulting data. In the first step in this project, our goal will be to develop in vitro assay systems for the measurement of individual biological activities of coenzyme Q, lipoic acid and melatonin, using pure commercial preparations of these compounds, taking into consideration the properties of both the ROS and the antioxidants involved. In the second step, we will develop an in vivo method using for determining antioxidant activity using intact cells and intracellular macromolecules as targets. The results of the two systems will be analyzed to yield an approach which can be employed for the determination of biological activities of known or unknown mixtures of antioxidants using a minimum number of simple assay procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PAINFUL HIV NEUROPATHY: TREATMENT WITH ALPHA-LIPOIC ACID Principal Investigator & Institution: Mann, John D.; Neurology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2005 Summary: (provided by applicant): HIV infection is associated with painful distal peripheral polyneuropathy in up to 35 to 50% of those without AIDS and in more than 70% of those with advanced disease. Pain is located distally in the extremities, is symmetrical, spontaneous, moderate to severe and associated with varying degrees of weakness and sensory loss. The pain is described as burning, pressure and shock-like with both constant and intermittent features. The condition is progressive but may be halted with disease remission. Disability is often significant, arising from the fluctuating intensity of the pain and the character of the pain itself. Peripheral nerve axons and sensory, neuron cell bodies in the dorsal root ganglia are the principal targets of the process leading to symptoms. Conventional medical treatment consists of anticonvulsants, tricyclic antidepressants, opiates and adjuvant medications, all of which have significant side effects and limited effectiveness. Alpha-lipoic acid is an eight carbon disulfide, naturally occurring in all cells of the body, which serves as a critical cofactor for key mitochondrial enzymatic reactions leading to energy production. In high concentrations it acts as an antioxidant directly, regenerates other anti-oxidants such as glutathione and vitamins C and E, and promotes glutathione synthesis. Clinical studies in using alpha-lipoic acid for painful diabetic neuropathy have shown significant benefit at daily oral doses that are well tolerated: Diabetic neuropathy shares both clinical and some pathological features with painful HIV neuropathy. The present study is designed to evaluate the effects of using daily oral supplements of alpha-lipoic acid plus standard medical care in the treatment of painful HIV-associated neuropathy over a 6 month period in subjects 18 and older. A control group will receive standard medical care plus placebo for six months. Primary endpoints include pain, use of pain medication and peripheral nerve function. Measures of current mood, depression and quality of life along with serum markers of HIV disease activity and mitochondrial function will be obtained at baseline and study termination for correlation with clinical outcomes. Possible benefits of the study to patients with HIV-associated painful neuropathy include reduction in pain and disability, reduced use of medications and enhanced cellular metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTECTION
PENTACHLOROPHENOL
TOXICITY
AND
ANTIOXIDANT
Principal Investigator & Institution: Zhu, Ben-Zhan; None; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) Pentachlorophenol (PCP) is one of the most widely used biocides, primarily for wood preservation. PCP is now considered to be ubiquitously present in our environment and even found in people who are not occupationally exposed to it. PCP has been listed as a priority pollutant by the U. S. Environmental Protection Agency (EPA), and classified as a Group 2B environmental carcinogen by the International Association of Research on Cancer (IARC). The genotoxicity of PCP has been attributed to its two major metabolites: tetrachlorohydroquinone and tetrachloro-1,4-benzoquinone. Recently, the investigators
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Lipoic Acid
found that hydroxyl radicals (-OH) are produced by these PCP metabolites through a novel, metal-independent mechanism (the so-called organic Fenton reaction); and that dietary antioxidants markedly inhibit -OH production from PCP metabolites. These preliminary in vitro data suggest that dietary antioxidants may play an important role in modulating the genotoxicity of PCP metabolites. Therefore, in this proposal, the researchers plan to extend their studies from a purely chemical system to a cell culture system, using human fibroblasts. Specifically, the following questions will be addressed: (1) Can this novel mechanism of metal-independent -OH production be detected in cells? The production of -OH will be measured by secondary radical ESR spin-trapping techniques; and the role of metals will be studied by using specific intra-and extracellular iron and copper chelating agents. (2) Can dietary antioxidants, viz., lipoic acid and ascorbic acid, protect against cytotoxicity and genotoxicity induced by PCP metabolites? Cytotoxic and genotoxic effects of PCP metabolites will be evaluated, respectively, by the MTT assay and the comet assay. (3) What are the molecular mechanisms of the modulatory effects of these dietary antioxidants? The interaction between PCP metabolites and antioxidants will be studied by various spectral methods (UV-visible, ESR) and by high-pressure liquid chromatography with photodiode array or electrochemical detection. This project should result in a better understanding of the molecular mechanisms underlying the cytotoxic and genotoxic effects of PCP metabolites and related environmental agents, and may lead to novel strategies for the prevention and treatment of these toxic effects by dietary antioxidants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHOTOPROTECTION OF SKIN BY TOPICAL SELENIUM Principal Investigator & Institution: Omar, Mostafa M.; Phytoceuticals, Inc. 37 Midland Ave Elmwood Park, Nj 07407 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 29-SEP-2003 Summary: (provided by applicant): Ultraviolet (UV) radiation causes oxidative damage to skin which can cause skin cancer, alter the behavior of skin cancer (typically making the cancer more aggressive), and/or cause photoaging. Topical selenium compounds may prevent this damage. In an attempt to moderate UV-induced photodamage, we will formulate topical selenium products and test them in pig skin. Formulations - including selenium sulfite, L-selenomethionine, selenotrisulfide, derivatives of lipoic acid and lipoamide - will be tested for percutaneous absorption in pig skin. Those formulations having the best characteristics will be chosen for further study. We will irradiate normal pig skin with UV radiation. We will assess histological changes and quantitate damage by measuring apoptosis, nucleic acid oxidation, and matrix metalloproteinase induction. We will determine the relative protection of topical selenium formulations to inhibit photodamage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REACTIVE NITROGEN & CEREBRAL ISCHEMIC INJURY Principal Investigator & Institution: Khan, Mush; Arizona Institute for Bio-Medical Res Bio-Medical Research Scottsdale, Az 85260 Timing: Fiscal Year 2001; Project Start 15-APR-2000; Project End 15-OCT-2001 Summary: (Verbatim from the Applicant's Abstract) Acute ischemic stroke is a major cause of disability especially among the elderly and is the third leading cause of death. Reactive nitrogen species (NO and ONOO') are being increasingly implicated in the pathophysiology of cerebral ischemia-reperfusion injury. Since inducible nitric oxide
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synthase (iNOS) is a high output enzyme and it is active for days when induced, we hypothesized that NO produced by iNOS is an important factor in the pathophysiology of cerebral ischemia-reperfusion injury. We have identified a number of compounds (Nacetylcysteine, lovastatin, mevastatin and sodium phenylacetic acid) which will inhibit the induction of iNOS and proinflammatory cytokines in brain cells in culture. The proposed studies will test the therapeutic potential of these drugs against cerebral ischemia-reperfusion injury. The first and second specific aims are designed to investigate whether N-acetylcysteine, alpha-lipoic acid and/or lovastatin will block/down regulated the induction of proinflammatory cytokines and iNOS in brain exposed to ischemia/reperfusion injury. The third specific aims is designed to investigate whether N-acetylcysteine or lipoic acid and/or lovastatin will block/down regulate the induction of delayed cell loss by apoptosis in brain exposed to ischemia/reperfusion injury. From these studies we will seek to answer the following questions: 1) Does treatment with the drugs prevent the neuronal injury given prior to the onset of ischemia? 2) Does treatment with the drugs prevent the neuronal injury by altering the course of the disease when given after the ischemic insult. These are relatively nontoxic compounds and are presently being prescribed for human consumption in other diseases. Therefore, demonstration of beneficial effects of these drugs in an animal model of cerebral ischemia-reperfusion injury will help identify the ideal candidates for subsequent use in clinical trials involving cerebral ischemia and stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RICKETTSIA RICKETTSII IN HUMAN ENDOTHELIAL CELLS Principal Investigator & Institution: Silverman, David J.; Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-DEC-1980; Project End 31-JUL-2003 Summary: (Adapted from the Applicant's Abstract): The long-term objectives and specific aims of this application are to understand the pathogenesis of Rickettsia rickettsii, and other members of the spotted fever group of rickettsiae by better studying the processes involved in causing cell injury. The investigators are interested in the interaction of R. rickettsii (Rocky Mountain spotted fever) with the endothelial cell, the target cell in human infection, and the mechanism(s) of cell injury caused by this obligate intracellular bacterium. It has been determined by the Principal Investigator's laboratory that cell injury appears to be initiated by reactive oxygen species produced during internalization and intracellular rickettsial growth. With an interest in abrogating endothelial cell injury, they have incorporated antioxidants into infected cell culture systems. One antioxidant, (alpha-lipoic acid, was able to effectively reverse the leading predictors of cell injury due to reactive oxygen species and to substantially prolong the viability of infected cell cultures. Studies to date have been carried out both in human umbilical vein endothelial cells and the permanent human endothelial cell line, EA.hy926. The investigators will continue to carry out experiments in these cells to characterize changes in the cytoskeleton of endothelial cells following R. rickettsii infection and to evaluate the link between these changes and increases in endothelial permeability. They will determine whether R. rickettsii-induced oxidative injury is responsible for the alterations in the actin pools and whether these changes can be prevented (controlled) by the use of antioxidants. They believe that it is also important to test our in vitro observations on oxidant-mediated injury in a relevant animal model to determine whether oxidant injury occurs and if antioxidants are effective in altering the course of disease. The most suitable model for these studies is the Rickettsia conorii-
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Lipoic Acid
C3H/HeN mouse model which has been extensively studied by Walker and his colleagues. R. conorii is closely related to R. rickettsii, causes Mediterranean spotted fever, a syndrome clinically similar to RMSF, and as they have demonstrated, results in the same dramatic morphological manifestations of cell injury as R. rickettsii in human endothelial cells. These preliminary in vitro studies and those in the mouse model, indicate that this rickettsia is also able to cause oxidative stress. They propose to test the hypothesis that oxidant injury contributes to the pathologic changes within the animal. They will determine whether oxidative injury correlates with the local presence of rickettsiae within particular organs and tissues and whether the antioxidant, alphalipoic acid, can ameliorate oxidative injury as they have shown in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ULTRASOUND, INTESTINAL AND CARDIAC FUNCTION IN RATS Principal Investigator & Institution: Baldwin, Ann L.; Professor; Physiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Environmental factors in animal facilities can cause distress if not properly controlled. Noise is particularly important because it has nonauditory effects that alter the physiology of the whole body. Studies on the effect of lowfrequency sounds on rodents have established that both physiological and behavioral responses are common. A stress response in rats is produced, as indicated by a rapid transient increase in plasma corticosterone, and gastrointestinal, cardiac and immunological functions are also affected. Rats are extremely sensitive to sounds in the ultrasonic range (12-40kHZ) and these are routinely encountered in animal facilities. It is likely that ultrasound has similar effects, but no data are available. It is essential that environmental stressors in animal facilities are minimized, not only for animal welfare, but because the results of biomedical research depend on the animals showing standard responses to clearly defined experimental procedures. The purpose of this study is to test the hypothesis that: exposure of research rats to daily periods of ultrasound affects gastrointestinal and cardiac function and that antioxidants reduce these effects. The applicant's long-term goal is to convince scientists to demand better environments for their animals. The specific aims of this study are to: 1. Determine whether subjecting rats to a short period of daily ultrasound increases: a) Production of reactive oxidant species (ROS) in the intestinal mucosa, and epithelial disruption; b) Particulate uptake from the intestinal lumen by M cells in the mucosa, thus overtaxing the immune system; e) Mesenteric microvascular permeability, thus reducing selective barriers to transvascular exchange; d) Increases heart rate but decreases heart rate variability, both markers of stress. 2. Determine whether dietary vitamin E and/or lipoic acid reduce the deleterious effects of ultrasound as demonstrated in Aim 1. Production of reactive oxygen species (ROS) will be assessed using a fluorescent probe; epithelial sloughing and mucosal mast cell degranulation by microscopy. Lack of selective exclusion of foreign particles by the M cells will be tested by orally administering polystyrene particles and measuring their concentrations in Peyer's patches and lymph nodes. Microvascular endothelial leakage and mesenteric mast cell degranulation will be assessed using intravital epifluorescence microscopy and image analysis. The effects of noise-induced stress on heart rate, heart rate variability and cardiac performance will be determined in conscious, freely moving rats by radiotelemetry. Rat behavior, another indicator of stress, will be assessed by videotaping pairs of rats in their cages before and after ultrasound. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VASCULAR DISEASE IN DIABETIC NEUROPATHY Principal Investigator & Institution: Yorek, Mark A.; Professor of Medicine; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: The objective of this proposal is to determine the effect of diabetes on endoneural blood flow (EBF), motor nerve conduction velocity (MNCV) and vasorelaxation of arteriole branches that supply circulation to the sciatic nerve. Since nerve ischemia is a primary factor in the development of diabetic neuropathy (DN), understanding the effect of diabetes on the vascular responsiveness of blood vessels that supply neural tissue is important. The long-rang goal of my laboratory has been to identify the diabetes-induced defects that contribute to the development of DN. Consequently, others and we have shown that slowing in MNCV is accompanied by a reduction in EBF. The etiology of these abnormalities is not well understood and has been attributed to a variety of defects affective nerve and vascular tissue. Because of the multiple abnormalities is not well understood and has been attributed to a variety of defects affecting nerve and vascular tissue. Because of the multiple abnormalities contributing to DN it is impractical to treat this disease by correcting each of them. Therefore, investigators are faced with the problem of determining which vascular or metabolic related defects have the greatest impact on the clinical features of DN and then design strategies to treat the more clinically relevant defects. We have shown that vascular relaxation of arterioles that supply circulation to the sciatic nerve is impaired by diabetes and, in this proposal, will test the hypothesis that the origin of the vascular defects, and thus a major cause of DN, is an impairment in the regulation of vascular tone mediated by nitric oxide (NO) and arachidonic acid metabolites. We propose that combining alpha-lipoic acid (an antioxidant) and/or evening primrose oil (a natural source of gamma-linolenic acid) treatment will correct the vascular defects and improve EBV and MNCV. The specific objectives of this proposal are: 1) Determine if treating streptozotoxin- induced diabetic rats with alpha-lipoic acid and/or evening primrose oil prevents diabetes-induced impairment in vascular relaxation in arterioles that provide circulation to the sciatic nerve, the reduction in EBV and slowing of MNCV, 2) Determine whether exogenous treatment of arterioles with L-arginine, superoxide dismutase (SOD) with and without catalase, or arachidonic acid, improves the diabetesinduced defect in endothelium- dependent vasorelaxation, and 3) determine whether exogenous treatment of arterioles with adenoviruses containing endothelial nitric oxide synthase (eNOS), superoxide dismutase (SOD) with and without catalase or delta-6 desaturase prevents the diabetes-induced defect in endothelium-dependent vasorelaxation. In summary, these studies will provide us with a better understanding of the etiology of DN and improved treatments for preventing the diabetes-induced changes in vascular and neural function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VITAMIN C, GLUTATHIONE AND MITOCHONDRIAL FUNCTION Principal Investigator & Institution: Hagen, Tory M.; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001 Summary: Cardiovascular diseases are the major cause of death for people over the age of 65 in the U.S. In particular, vascular endothelial cell function markedly declines, contributing to the profound vessel rigidity evident with age. Increased oxidative stress, cellular redox changes, and altered calcium homeostasis may be underlying factors in
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age-related endothelial cell dysfunction, which in turn, could be caused by mitochondrial decay. However, there is nothing known about mitochondrial function in vascular endothelial cells, the extent or precise nature of mitochondrial decay with age, or the significance of such decay on endothelial cell function. This proposal is intended to fill these significant gaps in endothelial cells with age? B) does mitochondrial decay affect endothelial cell function and vessel tone?, and C) does manipulation of cellular and/or mitochondrial antioxidant levels by addition of ascorbic acid (AA) or lipoic acid (LA) reverse the consequences of mitochondrial decay to endothelial function? We propose to investigate these questions in 3 specific aims: 1) Compare age-related changes in mitochondrial function and oxidant flux in freshly isolated porcine aortic endothelial cells (PAEC) from young and old pigs. These studies will define how aging affects mitochondrial function (bioenergetics, superoxide production and calcium homeostasis) in PAEC. In particular, we will test how mitochondrial function derived reactive oxygen species (ROS) alter cellular antioxidant status and oxidative stress. 2) Assess the impact of mitochondrial decay of PAEC function. We will correlate mitochondrial decay, especially in terms in terms of increased ROS and altered thiol redox status, to PAEC nitric oxide synthase (eNOS) activity and availability of nitric oxide (EDNO). 3) Determine whether manipulation of cellular antioxidant of cellular antioxidant and thiol redox status by addition of AA or LA in vitro (PAEC) or in vivo (guinea pig aortic rings) improves mitochondrial function and endothelial-dependent biological activity. AA or LA will be added to freshly isolated PAEC from young and old pigs to determine whether these agents reverse or "mask" mitochondrial-dependent alterations to cellular redox status, oxidative stress (Aim 1) and endothelial biological activity (Aim 2). These studies will be augmented by supplemental feeding of guinea pigs with AA and LA to determine whether increased mitochondrial function (LA) and/or increased antioxidant and thiol redox status (AA or LA) may reverse the agerelated loss in vascular tone in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VITAMIN C, GLUTATHIONE AND NO ACTION IN HUMANS Principal Investigator & Institution: Vita, Joseph A.; Associate Professor; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001 Summary: Loss of the vasodilator, anti-thrombotic, and anti-inflammatory actions of endothelial-l-derived NO (EDNO) in atherosclerosis contribute to the clinical manifestations of coronary artery disease. Increased vascular oxidative stress has been linked to impaired EDNO action in atherosclerosis. Specifically, oxidized LDL, increased production of superoxide anion, and decreased availability of cellular antioxidant species may all contribute to impaired EDNO action. Prior studies investigating interactions between antioxidant species may all contribute to impaired EDNO action. Prior studies investigating interactions between antioxidants and EDNO have focused principally on lipid- soluble and extracellular antioxidants. However, the importance of intracellular redox status for EDNO action has been much less well characterized. Ascorbic acid (AA) and glutathione (GSH) are the principal water-soluble antioxidants in cells. We recently demonstrated that AA treatment improves EDNO-action in patients with atherosclerosis. We recently demonstrated that EDNO action is improved by oxothiazolidine-4-carboxylic acid (OTC), a cysteine pro-drug that augments cellular GSH stores. The goal of this project is to investigate the importance of cellular redox status in EDNO bioactivity in humans with coronary atherosclerosis with particular emphasis of the roles played by AA and GSH. We will use well-established methods to
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assess EDNO- dependent vasodilation including high-resolution brachial ultrasound, intra-arterial agonist infusion with venous occlusion plethysmography in the forearm of quantitative angiography and Doppler ultrasound in the coronary artery. Cellular redox state will be manipulated by acute or chronic administration of AA, OTC, EUK-8, an intracellularly-effective superoxide dismutase mimic, or lipoic acid, a thiol compound that reverse mitochondrial decay. The effects of these agents on cellular redox status will be confirmed by examining AA and GSH concentrations in vascular tissue collected intra-operatively and blood cells from patients. These parameters will be correlated with vasomoter responses. Since loss of EDNO action may contribute to the pathophysiology of ischemic syndromes in atherosclerosis, these studies have the potential to provide important insights for the management of coronary artery disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: XENOBIOTICS AND PRIMARY BILIARY CIRRHOSIS Principal Investigator & Institution: Gershwin, M. Eric.; Professor of Medicine; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 29-SEP-2003 Summary: Primary biliary cirrhosis (PBC) is an autoimmune disease that primarily affects women and includes destruction of intrahepatic bile ducts and antimitochondrial antibodies (AMAs). AMAs are directed at the E2 components of the 2-oxo acid dehydrogenase pathway, particularly PDC-E2; 95 percent of patients with PBC have a positive AMA. The etiology of PBC likely occurs via the interaction of genetics and environment. Although there is no correlation between sera AMAs and clinical severity, a positive AMA using recombinant auto-antigens is virtually pathognomonic of PBC. We also have data suggesting that IgA AMAs may be causally related to biliary pathology. Halogen substituted organic compounds such as chlorofluorohydrocarbon substitutes can form protein adducts through acyl halide intermediates and covalently attach to L-lysine. Antibodies to trifluoroacetic acid (TFA)-albumin recognize a similar epitope on PDC-E2 as AMAs. We hypothesize that exposure to a molecule similar to TFA will interact with the lipoic acid-lysine region of the inner lipoyl domain (the immunodominant T and B cell epitope) of PDC-E2. This conjugation will either lead directly to cell death or, alternatively, to a mucosal IgA response. We propose to extend the finding that exposure to fluorinated acylating compounds results in antibodies that react with PDC-E2 by exploring the true mechanistic insult that induces PBC. Our hypothesis for this exploratory grant evolved after an unsuccessful exhaustive search for infectious agents in PBC. The overall data puts into focus the distinct possibility that PBC may be related to exposure to a xenobiotic agent. Thus our thesis is that a molecule similar to TFA alters the immunogenicity of PDC-E2 and leads to an autoimmune response and immunopathology. Our strategy to address this thesis will be to 1) synthesize a family of organic molecules starting with the basic structure of TFA; 2) couple these compounds to the inner lipoyl domain of PDC-E2; 3) develop in vitro assays to screen these modified peptides to define the motif recognized by AMAs and 4) develop an animal model, based on our knowledge of mucosal immune responses, that will lead to an AMA response and potential liver pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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 “lipoic acid” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for lipoic acid in the PubMed Central database: •
Age-associated mitochondrial oxidative decay: Improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-l- carnitine and /or R-[alpha]-lipoic acid. by Liu J, Killilea DW, Ames BN.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122287
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Bacteriological analysis of water by potentiometric measurement of lipoic acid reduction: preliminary assays for selective detection of indicator organisms. by Charriere G, Jouenne T, Lemeland JF, Selegny E, Junter GA.; 1984 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=239629
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Biosynthesis of Lipoic Acid in Arabidopsis: Cloning and Characterization of the cDNA for Lipoic Acid Synthase. by Yasuno R, Wada H.; 1998 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34804
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Chromosomal Amplification of the Escherichia coli lipB Region Confers High-Level Resistance to Selenolipoic Acid. by Jordan SW, Cronan, Jr. JE.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135368
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Effects of the Antioxidant [alpha]-Lipoic Acid on Human Umbilical Vein Endothelial Cells Infected with Rickettsia rickettsii. by Eremeeva ME, Silverman DJ.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108194
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Feeding acetyl-l-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. by Hagen TM, Liu J, Lykkesfeldt J, Wehr CM, Ingersoll RT, Vinarsky V, Bartholomew JC, Ames BN.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122286
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Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. by Vanden Boom TJ, Reed KE, Cronan JE Jr.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208974
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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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Lipoic acid metabolism in Escherichia coli: sequencing and functional characterization of the lipA and lipB genes. by Reed KE, Cronan JE Jr.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=193218
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Lipoic acid metabolism in Escherichia coli: the lplA and lipB genes define redundant pathways for ligation of lipoyl groups to apoprotein. by Morris TW, Reed KE, Cronan JE Jr.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176549
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Memory loss in old rats is associated with brain mitochondrial decay and RNA /DNA oxidation: Partial reversal by feeding acetyl-l-carnitine and /or R-[alpha]-lipoic acid. by Liu J, Head E, Gharib AM, Yuan W, Ingersoll RT, Hagen TM, Cotman CW, Ames BN.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122369
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Mutants of Escherichia coli K-12 that are Resistant to a Selenium Analog of Lipoic Acid Identify Unknown Genes in Lipoate Metabolism. by Reed KE, Morris TW, Cronan JE Jr.; 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43653
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Possible involvement of lipoic acid in binding protein-dependent transport systems in Escherichia coli. by Richarme G.; 1985 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218987
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Selective detection and enumeration of fecal coliforms in water by potentiometric measurement of lipoic acid reduction. by Jouenne T, Junter GA, Charriere G.; 1985 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238726
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Synthesis and characterization of selenotrisulfide-derivatives of lipoic acid and lipoamide. by Self WT, Tsai L, Stadtman TC.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18789
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Why do mitochondria synthesize fatty acids? Evidence for involvement in lipoic acid production. by Wada H, Shintani D, Ohlrogge J.; 1997 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19836
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 6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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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 lipoic acid, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “lipoic acid” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for lipoic acid (hyperlinks lead to article summaries): •
A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Author(s): Berkson BM. Source: Medizinische Klinik (Munich, Germany : 1983). 1999 October 15; 94 Suppl 3: 849. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554539&dopt=Abstract
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A positively charged alpha-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity. Author(s): Sen CK, Tirosh O, Roy S, Kobayashi MS, Packer L. Source: Biochemical and Biophysical Research Communications. 1998 June 18; 247(2): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9642107&dopt=Abstract
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Activation of aldose reductase in rat lens and metal-ion chelation by aldose reductase inhibitors and lipoic acid. Author(s): Ou P, Nourooz-Zadeh J, Tritschler HJ, Wolff S. Source: Free Radical Research. 1996 October; 25(4): 337-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8889497&dopt=Abstract
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Activity of alpha-lipoic acid in the protection against oxidative stress in skin. Author(s): Podda M, Zollner TM, Grundmann-Kollmann M, Thiele JJ, Packer L, Kaufmann R. Source: Current Problems in Dermatology. 2001; 29: 43-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11225200&dopt=Abstract
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Advanced glycation end product-induced activation of NF-kappaB is suppressed by alpha-lipoic acid in cultured endothelial cells. Author(s): Bierhaus A, Chevion S, Chevion M, Hofmann M, Quehenberger P, Illmer T, Luther T, Berentshtein E, Tritschler H, Muller M, Wahl P, Ziegler R, Nawroth PP. Source: Diabetes. 1997 September; 46(9): 1481-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9287050&dopt=Abstract
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Alpha lipoic acid: a novel treatment for depression. Author(s): Salazar MR. Source: Medical Hypotheses. 2000 December; 55(6): 510-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090300&dopt=Abstract
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alpha-Lipoic acid as a biological antioxidant. Author(s): Packer L, Witt EH, Tritschler HJ. Source: Free Radical Biology & Medicine. 1995 August; 19(2): 227-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7649494&dopt=Abstract
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Alpha-lipoic acid blocks HIV-1 LTR-dependent expression of hygromycin resistance in THP-1 stable transformants. Author(s): Merin JP, Matsuyama M, Kira T, Baba M, Okamoto T. Source: Febs Letters. 1996 September 23; 394(1): 9-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8925935&dopt=Abstract
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alpha-Lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria. Author(s): Borcea V, Nourooz-Zadeh J, Wolff SP, Klevesath M, Hofmann M, Urich H, Wahl P, Ziegler R, Tritschler H, Halliwell B, Nawroth PP. Source: Free Radical Biology & Medicine. 1999 June; 26(11-12): 1495-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10401614&dopt=Abstract
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Alpha-lipoic acid in liver metabolism and disease. Author(s): Bustamante J, Lodge JK, Marcocci L, Tritschler HJ, Packer L, Rihn BH. Source: Free Radical Biology & Medicine. 1998 April; 24(6): 1023-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9607614&dopt=Abstract
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alpha-Lipoic acid in NIDDM patients with cardiac autonomic neuropathy. Author(s): Kobberling J, Hompesch M. Source: Diabetes Care. 1997 December; 20(12): 1918-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9405919&dopt=Abstract
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Alpha-lipoic acid in the treatment of diabetic peripheral and cardiac autonomic neuropathy. Author(s): Ziegler D, Gries FA. Source: Diabetes. 1997 September; 46 Suppl 2: S62-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9285502&dopt=Abstract
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Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Author(s): Ziegler D, Reljanovic M, Mehnert H, Gries FA. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 1999; 107(7): 421-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10595592&dopt=Abstract
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Alpha-lipoic acid increases intracellular glutathione in a human T-lymphocyte Jurkat cell line. Author(s): Han D, Tritschler HJ, Packer L. Source: Biochemical and Biophysical Research Communications. 1995 February 6; 207(1): 258-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7857274&dopt=Abstract
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Alpha-lipoic acid induces p27Kip-dependent cell cycle arrest in non-transformed cell lines and apoptosis in tumor cell lines. Author(s): van de Mark K, Chen JS, Steliou K, Perrine SP, Faller DV. Source: Journal of Cellular Physiology. 2003 March; 194(3): 325-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548552&dopt=Abstract
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Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. Author(s): Zhang WJ, Frei B. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2001 November; 15(13): 2423-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11689467&dopt=Abstract
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Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Author(s): Suzuki YJ, Aggarwal BB, Packer L. Source: Biochemical and Biophysical Research Communications. 1992 December 30; 189(3): 1709-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1482376&dopt=Abstract
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Alpha-lipoic acid modulates NF-kappaB activity in human monocytic cells by direct interaction with DNA. Author(s): Lee HA, Hughes DA. Source: Experimental Gerontology. 2002 January-March; 37(2-3): 401-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772527&dopt=Abstract
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Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats. Author(s): Maitra I, Serbinova E, Trischler H, Packer L. Source: Free Radical Biology & Medicine. 1995 April; 18(4): 823-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750805&dopt=Abstract
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alpha-Lipoic acid protects against hemolysis of human erythrocytes induced by peroxyl radicals. Author(s): Constantinescu A, Tritschler H, Packer L. Source: Biochem Mol Biol Int. 1994 July; 33(4): 669-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7981654&dopt=Abstract
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Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Author(s): Kunt T, Forst T, Wilhelm A, Tritschler H, Pfuetzner A, Harzer O, Engelbach M, Zschaebitz A, Stofft E, Beyer J. Source: Clinical Science (London, England : 1979). 1999 January; 96(1): 75-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9857109&dopt=Abstract
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Alpha-lipoic acid reduction by mammalian cells to the dithiol form, and release into the culture medium. Author(s): Handelman GJ, Han D, Tritschler H, Packer L. Source: Biochemical Pharmacology. 1994 May 18; 47(10): 1725-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8204089&dopt=Abstract
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alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes. Author(s): Konrad T, Vicini P, Kusterer K, Hoflich A, Assadkhani A, Bohles HJ, Sewell A, Tritschler HJ, Cobelli C, Usadel KH. Source: Diabetes Care. 1999 February; 22(2): 280-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10333946&dopt=Abstract
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Alpha-lipoic acid: a metabolic antioxidant and potential redox modulator of transcription. Author(s): Packer L, Roy S, Sen CK. Source: Adv Pharmacol. 1997; 38: 79-101. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895805&dopt=Abstract
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alpha-Lipoic acid: a metabolic antioxidant which regulates NF-kappa B signal transduction and protects against oxidative injury. Author(s): Packer L. Source: Drug Metabolism Reviews. 1998 May; 30(2): 245-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9606603&dopt=Abstract
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Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Author(s): Evans JL, Goldfine ID. Source: Diabetes Technology & Therapeutics. 2000 Autumn; 2(3): 401-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11467343&dopt=Abstract
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Alpha-lipoic acid: the metabolic antioxidant. Author(s): Packer L, Tritschler HJ. Source: Free Radical Biology & Medicine. 1996; 20(4): 625-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8904306&dopt=Abstract
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Amelioration of docetaxel/cisplatin induced polyneuropathy by alpha-lipoic acid. Author(s): Gedlicka C, Kornek GV, Schmid K, Scheithauer W. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 339-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562664&dopt=Abstract
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Analysis of reduced and oxidized lipoic acid in biological samples by highperformance liquid chromatography. Author(s): Han D, Handelman GJ, Packer L. Source: Methods Enzymol. 1995; 251: 315-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7651212&dopt=Abstract
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Antioxidant adaptive response of human mononuclear cells to UV-B: effect of lipoic acid. Author(s): Alvarez S, Boveris A. Source: Journal of Photochemistry and Photobiology. B, Biology. 2000 April-May; 55(23): 113-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942075&dopt=Abstract
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Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Author(s): Moini H, Packer L, Saris NE. Source: Toxicology and Applied Pharmacology. 2002 July 1; 182(1): 84-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127266&dopt=Abstract
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Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts. Author(s): Packer L. Source: Annals of the New York Academy of Sciences. 1994 November 17; 738: 257-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7832436&dopt=Abstract
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Ataxia-telangiectasia: chronic activation of damage-responsive functions is reduced by alpha-lipoic acid. Author(s): Gatei M, Shkedy D, Khanna KK, Uziel T, Shiloh Y, Pandita TK, Lavin MF, Rotman G. Source: Oncogene. 2001 January 18; 20(3): 289-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11313957&dopt=Abstract
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Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Author(s): Heitzer T, Finckh B, Albers S, Krohn K, Kohlschutter A, Meinertz T. Source: Free Radical Biology & Medicine. 2001 July 1; 31(1): 53-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11425490&dopt=Abstract
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Burning mouth syndrome (BMS): an open trial of comparative efficacy of alpha-lipoic acid (thioctic acid) with other therapies. Author(s): Femiano F. Source: Minerva Stomatol. 2002 September; 51(9): 405-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473978&dopt=Abstract
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Burning mouth syndrome (BMS): double blind controlled study of alpha-lipoic acid (thioctic acid) therapy. Author(s): Femiano F, Scully C. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2002 May; 31(5): 267-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110042&dopt=Abstract
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Capillary zone electrophoresis study of cyclodextrin--lipoic acid host-guest interaction. Author(s): Trentin M, Carofiglio T, Fornasier R, Tonellato U. Source: Electrophoresis. 2002 December; 23(24): 4117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481268&dopt=Abstract
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Chromatographic analysis of lipoic acid and related compounds. Author(s): Kataoka H. Source: J Chromatogr B Biomed Sci Appl. 1998 October 9; 717(1-2): 247-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9832248&dopt=Abstract
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Comparative immunoreactivity of anti-trifluoroacetyl (TFA) antibody and anti-lipoic acid antibody in primary biliary cirrhosis: searching for a mimic. Author(s): Sasaki M, Ansari A, Pumford N, van de Water J, Leung PS, Humphries KM, Szweda LI, Nakanuma Y, Roche TE, Coppel RL, Bach JF, Gershwin ME. Source: Journal of Autoimmunity. 2000 August; 15(1): 51-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936028&dopt=Abstract
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Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Author(s): Marangon K, Devaraj S, Tirosh O, Packer L, Jialal I. Source: Free Radical Biology & Medicine. 1999 November; 27(9-10): 1114-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569644&dopt=Abstract
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Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Author(s): Casciari JJ, Riordan NH, Schmidt TL, Meng XL, Jackson JA, Riordan HD. Source: British Journal of Cancer. 2001 June 1; 84(11): 1544-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384106&dopt=Abstract
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Decrease of red cell membrane fluidity and -SH groups due to hyperglycemic conditions is counteracted by alpha-lipoic acid. Author(s): Hofmann M, Mainka P, Tritschler H, Fuchs J, Zimmer G. Source: Archives of Biochemistry and Biophysics. 1995 December 1; 324(1): 85-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7503564&dopt=Abstract
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Determination of lipoic acid and dihydrolipoic acid in human plasma and urine by high-performance liquid chromatography with fluorimetric detection. Author(s): Haj-Yehia AI, Assaf P, Nassar T, Katzhendler J. Source: J Chromatogr A. 2000 February 18; 870(1-2): 381-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722093&dopt=Abstract
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Determination of lipoic acid by precolumn derivatization with monobromobimane and reversed-phase high-performance liquid chromatography. Author(s): Witt W, Rustow B. Source: J Chromatogr B Biomed Sci Appl. 1998 January 23; 705(1): 127-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9498679&dopt=Abstract
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Determination of lipoic acid in human plasma by high-performance liquid chromatography with electrochemical detection. Author(s): Teichert J, Preiss R. Source: Journal of Chromatography. B, Biomedical Applications. 1995 October 20; 672(2): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8581134&dopt=Abstract
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Determination of oxidized and reduced lipoic acid using high-performance liquid chromatography and coulometric detection. Author(s): Sen CK, Roy S, Khanna S, Packer L. Source: Methods Enzymol. 1999; 299: 239-46. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9916202&dopt=Abstract
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Differential effects of lipoic acid stereoisomers on glucose metabolism in insulinresistant skeletal muscle. Author(s): Streeper RS, Henriksen EJ, Jacob S, Hokama JY, Fogt DL, Tritschler HJ. Source: The American Journal of Physiology. 1997 July; 273(1 Pt 1): E185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9252495&dopt=Abstract
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Differential effects of the antioxidant alpha-lipoic acid on the proliferation of mitogen-stimulated peripheral blood lymphocytes and leukaemic T cells. Author(s): Pack RA, Hardy K, Madigan MC, Hunt NH. Source: Molecular Immunology. 2002 February; 38(10): 733-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11841833&dopt=Abstract
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Direct determination of glutathione in human blood by micellar electrokinetic chromatography: simultaneous determination of lipoamide and lipoic acid. Author(s): Panak KC, Ruiz OA, Giorgieri SA, Diaz LE. Source: Electrophoresis. 1996 October; 17(10): 1613-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8957191&dopt=Abstract
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Effect of alpha-lipoic acid on the progression of endothelial cell damage and albuminuria in patients with diabetes mellitus: an exploratory study. Author(s): Morcos M, Borcea V, Isermann B, Gehrke S, Ehret T, Henkels M, Schiekofer S, Hofmann M, Amiral J, Tritschler H, Ziegler R, Wahl P, Nawroth PP. Source: Diabetes Research and Clinical Practice. 2001 June; 52(3): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323087&dopt=Abstract
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Effect of lipoic acid in a patient with defective activity of pyruvate dehydrogenase, 2oxoglutarate dehydrogenase, and branched-chain keto acid dehydrogenase. Author(s): Yoshida I, Sweetman L, Kulovich S, Nyhan WL, Robinson BH. Source: Pediatric Research. 1990 January; 27(1): 75-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2104971&dopt=Abstract
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Effective treatment of oxaliplatin-induced cumulative polyneuropathy with alphalipoic acid. Author(s): Gedlicka C, Scheithauer W, Schull B, Kornek GV. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 August 1; 20(15): 3359-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149316&dopt=Abstract
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Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Author(s): Ruhnau KJ, Meissner HP, Finn JR, Reljanovic M, Lobisch M, Schutte K, Nehrdich D, Tritschler HJ, Mehnert H, Ziegler D. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 1999 December; 16(12): 1040-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10656234&dopt=Abstract
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Effects of a treatment with coenzyme A, alpha-lipoic acid, diphosphopyridine nucleotide and cocarboxylase on endogenous hepatic coma. Author(s): Tholen H, Colombi A, Duckert F, Huber F, Muller HR, Bigler F. Source: Helv Med Acta. 1967 August; 33(6): 492-504. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4295373&dopt=Abstract
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Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene cfos. Author(s): Mizuno M, Packer L. Source: Biochemical and Biophysical Research Communications. 1994 April 29; 200(2): 1136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8179594&dopt=Abstract
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Effects of alpha-lipoic acid on microcirculation in patients with peripheral diabetic neuropathy. Author(s): Haak E, Usadel KH, Kusterer K, Amini P, Frommeyer R, Tritschler HJ, Haak T. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2000; 108(3): 168-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10926311&dopt=Abstract
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Effects of the antioxidant alpha-lipoic acid on human umbilical vein endothelial cells infected with Rickettsia rickettsii. Author(s): Eremeeva ME, Silverman DJ. Source: Infection and Immunity. 1998 May; 66(5): 2290-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9573120&dopt=Abstract
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Effects of treatment with the antioxidant alpha-lipoic acid on cardiac autonomic neuropathy in NIDDM patients. A 4-month randomized controlled multicenter trial (DEKAN Study). Deutsche Kardiale Autonome Neuropathie. Author(s): Ziegler D, Schatz H, Conrad F, Gries FA, Ulrich H, Reichel G. Source: Diabetes Care. 1997 March; 20(3): 369-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9051389&dopt=Abstract
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Efficient reduction of lipoamide and lipoic acid by mammalian thioredoxin reductase. Author(s): Arner ES, Nordberg J, Holmgren A. Source: Biochemical and Biophysical Research Communications. 1996 August 5; 225(1): 268-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8769129&dopt=Abstract
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Elucidation of antioxidant activity of alpha-lipoic acid toward hydroxyl radical. Author(s): Matsugo S, Yan LJ, Han D, Trischler HJ, Packer L. Source: Biochemical and Biophysical Research Communications. 1995 March 8; 208(1): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7887924&dopt=Abstract
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Enantioselective high-performance liquid chromatography assay of (+)R- and (-)Salpha-lipoic acid in human plasma. Author(s): Niebch G, Buchele B, Blome J, Grieb S, Brandt G, Kampa P, Raffel HH, Locher M, Borbe HO, Nubert I, Fleischhauer I. Source: Chirality. 1997; 9(1): 32-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9094201&dopt=Abstract
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Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid. Author(s): Jacob S, Henriksen EJ, Schiemann AL, Simon I, Clancy DE, Tritschler HJ, Jung WI, Augustin HJ, Dietze GJ. Source: Arzneimittel-Forschung. 1995 August; 45(8): 872-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7575750&dopt=Abstract
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Evidence for the extracellular reduction of alpha-lipoic acid by Leishmania donovani promastigotes: a transplasma membrane redox system. Author(s): Datta G, Bera T. Source: Biochimica Et Biophysica Acta. 2001 June 6; 1512(2): 149-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406092&dopt=Abstract
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Fas mediated apoptosis of human Jurkat T-cells: intracellular events and potentiation by redox-active alpha-lipoic acid. Author(s): Sen CK, Sashwati R, Packer L. Source: Cell Death and Differentiation. 1999 May; 6(5): 481-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10381641&dopt=Abstract
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Folding kinetics of the lipoic acid-bearing domain of human mitochondrial branched chain alpha-ketoacid dehydrogenase complex. Author(s): Naik MT, Chang YC, Huang TH. Source: Febs Letters. 2002 October 23; 530(1-3): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387880&dopt=Abstract
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Glutathione reductase and lipoamide dehydrogenase have opposite stereospecificities for alpha-lipoic acid enantiomers. Author(s): Pick U, Haramaki N, Constantinescu A, Handelman GJ, Tritschler HJ, Packer L. Source: Biochemical and Biophysical Research Communications. 1995 January 17; 206(2): 724-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7826393&dopt=Abstract
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High-performance liquid chromatographic assay for alpha-lipoic acid and five of its metabolites in human plasma and urine. Author(s): Teichert J, Preiss R. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 April 5; 769(2): 269-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11996493&dopt=Abstract
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High-performance liquid chromatography methods for determination of lipoic and dihydrolipoic acid in human plasma. Author(s): Teichert J, Preiss R. Source: Methods Enzymol. 1997; 279: 159-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9211267&dopt=Abstract
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HPLC-methods for determination of lipoic acid and its reduced form in human plasma. Author(s): Teichert J, Preiss R. Source: Int J Clin Pharmacol Ther Toxicol. 1992 November; 30(11): 511-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1490813&dopt=Abstract
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Hyperalaninemia hyperpyruvicemia and lactic acidosis due to pyruvate carboxylase deficiency of the liver; treatment with thiamine and lipoic acid. Author(s): Maesaka H, Komiya K, Misugi K, Tada K. Source: European Journal of Pediatrics. 1976 May 4; 122(2): 159-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=817914&dopt=Abstract
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Hypochlorous acid-modified low-density lipoprotein inactivates the lysosomal protease cathepsin B: protection by ascorbic and lipoic acids. Author(s): Carr AC. Source: Redox Report : Communications in Free Radical Research. 2001; 6(6): 343-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11865974&dopt=Abstract
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Identification of the dihydrolipoamide acetyltransferase subunit of the human pyruvate dehydrogenase complex as an autoantigen in halothane hepatitis. Molecular mimicry of trifluoroacetyl-lysine by lipoic acid. Author(s): Christen U, Quinn J, Yeaman SJ, Kenna JG, Clarke JB, Gandolfi AJ, Gut J. Source: European Journal of Biochemistry / Febs. 1994 August 1; 223(3): 1035-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7519986&dopt=Abstract
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Idiopathic dysgeusia; an open trial of alpha lipoic acid (ALA) therapy. Author(s): Femiano F, Scully C, Gombos F. Source: International Journal of Oral and Maxillofacial Surgery. 2002 December; 31(6): 625-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521319&dopt=Abstract
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In vivo effect of lipoic acid on lipid peroxidation in patients with diabetic neuropathy. Author(s): Androne L, Gavan NA, Veresiu IA, Orasan R. Source: In Vivo. 2000 March-April; 14(2): 327-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10836205&dopt=Abstract
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Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, lipoic acid and Ldeprenyl on the interplay between cellular redox systems. Author(s): Gotz ME, Dirr A, Gsell W, Burger R, Janetzky B, Freyberger A, Reichmann H, Rausch WD, Riederer P. Source: Journal of Neural Transmission. Supplementum. 1994; 43: 145-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7884397&dopt=Abstract
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Interaction of alpha-lipoic acid enantiomers and homologues with the enzyme components of the mammalian pyruvate dehydrogenase complex. Author(s): Loffelhardt S, Bonaventura C, Locher M, Borbe HO, Bisswanger H. Source: Biochemical Pharmacology. 1995 August 25; 50(5): 637-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7669066&dopt=Abstract
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Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Author(s): Teichert J, Kern J, Tritschler HJ, Ulrich H, Preiss R. Source: Int J Clin Pharmacol Ther. 1998 December; 36(12): 625-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9876998&dopt=Abstract
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Lipoamide dehydrogenase deficiency with primary lactic acidosis: favorable response to treatment with oral lipoic acid. Author(s): Matalon R, Stumpf DA, Michals K, Hart RD, Parks JK, Goodman SI. Source: The Journal of Pediatrics. 1984 January; 104(1): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6418873&dopt=Abstract
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Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status. Author(s): Visioli F, Smith A, Zhang W, Keaney JF Jr, Hagen T, Frei B. Source: Redox Report : Communications in Free Radical Research. 2002; 7(4): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396668&dopt=Abstract
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Lipoic acid as an antioxidant. The role of dihydrolipoamide dehydrogenase. Author(s): Patel MS, Hong YS. Source: Methods in Molecular Biology (Clifton, N.J.). 1998; 108: 337-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9921542&dopt=Abstract
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Lipoic acid confers protection against oxidative injury in non-neuronal and neuronal tissue. Author(s): Lynch MA. Source: Nutritional Neuroscience. 2001; 4(6): 419-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843262&dopt=Abstract
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Lipoic acid decreases lipid peroxidation and protein glycosylation and increases (Na(+) + K(+))- and Ca(++)-ATPase activities in high glucose-treated human erythrocytes. Author(s): Jain SK, Lim G. Source: Free Radical Biology & Medicine. 2000 December; 29(11): 1122-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11121719&dopt=Abstract
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Lipoic acid dependency of human branched chain -ketoacid oxidase. Author(s): Rudiger HW, Langenbeck U, Brackertz D, Goedde HW. Source: Biochimica Et Biophysica Acta. 1972 March 30; 264(1): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4623287&dopt=Abstract
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Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Author(s): Nagamatsu M, Nickander KK, Schmelzer JD, Raya A, Wittrock DA, Tritschler H, Low PA. Source: Diabetes Care. 1995 August; 18(8): 1160-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7587852&dopt=Abstract
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Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Author(s): Hummel T, Heilmann S, Huttenbriuk KB. Source: The Laryngoscope. 2002 November; 112(11): 2076-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439184&dopt=Abstract
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Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Author(s): Han D, Handelman G, Marcocci L, Sen CK, Roy S, Kobuchi H, Tritschler HJ, Flohe L, Packer L. Source: Biofactors (Oxford, England). 1997; 6(3): 321-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288403&dopt=Abstract
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Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines. Author(s): Hultberg B, Andersson A, Isaksson A. Source: Toxicology. 2002 June 14; 175(1-3): 103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049840&dopt=Abstract
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Lipoic acid. Author(s): Kirk JE. Source: Monogr Atheroscler. 1974; 4(0): 49-55. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4602305&dopt=Abstract
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Lipoic acid-derived amphiphiles for redox-controlled DNA delivery. Author(s): Balakirev M, Schoehn G, Chroboczek J. Source: Chemistry & Biology. 2000 October; 7(10): 813-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11033084&dopt=Abstract
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Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 December; 7(6): 456-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495372&dopt=Abstract
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Modulation of cellular reducing equivalent homeostasis by alpha-lipoic acid. Mechanisms and implications for diabetes and ischemic injury. Author(s): Roy S, Sen CK, Tritschler HJ, Packer L. Source: Biochemical Pharmacology. 1997 February 7; 53(3): 393-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9065743&dopt=Abstract
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Molecular aspects of lipoic acid in the prevention of diabetes complications. Author(s): Packer L, Kraemer K, Rimbach G. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 October; 17(10): 888-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684397&dopt=Abstract
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Myeloperoxidase-dependent caspase-3 activation and apoptosis in HL-60 cells: protection by the antioxidants ascorbate and (dihydro)lipoic acid. Author(s): Myzak MC, Carr AC. Source: Redox Report : Communications in Free Radical Research. 2002; 7(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981455&dopt=Abstract
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NAC, glutamine, and alpha lipoic acid. Interview by John S. James. Author(s): Lands L. Source: Aids Treat News. 1997 April 4; (No 268): 2-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11364196&dopt=Abstract
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Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Author(s): Packer L, Tritschler HJ, Wessel K. Source: Free Radical Biology & Medicine. 1997; 22(1-2): 359-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8958163&dopt=Abstract
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New metabolic pathways of alpha-lipoic acid. Author(s): Schupke H, Hempel R, Peter G, Hermann R, Wessel K, Engel J, Kronbach T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 June; 29(6): 855-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11353754&dopt=Abstract
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NMR study of lipoic acid binding to bovine serum albumin. Author(s): Schepkin V, Kawabata T, Packer L. Source: Biochem Mol Biol Int. 1994 August; 33(5): 879-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7987256&dopt=Abstract
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Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2000 August; 5(4): 290-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956377&dopt=Abstract
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One-electron reduction of chromium(VI) by alpha-lipoic acid and related hydroxyl radical generation, dG hydroxylation and nuclear transcription factor-kappaB activation. Author(s): Chen F, Ye J, Zhang X, Rojanasakul Y, Shi X. Source: Archives of Biochemistry and Biophysics. 1997 February 15; 338(2): 165-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9028868&dopt=Abstract
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Oral administration of RAC-alpha-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Author(s): Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W, Augustin HJ, Dietze GJ, Rett K. Source: Free Radical Biology & Medicine. 1999 August; 27(3-4): 309-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468203&dopt=Abstract
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Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid. Author(s): Evans JL, Heymann CJ, Goldfine ID, Gavin LA. Source: Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2002 January-February; 8(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11951812&dopt=Abstract
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Plasma alpha-lipoic acid and total glutathione levels in patients on maintenance hemodialysis. Author(s): Reddi AS, Baskin S, Wassel E, DeAngelis B, Baker H. Source: Nephron. 1999; 82(4): 357. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10450040&dopt=Abstract
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Primary biliary cirrhosis. Inhibition of pyruvate dehydrogenase complex activity by autoantibodies specific for E1 alpha, a non-lipoic acid containing mitochondrial enzyme. Author(s): Fregeau DR, Roche TE, Davis PA, Coppel R, Gershwin ME. Source: Journal of Immunology (Baltimore, Md. : 1950). 1990 March 1; 144(5): 1671-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2106552&dopt=Abstract
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Protection against peroxynitrite-dependent tyrosine nitration and alpha 1antiproteinase inactivation by oxidized and reduced lipoic acid. Author(s): Whiteman M, Tritschler H, Halliwell B. Source: Febs Letters. 1996 January 22; 379(1): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8566234&dopt=Abstract
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Reduction and transport of lipoic acid by human erythrocytes. Author(s): Constantinescu A, Pick U, Handelman GJ, Haramaki N, Han D, Podda M, Tritschler HJ, Packer L. Source: Biochemical Pharmacology. 1995 July 17; 50(2): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7632170&dopt=Abstract
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Regulation of cellular thiols in human lymphocytes by alpha-lipoic acid: a flow cytometric analysis. Author(s): Sen CK, Roy S, Han D, Packer L. Source: Free Radical Biology & Medicine. 1997; 22(7): 1241-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9098099&dopt=Abstract
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Restoration of functional defects in peripheral blood mononuclear cells isolated from cancer patients by thiol antioxidants alpha-lipoic acid and N-acetyl cysteine. Author(s): Mantovani G, Maccio A, Melis G, Mura L, Massa E, Mudu MC. Source: International Journal of Cancer. Journal International Du Cancer. 2000 June 15; 86(6): 842-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10842199&dopt=Abstract
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Selective detection and enumeration of fecal coliforms in water by potentiometric measurement of lipoic acid reduction. Author(s): Jouenne T, Junter GA, Charriere G. Source: Applied and Environmental Microbiology. 1985 November; 50(5): 1208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4091553&dopt=Abstract
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Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex. Author(s): Chang CF, Chou HT, Chuang JL, Chuang DT, Huang TH. Source: The Journal of Biological Chemistry. 2002 May 3; 277(18): 15865-73. Epub 2002 February 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839747&dopt=Abstract
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Studies on the effect of alpha-lipoic acid on disturbances in histidine metabolism. Author(s): Galamon T, Szulc-Kuberska J, Tronczynska J. Source: Pol Med J. 1971; 10(1): 31-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4929904&dopt=Abstract
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Synthesis and characterization of selenotrisulfide-derivatives of lipoic acid and lipoamide. Author(s): Self WT, Tsai L, Stadtman TC. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 November 7; 97(23): 12481-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050172&dopt=Abstract
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The effect of alpha-lipoic acid on the neurovascular reflex arc in patients with diabetic neuropathy assessed by capillary microscopy. Author(s): Haak ES, Usadel KH, Kohleisen M, Yilmaz A, Kusterer K, Haak T. Source: Microvascular Research. 1999 July; 58(1): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10388600&dopt=Abstract
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The lipoic acid analogue 1,2-diselenolane-3-pentanoic acid protects human low density lipoprotein against oxidative modification mediated by copper ion. Author(s): Matsugo S, Yan LJ, Konishi T, Youn HD, Lodge JK, Ulrich H, Packer L. Source: Biochemical and Biophysical Research Communications. 1997 November 26; 240(3): 819-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9398652&dopt=Abstract
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The lipoic acid containing components of the 2-oxoacid dehydrogenase complexes mimic trifluoroacetylated proteins and are autoantigens associated with halothane hepatitis. Author(s): Frey N, Christen U, Jeno P, Yeaman SJ, Shimomura Y, Kenna JG, Gandolfi AJ, Ranek L, Gut J. Source: Chemical Research in Toxicology. 1995 July-August; 8(5): 736-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7548757&dopt=Abstract
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The pharmacology of the antioxidant lipoic acid. Author(s): Biewenga GP, Haenen GR, Bast A. Source: General Pharmacology. 1997 September; 29(3): 315-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9378235&dopt=Abstract
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The role of lipoic acid in the treatment of diabetic polyneuropathy. Author(s): Biewenga G, Haenen GR, Bast A. Source: Drug Metabolism Reviews. 1997 November; 29(4): 1025-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9421684&dopt=Abstract
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The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Author(s): Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O'Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D; SYDNEY Trial Study Group. Source: Diabetes Care. 2003 March; 26(3): 770-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610036&dopt=Abstract
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Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha Lipoic Acid in Diabetic Neuropathy. Author(s): Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Moller W, Tritschler HJ, Mehnert H. Source: Free Radical Research. 1999 September; 31(3): 171-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10499773&dopt=Abstract
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Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study). Author(s): Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA. Source: Diabetologia. 1995 December; 38(12): 1425-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8786016&dopt=Abstract
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Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Author(s): Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R. Source: Diabetes Care. 1999 August; 22(8): 1296-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10480774&dopt=Abstract
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Uptake, recycling, and antioxidant actions of alpha-lipoic acid in endothelial cells. Author(s): Jones W, Li X, Qu ZC, Perriott L, Whitesell RR, May JM. Source: Free Radical Biology & Medicine. 2002 July 1; 33(1): 83-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086686&dopt=Abstract
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CHAPTER 2. NUTRITION AND LIPOIC ACID Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and lipoic acid.
Finding Nutrition Studies on Lipoic Acid 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 “lipoic acid” (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 “lipoic acid” (or a synonym): •
A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Author(s): Integrative Medical Center of New Mexico, New Mexico State University, Las Cruces, USA.
[email protected] Source: Berkson, B M Med-Klin. 1999 October 15; 94 Suppl 384-9 0723-5003
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A lipoic acid-gamma linolenic acid conjugate is effective against multiple indices of experimental diabetic neuropathy. Author(s): Department of Pharmacology, Queen Mary and Westfield College, London, UK. Source: Hounsom, L Horrobin, D F Tritschler, H Corder, R Tomlinson, D R Diabetologia. 1998 July; 41(7): 839-43 0012-186X
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Activation of choline acetyl transferase by dihydrolipoic acid. Author(s): Division of Urology, School of Medicine, University of Pennsylvania, Philadelphia 19104-4283, USA. Source: Haugaard, N Levin, R M Mol-Cell-Biochem. 2002 January; 229(1-2): 103-6 03008177
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Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Author(s): Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA. Source: Liu, Jiankang Killilea, David W Ames, Bruce N Proc-Natl-Acad-Sci-U-S-A. 2002 February 19; 99(4): 1876-81 0027-8424
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Allosteric modulation of the NMDA receptor by dihydrolipoic and lipoic acid in rat cortical neurons in vitro. Author(s): Department of Neurobiology, University of Pittsburgh School of Medicine, Pennsylvania 15261. Source: Tang, L H Aizenman, E Neuron. 1993 November; 11(5): 857-63 0896-6273
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Alpha lipoic acid changes iron uptake and storage in lens epithelial cells. Author(s): Department of Molecular Biomedical Sciences, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA. Source: Goralska, M Dackor, R Holley, B McGahan, M C Exp-Eye-Res. 2003 February; 76(2): 241-8 0014-4835
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Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. Author(s): Department of Neurology, Oregon Health and Science University, Portland, OR 97201, USA. Source: Marracci, G H Jones, R E McKeon, G P Bourdette, D N J-Neuroimmunol. 2002 October; 131(1-2): 104-14 0165-5728
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Amino acid sequence surrounding the lipoic acid cofactor of bovine kidney 2oxoglutarate dehydrogenase complex. Author(s): Department of Biochemistry, University of Newcastle upon Tyne, England. Source: Bradford, A P Aitken, A Beg, F Cook, K G Yeaman, S J FEBS-Lett. 1987 September 28; 222(1): 211-4 0014-5793
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Antioxidant properties of lipoic and dihydrolipoic acid in vegetable oil and lard. Source: Drinda, H. Baltes, W. Zeitschrift-fuer-Lebensmittel-Untersuchung-undForschung (Germany). (1999). volume 208(4) page 270-276. plant oils backfat lipoic acid antioxidants analytical methods 1431-4630
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Biosynthesis of biotin and lipoic acid. Author(s): Laboratoire de Chimie Organique Biologique, Universite Pierre et Marie Curie, 75252 Paris, France. Source: Marquet, A Bui, B T Florentin, D Vitam-Horm. 2001; 61: 51-101 0083-6729
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Cathepsin B responsiveness to glutathione and lipoic acid redox. Author(s): Department of Pharmacology and Toxicology, Wright State University, School of Medicine, Dayton, OH 45435, USA.
[email protected] Source: Lockwood, T D Antioxid-Redox-Signal. 2002 August; 4(4): 681-91 1523-0864
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Combined effect of lipoic acid and doxorubicin in murine leukemia. Author(s): Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic. Source: Dovinova, I Novotny, L Rauko, P Kvasnicka, P Neoplasma. 1999; 46(4): 237-41 0028-2685
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Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Author(s): Bio-Communications Research Institute, Center for the Improvement of Human Functioning International, 3100 North Hillside Avenue, Wichita, KS 67219, USA. Source: Casciari, J J Riordan, N H Schmidt, T L Meng, X L Jackson, J A Riordan, H D BrJ-Cancer. 2001 June 1; 84(11): 1544-50 0007-0920
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Determination of lipoic acid in meat of commercial quality. Author(s): Institut fur Lebensmittelchemie der TU Berlin, Federal Republic of Germany. Source: Mattulat, A Baltes, W Z-Lebensm-Unters-Forsch. 1992 April; 194(4): 326-9 00443026
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Dietary lipoic acid supplementation prevents fructose-induced hypertension in rats. Author(s): Department of Medicine, Room H-4310, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6. Source: Vasdev, S Ford, C A Parai, S Longerich, L Gadag, V Nutr-Metab-Cardiovasc-Dis. 2000 December; 10(6): 339-46 0939-4753
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Direct determination of glutathione in human blood by micellar electrokinetic chromatography: simultaneous determination of lipoamide and lipoic acid. Author(s): Catedra de Quimica Analitica Instrumental, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires, Argentina. Source: Panak, K C Ruiz, O A Giorgieri, S A Diaz, L E Electrophoresis. 1996 October; 17(10): 1613-6 0173-0835
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Do mammalian cells synthesize lipoic acid? Identification of a mouse cDNA encoding a lipoic acid synthase located in mitochondria. Author(s): Department of Biology, Faculty of Sciences, Kyushu University, Ropponmatsu, Fukuoka 810-8560, Japan. Source: Morikawa, T Yasuno, R Wada, H FEBS-Lett. 2001 June 1; 498(1): 16-21 0014-5793
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Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats. Author(s): Department of Medical Biochemistry, Dr A.L. Mudaliar Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, 600-113, Chennai, India.
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Source: Arivazhagan, P Ramanathan, K Panneerselvam, C Chem-Biol-Interact. 2001 November 28; 138(2): 189-98 0009-2797 •
Effect of selenolipoic acid on peroxynitrite-dependent inactivation of NADPHcytochrome P450 reductase. Author(s): Institute of Chemical Kinetics & Combustion, Novosibirsk, 630090, Russia.
[email protected] Source: Sergeeva, S V Slepneva, I A Khramtsov, V V Free-Radic-Res. 2001 November; 35(5): 491-7 1071-5762
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Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on the glutathione, malonaldehyde, and fatty acids levels in erythrocytes of streptozotocin induced diabetic male rats. Author(s): Department of Biology, Faculty of Science, Firat University, 23169-Elazig, Turkey.
[email protected] Source: Yilmaz, O Ozkan, Y Yildirim, M Ozturk, A I Ersan, Y J-Cell-Biochem. 2002; 86(3): 530-9 0730-2312
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Electrocatalytic reduction of lipoic acid and electroenzymatic reduction of NAD(P)(+) for integrated dehydrogenase biosensors. Author(s): Lehrstuhl fur Biologische Chemie, Technische Universitat Munchen, An der Saatzucht 5, D-85350 Freising-Weihenstephan, Germany. Source: Eicher, I Schmidt, H L Biosens-Bioelectron. 2001 June; 16(4-5): 245-52 0956-5663
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Endogenous and new synthetic antioxidants for peroxynitrite: selective inhibitory effect of 5-methoxytryptamine and lipoic acid on tyrosine nitration by peroxynitrite. Author(s): Bioregulation Research Group, National Institute of Radiological Sciences, Chiba 263, Japan. Source: Nakagawa, H Sumiki, E Ikota, N Matsushima, Y Ozawa, T Antioxid-RedoxSignal. 1999 Summer; 1(2): 239-44 1523-0864
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Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Author(s): Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. Source: Hagen, Tory M Liu, Jiankang Lykkesfeldt, Jens Wehr, Carol M Ingersoll, Russell T Vinarsky, Vladimir Bartholomew, James C Ames, Bruce N Proc-Natl-Acad-Sci-U-S-A. 2002 February 19; 99(4): 1870-5 0027-8424
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Folding kinetics of the lipoic acid-bearing domain of human mitochondrial branched chain alpha-ketoacid dehydrogenase complex. Author(s): Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan. Source: Naik, M T Chang, Y C Huang, T H FEBS-Lett. 2002 October 23; 530(1-3): 133-8 0014-5793
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From lipoic acid to multi-enzyme complexes. Author(s): Department of Chemistry and Biochemistry, The University of Texas at Austin, 78712, USA. Source: Reed, L J Protein-Sci. 1998 January; 7(1): 220-4 0961-8368
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Hypochlorous acid-modified low-density lipoprotein inactivates the lysosomal protease cathepsin B: protection by ascorbic and lipoic acids. Author(s): Linus Pauling Institute, Oregon State University, Corvallis 97331-6512, USA.
[email protected] Source: Carr, A C Redox-Repage 2001; 6(6): 343-9 1351-0002
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Identification of the dihydrolipoamide acetyltransferase subunit of the human pyruvate dehydrogenase complex as an autoantigen in halothane hepatitis. Molecular mimicry of trifluoroacetyl-lysine by lipoic acid. Author(s): Department of Pharmacology, Biocenter of the University, Basel, Switzerland. Source: Christen, U Quinn, J Yeaman, S J Kenna, J G Clarke, J B Gandolfi, A J Gut, J EurJ-Biochem. 1994 August 1; 223(3): 1035-47 0014-2956
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Incorporation of the enantiomers of lipoic acid into the pyruvate dehydrogenase complex from Escherichia coli in vivo. Author(s): Physiologisch-Chemisches Institut Universitat Tubingen, Germany. Source: Oehring, R Bisswanger, H Biol-Chem-Hoppe-Seyler. 1992 June; 373(6): 333-5 0177-3593
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Influence of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, lipoic acid and Ldeprenyl on the interplay between cellular redox systems. Author(s): Department of Psychiatry, University of Wurzburg, Federal Republic of Germany. Source: Gotz, M E Dirr, A Gsell, W Burger, R Janetzky, B Freyberger, A Reichmann, H Rausch, W D Riederer, P J-Neural-Transm-Suppl. 1994; 43145-62 0303-6995
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Interactions of lipoic acid radical cations with vitamins C and E analogue and hydroxycinnamic acid derivatives. Author(s): Lehrstuhl fur Organische Chemie II der Ruhr-Universitat, Bochum, Germany.
[email protected] Source: Lu, C Liu, Y Arch-Biochem-Biophys. 2002 October 1; 406(1): 78-84 0003-9861
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Lipoic acid and vitamin C potentiate nitric oxide synthesis in human aortic endothelial cells independently of cellular glutathione status. Author(s): Linus Pauling Institute, Oregon State University, Corvallis, Oregon, USA.
[email protected] Source: Visioli, F Smith, A Zhang, W Keaney, J F Jr Hagen, T Frei, B Redox-Repage 2002; 7(4): 223-7 1351-0002
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Lipoic acid as an antioxidant in mature thoroughbred geldings: a preliminary study. Author(s): Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
[email protected] Source: Williams, Carey A Hoffman, Rhonda M Kronfeld, David S Hess, Tanja M Saker, Korinn E Harris, Pat A J-Nutr. 2002 June; 132(6 Suppl 2): 1628S-31S 0022-3166
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Lipoic acid confers protection against oxidative injury in non-neuronal and neuronal tissue. Author(s): Department of Physiology, Trinity College Institute for Neuroscience, Trinity College, Dublin, Ireland.
[email protected] Source: Lynch, M A Nutr-Neurosci. 2001; 4(6): 419-38 1028-415X
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Lipoic acid impairs glycine conjugation of benzoic acid and renal excretion of benzoylglycine. Author(s): Department of Pharmacology, University Medical School of Pecs, Hungary. Source: Gregus, Z Fekete, T Halaszi, E Klaassen, C D Drug-Metab-Dispos. 1996 June; 24(6): 682-8 0090-9556
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Lipoic acid improves survival in transgenic mouse models of Huntington's disease. Author(s): Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Source: Andreassen, O A Ferrante, R J Dedeoglu, A Beal, M F Neuroreport. 2001 October 29; 12(15): 3371-3 0959-4965
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Lipoic acid in the treatment of smell dysfunction following viral infection of the upper respiratory tract. Author(s): Department of Otorhinolaryngology, University of Dresden Medical School, Germany.
[email protected] Source: Hummel, T Heilmann, S Huttenbriuk, K B Laryngoscope. 2002 November; 112(11): 2076-80 0023-852X
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Lipoic acid increases glucose uptake by skeletal muscles of obese-diabetic ob/ob mice. Author(s): School of Pharmacy, Aston University, Birmingham, UK. Source: Eason, R C Archer, H E Akhtar, S Bailey, C J Diabetes-Obes-Metab. 2002 January; 4(1): 29-35 1462-8902
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Lipoic acid metabolism in Arabidopsis thaliana: cloning and characterization of a cDNA encoding lipoyltransferase. Author(s): Department of Biology, Faculty of Sciences, Kyushu University, Ropponmatsu, Fukuoka, 810-8560 Japan.
[email protected] Source: Wada, M Yasuno, R Jordan, S W Cronan, J E Jr Wada, H Plant-Cell-Physiol. 2001 June; 42(6): 650-6 0032-0781
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Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes. Author(s): S. Daniel Abraham International Centre for Health and Nutrition, BenGurion University of the Negev, Beer-Sheva, Israel. Source: Rudich, A Tirosh, A Potashnik, R Khamaisi, M Bashan, N Diabetologia. 1999 August; 42(8): 949-57 0012-186X
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Lipoic acid reduces ischemia-reperfusion injury in animal models. Author(s): Faculty of Medicine, University of Indonesia, Pascasarjana-Fakultas Kedokteran, Salemba Raya No. 4, Jakarta 10430, Indonesia. Source: Freisleben, H J Toxicology. 2000 August 7; 148(2-3): 159-71 0300-483X
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Lipoic acid: a unique antioxidant in the detoxification of activated oxygen species. Author(s): (Universita di Pisa (Italie). Dipartimento di Chimica e Biotechnologie Agrarie) Source: Navari Izzo, F. Quartacci, M.F. Sgherri, C. Plant-Physiology-and-Biochemistry (France). (Jun-Aou 2002). volume 40(6-8) page 463-470. Special issue: Free radicals and oxidative stress in plants: a new insight. P79. plants lipoic acid ascorbic acid glutathione tocopherols oxidation stress biosynthesis 0981-9428
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Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Author(s): Division of Biochemistry and Molecular Biology, University of California, Berkeley, CA 94720, USA. Source: Liu, Jiankang Head, Elizabeth Gharib, Afshin M Yuan, WenJune Ingersoll, Russell T Hagen, Tory M Cotman, Carl W Ames, Bruce N Proc-Natl-Acad-Sci-U-S-A. 2002 February 19; 99(4): 2356-61 0027-8424
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Mitochondrial acyl carrier protein is involved in lipoic acid synthesis in Saccharomyces cerevisiae. Author(s): Department of Biology, University of California at San Diego, La Jolla 92093, USA. Source: Brody, S Oh, C Hoja, U Schweizer, E FEBS-Lett. 1997 May 19; 408(2): 217-20 0014-5793
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Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Author(s): Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA.
[email protected] Source: Hagen, Tory M Moreau, Regis Suh, Jung H Visioli, Francesco Ann-N-Y-AcadSci. 2002 April; 959: 491-507 0077-8923
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Monoselenolipoic acid may be an outstanding pharmaceutical antioxidant with direct thioredoxin-like activity. Author(s): Pantox Laboratories, San Diego, California 92109, USA. Source: McCarty, M F Med-Hypotheses. 2000 September; 55(3): 185-6 0306-9877
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Neither desferrioxamine nor lipoic acid enhances the cold ischaemic tolerance of epigastric free flaps in rats. Author(s): Department of Plastic, Reconstructive and Hand Surgery, University Hospital Utrecht, The Netherlands. Source: Werker, P M Kon, M Green, C J Franken, R J Overgoor, M L Microsurgery. 1993; 14(9): 574-8 0738-1085
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Novel lipoic acid analogues that inhibit nitric oxide synthase. Author(s): Department of Medicinal Chemistry, Beaufour-Ipsen Research Laboratories, Institute Henri Beaufour, 5, Avenue du Canada, 91966 Cedex, Les Ulis, France.
[email protected] Source: Harnett, J J Auguet, M Viossat, I Dolo, C Bigg, D Chabrier, P E Bioorg-MedChem-Lett. 2002 June 3; 12(11): 1439-42 0960-894X
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Peroxynitrite reaction with the reduced and the oxidized forms of lipoic acid: new insights into the reaction of peroxynitrite with thiols. Author(s): Departamento de Bioquimica, Universidad de la Republica, 11800 Montevideo, Uruguay. Source: Trujillo, Madia Radi, Rafael Arch-Biochem-Biophys. 2002 January 1; 397(1): 91-8 0003-9861
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Prevention of hypertension, insulin resistance, and oxidative stress by alpha-lipoic acid. Author(s): Research group on Autonomic Nervous System, Department of Physiology, Faculty of Medecine, University of Montreal, Montreal, Quebec, Canada. Source: El Midaoui, Adil de Champlain, Jacques Hypertension. 2002 February; 39(2): 303-7 1524-4563
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Protection against peroxynitrite-dependent tyrosine nitration and alpha 1antiproteinase inactivation by oxidized and reduced lipoic acid. Author(s): Neurodegenerative Disease Research Centre, King's College, London, UK. Source: Whiteman, M Tritschler, H Halliwell, B FEBS-Lett. 1996 January 22; 379(1): 74-6 0014-5793
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Protective effects of DL-alpha-lipoic acid on cadmium-induced deterioration of rat hepatocytes. Author(s): Institute of Toxicology, University of Dusseldorf, F.R.G. Source: Muller, L Toxicology. 1989 October 2; 58(2): 175-85 0300-483X
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R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Author(s): Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles, California 90033, USA.
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Source: Moini, Hadi Tirosh, Oren Park, Young Chul Cho, Kyung Joo Packer, Lester Arch-Biochem-Biophys. 2002 January 15; 397(2): 384-91 0003-9861 •
Solution structure and dynamics of the lipoic acid-bearing domain of human mitochondrial branched-chain alpha-keto acid dehydrogenase complex. Author(s): Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 11529, Republic of China. Source: Chang, Chi Fon Chou, Hui Ting Chuang, Jacinta L Chuang, David T Huang, Tai Huang J-Biol-Chem. 2002 May 3; 277(18): 15865-73 0021-9258
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Subcellular localisation of dihydrolipoamide dehydrogenase and detection of lipoic acid in bloodstream forms of Trypanosoma brucei. Author(s): Department of Biochemistry, University of Bath, England. Source: Jackman, S A Hough, D W Danson, M J Stevenson, K J Opperdoes, F R Eur-JBiochem. 1990 October 5; 193(1): 91-5 0014-2956
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Sulfur-centered radical formation from the antioxidant dihydrolipoic acid. Author(s): Department of Chemistry, Luther College, Decorah, Iowa 52101, USA. Source: Mottley, C Mason, R P J-Biol-Chem. 2001 November 16; 276(46): 42677-83 00219258
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Susceptibility of agar-entrapped Escherichia coli cultures to cefotaxime as assessed by the potentiometric measurement of lipoic acid reduction. Author(s): Laboratoire des Polymeres, Biopolymeres, Membranes, URA 500 du CNRS, Universite de Rouen, Mont-Saint-Aignan, France. Source: Tresse, O Jouenne, T Junter, G A J-Chemother. 1994 December; 6(6): 388-91 1120009X
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The biosynthetic pathway for lipoic acid is present in plastids and mitochondria in Arabidopsis thaliana. Author(s): Department of Biology, Faculty of Sciences, Kyushu University, Ropponmatsu, Fukuoka, Japan. Source: Yasuno, Rie Wada, Hajime FEBS-Lett. 2002 April 24; 517(1-3): 110-4 0014-5793
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The C-terminal hinge region of lipoic acid-bearing domain of E2b is essential for domain interaction with branched-chain alpha-keto acid dehydrogenase kinase. Author(s): Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. Source: Chuang, J L Wynn, R M Chuang, D T J-Biol-Chem. 2002 October 4; 277(40): 36905-8 0021-9258
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The role of lipoic acid in the treatment of diabetic polyneuropathy. Author(s): Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, The Netherlands. Source: Biewenga, G Haenen, G R Bast, A Drug-Metab-Revolume 1997 November; 29(4): 1025-54 0360-2532
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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to lipoic acid; 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: •
Minerals Biotin Source: Healthnotes, Inc.; www.healthnotes.com Biotin Source: Prima Communications, Inc.www.personalhealthzone.com
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Selenium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html •
Food and Diet Abalone Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND LIPOIC ACID Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to lipoic acid. 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 lipoic acid 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 “lipoic acid” (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 lipoic acid: •
(R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. Author(s): Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1999 February; 13(2): 411-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9973329&dopt=Abstract
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A case of pyruvate carboxylase deficiency with later prenatal diagnosis of an unaffected sibling. Author(s): Tsuchiyama A, Oyanagi K, Hirano S, Tachi N, Sogawa H, Wagatsuma K, Nakao T, Tsugawa S, Kawamura Y. Source: Journal of Inherited Metabolic Disease. 1983; 6(3): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6422150&dopt=Abstract
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A comparative study of the reversibility of the reaction catalysed by bacterial lipoamide dehydrogenase. Author(s): McGarry JD. Source: Biochimica Et Biophysica Acta. 1968 April 24; 159(1): 9-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4384985&dopt=Abstract
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A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Author(s): Berkson BM. Source: Medizinische Klinik (Munich, Germany : 1983). 1999 October 15; 94 Suppl 3: 849. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10554539&dopt=Abstract
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A positively charged alpha-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity. Author(s): Sen CK, Tirosh O, Roy S, Kobayashi MS, Packer L. Source: Biochemical and Biophysical Research Communications. 1998 June 18; 247(2): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9642107&dopt=Abstract
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Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes--reversal with (R)-alpha-lipoic acid supplementation. Author(s): Lykkesfeldt J, Hagen TM, Vinarsky V, Ames BN. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1998 September; 12(12): 1183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9737721&dopt=Abstract
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Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. Author(s): Marracci GH, Jones RE, McKeon GP, Bourdette DN. Source: Journal of Neuroimmunology. 2002 October; 131(1-2): 104-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458042&dopt=Abstract
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Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency. Author(s): Podda M, Tritschler HJ, Ulrich H, Packer L. Source: Biochemical and Biophysical Research Communications. 1994 October 14; 204(1): 98-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7945398&dopt=Abstract
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Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise. Author(s): Khanna S, Atalay M, Laaksonen DE, Gul M, Roy S, Sen CK.
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Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 1999 April; 86(4): 1191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194202&dopt=Abstract •
Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. Author(s): Nickander KK, McPhee BR, Low PA, Tritschler H. Source: Free Radical Biology & Medicine. 1996; 21(5): 631-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8891666&dopt=Abstract
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Alternative therapies: Part I. Depression, diabetes, obesity. Author(s): Morelli V, Zoorob RJ. Source: American Family Physician. 2000 September 1; 62(5): 1051-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997530&dopt=Abstract
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Amelioration of docetaxel/cisplatin induced polyneuropathy by alpha-lipoic acid. Author(s): Gedlicka C, Kornek GV, Schmid K, Scheithauer W. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2003 February; 14(2): 339-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562664&dopt=Abstract
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An Escherichia coli protein with homology to the H-protein of the glycine cleavage enzyme complex from pea and chicken liver. Author(s): Stauffer LT, Steiert PS, Steiert JG, Stauffer GV. Source: Dna Sequence : the Journal of Dna Sequencing and Mapping. 1991; 2(1): 13-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1802033&dopt=Abstract
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An expanded concept of “insurance” supplementation--broad-spectrum protection from cardiovascular disease. Author(s): McCarty MF. Source: Medical Hypotheses. 1981 October; 7(10): 1287-1302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6169979&dopt=Abstract
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Antagonistic effects against single lethal doses of Amanita phalloides. Author(s): Floersheim GL. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1976 May; 293(2): 171-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=183152&dopt=Abstract
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Antimutagenic effect of alpha-lipoic acid on three model test systems. Author(s): Miadokova E, Vlckova V, Duhova V. Source: Pharmazie. 2000 November; 55(11): 862-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126010&dopt=Abstract
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Antioxidant inhibition of thymocyte apoptosis by dihydrolipoic acid. Author(s): Bustamante J, Slater AF, Orrenius S. Source: Free Radical Biology & Medicine. 1995 September; 19(3): 339-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7557548&dopt=Abstract
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Antioxidant regulation of gene expression: analysis of differentially expressed mRNAs. Author(s): Gohil K, Roy S, Packer L, Sen CK. Source: Methods Enzymol. 1999; 300: 402-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9919541&dopt=Abstract
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Antioxidant strategies for Alzheimer's disease. Author(s): Grundman M, Grundman M, Delaney P. Source: The Proceedings of the Nutrition Society. 2002 May; 61(2): 191-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133201&dopt=Abstract
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Atherosclerosis in Japanese quail and the effect of lipoic acid. Author(s): Shih JC. Source: Fed Proc. 1983 May 15; 42(8): 2494-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6404656&dopt=Abstract
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Characterization of the primary structure of H-protein from Pisum sativum and location of a lipoic acid residue by combined liquid chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry. Author(s): Merand V, Forest E, Gagnon J, Monnet C, Thibault P, Neuburger M, Douce R. Source: Biol Mass Spectrom. 1993 August; 22(8): 447-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8357858&dopt=Abstract
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Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Author(s): Marangon K, Devaraj S, Tirosh O, Packer L, Jialal I. Source: Free Radical Biology & Medicine. 1999 November; 27(9-10): 1114-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569644&dopt=Abstract
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Dietary alpha-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats. Author(s): Vasdev S, Ford CA, Parai S, Longerich L, Gadag V. Source: Journal of Hypertension. 2000 May; 18(5): 567-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10826559&dopt=Abstract
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Dietary lipoic acid supplementation prevents fructose-induced hypertension in rats. Author(s): Vasdev S, Ford CA, Parai S, Longerich L, Gadag V.
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Source: Nutr Metab Cardiovasc Dis. 2000 December; 10(6): 339-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11302009&dopt=Abstract •
Effect of alpha-lipoic acid supplementation on oxidative protein damage in the streptozotocin-diabetic rat. Author(s): Cakatay U, Telci A, Kayali R, Sivas A, Akcay T. Source: Research in Experimental Medicine. Zeitschrift Fur Die Gesamte Experimentelle Medizin Einschliesslich Experimenteller Chirurgie. 2000 February; 199(4): 243-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10743682&dopt=Abstract
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Effect of combined supplementation with vitamin E and alpha-lipoic acid on myocardial performance during in vivo ischaemia-reperfusion. Author(s): Coombes JS, Powers SK, Demirel HA, Jessup J, Vincent HK, Hamilton KL, Naito H, Shanely RA, Sen CK, Packer L, Ji LL. Source: Acta Physiologica Scandinavica. 2000 August; 169(4): 261-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951116&dopt=Abstract
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Effect of DL-alpha-lipoic acid on glutathione metabolic enzymes in aged rats. Author(s): Arivazhagan P, Ramanathan K, Panneerselvam C. Source: Experimental Gerontology. 2001 December; 37(1): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738149&dopt=Abstract
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Effects of dietary supplementation of alpha-lipoic acid on early glomerular injury in diabetes mellitus. Author(s): Melhem MF, Craven PA, Derubertis FR. Source: Journal of the American Society of Nephrology : Jasn. 2001 January; 12(1): 12433. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134258&dopt=Abstract
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Improved cardiac performance after ischemia in aged rats supplemented with vitamin E and alpha-lipoic acid. Author(s): Coombes JS, Powers SK, Hamilton KL, Demirel HA, Shanely RA, Zergeroglu MA, Sen CK, Packer L, Ji LL. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2000 December; 279(6): R2149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11080080&dopt=Abstract
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Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study. Author(s): Arend A, Zilmer M, Vihalemm T, Selstam G, Sepp E. Source: Annals of Nutrition & Metabolism. 2000; 44(5-6): 217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11146327&dopt=Abstract
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Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver. Author(s): Zempleni J, Trusty TA, Mock DM. Source: The Journal of Nutrition. 1997 September; 127(9): 1776-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9278559&dopt=Abstract
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Lipoic acid supplementation prevents angiotensin II-induced renal injury. Author(s): Mervaala E, Finckenberg P, Lapatto R, Muller DN, Park JK, Dechend R, Ganten D, Vapaatalo H, Luft FC. Source: Kidney International. 2003 August; 64(2): 501-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846745&dopt=Abstract
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Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2002 December; 7(6): 456-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495372&dopt=Abstract
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Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Author(s): Hagen TM, Moreau R, Suh JH, Visioli F. Source: Annals of the New York Academy of Sciences. 2002 April; 959: 491-507. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11976222&dopt=Abstract
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NAC, glutamine, and alpha lipoic acid. Interview by John S. James. Author(s): Lands L. Source: Aids Treat News. 1997 April 4; (No 268): 2-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11364196&dopt=Abstract
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Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2000 August; 5(4): 290-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956377&dopt=Abstract
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One-electron reduction of chromium(VI) by alpha-lipoic acid and related hydroxyl radical generation, dG hydroxylation and nuclear transcription factor-kappaB activation. Author(s): Chen F, Ye J, Zhang X, Rojanasakul Y, Shi X. Source: Archives of Biochemistry and Biophysics. 1997 February 15; 338(2): 165-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9028868&dopt=Abstract
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Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid. Author(s): Suh JH, Shigeno ET, Morrow JD, Cox B, Rocha AE, Frei B, Hagen TM. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2001 March; 15(3): 700-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11259388&dopt=Abstract
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Skeletal muscle and liver lipoyllysine content in response to exercise, training and dietary alpha-lipoic acid supplementation. Author(s): Khanna S, Atalay M, Lodge JK, Laaksonen DE, Roy S, Hanninen O, Packer L, Sen CK. Source: Biochem Mol Biol Int. 1998 October; 46(2): 297-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9801798&dopt=Abstract
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The effects of treatment with alpha-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat. Author(s): Ford I, Cotter MA, Cameron NE, Greaves M. Source: Metabolism: Clinical and Experimental. 2001 August; 50(8): 868-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474472&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: 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/
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The following is a specific Web list relating to lipoic acid; 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 Arteriosclerosis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Carpal Tunnel Syndrome Source: Integrative Medicine Communications; www.drkoop.com Cataracts (prevention) Source: Prima Communications, Inc.www.personalhealthzone.com Coronary Artery Disease Source: Integrative Medicine Communications; www.drkoop.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com Glaucoma Source: Healthnotes, Inc.; www.healthnotes.com Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Liver Disorders Source: Integrative Medicine Communications; www.drkoop.com Lyme Disease Source: Integrative Medicine Communications; www.drkoop.com Mushroom Poisoning Source: Integrative Medicine Communications; www.drkoop.com Nerve Pain Source: Integrative Medicine Communications; www.drkoop.com
Alternative Medicine 63
Pain Source: Integrative Medicine Communications; www.drkoop.com Parkinson's Disease Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Naturopathy Source: Integrative Medicine Communications; www.drkoop.com
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Herbs and Supplements Alpha Lipoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Alpha-lipoic Acid Source: Integrative Medicine Communications; www.drkoop.com Alpha-lipoic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10002,00.html Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html GLA (Gamma-Linolenic Acid) Source: Prima Communications, Inc.www.personalhealthzone.com Glutathione Source: Healthnotes, Inc.; www.healthnotes.com Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lipoic Acid Source: Prima Communications, Inc.www.personalhealthzone.com Oral Hypoglycemics Source: Prima Communications, Inc.www.personalhealthzone.com
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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. DISSERTATIONS ON LIPOIC ACID Overview In this chapter, we will give you a bibliography on recent dissertations relating to lipoic acid. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “lipoic acid” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lipoic acid, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Lipoic Acid ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to lipoic acid. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Aging and Peak Procedure Performance: Effects of Acetyl-l-carnitine and Lipoic Acid by Gharib, Afshin Mohammadhossein; PhD from University of California, Berkeley, 2002, 148 pages http://wwwlib.umi.com/dissertations/fullcit/3063377
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Effects of Lipoic Acid in Cats: Pharmacokinetics, Toxicity, and Antioxidant Activity by Hill, Ana Schmidt; PhD from University of California, Davis, 2002, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3074569
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Evaluation of the Acute Effects of Alpha-lipoic Acid and Fish Oil, Alone and in Combination, on the Postprandial Lipemic Response in Non-insulin-dependent Diabetes Mellitus by Kaye, Suzanne Avril; Msc from University of Guelph (Canada), 2002, 84 pages http://wwwlib.umi.com/dissertations/fullcit/MQ71198
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Gene Expression Profile of Aging and Its Modification by Caloric Restriction, Alphalipoic Acid, and Coenzyme Q10 in Mice by Lee, Cheol-koo; PhD from The University of Wisconsin - Madison, 2003, 216 pages http://wwwlib.umi.com/dissertations/fullcit/3089645
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Post-Translational Modification with Lipoic Acid in Escherichia Coli by Jordan, Sean Wesley; PhD from University of Illinois at Urbana-champaign, 2002, 96 pages http://wwwlib.umi.com/dissertations/fullcit/3044129
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND LIPOIC ACID Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning lipoic acid.
Recent Trials on Lipoic Acid The following is a list of recent trials dedicated to lipoic acid.8 Further information on a trial is available at the Web site indicated. •
Immune restoration by lipoic acid in AIDS Condition(s): Acquired Immunodeficiency Syndrome; HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The purpose of this study is to determine the immunomodulatory and antiviral effects of the glutathione-restoring dithiol, alpha lipoic acid (ALA) in HIVinfected persons unresponsive to highly active antiretroviral treatment (HAART). Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033176
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Antioxidant Functions of Lipoic Acid Condition(s): Hypercholesterolemia Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM)
8
These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: The goal of this study is to determine whether a short treatment with lipoic acid, an antioxidant used in the treatment of diabetic neuropathy, improves blood vessel reactivity and decreases oxidant stress in persons with elevated blood cholesterol. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065624
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “lipoic acid” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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•
For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON LIPOIC ACID Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “lipoic acid” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lipoic acid, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Lipoic Acid By performing a patent search focusing on lipoic acid, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on lipoic acid: •
Alleviation of the allergenic potential of airborne and contact allergens by thioredoxin Inventor(s): Buchanan; Bob B. (Berkeley, CA), del Val; Gregorio (El Cerrito, CA), Frick; Oscar L. (San Francisco, CA), Lozano; Rosa M. (Madrid, ES), Wong; Joshua H. (South San Francisco, CA), Yee; Boihon C. (Walnut Creek, CA) Assignee(s): Regents of the University of California (Oakland, CA) Patent Number: 6,555,116 Date filed: January 27, 1999 Abstract: Thioredoxin, a small dithiol protein, is a specific reductant for allergenic proteins and particularly allergenic proteins present in pollen and animal and plant sources. All targeted proteins contain disulfide (S--S) bonds that are reduced to the sulfhydryl (SH) level by thioredoxin. The proteins are allergenically active and less digestible in the oxidized (S--S) state. When reduced (SH state), they lose their allergenicity and/or become more digestible. Thioredoxin achieved this reduction when activated (reduced) either by NADPH via NADP-thioredoxin reductase (physiological conditions) or by lipoic acid chemical reductant. Skin tests carried out with sensitized dogs showed that treatment of the pollens with reduced thioredoxin prior to injection eliminated or decreased the allergenicity of the pollen. Studies showed increased digestion of the pollen proteins by pepsin following reduction by thioredoxin. Pollen proteins that have been reduced by thioredoxin are effective and safe immunotherapeutic agents for decreasing or eliminating an animal's allergic reaction that would otherwise occur upon exposure to the non-reduced pollen protein. Excerpt(s): The present invention relates to the use of thiol redox proteins to reduce seed proteins such as cereal proteins, and to reduce enzyme inhibitor proteins, venom toxin proteins, pollen proteins and the intramolecular disulfide bonds of certain other proteins. More particularly, the invention involves use of thioredoxin and glutaredoxin to reduce gliadins, glutenins, albumins and globulins to improve the characteristics of dough and baked goods and create new doughs and to reduce cystine containing proteins such as amylase and trypsin inhibitors so as to improve the quality of feed and cereal products. Additionally, the invention involves the isolation of a novel protein that inhibits pullulanase and the reduction of that novel protein by thiol redox proteins. The invention further involves the reduction by thioredoxin of 2S albumin proteins characteristic of oil-storing seeds. Also, the invention involves inactivating snake neurotoxins and certain insect and scorpion venom toxins in vitro and treating the corresponding toxicities in individuals. The invention also involves using thioredoxin to decrease the allergenicity of food and pollen allergens and to increase the proteolysis of food and pollen proteins and the digestibility of food and pollens. The invention also relates to pollen proteins which are reduced by lipoic acid or by reduced thiol-redox proteins or by thioredoxin in combination with lipoic acid for use in immunotherapy. The invention further involves use of thiol-redox proteins and lipoic acid to treat and prevent allergies and allergic symptoms. Thioredoxin h is also known to reductively activate cytosolic enzyme of carbohydrate metabolism, pyrophosphate fructose-6-P, 1phosphotransferase or PFP (Kiss, F. et al. (1991), Arch. Biochem. Biophys. 287:337-340). The seed is the only tissue for which the NADP/thioredoxin system has been ascribed physiological activity in plants. Also, thioredoxin h has been shown to reduce thionins in the laboratory (Johnson, T. C. et al. (1987), Plant Physiol. 85:446-451). Thionins are
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soluble cereal seed proteins, rich in cystine. In the Johnson, et al. investigation, wheat purothionin was experimentally reduced by NADPH via NADP-thioredoxin reductase (NTR) and thioredoxin h according to Eqs. 2 and 3. Web site: http://www.delphion.com/details?pn=US06555116__ •
Alpha-lipoic acid with novel modification Inventor(s): Beisswenger; Thomas (Radebeul, DE), Laban; Gunter (Langebruck, DE), Landgraf; Karl-Friedrich (Dresden, DE), Oestreich; Eberhard (Dresden, DE), Rischer; Matthias (Frankfurt, DE) Assignee(s): ASTA Medica Aktiengesellschaft (Dresden, DE) Patent Number: 5,994,393 Date filed: May 8, 1998 Abstract: The invention is relative to a thioctic acid with a predominant amount of an enantiomer and a novel modification, in the case of which the X-ray powder diffractograms show a characteristic reflex in the range of 23.4 to 22.7.degree. 2 theta(Cu) which shifts in the direction of the smaller angular values as the enantiomer content increases. Excerpt(s): Alpha-lipoic acid is used in pharmaceutical formulations both in infusion solutions as well as in solid galenic formulations for oral use. Synthetically produced, racemic DL-alpha-lipoic acid, also designated as RS-thioctic acid, is used for this. An enantiomer of alpha-lipoic acid, R-thioctic acid, occurs as natural substance in practically all animal and vegetable cells. R-thioctic acid is of essential significance as coenzyme in the oxidative decarboxylation of alpha-keto acids (e.g. pyruvic acid). Thioctic acid is pharmacologically active and exhibits antiphlogistic and antinoceceptive (analgetic) as well as cytoprotective properties. An important medical indication is the treatment of diabetic polyneuropathy. Furthermore, thioctic acid is used in cosmetics as well as in the supplementation of nutrition, e.g. on account of its antioxidative action. The use of R-thioctic acid appears to be especially advantageous thereby since it is present in a form identical to nature (see also EP 0,572,922 A1) and is inserted only in the natural form as cofactor into the pyruvate-dehydrogenase complex (Oehring et al., Biol. Chem. Hoppe-Seyler 373, 333-335, 1992). According to recent results (Baur et al., Klin. Wochenschr. 1991, 69(15), 722-4) thioctic acid can possibly become significant in the combating of disease caused by HIV-1- and HTLV IIIB viruses. In the case of the pure, optical isomers of thioctic acid (R and S form, that is, R-thioctic acid and S-thioctic acid), in contrast to the racemate the R enantiomer is primarily antiphlogistically and the S enantiomer primarily antinociceptively active (see also EP 0,427,247 A2). Therefore, in order to achieve a selective action the production and use of the pure enantiomers are of great importance. Web site: http://www.delphion.com/details?pn=US05994393__
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Antioxidant composition comprising acetyl L-carnitine and.alpha.-lipoic acid Inventor(s): Cavazza; Claudio (Rome, IT) Assignee(s): Sigma-Tau HealthScience S.p.A. (Rome, IT) Patent Number: 6,365,622 Date filed: March 12, 2001 Abstract: A composition containing the active ingredients acetyl L-carnitine and.alpha.lipoic acid for the prevention and/or therapeutic treatment of various alterations and pathological states induced by free radicals, that may be in the form of a dietary supplement, dietetic support or of an actual medicine. Excerpt(s): This is A 371 of PCT/1T99/00268 filed Aug. 19, 1999. The present invention relates to a composition for the prevention and/or treatment of tissular diseases brought about by the presence of free radicals due to environmental pollution; brain or myocardial damages induced by free radicals following cerebral or myocardial ischaemia and attendant riperfusion; of the toxic or diabetic neuropathies and of metabolic disorders in the glucose utilization. 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. Web site: http://www.delphion.com/details?pn=US06365622__
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Crystal modification of lipoic acid Inventor(s): Klatt; Martin Jochen (Bad Durkheim, DE), Niebel; Markus (Mannheim, DE), Paust; Joachim (Neuhofen, DE), Rieger; Jens (Ludwigshafen, DE) Assignee(s): BASF Aktiengesellschaft (Ludwigshafen, DE) Patent Number: 6,441,024 Date filed: January 17, 2001 Abstract: In the 2.THETA. diffractogram of an enantiomerically pure crystalline (R)- or (S)-lipoic acid, the most intense reflection line in the range from 13.degree. to 30.degree. is that at 2.THETA.=23.degree. Excerpt(s): The present invention relates to a process for preparing crystalline.alpha.lipoic acid in high yields, a new crystal modification of.alpha.-lipoic acid and its use.alpha.-Lipoic acid is used in the food industry and in pharmaceutical formulations. When lipoic acid is spoken of in the following, this always refers to the enantiomerically pure compounds ((R)- or (S)-lipoic acid). Web site: http://www.delphion.com/details?pn=US06441024__
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•
Dietary supplement and method of treatment for diabetic control Inventor(s): Fine; Stuart A. (Northbrook, IL) Assignee(s): Akesis Pharmaceuticals, Inc. (La Jolla, CA) Patent Number: 5,962,030 Date filed: November 5, 1997 Abstract: A daily nutritional supplement and method of administering it to assist in the metabolism of glucose for patients with diabetes and pre-diabetes is disclosed. The supplement preferably includes anchor components of Chromium Polynicotinate and Picolinate, Vanadyl Sulfate, Vitamin E Natural, Standardized Willow Bark (aspirin), and Magnesium Chloride, Citrate, Fumarate, Malate, Glutorate, and Succinate Complex, Folic Acid, and Alpha-Lipoic Acid. Excerpt(s): The present invention is related to a unique vitamin, mineral, and herbal supplement for the treatment of both type I and II diabetes, and for the prevention of type II diabetes in those individuals with pre-diabetes, or impaired glucose tolerance (IGT). Specifically, the present invention is directed towards a dietary supplement for diabetic control containing a plurality of compounds from the following group: Vanadyl sulfate, Chromium polynicotinate and picolinate, Magnesium chloride, citrate, fumarate, malate, glutorate, and succinate complex, Natural Vitamin E (free 2R, 4'R, 8'R-alpha tocopherol), Standardized Willow Bark (aspirin), Alpha-lipoic acid, and Folic acid. Diabetes has become a leading health care issue in the United States and other industrialized countries, accounting for one seventh of the entire national health care product. The incidence of diagnosed diabetes has increased five-fold in America over the past 35 years, with currently 8 million diagnosed diabetic patients, another estimated 8 to 12 million undiagnosed diabetic individuals, and still an additional 23 million Americans with pre-diabetes, or impaired glucose tolerance (IGT). As the American populace continues its strong trend towards aging, obesity and greater minority representation, the increasing rate of diagnosed diabetes is certain to continue. The tremendous economic and physical toll diabetes extracts from society is, in large part, secondary to both the short and long-term complications of the disease. While there have been great strides made in reducing the short term complications of diabetes, e.g. ketoacidosis, dehydration, and non-ketotic hyperosmolar coma, little, if any, headway has been made in preventing or even minimizing the devastating chronic complications of the disease, e.g. premature atherosclerosis, retinopathy, nephropathy, and neuropathy. Indeed, diabetes has become the leading cause of new cases of blindness in adults in the United States, and now accounts for over a third of all new cases of end-stage renal disease in this country. It is estimated that a diabetic patient's life is shortened by 10 to 15 years, and those years of life are distinguished by a health care tab four times that of a non-diabetic patient. Web site: http://www.delphion.com/details?pn=US05962030__
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Dietary supplemental method for fat and weight reduction Inventor(s): Carthron; James Alexander (4901 McWillie Cir., Apt-801, Jackson, MS 39206) Assignee(s): none reported Patent Number: 6,277,842 Date filed: October 17, 2000
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Abstract: A natural method for promoting fat, and weight loss while decreasing food cravings comprising administrating to an individual in need thereof L-carnitine, chromium, coenzyme Q10, creatine, lipoic acid, niacin, pyruvate, riboflavin, and thiamine. Pyruvate is a major promoter of the oxidation of dietary fuels like carbohydrates and fatty acids in the citric acid cycle. L-carnitine allow the transport of fatty acids into the mitochondria were they can be degraded in the citric acid cycle. Lipoic acid is a major intracellular antioxidant, and component of key enzymes in the citric acid cycle. Niacin, riboflavin, and thiamine are key components of enzymes that lead to the breakdown of dietary fuel molecules such as fatty acids, amino acids, and carbohydrates that enter the citric acid cycle. The breakdown of these dietary fuels leads to the production of high energy hydrogen atoms. Coenzyme Q10 accepts these hydrogen atoms and utilizes them for cellular energy production. Chromium helps reduce food cravings by normalizing insulin levels. Creatine allows increased storage of cellular energy, and promotes lean muscle tissue. Excerpt(s): The present invention relates to a method for promoting fat, and weight loss. This method also helps increase lean muscle mass in the individual user. More particularly, the invention relates to coadministration of L-carnitine, chromium, creatine, lipoic acid, niacin, pyruvate, riboflavin, thiamine, and Coenzyme Q10. Many current weight-lose strategies require significant limitations on the amount of caloric intake, and the amount of fat, and carbohydrates consumed by an individual. However, due to the inherent causes of obesity, and overeating, dieting by itself is often unsuccessful in achieving individual goals. There are two primary reasons for this. First, there is an immense amount of patience required by the dieter to lose significant amounts of weight. Second, and perhaps more important, are the inherent reasons that the vast majority of over-eating is done to satisfy anxiety. This fact lead to the development of another type of weight control method known collectively as the appetite suppression. In the past, appetite suppression has been accomplished by the use of centrally-acting neuro-stimulants such as cocaine, caffeine, methamphetamine hydrochloride, dextroamphetamine sulfate, and other derivatives of the amphetamine molecule. These drugs typically are effective for a short period of time, but tachyphylaxis invariably develops, and there are other inherent side-effects, such as nervousness, insomnia, and GI tract irritation, which develop with the use of such drugs. Web site: http://www.delphion.com/details?pn=US06277842__ •
Facilitated administration of.alpha.-lipoic acid or derivatives thereof Inventor(s): Auge; Mechthild (Wehrheim, DE), Hermann; Robert (Hanau, DE), Wessel; Klaus (Bad Vilbel, DE), Wicke; Claudia (Florsheim, DE) Assignee(s): Viatris GmbH & Co. KG (DE) Patent Number: 6,545,039 Date filed: November 9, 2000 Abstract: Racemic.alpha.-lipoic acid or its enantiomers or pharmaceutically acceptable salts, esters or amides thereof can be administrated parenterally at a rate of 50 to 600 mg of active compound, based on racemic.alpha.-lipoic acid, per minute. Excerpt(s): The invention relates to a process for the administration of racemic.alpha.lipoic acid or its enantiomers or pharmaceutically acceptable salts, esters or amides thereof within a certain rate range.alpha.-Lipoic acid is a naturally occurring antioxidant
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and a cofactor of the glucose-metabolizing pyruvate dehydrogenase (Packer, L. et al., Free Radicals in Biology & Medicine 19 (2): 227-250; 1995) and is used to a wide extent for the treatment of diabetic polyneuropathy (Ziegler, D. et al., Diabetologia 38: 14251433; 1995). Moreover,.alpha.-lipoic acid has been used for decades for the treatment of liver disorders (Bode, J. Ch. et al., DMW 112 (9), 349-352; 1987) and fungal intoxications (Brunn, J. et al., Internist. Prax. 19: 475-478, 1979). The molecular mode of action has recently been characterized as that of a diabetes-specific antioxidant (Nagamatsu, M. et al., Diabetes Care 18 (8): 1160-1167; 1995). Medicaments containing.alpha.-lipoic acid are obtainable in the form of tablets for oral assimilation as well as ampoules and ready-touse infusion devices for infusion or intramuscular injection. According to standard technical information.alpha.-lipoic acid injection solution, BfArM 8.3.96, No. Fi44002V.doc, of the Federal Institute for Pharmaceutical Products (BfArM), i.v. injection was previously restricted to low infusion rates and i.m. injection was not recommended. The parenteral products contain water-soluble salts of.alpha.-lipoic acid. At present, the trometamine salt, the ethylenediamine salt and the meglumine salt are used. The tolerability is regarded as dose-dependent (Ziegler, et al., loc.cit.). In the abovementioned information of the BfArM, the physician is explicitly warned against carrying out the administration more rapidly than 50 mg of.alpha.-lipoic acid or an equivalent amount of the salt per minute. Web site: http://www.delphion.com/details?pn=US06545039__ •
Food supplements and methods comprising lipoic acid and creatine Inventor(s): Gardiner; Paul T. (46 Gladstone Square, Brampton, Ontario, CA) Assignee(s): none reported Patent Number: 6,136,339 Date filed: August 21, 1998 Abstract: Food supplement compositions comprise lipoic acid or a derivative thereof and creatine or a derivative thereof. The compositions optionally, but preferably, further comprise dextrose. The food supplement compositions are suitable for supplementing the diet of an athlete and particularly for enhancing an athlete's muscle size or strength. Excerpt(s): The present invention is directed to food supplements which comprise lipoic acid or derivative thereof and creatine or a derivative thereof, and to methods for supplementing the diet of an athlete and methods for enhancing an athlete's muscle size or strength, which methods employ these food supplements. Creatine (also known as Nmethyl-N-guanyl glycine or (alpha methyl guanido) acetic acid) is an amino acid compound produced naturally in the liver and kidneys and obtained from food such as meat and fish. Food supplements containing creatine, typically creatine monohydrate, are commonly used by athletes to allow them to train harder and enhance muscle size and strength. Various commercial products containing creatine monohydrate are available. Lipoic acid (also known as alpha-lipoic acid, thioctic acid or 6,8-dithio octanoic acid) is a nutrient that the human body makes in minute quantities and may be obtained from yeast and liver. Studies have shown that lipoic acid can significantly increase the body's utilization of blood sugar in type II diabetics and that lipoic acid may increase the metabolic clearance rate of glucose by 50% in diabetics. In Europe, lipoic acid has been used as a substitute for insulin in the treatment of Type II diabetes. Web site: http://www.delphion.com/details?pn=US06136339__
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Insulin sensitivity maintenance and blood sugar level maintenance formulation for the prevention and treatment of diabetes Inventor(s): Gorsek; Wayne F. (Boynton Beach, FL) Assignee(s): Vitacost.com, Inc. (Boynton Beach, FL) Patent Number: 6,572,897 Date filed: July 3, 2002 Abstract: A composition that contains the most potent combination of nutrients with clinical studies proven to assist in the maintenance of insulin sensitivity and healthy blood sugar levels. The formulation contains essential amounts of Alpha Lipoic Acid, Chromium, Lutein, Bioflavonoids(quercetin and rutin), Mormordica Charantia extract, Corosolic Acid, and Gymnema Sylvestre Extract, as well as other ingredients and healthy filler ingredients. Excerpt(s): The invention relates to a composition that contains the most potent combination of nutrients with clinical studies proven to assist in the maintenance of insulin sensitivity and healthy blood sugar levels. The advanced formulation is designed to promote healthy blood sugar levels as people age which is critical to good health. High levels of blood sugar are associated with adverse affects on our vision, heart/circulation, kidneys and nervous system. This is commonly associated with the disease of diabetes. Individual vitamins, minerals, herbs and antioxidants have been studied for their efficacy at promoting healthy blood sugar and protecting cells from the damage of elevated blood sugar levels. This prevents heart disease and strokes. Web site: http://www.delphion.com/details?pn=US06572897__
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Lipoic acid derivatives, their preparation, and pharmaceutical compositions containing them Inventor(s): Auguet; Michel (Palaiseau, FR), Chabrier de Lassauniere; Pierre-Etienne (Paris, FR), Harnett; Jeremiah (Gif-sur-Yvette, FR) Assignee(s): Societe de Conseils de Recherches et d'Applications Scientifiques (FR) Patent Number: 6,605,637 Date filed: September 27, 2001 Abstract: The invention concerns novel lipoic acid derivatives, which have an inhibiting action with respect to NO-synthase enzymes producing nitrogen monoxide NO and/or are agents enabling the regeneration of antioxidants or entities trapping reactive oxygen species (ROS) and intervening in a more general manner in the redox status of thiol groups. The invention also concerns methods for preparing them, pharmaceutical compositions containing them and their use for therapeutic purposes, particularly their use as NO-synthase inhibitors and/or as agents acting more generally in the redox status of thiol groups. Excerpt(s): This application is a 371 of PCT/FR00/00814 filed Mar. 31, 2000. A subject, of the present invention is new derivatives of lipoic acid, which have an inhibitory activity on NO-synthase enzymes producing nitrogen monoxide NO and/or are agents which allow the regeneration of antioxidants or entities which trap the reactive oxygen species (ROS) and which intervene in a more general fashion in the redox status of thiol groups. These antioxidants or entities which trap the reactive oxygen species can be of natural origin, such as for example vitamin E or glutathione, or of synthetic origin such as
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certain products which trap the ROS or products having both an inhibitory activity on NO-synthase enzymes and an activity which traps the ROS. Examples of such products of synthetic origin can in particular be found in the PCT Patent Applications WO 96/09653, WO 98/42696 and WO 98/58934. Therefore, the invention relates in particular to the derivatives corresponding to general formula (I) defined below, their preparation methods, the pharmaceutical preparations containing them and their use for therapeutic purposes, in particular their use as NO-synthase inhibitors and/or as agents which allow the regeneration of antioxidants or entities which trap the ROS's and which intervene in a more general fashion in the redox status of thiol groups. Web site: http://www.delphion.com/details?pn=US06605637__ •
Method and composition for treating and preventing retinal damage Inventor(s): Hacker; Henry (Temple, TX), Koenig; Michael L. (Silver Spring, MD), Meyerhoff; James (Silver Spring, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,339,102 Date filed: June 9, 2000 Abstract: The use of dihydrolipoic acid (DEL) and alpha-lipoic acid to treat and prevent damage to the retina arising from physical forces such as exposure to laser beams, and to compositions containing phenyl nitrones and DHL or alpha-lipoic acid as neuroprotective agents. Excerpt(s): This invention relates to use of dihydrolipoic acid (DHL) and a-lipoic acid to treat and prevent damage to the retina arising from physical forces such as exposure to laser beams, and to compositions containing phenyl nitrones and DHL or a-lipoic acid as neuroprotective agents. The retina is part of the central nervous system and contains both neurons and glia, as well as photo receptors. Although the immediate mechanisms vary, many forms of neuro-trauma are believed to share a common final pathway: the formation of neurotoxic free radicals. Web site: http://www.delphion.com/details?pn=US06339102__
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Method for supplementing the diet Inventor(s): Deffner; Kathleen (Taylorsville, UT), Rosenberg; Thomas D. (Salt Lake City, UT) Assignee(s): Nutriex, L.L.C. (Salt Lake City, UT) Patent Number: 6,579,544 Date filed: May 31, 2000 Abstract: A dietary supplement blend composition is disclosed, the basic formulation of the composition containing vitamins, minerals, and carotenoids. The composition can also contain bioflavonoids, cartilage protectors such as glucosamine or chondroitin,.alpha.-lipoic acid, coenzyme Q10, and a source of omega-3 fatty acids such as flax seed oil. The composition is beneficial for improving health and preventing disease, particularly for degenerative conditions. A method for supplementing the diet
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is also disclosed, wherein the quantity of daily rations of the dietary supplement blend composition is determined based on the person's age, body weight, and quality of diet. Excerpt(s): Not Applicable. This invention relates to dietary supplements. More particularly, the invention relates to compositions and methods for supplementing the diet for improving health and preventing disease. Web site: http://www.delphion.com/details?pn=US06579544__ •
Method for the production of a solvent-free.alpha.-liponic acid Inventor(s): Gruber; Ansgar (Altenmarkt, DE), Schuhbauer; Hans (Trostberg, DE), Winkler; Stefan (Obing, DE) Assignee(s): Degussa AG (Trostberg, DE) Patent Number: 6,462,202 Date filed: October 25, 2001 Abstract: Solvent-free.alpha.-lipoic acid is produced by dissolvinga) the.alpha.-lipoic acid to be purified in aqueous alkaline solution, or dissolving the salt thereof in water and adjusting an alkaline pH,b) removing solid impurities present where appropriate from the aqueous solution from stage a),c) adjusting the aqueous solution from stage a) or b) to a pH of from 1.0 to 5.0 with the aid of an acid andd) isolating the precipitated.alpha.-lipoic acid by known methods.This results in a solvent-free.alpha.lipoic acid with improved chemical purity. Excerpt(s): The present invention relates to a method for the production of solventfree.alpha.-lipoic acid.alpha.-Lipoic acid (thioctic acid, 1,2-dithiolane-3-pentanoic acid) is a natural substance which occurs in the form of the R enantiomer in low concentrations in plant and animal cells. The physiological action of.alpha.-lipoic acid, which was originally discovered as a growth factor, in hydrophilic and lipophilic media is as a coenzyme of the oxidative decarboxylation of.alpha.-keto carboxylic acids (e.g. pyruvates) and as an antioxidant, and it is able to regenerate vitamin C, vitamin E, glutathione and coenzyme Q10. Racemic.alpha.-lipoic acid is approved for the treatment of liver disorders and neuropathies (e.g. diabetic poly-neuropathies); its use as an effective inhibitor of the replication of HIV-1 viruses has been suggested (cf. Klin. Wochenschr. 1991, 69(15), 722-724). The racemate of.alpha.-lipoic acid also displays cytoprotective, antiinflammatory and antinociceptive (analgesic) properties, and it has emerged for the pure optical isomers of.alpha.-lipoic acid (R-.alpha.-lipoic acid and S.alpha.-lipoic acid) that, in contrast to the racemate, the R enantiomer shows a predominantly antiinflammatory, and the S enantiomer shows a predominantly antinociceptive, profile of actions (cf. EP 0 812 590 A2). The syntheses of crude racemic.alpha.-lipoic acid and of enantiopure R- or S-.alpha.-lipoic acid takes place by known methods or ones analogous thereto, as described or summarized, for example, in Crevisy et al., Eur. J. Org. Chem. 1998, 1949, Fadnavis et al., Tetrahedron Asym. 1998, 9, 4109, Dhar et al., J. Org. Chem. 1992, 57, 1699, Adger et al., J. Chem. Soc. Chem. Commun. 1995, 1563, Dasaradhi et al., J. Chem. Soc. Chem. Commun. 1990, 729, Gopalan et al., J. Chem. Soc. Perkin Trans. I 1990, 1897, Yadav et al., J. Sci. Ind. Res. 1990, 49, 400, Tolstikov et al., Bioorg. Khim. 1990, 16, 1670, Gopalan et al., Tetrahedron Lett. 1989, 5705. Web site: http://www.delphion.com/details?pn=US06462202__
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Method of reducing serum glucose levels Inventor(s): Byrd; Edward A. (San Francisco, CA), Janjikhel; Rajiv (Owings Mills, MD) Assignee(s): Medical Research Institute (San Bruno, CA) Patent Number: 6,191,162 Date filed: April 8, 1999 Abstract: A controlled release formulation of lipoic acid is administered to a patient resulting in reduced serum glucose levels. The formulation comprises a pharmaceutically acceptable carrier and is designed to prevent degradation of the lipoic acid in the gastrointestinal tract and to release the lipoic acid in a controlled manner thereby obtaining a desired lipoic acid serum level over an extended period resulting in reduced serum glucose levels over that period. Excerpt(s): This invention relates to a method of reducing serum glucose levels. More particularly, the invention relates to the administration of controlled release formulations of lipoic acid to reduce a human patients' glucose levels. The compound.alpha.-lipoic acid was first isolated by Reed and coworkers as an acetate replacing factor. It is assumed to be substantially insoluble in water, but soluble in organic solvents.alpha.-lipoic acid is a chiral molecule and is known by a variety of names, including thioctic acid; 1,2-diethylene-3 pentanoic acid; 1,2-diethylene-3 valeric acid; and 6,8-thioctic acid. See Gerreke Biewenga et a., An Overview of Lipoate Chemistry, Lipoic Acid in Health and Disease 1 (1997) (Marcel Dekker). This document, and all other documents cited to herein, is incorporated by reference as if reproduced fully herein. After being isolated.alpha.-lipoic acid was tentatively classified as a vitamin, but it was later found to be synthesized by animals and humans. The complete enzyme pathway that is responsible for the de novo synthesis has not yet been definitively elucidated. Several studies indicate that octanoate serves as the immediate precursor for the 8-carbon fatty acid chain, and cysteine appears to be the source of sulfur. As a lipoamide, it functions as a cofactor in the multienzyme complexes that catalyze the oxidative decarboxylation of.alpha.-keto acids such as pyruvate,.alpha.-keto glutarate, and branched chain.alpha.-keto acids. Web site: http://www.delphion.com/details?pn=US06191162__
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Method of treating benign forgetfulness Inventor(s): Hamilton; Nathan D. (Palo Alto, CA) Assignee(s): Juvenon Inc. (Orinda, CA) Patent Number: 6,335,361 Date filed: November 2, 2000 Abstract: Disclosed herein are methods to treat cognition disorders, particularly those associated with aging. The method comprises administering a combination of a carnitine and an oxidant. Preferably the oxidant is thioctic acid. Preferably 0.12 grams to 3 grams of carnitine (particularly ALC) and 0.12 and 1.5 grams of R-.alpha.-lipoic acid are administered. Optionally, coenzyme Q and/or creatine also are administered. Preferably 10 mg to 500 mg/day of coenzyme Q10 and 1 to 30 grams/day of creatine are administered. The same method can be used to treat cognition deficits associated with carbon monoxide poisoning, mild traumatic brain injury, Type 2 diabetes mellitus, obsessive-compulsive disorder, environmental toxin exposure, and other conditions.
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Excerpt(s): This invention is related to the prevention and amelioration of memory deficits related to aging and other causes. More specifically, this invention is related to the administration of micronutrients, such as an antioxidant, a canitine product, and optionally coenzyme Q and/or creatine to those at risk of memory loss. Many adults gradually develop noticeable difficulties in memory, at first for names, then for events, and sometimes even occasionally for spatial relationships. The majority of healthy older people complain about forgetfulness and decreased concentration, and this compromises their quality of life. It is well established that virtually all aspects of cognitive functioning deteriorate with age. There has also been a rapid increase in the interest of clinicians, researchers and the pharmaceutical industry in the development of new classes of drugs for the palliative treatment of age-related cognitive deficits and dementing conditions. This widely experienced so-called benign forgetfulness, or benign senescent forgetfulness, bears no proven relationship to degenerative dementia but may be a forewarning, since there are some similarities. Kral was the first to introduce diagnostic terminology for age-associated changes in memory (J Gerontol 13: 169-176, 1958; Can Med Assoc J 86: 257-260, 1962). He used the term "benign senescent forgetfulness" (BSF) to distinguish subjects with mild memory decline from those with more severe, "malignant" changes (MSF), and also from those with normal memory functions. Web site: http://www.delphion.com/details?pn=US06335361__ •
Method of treatment of glutathione deficient mammals Inventor(s): Keller; Robert H (Weston, FL), Kirshenbaum; David W (Weston, FL) Assignee(s): Vit-Immune, L. C. (Hollywood, FL) Patent Number: 6,262,019 Date filed: April 29, 1999 Abstract: Glutathione (GSH) is a tripeptide of extreme importance as a catalyst, reductan, and reactant. It can be depleted intracellulary either by forming a direct complex with an electrophilic agent (accomplished investigationally by agents such as bromobenzene or diethyl maleate), by way of inhibition of synthesis, or by subjecting cells to oxidant stress. Most cells, except for epithelia cells, do not have a direct transport capacity for intact GSH. Non-epithelial cells must either transport precursor substrates for GSH synthesis or salvage amino acids from circulating GSH for reuse in intracellular resynthesis. Dietary cysteine is a rate limiting substrate for the synthesis of glutathione and also inhibits GSH efflux. Although GSH is synthesized from precursors in virtually all cells, the liver is the main source of plasma GSH. Protection and support of liver function is paramount to elevating GSH levels. The disclosure is also of a unique combination of nutritional supplements including n-acetyl cysteine, vitamin C, lglucosamine, n-acetyl d-glucosamine, quercitin, sylimarin, Alpha lipoic acid and high protein, low fat whey that are combined to support various bodily systems involved in glutathione synthesis, reutilization and storage; all intended to elevate glutathione concentration in the mammalian cell. Excerpt(s): This invention provides a method of improving glutathione (GSH) concentrations, both intra and extra-cellularly, in mammals, thereby improving the cellular and humoral immune response. It comprises oral administration of a therapeutically effective amount of nutritional supplement which is composed of critical and synergistic quantities of amino acids, peptides, and bioflavanoids. Glutathione is a well-known tripeptide, which exists in two basic forms. The antioxidant form or
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"reduced glutathione" tripeptide is conventionally called "glutathione" and abbreviated as "GSH". The oxidized form is a sulfur-sulfur linked compound known as glutathione disulfide (GSSG). and is appropriately named.gamma.-L-Glutamyl-L-cysteinylglycine. It is ubiquitous in animals, plants, and microorganisms and being water soluble is found mainly in the cell cytosol and other aqueous phases of the living system. Glutathione often attains millimolar levels inside living cells, which makes it one of the most highly concentrated intracellular antioxidants. Web site: http://www.delphion.com/details?pn=US06262019__ •
Methods for producing L-valine and L-leucine Inventor(s): Hashiguchi; Kenichi (Kawasaki, JP), Ishigooka; Masako (Kawasaki, JP), Kurahashi; Osamu (Kawasaki, JP), Tomita; Fusao (Sapporo, JP), Yokota; Atsushi (Sapporo, JP) Assignee(s): Ajinomoto Co., Inc. (Tokyo, JP) Patent Number: 6,214,591 Date filed: January 14, 1999 Abstract: L-valine is produced by culturing a microorganism belonging to the genus Escherichia with the capability of producing L-valine or L-leucine wherein it requires lipoic acid for growth, a microorganism belonging to the genus Escherichia with the capability of producing L-valine or L-leucine wherein it is deficient in H.sup.+ -ATPase activity, a microorganism belonging to the genus Escherichia wit the capability of producing L-valine or L-leucine wherein it requires lipoic acid for growth and is deficient in H.sup.+ -ATPase activity, in the liquid medium to allow the L-valine to be produced and accumulated in a culture medium, and collecting it. Excerpt(s): This invention relates to a microorganism belonging to the genus Escherichia having the capability of producing L-valine or L-leucine and, more particularly, a microorganism whose capability of producing L-valine or L-leucine is enhanced. In the past, L-valine and L-leucine have been produced by a method of fermentation primarily using a microorganism belonging to the genus Brevibacterium, Corynebacterium or Serratia or a mutant thereof which produces L-valine or L-leucine (Amino acid fermentation, JAPAN SCIENTIFIC SOCIETY'S PRESS, pp.397-422, 1986). Although the conventional methods have considerably enhanced the productivity of these amino acids, the development of a more efficient, cost-effective technique is required in order to meet increasing demand for L-valine and L-leucine in the future. On the other hand, a microorganism belonging to the genus Escherichia is potentially utilized as a potent Lvaline or L-leucine-producing microorganism due to its rapid growth rate, progress in genetic analysis and plentiful genetic materials. However, there are few reports documenting the production of these amino acids with from Escherichia microorganisms, and as for L-branched chain amino acids, only a few reports deal with the production of L-isoleucine (Japanese Patent Application Laid-Open No. 5304969(1993) and Japanese Patent Application Laid-Open No. 5-130882(1993). Web site: http://www.delphion.com/details?pn=US06214591__
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Nutraceutical composition for protection against solar radiation Inventor(s): Bragaglia; Anthony Joseph (Boston, MA) Assignee(s): Protective Factors, Inc. (Boston, MA) Patent Number: 6,254,898 Date filed: May 25, 2000 Abstract: A nutraceutical composition, for the inhibition of photochemical damage to the skin and eyes induced by sunlight, particularly by exposure to ultraviolet radiation is disclosed. The blend is multifunctional and comprises a blend of chemopreventive natural products, which exert anti-radical mechanisms of prevention and intervention, anti-inflammatory effects, enhance the endogenous defense mechanisms, and also have the potential to reduce the radiation induced pigmentation. The active ingredients in the blend include green tea extract, lutein (zeaxanthin), lipoic acid, and selenomethionine. Excerpt(s): Not applicable. The present invention relates to the development of a nutraceutical composition for the prevention and protection of photodamage to the skin and eyes resulting from solar or solar simulated radiation. Exposure of human skin to sunlight and, in particular, to the ultraviolet band of the spectrum, has many deleterious effects, including sunburn, erythema, photoallergic reactions, photoaging, hyperpigmentation, and the promotion of skin cancers. Sunlight induced nonmelanoma skin cancer is a major cancer in the United States and in other temperate parts of the world. Solar radiation also has been suggested as one of the etiological factors in the development of degenerative diseases of the eyes, such as, age-related macular degeneration and cataract formation. Epidemiological studies have revealed a close correlation between photochemical damage and macular degeneration (Schalch, W., EXS, 62:280-98, 1992). Similarly, cataract formation is mainly due to changes in the lens proteins continually exposed to solar radiation (Varma, S. D., Chand, D., Sharma, Y. R., Kuck, J. F., and Richards, R. D., Current Eye Res., 3:35, 1984). The risks of overexposure to UV radiation will become greater with continued depletion of stratospheric ozone. The deleterious effects of ultraviolet radiation have been attributed largely to the generation of free radicals, such as superoxide and hydrogen peroxide. Web site: http://www.delphion.com/details?pn=US06254898__
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Nutritional supplement for increased energy and stamina Inventor(s): Hamilton; Nathan D. (San Francisco, CA) Assignee(s): Juvenon, Inc. (Orinda, CA) Patent Number: 6,479,069 Date filed: September 8, 2000 Abstract: Disclosed herein are compositions to meet the needs of individuals, including humans and pets. Nutritional beverages, powders to make the same, a pudding and a nutritional bar are disclosed whose compositions include the R-.alpha.-lipoic acid in the amount of 0.12 grams to 1.5 grams and L-carnitine in the amount of 0.12 grams to 3 grams in addition to the usual composition. Optionally, effective amounts of coenzyme Q and/or creatine also are added. These additional components fight age-related declines in mitochondrial function which result in less energy and other signs of aging. Excerpt(s): The present invention is generally directed to dietary supplements and nutritional beverages. More specifically, the present invention relates to the addition of
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the combination of lipoic acid and carnitine to these compositions. Liquid diet supplements or nutritional drinks have been used for years to provide needed calories, protein, vitamins and minerals to people too sick or frail to eat sufficient amounts of solid food. Now these products are being marketed as energy boosters to people who want to remain energetic, particularly those aged 50 and older. The oldest and by far the best selling nutritional drink is made by the Ross Products Division of Abbott Laboratories (Columbus, Ohio). For 1997, its sales exceeded $170 million, which does not even include the higher-calorie Ensure Plus.RTM. or the lower calorie Ensure Light.RTM. beverages. Another competitor for active older consumers include Sandoz Nutrition (Minneapolis, Minn.) which sells ReSource.RTM., the official nutritional drink of the senior Professional Golf Association tour. Mead Johnson Nutritionals (Evansville, Ind.) also has been marketing its Boost.RTM. drink to seniors. Registered dietitians state that these nutritional drinks are better than a snack such as a bag of cheese curls and a soda. Although the nutritional drinks are being marketed as meal replacements, dietitians warn that the drinks are an inadequate substitute for three balanced meals. Each 8-ounce can or carton has about 20-25% of the Recommended Daily Allowance of an assortment of vitamins and minerals but lacks fiber and other nutrients found in nature. Web site: http://www.delphion.com/details?pn=US06479069__ •
Pharmaceutical compositions containing R-.alpha.-lipoic acid or S-.alpha.-lipoic acid as active ingredient Inventor(s): Engel; Jurgen (Alzenau, DE), Hettche; Helmut (Dietzenbach, DE), Ulrich; Heinz (Niedernberg, DE), Weischer; Carl-Heinrich (Bonn, DE) Assignee(s): ASTA Pharma Aktiengesellschaft (Frankfurt, DE) Patent Number: 6,271,254 Date filed: February 2, 1998 Abstract: Pharmaceutical compositions and processes for their preparation containing R.alpha.-lipoic acid or S-.alpha.-lipoic acid or pharmaceutically acceptable salts thereof. The pharmaceutical compositions have a cytoprotective activity and are suitable for combatting pain and inflammation. Excerpt(s): The present invention relates to pharmaceutical compositions containing R.alpha.-lipoic acid or S-.alpha.-lipoic acid as an active ingredient. The compositions are useful because they inhibit, for example, acute inflammation as well as inflammatory pain and they possess a specific cytoprotective activity.alpha.-lipoic acid is 1,2dithiacyclopentane-3-valeric acid.alpha.-lipoic acid is widely distributed in plants and animals in the form of the R-enantiomer; it acts as coenzyme in many enzymatic reactions, constitutes a growth factor for a number of bacteria and protozoa and is used in death-head fungus poisoning. In addition, the.alpha.-lipoic acid racemate displays anti-inflammatory, antinociceptive (analgesic) and cytoprotective properties. Web site: http://www.delphion.com/details?pn=US06271254__
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Process for the production of lipoic acid Inventor(s): Adger; Brian Michael (Cambridge, GB), McCague; Raymond (Cambridge, GB), Roberts; Stanley Michael (Liverpool, GB) Assignee(s): ASTA Medica Aktiengesellschaft (DE) Patent Number: 6,140,512 Date filed: May 12, 1999 Abstract: A process for the preparation of lipolic acid (thioctic acid), or a derivative thereof, is one in which a 2-substituted cyclohexanone is transformed in an oxidation reaction to a lactone having formula (I), wherein X is a heteroatom substituent. Excerpt(s): The present invention relates to a novel process for obtaining lipoic acid (thioctic acid) either in racemic or single enantiomer form, and intermediates in that process. Lipoic acid (thioctic acid) has been reported to have utility for a wide range of therapeutic applications, including liver disease and poisoning (see DE-A-4338508), hypertension (see DE-A-4343647), pain and infection, especially retroviral infection such as HIV (see EP-A-0427247). It has been reported that (R)-lipoic acid is preferred for conditions associated with diabetes such as polyneuropathy and nephropathy (see DEA-4343593), and for treating chronic degenerative diseases of the central nervous system (CNS) (see DE-A-4343592). Whereas in EP-A-0572922, it has been reported that a combination of the unnatural (S)-enantiomer and vitamin E provides effective analgesia. Thus, synthetic routes to single enantiomer lipoic acid have been sought. There are already various synthetic approaches reported, such as in Y. S. Yadav et al, J. Sci. Ind. Rev., (1990) 49: 400-409; P. C. Bullman Page et al, J. Chem. Soc. Perkin Trans. 1, (1990), 1615-18; B. R. Menon et al, Tetrahedron Lett., (1987) 28: 2183-6; S. A. Gopalan and J. H. Jacobs, J. Chem. Soc. Perkin Trans. 1, (1990), 1897-1900; J. D. Elliot et al, Tetrahedron Lett., (1985) 26: 2535-8; M. H. Brookes et al, J. Chem. Soc. Chem. Commun., (1983), 10513; and L. G. Chebotareva, Zhim.-Farm. Zh.,(1980) 14: 92-9, including classical resolution; asymmetric epoxidation of an intermediate; enantiomeric control by a chiral auxiliary; or derivation from an available chirality pool material. The existing routes are generally not ideal as they involve many steps, use expensive reagents or starting materials, or result in loss of half the desired material following resolution of a racemate. As a result there is a continuing need for a more economical synthetic route. Web site: http://www.delphion.com/details?pn=US06140512__
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Processes for the synthesis and use of various.alpha.-lipoic acid complexes Inventor(s): Pearson; Don C. (Lakewood, WA), Richardson; Kenneth T. (Anchorage, AK) Assignee(s): ChronoRX, LLC (Anchorage, AK) Patent Number: 6,288,106 Date filed: May 3, 2000 Abstract: This invention is in the fields of pharmacology and biochemistry. It relates to processes for the synthesis of certain complexes of.alpha.-lipoic acid and the nutritional or therapeutic use of these and other related individual or complexed antioxidant, proglutathione molecules. Therapeutic uses for these molecules and complexes in the clinical management of conditions and functions associated with chronic glaucoma, insulin resistance, macular degeneration, lenticular cataract, neurodegenerative
Patents 87
diseases, essential hypertension, atherosclerosis and vasoconstriction are described in particular. Excerpt(s): The eye is maintained in a homeostatic shape by a relatively stable intraocular pressure (IOP), which varies within a reasonably narrow range so long as the intraocular production of aqueous fluid remains equal to its exit from the eye. The optic nerve head can tolerate relatively high levels of IOP if the availability of oxygen from posterior ciliary arteries and optic nerve head arterioles remains adequate. However, if the intraocular (extravascular) pressure is higher than the perfusion (intravascular) pressure driving oxygen through the arteriole into the surrounding tissues, decreasing amounts of oxygen will reach the optic nerve head and nerve disability will result. Web site: http://www.delphion.com/details?pn=US06288106__ •
Production and use of salts of 6,8-bis (amidiniumthio)-octanoic acid Inventor(s): Beisswenger; Thomas (Radebeul, DE), Bethge; Horst (Rodenbach, DE), Gewald; Rainer (Dresden, DE), Hubner; Frank (Ober-Ramstadt, DE), Huthmacher; Klaus (Gelnhausen, DE), Klenk; Herbert (Hanau, DE), Moller; Roland (Hammersbach, DE), Olbrich; Alfred (Obertshausen, DE), Rautenberg; Stephan (Hanau, DE), Sator; Gerhard (Dieburg, DE) Assignee(s): ASTA Medica Aktiengesellschaft (Dresden, DE) Patent Number: 6,013,815 Date filed: March 18, 1998 Abstract: The invention relates to the production and purification of salts of 6,8-bis (amidiniumthio)octanoic acid, its enantiomers (+)-6,8-bis(amidiniumthio)octanoic acid and (-)-6,8-bis (amidiniumthio)octanoic acid and of the esters of these compounds as well as to their use to produce dihydrolipoic acid and.alpha.-lipoic acid. Excerpt(s): This application claims priority from German Application No. 19601787.4, filed on Jan. 19, 1996, the subject matter of which is incorporated herein by reference. The invention relates to the production, purification and use of salts of 6,8bis(amidiniumthio)octanoic acid, its enantiomers and esters of these compounds. 6,8bis(amidiniumthio)octanoic acid can be converted by hydrolysis of the isothiuronium grouping to 6,8-dimercaptooctanoic acid (also designated as dihydrolipoic acid), which for its part serves as precursor for the pharmacologically active.alpha.-lipoic acid. The R enantiomer of.alpha.-lipoic acid is a natural substance occurring in practically all animal and vegetable cells.alpha.-lipoic acid is of essential physiological significance as coenzyme in the oxidative decarboxylation of.alpha.-ketocarboxylic acids (e.g. pyruvic acid). An important pharmacological indication of racemic.alpha.-lipoic acid is diabetic polyneuropathy. In the case of the pure, optical isomers of.alpha.-lipoic acid (R and S form, that is, R.alpha.-lipoic acid and S.alpha.-lipoic acid), in contrast to the racemate the R enantiomer is primarily antiphlogistically and the S enantiomer primarily antinociceptively active (EP 0,427,247, Nov. 8, 1990). Therefore, in addition to the synthesis of racemic.alpha.-lipoic acid the synthesis of the pure enantiomers for purposeful pharmaceutical use is also of great importance. Web site: http://www.delphion.com/details?pn=US06013815__
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Therapeutic treatment for auditory function Inventor(s): Seidman; Michael D. (5310 Putman, West Bloomfield, MI 48323) Assignee(s): none reported Patent Number: 5,977,162 Date filed: September 16, 1997 Abstract: A nutritional supplement for enhancing mitochondrial function in cells includes 10-1000 mg of alpha-lipoic acid, 10-1000 mg acetyl-L-carnitine, 15-360 mg coenzyme Q-10, and 15-360 mg glutathione. The composition may further comprise a carrier for these components such as a liquid or tablet for oral ingestion on a daily basis. Excerpt(s): This invention relates generally to methods and compositions for supplementing nutritional intake, and in particular, to methods and compositions for supplementing nutritional intake in such a way so as to enhance mitochondrial function. Most specifically, the present invention relates to a nutritional supplement containing alpha-lipoic acid, acetyl-L-carnitine, coenzyme Q-10, and glutathione. Aging is a progressive accumulation of metabolic and physiologic changes associated with an increasing susceptibility to disease. Several explanations for the aging process are described in the contemporary literature. Among the most prominent is the dysdifferentiation hypothesis of aging and the membrane hypothesis of aging. The dysdifferentiation hypothesis proposes that aging is the result of a continued programmed differentiation leading to either a cessation of normal gene activity or a systematic activation of genes whose effects are deleterious to cellular function. Conversely, the membrane hypothesis of aging (MHA) states that aging is related to decreasing effectiveness of cellular protective and reparative mechanisms secondary to damage from oxygen radicals. This yields biochemical and metabolic errors, which progressively accumulate, resulting in cell aging and ultimately death. Therefore the MHA suggests that reactive oxygen metabolite (ROM) induced cell membrane structural damage is the primary mediator in cellular aging. Reactive oxygen metabolites, also known as free oxygen radicals (FOR) are the putative initiators in the membrane hypothesis of aging. ROMs are a normal by-product of oxidative phosphorylation, and are also formed under conditions of ischemia, hypoperfusion and because of environmental contaminants. Among the many detrimental activities of ROM, or free oxygen radicals, is direct damage to mitochondrial DNA (mtDNA). Progressive accumulation of mtDNA damage renders cells unable to conduct oxidative phosphorylation reactions effectively, thereby leading to a bioenergetically deficient cell. Over time, mitochondrial DNA damage accumulates and leads to cellular dysfunction with subsequent organ failure, aging and ultimately death. This sequence forms the basis of the MHA. Additionally, there is evidence of a reduction in the oxidantprotective enzymes superoxide dis-mutase and catalase associated with aging. Thus not only are there increases in the deleterious effects of ROMs, but there is a reduction in the enzymes and mitochondrial metabolites necessary for protection from ROM and for effective mitochondrial function. Web site: http://www.delphion.com/details?pn=US05977162__
Patents 89
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Topical scar treatments using alkanolamines Inventor(s): Perricone; Nicholas V. (27 Coginchaug Ct., Guilford, CT 06437) Assignee(s): none reported Patent Number: 6,319,942 Date filed: June 6, 2001 Abstract: Cutaneous scars are reduced by the topical application of compositions containing an alkanolamine such as ethylaminoethanol, methylaminoethanol, dimethylaminoethanol, isopropanolamine, triethanolamine, isopropanoldimethylamine, ethylethanolamine, 2-butanolamine, choline, serine, and mixtures thereof. Compositions may be applied directly to scar tissue, or embedded in linaments held against the scars. Dimethylaminoethanol in amounts ranging from about 0.1% to about 10% by weight of the total composition is particularly preferred. Adjunct ingredients such as lipoic acid, tyrosine, ascorbyl palmitate, and glycolic acid may be added to scar-reducing formulations, and are desirable in many embodiments. Excerpt(s): This invention relates primarily to methods and compositions for the treatment of scar tissue, particularly hypertrophic and keloid scars and straie distensae (stretch marks). Scars typically result from repair of damaged tissue, and this damage may be following trauma, burns, or disease. Because scars are cosmetically distracting and sometimes symptomatic, producing bothersome itching, burning, stinging or painful sensations, there is considerable interest in their treatment. Scars result from wound healing, which occurs in three separate phases: inflammation, formation of granulation tissue, and matrix formation. (For a review, see Sahl, W. J., and Clever, H., Internat. J. Derm., 1994, 33: 681-691 (part I) and 763-769 (part II); this paper, and others and patents cited below are expressly incorporated herein in their entireties by reference). During the first phase, damage to endothelial cells, complement, and platelets at the wound site release chemotactic factors that result in the infusion of neutrophils, lymphocytes and macrophages, which aids in the removal of infection and foreign debris. As in all inflammatory processes, there is generation of free radicals, which damages cell membranes and results in formation of oxidized proteins and fats, and cross-linked new collagen, laying a scaffold for the next phase. At the end of the inflammatory phase, the granulation phase begins with an influx of fibroblasts and endothelial cells to the wound. Other key cells in this phase are macrophages and platelets. Macrophages induce the beginning of granulation by relasing platelet-derived growth factor (PDGF), tumor necrosis growth factor (TGF)-.alpha., and an epidermal growth factor-like substance. Activated platelets release epidermal growth factor (EGF), PDGF, TGF-.alpha., and TGF-.beta. Together these play roles in the re-epithelialization process wherein keratinocytes cells migrate in sheaths over a provisional matrix consisting primarily of fibrin, fibronectin, type V collagen, and tenascin, and produce their own fibronectin receptors. Web site: http://www.delphion.com/details?pn=US06319942__
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Treatment of acne using lipoic acid Inventor(s): Perricone; Nicholas V. (27 Coginchaug Ct., Guilford, CT 06437) Assignee(s): none reported Patent Number: 6,365,623 Date filed: December 30, 1999
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Abstract: Active acne and acneiform scars are treated by topical application of a composition containing lipoic acid and/or a lipoic acid derivative such as dihydrolipoic acid, a lipoic or dihydrolipoic acid ester, a lipoic or dihydrolipoic acid amide, a lipoic or dihydrolipoic acid salt, and mixtures of any of these to reduce erythema, pore size, and scarring. Topical application of lipoic acid and/or a lipoic acid derivatives are advantageously used with at least one adjunct ingredient such as a retinoid, an antibiotic, or benzoyl peroxide conventionally used for acne, alone or in combination with dimethylaminoalcohol, an.alpha.-hydroxy acid such as glycolic acid, a tyrosine, tocotrienol, and/or a fatty acid ester of ascorbic acid. One preferred embodiment contains a combination of lipoic acid, an.alpha.-hydroxy acid, and dimethylaminoalcohol. Excerpt(s): This invention relates primarily to methods and compositions for the treatment of acne vulgaris. Acne is the most common pustular condition of the skin, disfiguring afflicted persons with inflammatory and noninflammatory lesions (including pustules, papules and comedones) during the active phase, and with atrophic scars afterwards. It occurs most commonly in teenagers, but is not confined to adolescents, as increasing numbers of persons aged >20 years are seeking advice on treatment for acne (Brogden, R. N., and Goa, K. L., Drugs, 1997, 53: 511-519; this reference and others cited below are hereby incorporated herein in their entireties by reference). Although acne is generally considered to be self-limiting, its social effects can be substantial, and it may have its most severe effects on the psyche (ibid.). In about 60% of teenagers, disease severity is sufficient for them to self-medicate with proprietary preparations, or seek medical advice. Acne is a multifactorial disease affecting the pilosebaceous units of the skin. Each unit consists of a large, multilobed sebaceous gland, a rudimentary hair and a wide follicular canal lined with stratefied squamous epithelium. They are found over most of the body surface but are largest and most numerous on the face, chest, and upper back. Normally, desquamated follicular cells are carried to the surface by the flow of sebum. Under the abnormal circumstances of acne vulgaris, an abnormal desquamination process provokes increased sloughing of the epithelium, which becomes more cohesive because of defective keratinization. This process causes blockage of the follicular orifice with accumulation of dead cells. Androgen stimulates the undifferentiated hormonally responsive cells making up the outer layer of the sebaceous gland lobule to divide and differentiate. Sebum production favors proliferation of the anaerobe Propionibacterium acnes, which is a normal commensal to the pilosebaceous unit, which can elicit hypersensitivity responses in acne. The basic lesion of acne is the microcomedo. Accumulation of sebum and keratinous debris results in a visible closed comedo, or whitehead, and its continued distension causes an open comedo, or blackhead. The dark color of blackheads is due to oxidized melanin. Blackheads and microcysts are noninflammatory lesions of acne, but some comedones evolve into inflammatory papules, pustules, or nodules, and can become chronic granulomatous lesions. The initial inflammatory cell in an acute acne papule is the CD4+T lumphocyte. Duct rupture is not a prerequisite for inflammation, which is due to the release of pro-inflammatory substances from the duct. When inflammation develops, neutrophil chemotaxis occurs. These neutrophils secrete hydrolytic enzymes that cause further damage and increased permeability of the follicular wall. In pustules, neutrophils are present much earlier. More persistent lesions exhibit granulomatous histology that can lead to scarring. Web site: http://www.delphion.com/details?pn=US06365623__
Patents 91
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Treatment of and/or prophylaxis against brain and spinal cord injury Inventor(s): Koenig; Michael (Silver Spring, MD), Long; Joseph (Clarksville, MD), Meyerhoff; James L. (Silver Spring, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,432,434 Date filed: April 21, 2000 Abstract: The administration of.alpha.-lipoic acid (.alpha.LA) and dihydrolipoic acid (DHL) both as a preventive measure before exposure to conditions which may cause damage, such as rapid changes in atmospheric pressure, and as a means of preventing or ameliorating damage arising from such injury provides benefits not currently available. The active agents may be administered systemically or to the injured tissue. For example, when there is spinal cord injury, the active agents may be administered intrathecally. Excerpt(s): This invention relates to the field of prevention of damage arising from spinal cord injury and trauma to the brain, including that which occurs secondary to decompression sickness (DCS). At present, spinal injury, whether arising from trauma or disease, disables many Americans of all ages. There is need for means of effective treatment to prevent such disabilities. Alpha lipoic acid (.alpha.LA) is an antioxidant currently used clinically to treat diabetic neuropathy. It has been shown to be clinically safe and was shown to be neuroprotective against ischemia-reperfusion injury in both the rat and the gerbil. It was also effective against NMDA and malonic acid lesions of striatum in rats. However, its effects in preventing or ameliorating damage arising because of pathologies and trauma to the spinal cord or trauma-induced injury to the brain, including spinal cord injury secondary to decompression sickness (DCS), has not been known. Web site: http://www.delphion.com/details?pn=US06432434__
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Treatment of lipid metabolic disorders using 5-(1,2-dithiolan-3-yl) valeric acid (.alpha.-lipoic acid) or its physiologically compatible salts Inventor(s): Alken; Rudolf-Giesbert (Zepernick, DE), Fries; Gerhard (Wahlitz, DE), Koegst; Dieter (Wahlitz, DE) Assignee(s): BiRD Berolina innovative Research and Development GmbH (DE), esparma GmbH (DE) Patent Number: 6,518,300 Date filed: October 9, 2001 Abstract: Lipid metabolic disorders, such as hyperlipidemia or hyperlipoproteinemia can be treated by administering to an afflicted individual an effective amount of 5-(1,2dithiolan-3-yl) valeric acid (.alpha.-lipoic acid) or one of its physiologically acceptable salts. Pharmaceutical compositions containing (.alpha.-lipoic acid) and methods for making such compositions also are disclosed. Excerpt(s): The invention concerns the use of 5-(1,2-dithiolan-3-yl) valeric acid (.alpha.lipoic acid) or its physiologically compatible salts for the treatment of disturbances of lipid metabolism. Arteriosclerosis, after heart disease and cancer, is one of the primary causes of death in humans. A risk factor for the disease of arteriosclerosis is an increased
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quantity of serum lipids and lipoproteins, so that a decrease in the level of serum lipids and lipoproteins is important for therapy. An object of the present invention is thus to make available an active ingredient, which is suitable for the treatment of disturbances of lipid metabolism. Web site: http://www.delphion.com/details?pn=US06518300__ •
Ultrasonicated.alpha.-lipoic acid solutions for attenuating microvascular injury Inventor(s): Samson; Frederick E. (171 Lake Shore S., Lake Quivira, KS 66106-9516), Wood; John G. (20922 W. 63rd Terrace, Shawnee, KS 66218) Assignee(s): none reported Patent Number: 5,990,153 Date filed: May 5, 1998 Abstract: A pharmaceutical composition comprising an ultrasonicated formulation of.alpha.-lipoic acid and an aqueous solution which may also contain other antioxidants and/or metal chelators is disclosed.Also disclosed is a method of ultrasonically preparing pure or mixed micelles of lipid-soluble antioxidants and.alpha.-lipoic acid in aqueous solutions for intravenous delivery to mitigate microvascular dysfunction in hemorrhagic shock and other conditions of acute microvascular injury. Excerpt(s): This invention pertains to the prevention and treatment of mammalian blood vessel injury. More particularly, this invention relates to an ultrasonication method of solubilizing highly lipophilic antioxidants, such as.alpha.-lipoic acid, for delivery to the lipid membranes of microvascular cells where such antioxidants mitigate vascular dysfunction following a variety of systemic insults, such as hemorrhagic shock. Hemorrhagic shock is the clinical condition of inadequate perfusion (ischemia) of the tissues as a result of blood loss. The treatment of hemorrhagic shock requires prompt restoration of tissue perfusion by infusing large volumes of lactated Ringer's solution, saline, albumin solutions, whole blood, dextran, or solutions containing stabilized hemoglobin. Despite prompt restoration of intravascular volume, the morbidity and mortality due to hemorrhagic shock remain unacceptably high. A key reason for the frequent failure of fluid resuscitation in hemorrhagic shock is the generalized and progressive microvascular injury which is a consequence of tissue ischemia. The microvasculature consists of venules, arterioles and their intervening capillary bed. Following a period of ischemia and reperfusion (as occurs in hemorrhagic shock followed by fluid resuscitation), the capillaries and venules become excessively permeable and the arterioles constrict. The leaking of blood proteins from the excessively permeable venules into the tissue interstitium causes additional fluid loss and edema (swelling), which further compromises blood flow and leads to organ dysfunction. Arteriolar constriction results in areas of persistent tissue ischemia and local hypoxia. Because of a forced state of anaerobic metabolism resulting in lactic acid accumulation and tissue acidosis, hemorrhagic shock may be followed by multiple organ failure and death several days after prompt and seemingly successful restoration of circulating volume sufficient to reperfuse vital organs. Web site: http://www.delphion.com/details?pn=US05990153__
Patents 93
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Use of R-(+)-.alpha.-lipoic acid, R-(-)-dihydrolipoic acid and metabolites in the form of the free acid or as salts or esters or amides for the preparation of drugs for the treatment of diabetes mellitus as well as of its sequelae Inventor(s): Bisswanger; Hans (Bodelshausen, DE), Borbe; Harald (Mainz, DE), Hettche; Helmut (Dietzenbach, DE), Klip; Amira (Toronto, CA), Packer; Lester (Orinda, CA), Ulrich; Heinz (Niedernberg, DE), Wessel; Klaus (Frankfurt, DE) Assignee(s): Asta Medica Aktiengesellschaft (Dresden, DE) Patent Number: 5,948,810 Date filed: June 19, 1997 Abstract: The invention relates to the use of R-(+)-.alpha.-lipoic acid, R-(-)-dihydrolipoic acid or their metabolites, salts, esters and amides for the synthesis of drugs for the treatment of diabetes mellitus of types I and II, compensated and decompensated insulin resistance and sequelae or late complications of diabetes mellitus, such as cataracts, polyneuropathy, nephropathy, as well as sequelae or late complications of insulin resistance. Excerpt(s): The invention relates to drugs for the treatment of diabetes mellitus types I and II and its late complications and sequelae or of subclinically existing insulin resistance and its late complications and sequelae, as well as to their synthesis. R-(+).alpha.-lipoic acid is the physiologically occurring enantiomer of 1,2-dithiocyclopentane3-valeric acid. R-(+)-.alpha.-lipoic acid is a coenzyme of.alpha.-ketoacid dehydrogenases (pyruvate dehydrogenase,.alpha.-ketoglutarate dehydrogenase, etc.) and acts at a key site in the sugar and energy metabolism of the cell. In its function as an intramolecular redox system, it is oxidized (.alpha.-lipoic acid) and reduced (dihydrolipoic acid). The racemate is used as a 50/50 mixture of R-(+)-.alpha.-lipoic acid and S-(-)-.alpha.-lipoic acid for the treatment of diabetic and alcoholic polyneuropathy, as well as for the treatment of Amanita phalloides poisoning and of chronic and alcoholic liver diseases. Web site: http://www.delphion.com/details?pn=US05948810__
Patent Applications on Lipoic Acid As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to lipoic acid: •
Active ingredient combinations of surface-active citric esters and alpha-lipoic acid, and cosmetic and dermatological preparations containing such mixtures Inventor(s): Kruse, Inge; (Hamburg, DE), Raschke, Thomas; (Hamburg, DE), Schonrock, Uwe; (Nahe, DE) Correspondence: Kurt Briscoe; Norris, Mclaughlin & Marcus, P.A.; 220 East 42nd Street, 30th Floor; New York; NY; 10017; US Patent Application Number: 20020119114 Date filed: December 12, 2001
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This has been a common practice outside the United States prior to December 2000.
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Abstract: Combinations of:(a) one or more partially neutralized esters of monoglycerides and/or diglycerides of saturated fatty acids with citric acid; and(b).alpha.-lipoic acid. Excerpt(s): The present invention relates to active ingredient combinations of surfaceactive citric acids and.alpha.-lipoic acid, and to cosmetic and dermatological preparations containing such mixtures, and to the use of surface-active citric acid esters of stabilizing.alpha.-lipoic acid against chemical degradation reactions, in particular photochemical degradation reactions and/or oxidation-induced degradation reactions. Moreover, the invention relates to synergistic mixtures of.alpha.-lipoic acid and surfaceactive substances, and to cosmetic and dermatological preparations containing such mixtures. The present invention preferably relates to cosmetic preparations with effective protection against harmful oxidation processes in the skin, but also for the protection of cosmetic preparations themselves or for the protection of the constituents of cosmetic preparations against harmful oxidation processes. The present invention accordingly relates, in preferred embodiments, to cosmetic or dermatological preparations comprising active ingredients for the care and protection of the skin, in particular sensitive skin and, very particularly, skin aging or aged by intrinsic and/or extrinsic factors, and to the use of such active ingredients and combinations of such active ingredients in the field of cosmetic and dermatological skincare. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Alpha lipoic acid based food supplement for increasing lean muscle mass and strength Inventor(s): Gardiner, Paul; (Mississaugu, CA), Woodgate, Derek; (Brampton, CA) Correspondence: Patrick J. Birde; Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20020006907 Date filed: February 1, 2001 Abstract: Food supplement compositions and their methods of use in increasing lean mass and/or muscle size and/or strength in individuals, particularly, athletes is described. The food supplements described comprise.alpha. lipoic acid or a derivative thereof, and an amino acid. Other food supplements described comprise a substance which can enhance and/or mimic activity of.alpha. lipoic acid, and a source of amino acid. The food supplement compositions described are suitable for supplementing the diet of an athlete and particularly for enhancing an athlete's muscle size and/or strength. Excerpt(s): This application claims the benefit of the U.S. provisional application Ser. No. 60/178,957, filed Feb. 1, 2000, the content of which is incorporated herein by reference. The present invention is directed to food supplements which comprise.alpha. lipoic acid or a derivative thereof, and a source of amino acids or derivatives thereof, and to methods for supplementing the diet of an athlete and methods for enhancing an athlete's muscle size and/or strength, which methods employ these food supplements. Food supplements based on natural products and approaches for enhancing an athlete's muscle size and/or strength have become popular exigencies in various sports and body building regimes. However, as athletes continually strive for improved performance, there is a continuing need for new more effective technologies to aid in increasing lean muscle mass, muscle size and/or strength. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 95
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Anti-aging skin care composition and uses thereof Inventor(s): Klysz, Beatrice M.; (New York, NY) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20030095933 Date filed: November 14, 2002 Abstract: The present invention is directed toward anti-aging skin care compositions comprising Vitamin B1, Vitamin B5, Vitamin C, N-acetyl-cysteine and, optionally, lipoic acid. The present invention is further directed toward methods for therapeutically or prophylactically treating the consequences of aging on the condition or appearance of the skin. The present invention further provides one or more kits that are useful for delaying, treating or preventing the consequences of aging on the condition or appearance of the skin. Excerpt(s): This application is a non-provisional application of U.S. Provisional Patent Application Serial No. 60/331,455 of Klysz, filed Nov. 16, 2001, the contents of which are incorporated herein by reference. This invention relates to anti-aging skin care compositions for application to skin and to their use in improving the condition and appearance of skin. The present invention further relates to kits for use in improving the condition or appearance of skin, wherein the individual components of the anti-aging skin care composition may be packaged separately from, but may be readily combined with, its dermatologically-acceptable vehicle immediately prior to use. Such kits may facilitate ease of use, long-term storage, and/or efficacy of the anti-aging skin care composition. The appearance and condition of the skin may be degraded through the effects of environmental factors, either naturally occurring (sunlight, wind abrasion, humidity, etc.) or man-made (heating, air condition, pollutants, etc.), pathological processes such as dermatological diseases, or the normal aging process. The various insults to which the skin is exposed may act individually or synergistically. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antioxidant combination composition and use thereof Inventor(s): De Simone, Claudio; (Ardea RM, IT) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe RD.; Arlington; VA; 22201-4714; US Patent Application Number: 20030068309 Date filed: October 3, 2001 Abstract: An orally or parenterally administrable composition which comprises the following components:(a) L-carnitine inner salt or a pharmacologically acceptable salt thereof;(b) acetyl L-carnitine inner salt or a pharmacologically acceptable salt thereof;(c).alpha.-lipoic acid;(d) coenzyme Q.sub.10;(e) Vitamin E; and(f) selenomethionine,suitable for counteracting oxidative stress and use thereof are disclosed. Excerpt(s): The present invention relates to a combination composition for the prevention and/or treatment of disorders or diseases brought about by oxidative stress, untimely early physiological apoptotic phenomena following oxidative stress and/or environmental agent-induced apoptosis. Accordingly, the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending
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upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in. Diseases which can effectively be prevented or treated with the composition of the present invention include atherosclerosis, ischaemia-reperfusion injuries, rheumatoid arthritis, cancer, stroke, cataract and other eye diseases, thyroid diseases, liver diseases, sexual impotence, Parkinson's disease, Alzheimer's disease and degenerative disorders affecting virus-infected patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combination and method of treatment of cancer utilizing a COX-2 inhibitor and A 3hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitor Inventor(s): Guilford, F. Timothy; (Palo Alto, CA), Kindness, George; (Middletown, OH), Schumm, Brooke III; (Ellicott City, MD) Correspondence: Brooke Schumm, Iii; Daneker, Mcintire, Schumm, Prince, Goldstein, ET A; 210 N Charles ST; Suite 800; Baltimore; MD; 21201; US Patent Application Number: 20020132781 Date filed: November 17, 2001 Excerpt(s): For purposes of priority, including in the United States of America, this invention is a continuation-in-part of Provisional Applications Nos. 60/238,505 and 60/238,506 filed Oct. 6, 2000, Provisional Applications Nos. 60/243,901 and 243,902 filed Oct. 27, 2000, Provisional Application No. 60/245,592 filed Nov. 17, 2000, Provisional Application No. 60/264,511 filed Jan. 26, 2001, and Provisional application No. 60/307,689 and Utility Application Ser. No. 09/912,703 both filed on Jul. 25, 2001, and PCT/US01/31328 which provisional applications and utility application and other application(s) are incorporated by reference. The inventors propose a combination of an HMG-CoA reductase inhibitor (also referred to as "HMG-CoA inhibitor(s)"), and COX-2 inhibitor for the treatment of cancer especially prostate cancer and a method of treatment of cancer by that combination, especially prostate cancer. The inventors propose a combination of an HMG-CoA reductase inhibitor, COX-2 inhibitor, and glutathione pathway enhancing and detoxifying compound, particularly cystine, for the treatment of cancer especially prostate cancer and a method of treatment of cancer by that combination, especially prostate cancer. Methods of manufacturing are also claimed. The invention, however, is applicable to cancers generally in mammals and the reference to human biochemistry is not intended to be limiting, but illustrative. The term patient or body or reference to humans is utilized for convenience, but includes all mammalian patients or bodies. Traditional cancer treatments have generally used an approach which is focused on directly attacking cells with a propensity to divide. The cancer cell is viewed as a bad cell that must be eliminated. The methods and combinations chosen focus on destruction of the dividing cell, or chemical attack of the cell. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 97
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Combination of lipoic acid and c1 donors for the treatment of disorders of the central nervous system Inventor(s): Eckert, Gunther P; (Liederbach a. T., DE), Hahnlein, Wolfgang P; (Freinsheim, DE), Hasselwander, Oliver; (Landau, DE), Kramer, Klaus; (Landau, DE), Muller, Walter E; (Worms, DE) Correspondence: Keil & Weinkauf; 1350 Connecticut Avenue, N.W.; Washington; DC; 20036; US Patent Application Number: 20030148991 Date filed: November 7, 2002 Abstract: The present invention relates to the use of lipoic acid and C.sub.1 donors, in particular S-adenosylmethionine and/or 5-methyltetrahydrofolat- e, for the treatment of central nervous system disorders, to compositions with a corresponding active ingredient combination and to compositions in the form of commercial packs with corresponding combination products or single component products for combined use. Excerpt(s): The present invention relates to the use of lipoic acid and C.sub.1 donors for nutritional supplementation, in functional foods and for therapeutic purposes in the treatment of central nervous system disorders, to compositions having a corresponding active ingredient combination, and to compositions in the form of commercial packs with corresponding combination products or single component products for combined use. Lipoic acid is a coenzyme in the oxidative decarboxylation of.alpha.-keto acids and is found in virtually every cell in the body. The antiinflammatory, analgesic and cytoprotective properties of lipoic acid, and its antioxidant effect, make it an interesting active ingredient for pharmacy, cosmetics, food science and adjacent areas (Biothiols in Health and Disease, Herausgeber Packer L. and Cadenas E., Marcel Dekker Inc., New York, Basel, Hongkong). Thus, Stoll et al. reported, in Pharmacology Biochemistry and Behavior, Vol. 46, pp. 799-805 (1993) and in Ann. NY Acad. Sci., Vol. 717, pp. 122-128 (1994), respectively that lipoic acid is able to improve the long-term memory of aged mice and the cognitive abilities of rodents. Han D. et al. postulate, in American Journal of Physiology 273: R 1771-1778 (1997), a lipoic acid-mediated protection against glutamate-induced depletion of intracellular glutathione and use this in an attempt to give a mechanistic explanation of the neuroprotective effects of lipoic acid which are observed in rat ischemia models. Lipoic acid-containing products are currently listed for the treatment of abnormal sensation associated with diabetic polyneuropathy. Formulations of solid salts of lipoic acid are proposed in U.S. Pat. No. 5,990,152. U.S. Pat. No. 5,994,393 relates to another modification of lipoic acid. Useful lipoic acid analogs are proposed in WO 99/45922. Combinations of lipoic acid and vitamins for producing pharmaceuticals are described in EP 0 572 922 A1. A combination of lipoic acid as biocompatible disulfide with an essential fatty acid and, where appropriate, other essential nutrients is mentioned in WO 99/04782. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Composition and method for modulating nutrient partitioning Inventor(s): McCleary, Larry; (Golden, CO) Correspondence: Glenn Parma; 1104 Biemert Street; Green Bay; WI; 54304 Patent Application Number: 20020132219 Date filed: December 28, 2000
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Abstract: A nutritional supplement composition for modulating nutrient partitioning in a human so as to increase oxidation of fat and promote increased storage of glycogen is composed of hydroxycitric acid, carnitine, biotin, a gluconeogenic substrate, and, optionally, one or more of chromium, conjugated linoleic acid, coenzyme Q10, eicosapentaenoic acid, pyridoxine, alpha-lipoic acid, magnesium, and gymnema sylvestre. A method for modulating nutrient partitioning in a human involves orally or parenterally administering the aforementioned composition to the human, preferably on a daily basis, for a therapeutically effective period of time. Preferably, the method further involves having the human follow a specific dietary regimen wherein the glycemic index is less than 60 and the daily calorie consumption from carbohydrates is less than about 50% and the daily calorie consumption from protein is at least about 20%. Optionally, the method further involves an exercise program, a stress reduction program and/or a blood donation program. Excerpt(s): This invention relates to compositions and methods for modulating nutrient partitioning. More particularly, the present invention provides a composition and a method for modulating nutrient partitioning in humans so as to normalize nutrient pathways which play a key role in numerous metabolic disorders, the composition and method being designed to prevent, delay or reverse such disorders. Disorders of nutrient partitioning leading to biochemical signaling abnormalities form the basis for a group of metabolic disorders. These include but are not limited to insulin resistance, hyperinsulinemia, Syndrome X, hypertriglyceridemia and/or low HDL syndrome, high RQ (respiratory quotient) syndrome, obesity, chronic fatigue syndrome, small dense LDL syndrome, recidivism from weight loss, glucolipoxia, premature aging, memory loss, endothelial dysfunction, vascular disease, hypertension, postprandial hyperlipidemia, certain types of cancer, metabolic inflexibility and others. The basic abnormality is similar in each circumstance but manifests clinically in different ways depending upon the organ involved, the individual's genetic makeup, age, sex and other factors. The two major macronutrient fuels are fat and carbohydrate (which is stored in the body as glycogen). In the body, fat and carbohydrate are combined in certain proportions to generate the fuel mix the body burns at any point in time. If the fuel mix contains more carbohydrate, it contains relatively less fat and vice versa. Because there is minimal metabolic transformation between carbohydrate and fat, if more fat is being burned, then less is being stored and vice versa. The same holds true for carbohydrate, i.e., if more carbohydrate is being burned, then less is being stored and vice versa. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition exhibiting synergistic antioxidant activity Inventor(s): Babish, John G.; (Brooktondale, NY), Howell, Terrence; (Freeville, NY) Correspondence: Thorpe North Western; 8180 South 700 East, Suite 200; P.O. Box 1219; Sandy; UT; 84070; US Patent Application Number: 20020110604 Date filed: August 9, 2001 Abstract: A novel formulation is provided that serves to synergistically inhibit the generation of free radicals and oxidative stress in animals. The formulation comprises as a first component a carotenoid species, and, as a second component, at least one member selected from the group consisting of lipoic acid, dihydrolipoic acid (DHLA), a stilbene species, ergothioneine, a flavone species, a triterpene species, ascorbic acid and derivatives thereof.
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Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/224,678 filed Aug. 11, 2000. The present invention relates generally to a composition exhibiting synergistic antioxidant activity. More particularly, the composition comprises, as a first component, a carotenoid species, and, as a second component, at least one member selected from the group consisting of lipoic acid, dihydrolipoic acid (DHLA), a stilbene species, ergothioneine, a flavone species, a triterpene species and ascorbic acid or derivatives thereof. The composition exhibits synergistic antioxidant activity. Oxygen is essential for aerobic life, but is also a precursor to the formation of harmful reactive oxygen species (ROS). Oxidative stress refers to the cytotoxic consequences of a mismatch between the production of free radicals and the ability of the cell to defend against them. Oxidative stress can thus occur when the formation of ROS increases, scavenging of ROS or repair of oxy-modified macromolecules decreases, or both. ROS may be oxygen-centered radicals possessing unpaired electrons, such as superoxide and hydroxyl radicals, or covalent molecules, such as hydrogen peroxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for promoting a healthy cardiovascular system and enhancing blood flow Inventor(s): Yegorova, Inna; (Northridge, CA) Correspondence: Sierra Patent Group, LTD.; P O Box 6149; Stateline; NV; 89449; US Patent Application Number: 20020176900 Date filed: March 15, 2002 Abstract: Compositions and methods for promoting a healthy cardiovascular system and enhancing healthy blood flow by gently removing toxic buildup from the arterial walls and dilating and strengthening the arterial walls, in a mammal. The compositions comprise calcium; magnesium; selenium; manganese; zinc; potassium; vitamin E; vitamin A; alpha-lipoic acid; Allium sativum extract; Medicago sativa extract; Chondrus crispus extract; L-cysteine; L-glutamic acid; glycine; and glutathione. Excerpt(s): The present invention relates to compositions and methods for promoting a healthy cardiovascular system and enhancing healthy blood flow by, e.g., gently removing toxic buildup from the arterial walls and dilating and strengthening the arterial walls. Cardiovascular disease (CVD) is the leading cause of death in the industrialized countries. According to the American Heart Association, in 1997 alone, 59.7 million Americans were estimated to have one or more forms of cardiovascular disease including high blood pressure, coronary heart disease, stroke and rheumatic heart disease. Of those, 953,110 Americans died of some form of CVD, attributing 41.2% of all deaths to CVD. Coronary heart disease (CHD) by itself can be attributed to causing about half of all deaths associated with cardiovascular diseases (49%). The primary cause of CHD is artheriosclerosis, a degenerative change in the arteries whereby the arterial walls thicken and lose elasticity. One key process of artheriosclerosis is the accumulation of lipids resulting in distribution of atheromatous plaque. As plaque accumulates in the inner artery wall, the restricted artery is weakened, bulging with cholesterol and toxic deposits. Eventually, the plaque blocks the arteries and interrupts blood flow to the organs they supply. It is now well established that vascular blockage and cardiovascular disorders including myocardial infarction, coronary heart disease, hypertension and hypotension, cerebrovascular disorders including stroke, cerebral thrombosis and memory loss due to stroke; peripheral vascular disease and intestinal infarction are caused by blockage of arteries and arterioles by atherosclerotic plaque.
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The production of atherosclerotic plaque formation is multi-factorial in its production. Hypercholesterolemia, especially elevated levels of low-density lipoprotein cholesterol (LDL) is an important risk factor for atherosclerosis and arteriosclerosis and associated diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for promoting healthy joints Inventor(s): Bland, Jeffrey S.; (Fox Island, WA) Correspondence: Grant R Clayton; Clayton Howarth & Cannon, PC; P O Box 1909; Sandy; UT; 84091-1909; US Patent Application Number: 20020025310 Date filed: February 2, 2001 Abstract: A dietary supplement for promoting healthy joints and joint tissues is disclosed. The dietary supplement comprises a member selected from the group consisting of niacinamide, niacin, and mixtures thereof and an antioxidant nutrient. Illustrative antioxidant nutrients include N-acetylcysteine, lipoic acid, coenzyme Q10, vitamin E, carotenoids, and zinc. The dietary supplement supports optimal function and health of joints and joint tissues by interrupting a cascade of events involving reactive oxygen species, cytokines, and poly(ADP-ribose) synthetase, which self-amplifying, positive feed-forward cycle is inversely correlated with joint tissue integrity. A method for promoting healthy joints and joint tissues is also described. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/179,885, filed Feb. 2, 2000. Not applicable. This invention relates to dietary supplements. More particularly, this invention relates to compositions and methods for providing nutritional support for healthy joints. In its most basic form, the invention comprises a mixture of niacinamide or niacin and an antioxidant nutrient, such as Nacetylcysteine, in a formula designed to support the optimal function and health of joints and joint tissues. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for prophylactic and therapeutic supplementation of nutrition in subjects Inventor(s): Balzer, Charles; (Lavalette, NJ), Giordano, John A.; (West Orange, NJ) Correspondence: Mckenna & Cuneo, Llp; 1900 K Street, NW; Washington; DC; 20006; US Patent Application Number: 20030012826 Date filed: October 19, 2001 Abstract: The present invention relates to compositions without added iron and methods for prophylactic nutritional supplementation and therapeutic nutritional supplementation. Specifically, the method involves administering to an individual a composition comprising carotenoids, vitamin E, vitamin D, vitamin C, thiamine, riboflavin, niacin, folic acid, pyridoxine, biotin, pantothenic acid, cobalamin, magnesium, manganese, zinc, selenium, chromium, copper, alpha lipoic acid, and lutein, wherein the composition is free of added iron.
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Excerpt(s): The present invention is related to and, in accordance with the provisions of 35 U.S.C.sctn.119(e), claims the benefit of provisional patent application Serial No. 60/301,443 filed Jun. 29, 2001, which is expressly incorporated fully herein by reference. The present invention relates to compositions comprising various vitamins and minerals, and without added iron, and methods for using these compositions for prophylactic nutritional supplementation and therapeutic nutritional supplementation in, for example, physiologically stressful conditions and to minimize the effect of exogenous iron supplementation. Nutrition plays a critical role in maintaining good health. Proper nutrition prevents dietary deficiencies, and also protects against the development of disease. Proper nutrition plays an increasingly important role as the body faces physiological stress. For example, as the body ages it suffers significant physiological stresses. Specifically, as the body metabolism shifts to accumulating larger fat stores and decreasing lean body mass, this increase in body weight may lead to obesity and associated conditions such as diabetes, cardiovascular disease, hypertension, osteoarthritis, and cancer. Other conditions, such as anorexia, malnutrition, gastrointestinal disorders, chronic alcoholism, chronic infections, acute infections, congestive heart failure, hyperthyroidism, poorly controlled diabetes, cheilosis, gingivitis, stomatitis and dietary restrictions, often result in physiological stresses that may be exacerbated by poor nutrition. In particular, these disease states may result in increased oxidative stress or elevated homocysteine levels that further compromise health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Controlled release lipoic acid Inventor(s): Byrd, Edward A.; (San Francisco, CA) Correspondence: Karl Bozicevic; Bozicevic, Field & Francis Llp; 200 Middlefield Road, Suite 200; Menlo Park; CA; 94025; US Patent Application Number: 20010028896 Date filed: January 5, 2001 Abstract: A controlled release formulation of lipoic acid is disclosed. The lipoic acid is combined with excipient materials in such a way that those materials provide for gradual release of the lipoic acid in a manner which makes it possible to substantially increase the period of time over which therapeutic levels of lipoic acid are maintained relative to a quick release formulation. These features make it possible to use lipoic acid to reduce serum glucose levels and maintain those levels over time thereby obtaining a range of desired therapeutic results. Excerpt(s): This application is a continuation-in-part of earlier filed patent application Ser. No. 09/288,245, filed Apr. 8, 1999, which is a continuation-in-part of earlier filed provisional patent application Ser. No. 60/102,605, filed Oct. 1, 1998 and patent application Ser. No. 09/112,623, filed Jul. 9, 1998, which is the converted patent application of provisional patent application Ser. No. 60/087,203, filed May 28, 1998 to which we claim priority under 35 U.S.C.sctn.120 and.sctn.119(e) each of which is incorporated herein by reference in their entirety. The invention relates generally to a controlled release oral formulation of pharmaceutically active compounds. More particularly the invention relates to controlled release lipoic acid oral formulations. A compound known as.alpha.-lipoic acid was first isolated by Reed and coworkers as an acetate replacing factor. It is slightly soluble in water, and soluble in organic solvents.alpha.-lipoic acid is a chiral molecule and is known by a variety of names,
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including thioctic acid; 1,2-diethylene-3 pentanoic acid; 1,2-diethylene-3 valeric acid; and 6,8-thioctic acid.alpha.-lipoic acid was tentatively classified as a vitamin after its isolation, but it was later found to be synthesized by animals and humans. The complete enzyme pathway that is responsible for the de novo synthesis has not yet been definitively elucidated. Several studies indicate that octanoate serves as the immediate precursor for the 8-carbon fatty acid chain, and cysteine appears to be the source of sulfur. As a lipoamide, it functions as a cofactor in the multienzyme complexes that catalyze the oxidative decarboxylation of.alpha.-keto acids such as pyruvate,.alpha.-keto glutarate, and branched chain.alpha.-keto acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cosmetics to support skin metabolism Inventor(s): Hamilton, Nathan D.; (Palo Alto, CA) Correspondence: Barbara J. Luther, Chartered; 18124 Wedge Parkway, #516; Reno; NV; 89511; US Patent Application Number: 20020044913 Date filed: February 12, 2001 Abstract: Disclosed herein are cosmetic compositions to support skin metabolism and ameliorate the appearance of aging. Cosmetics such as masks, sunscreens, and lotions are particularly preferred. The compositions contain 0.01-30% of an antioxidant (preferably R-.alpha.-lipoic acid), 0.01-30% of a carnitine (preferably ALC), and optionally 0.01-15% of a coenzyme Q (preferably Q10), and/or 0.01-30% of a creatine. Also disclosed are methods of treatment of aged, photoaged, dry, lined or wrinkled skin. A method of protecting skin from the deleterious effects of sun exposure includes applying a sunscreen composition containing 0.001-10% antioxidant, 0.001-10% carnitine, and optionally 0.001-10% coenzyme Q and/or 0.140% creatine. The antioxidant, a carnitine, and optionally coenzyme Q and/or creatine fight age-related declines in skin mitochondrial function, which result in the appearance of aging. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/181,793, filed Feb. 11, 2000, and U.S. Provisional Application No. 60/223,584, filed Aug. 7, 2000. The present invention is generally directed to cosmetics. More specifically, the present invention relates to the addition of the combination of lipoic acid, carnitine, and optionally coenzyme Q and/or creatine to cosmetic compositions. The skin is the largest organ in the body. The skin protects the deeper tissues from injury, drying, and invasion by foreign organisms. The skin contains the peripheral endings of many sensory nerves, as well as blood vessels. It plays an important part in regulating body temperature and also has limited excretory and absorbing powers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Formulation based on lipoic acid, process for its production and the use of this formulation for oral administration of lipoic acid Inventor(s): Breitenbach, Jorg; (Mannheim, DE), Hantke, Thomas; (Mannheim, DE), Liepold, Bernd; (Mannheim, DE), Rosenberg, Jorg; (Ellerstadt, DE) Correspondence: Herbert B. Keil; Keil & Weinkauf; 1101 Connecticut AVE., N.W.; Washington; DC; 20036; US Patent Application Number: 20020151578 Date filed: February 25, 2002 Abstract: A formulation based i) on lipoic acid or a physiologically acceptable salt thereof and, where appropriate, other active substances, and a formulation base having ii) a binder component and iii) where appropriate other physiologically acceptable excipients is described. Lipoic acid is in the form of a molecular dispersion in these formulations. An advantageous process for their preparation, in particular by melt extrusion, and the use of this formulation for oral administration of lipoic acid are likewise described. Excerpt(s): Formulation based on lipoic acid, process for its production and the use of this formulation for oral administration of lipoic acid. The present invention relates to formulations based on lipoic acid in molecular dispersion, a process for their production, in particular by melt extrusion, and the use of this formulation for oral administration of lipoic acid. As coenzyme in the oxidative decarboxylation of.alpha.keto acids, lipoic acid is present in virtually every cell in an organism. Antiinflammatory, analgesic and cytoprotective properties, as well as its antioxidant effect, make lipoic acid an active substance of interest for pharmacy, cosmetics, food science and adjacent areas. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Fruit and vegetable preservative Inventor(s): Selleck, Rhonda; (Barham, AU) Correspondence: Connolly Bove Lodge & Hutz Llp; Suite 800; 1990 M Street, N.W.; Washington; DC; 20036-3425; US Patent Application Number: 20020054950 Date filed: September 4, 2001 Abstract: Minimally processed fruits and vegetables are preserved by use of a flavonoid. Cut and peeled fruits or vegetables are prayed or dipped in a solution containing a flavonoid and an anti oxidant such as ascorbic acid, erythorbic acid or alpha lipoic acid. Juices are also preserved by the addition of a flavonoid and ascorbic acid if it is not already present. Excerpt(s): This invention relates to the preservation of minimally processed fruits and vegetables and flowers, particularly cut and peeled or juiced fruits and vegetables. Most fruits and vegetables are subject to discolouration and spoilage once they are cut and peeled. This is usually due to enzymatic and bacterial action. Patent application WO 97/16976 discloses a method of storing cut apple pieces in which whole apples are washed in chlorinated water to inactivate microorganisms, the apples are then cored, peeled and sliced and immersed in an ascorbic acid solution having a pH of 2.2 to 2.7 and are then drained and stored in modified atmosphere containers.
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GABA-Receptor modulators with NMDA-Antagonistic activity Inventor(s): Bruckner, Christopher; (Berlin, DE), Dorow, Rainer; (Berlin, DE), Neuhaus, Roland; (Berlin, DE) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030045541 Date filed: July 19, 2002 Abstract: The use of GABA.sub.A-receptor modulators with NMDA-antagonistic activity for the production of a pharmaceutical agent for neuroprotection and the combination of GABA.sub.A-receptor modulators with NMDA-antagonistic action and.alpha.-lipoic acid or dihydro-.alpha.-lipoic acid is described. Excerpt(s): This application claims the benefit of the filing date of U.S. Provisional Application Serial No. 60/313,019 filed Aug. 20, 2001. The invention relates to the use of GABA.sub.A-receptor modulators with NMDA-antagonistic activity for the production of a pharmaceutical agent for neuroprotection and the combination of GABA.sub.Areceptor modulators with NMDA-antagonistic action and.alpha.-lipoic acid or dihydro.alpha.-lipoic acid. Glutamate is an essential exciting transmitter in the human and mammalian body. Elevated glutamate levels lead to serious damage of the nerve tissue, which can lead to neurodegeneration. Within the glutamate receptors, the NMDA (Nmethyl-D-aspartate) receptor plays the most important role pathologically. The NMDA receptor simultaneously acts in a stress- and ligand-dependent manner. At the normal resting potential of the neuron of -60 mV, the ion channel of the receptor is sealed by Mg.sup.2+ ions (Mayer, M. L. et al., Nature 1984; 309 (5965): 261-3), and a ligand cannot activate the receptor. If, however, the membrane is depolarized, Mg.sup.2+ leaves the ion channel, and the receptor can be activated by a ligand, which results in the inflow of Ca.sup.2+ and Na.sup.+, and the outflow of K.sup.+. The non-NMDA receptors are almost impermeable for Ca.sup.2+. An excessive activation of the NMDA receptor produces an intensified Ca.sup.2+ inflow, which has a cytotoxic effect. Apoptosis processes (Riveros, N. et al., Neuroscience 1986; 17 (3): 541-6) and later necrosis processes that ultimately lead to cell death are triggered by this Ca.sup.2+ inflow. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Ingestible composition for enhancing athletic performance Inventor(s): Meehan, Kevin J.; (Victor, ID) Correspondence: Dale F. Regelman; Law Office OF Dale F. Regelman, P.C.; 4231 S. Fremont Avenue; Tucson; AZ; 85714; US Patent Application Number: 20030211133 Date filed: March 12, 2003 Abstract: An ingestible composition for enhancing athletic performance, which includes Methylcobalamine, a plurality of B vitamins, one or more Group VI element-containing compounds, one or more Group VIII element-containing compounds, and optionally one or more Group I element-containing compounds and one or more Group II element-
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containing compounds, Camitin, Citrulline, Thiamine, Lipoic Acid, Lysine, one or more proteolytic enzymes, one or more amylolytic enzymes, one or more lipolytic enzymes, one or more coenzymes, and one or more herbal extracts. Excerpt(s): This invention relates to an ingestible composition for enhancing athletic performance. In certain embodiments, Applicant's invention further relates to a waterbased composition which is isotonic with normal bodily fluids. There are a number of liquid compositions or diluted mixtures sold in commerce having names such as "Activity drinks," "Sports drinks," "Energy drinks," "Nutrient drinks," and the like. These beverages are advertised to ameliorate physiologic symptoms resulting from the loss of carbohydrates, electrolytes, vitamins, minerals, amino acids, and other important nutrients, during heavy exercise. As those skilled in the art will appreciate, athletic performance, i.e. physical exercise, comprises many different categories of activities, including activities requiring strength, speed, and/or endurance. As those skilled in the art will further appreciate, environmental factors, including temperature, air purity, elevation, humidity, and the like, can markedly affect a person's physical work capacity. It is thought that muscle activity is primarily based on a very fundamental biochemical mechanism, the breakdown of energy-rich phosphate bonds. Adenosine triphosphate ("ATP") is one source of such phosphate bonds at the cellular level. ATP is the direct source of energy for muscle work and, some believe, comprises the only form of chemical energy which can be converted by muscle tissue into mechanical work. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
INTEGRATED MULTI-VITAMIN AND MINERAL COMBINATION Inventor(s): BENJAMIN, SAMUEL D.; (EAST SETAUKET, NY), WEIL, ANDREW; (VAIL, AZ) Correspondence: Richard B. Klar; 875 Avenue OF The Americas; Suite 2301; New York; NY; 10001; US Patent Application Number: 20020155163 Date filed: December 27, 1999 Abstract: A daily multi-vitamin and mineral combination for use in the adjunct care of humans with asthma comprising thiamin, riboflavin, niacin, Vitamin B.sub.6, folate, Vitamin B.sub.12, biotin, pantothenic acid, choline, inositol, para-amino benzoic acid, Vitamin C, calcium, magnesium, iodine, selenium, manganese, chromium, molybdenum, boron, zinc, potassium, silicon, sulfur, vanadium, citrus bioflavonoid complex, hesperidin complex, rutin, Vitamin A, Vitamin D, Vitamin E, lycopene, lutein, Coenzyme Q10 and N-acetyl cysteine. For adjunct care of humans with diabetes, alphalipoic acid is substituted for N-acetyl cysteine and the amount of inositol is increased. A method of supplementing the nutritional intake of humans with diabetes and/or asthma through daily oral administration of the appropriate multi-vitamin and mineral combination. Excerpt(s): The present invention relates to a daily integrated multi-vitamin and mineral combination, and more particularly pertains to a daily multi-vitamin and mineral combination containing phytonutrients that is useful in the adjunct care of asthma and/or diabetes. The use of multi-vitamin and mineral combination formulations to supplement the nutritional needs of humans is known. It is recognized that vitamins and minerals play important physiological roles, and that a deficiency or excess of certain vitamins and minerals has been linked to the etiology of certain diseases. The B
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vitamins perform several well-known functions. Vitamin B.sub.1, thiamin, helps maintain smooth muscle and helps in the formation of blood cells. It is necessary, also, for proper nervous system function. Vitamin B.sub.2, riboflavin, is necessary for healthy hair, nails and mucous membranes. It also plays an important role in the formation of red blood cells and the production of antibodies. Vitamin B.sub.3, niacin, helps in the production of most sex hormones, and also helps to lower cholesterol and maintain blood circulation. Vitamin B.sub.6, pyridoxine, is involved in the synthesis of RNA and DNA, and helps relieve water retention in women. Folic acid is essential to the production of red blood cells and hormones, and is involved, as well, in DNA synthesis. Vitamin B.sub.12, cyanocobalamin, is necessary for overall metabolism and nervous system function, and is essential for the metabolism of folic acid. It also is necessary to prevent anemia. Biotin is necessary for the metabolism of proteins, carbohydrates and fats, as well as for healthy hair and skin. Vitamin B.sub.5, pantothenic acid, is important for the production of adrenal gland hormones. It is referred to as the "anti-stress vitamin." Choline is necessary for nervous system and brain function, and is important in gall bladder and liver function. Inositol helps remove fats from arteries and from the liver, and has been noted to be necessary for brain function. Para-amino benzoic acid ("PABA") aids in the metabolism of proteins and in the production of red blood cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Lipoic acid analogs Inventor(s): Packer, Lester; (Berkeley, CA), Roy, Sashwati; (Berkeley, CA), Sen, Chandan K.; (Berkeley, CA), Tirosh, Oren; (Berkeley, CA) Correspondence: Reginald J. Suyat; Fish & Richardson P.C.; 2200 Sand Hill Road; Menlo Park; CA; 94025; US Patent Application Number: 20010039292 Date filed: May 9, 2001 Abstract: A compound is provided having the formula I: 1whereinR.sup.1 and R.sup.2 independently denote a methylene, ethylene or unbranched or branched C.sub.3-16 alkylene, alkenylene or alkynylene group which is unsubstituted or substituted with one or more halogen, hydroxyl or amine groups, wherein in the unbranched or branched C.sub.3-16 alkylene, alkenylene or alkynylene group an internal alkylene carbon atom in the carbon backbone thereof can be replaced by an oxygen atom,R.sup.3 and R.sup.4(i) independently denote(a) hydrogen,(b) a methyl, ethyl, vinyl or unbranched or branched C.sub.3-16 alkyl, alkenyl or alkynyl group which is unsubstituted or substituted with one or more halogen, hydroxyl or amine groups, wherein in said unbranched or branched C.sub.3-16 alkyl, alkenyl or alkynyl group an internal alkylene carbon atom in the carbon backbone thereof can be replaced by an oxygen atom,(c) a cycloalkyl, alkylcycloalkyl, alkenylcycloalkyl or alkynylcycloalkyl group having 15 to 16 carbon atoms which is unsubstituted or substituted with one or more halogen, hydroxyl or amine groups, or(d) an aryl, alkaryl, aralkyl, alkenylaryl, aralkenyl, alkynylaryl or aralkynyl group having 6 to 16 carbon atoms which is unsubstituted or substituted with one or more halogen, hydroxyl or amine groups, or(ii) jointly with the nitrogen atom form a cyclic or aromatic amine which is unsubstituted or substituted with one or more alkyl, alkenyl, alkynyl, halogen, hydroxyl or amine groups,X denotes O, S, --NH-- or -NR.sup.5--, andR.sup.5 denotes methyl, ethyl, or unbranched or branched C.sub.3-16 alkyl,or a pharmaceutically acceptable salt thereof, wherein the compound is in equilibrium at physiological pH with a protonated form thereof.Methods of making the
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compounds, compositions including the compounds and methods of treatment of conditions involving reactive oxygen species are also provided. Excerpt(s): The present invention relates to analogs of lipoic acid, in particular lipoic acid analogs that are positively charged. Throughout the evolution of life on Earth, the level of oxygen in the atmosphere increased. As a result, aerobic organisms had to develop efficient defense mechanisms in order to cope with increasing oxidative stress. The toxicity of oxygen is known to be due to the formation of reactive oxygen species (ROS) during the normal metabolism of a living organism. ROS include oxygen-derived free radicals and non-radical derivatives that are capable of inciting oxidative damage to biological structures. ROS have also been shown to be involved in more than one hundred different pathological syndromes and in the aging process. There are several lines of defense against oxidative stress, including (i) macromolecules, such as enzymes, that can interact with ROS directly and remove them, or chelate metals and prevent the augmentation of oxidative damage; (ii) low molecular weight antioxidants that can interact directly with ROS, including both synthetic antioxidants and antioxidants from natural sources; and (iii) damage repair mechanisms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Lipoic acid derivatives and their use in treatment of disease Inventor(s): Bingham, Paul M.; (Centereach, NY), Zachar, Zuzana; (Centereach, NY) Correspondence: Ann R. Pokalsky, ESQ.; Nixon Peabody Llp; 990 Stewart Avenue; Garden City; NY; 11530-4838; US Patent Application Number: 20020107234 Date filed: September 24, 2001 Abstract: This invention relates to the identification of a novel class of therapeutic agents which selectively target and kill tumor cells and certain other types of diseased cells, and to compositions comprising lipoic acid derivatives which poison the pyruvate dehydrogenase complex specifically in such cells. This invention also provides for methods of using therapeutically effective amounts of the lipoic acid derivatives for the treatment of cancer and other diseases. The lipoic acid derivatives described herein have a wide range of preventive and therapeutic applications. Excerpt(s): This application claims priority to provisional patent application U.S. Ser. No. 60/105,628 filed Oct. 26, 1998. The present invention relates to therapeutics and diagnostics for cancer and other diseases associated with altered metabolic enzymes. In particular, the invention relates to a novel class of therapeutic agents which selectively target and kill tumor cells, and certain other types of cells involved in disease processes. All mammalian cells require energy to live and grow. Cells obtain this energy by metabolizing food molecules. The vast majority of normal cells utilize a single metabolic pathway to metabolize their food. The first step in this metabolic pathway is the partial degradation of glucose molecules to pyruvate in a process known as glycolysis or glycolytic cycle. The pyruvate is further degraded in the mitochondrion by a process known as the tricarboxylic acid (TCA) cycle to water and carbon dioxide, which is then eliminated. The critical link between these two processes is a large multi-subunit enzyme complex known as the pyruvate dehydrogenase ("PDH") complex (hereinafter "PDC"). PDC functions as a catalyst which funnels the pyruvate from the glycolytic cycle to the TCA cycle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Liver function improvement formulation Inventor(s): Smith, Leonard O.; (Gainesville, FL), Watson, Brenda F.; (Dunedin, FL) Correspondence: Macmillan Sobanski & Todd, Llc; One Maritime Plaza Fourth Floor; 720 Water Street; Toledo; OH; 43604-1619; US Patent Application Number: 20030044512 Date filed: August 30, 2002 Abstract: A food supplement formulation effective to improve the function of the liver comprises selenium, milk thistle seed, phosphatidyl choline, dandelion root, lmethionine, l-taurine, N-acetyl-cysteine, alpha lipoic acid, artichoke leaf, green tea leaf, turmeric root, belleric myrobalan fruit, boerhavia diffusa, eclipta alba, waldelactones, tinospora cordifolia, andrographis paniculata, and picrorhiza kurroa. Excerpt(s): This application claims the benefit of U.S. provisional patent application Serial No. 60/316,542, filed Aug. 31, 2001. The present invention relates generally to a liver function improvement formulation. More particularly, the invention is directed to a two-part organic food supplement formulation that improves the function of the human liver, by supporting the body's process for cleansing and detoxifying the liver. The liver is the largest human internal organ. It performs a number of functions, including detoxifying the body. The liver cleanses the body by filtering, or changing the compositions of toxins so that they can be removed from the blood stream, generally at a processing rate of about one liter of blood each minute. Endotoxins, exotoxins, and other wastes are directed to the kidneys or colon. A number of toxins, however, are made up of compounds that are difficult for the liver to filter and remove from the blood stream. These toxins are broken down by various enzymes so that they too may be removed from the body. Accordingly, a properly-functioning liver plays a critical role in determining a person's overall health. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for the enantioselective reduction of 8-chloro-6-oxo-octanoic acid alkyl esters Inventor(s): Gewald, Rainer; (Dresden, DE), Olbrich, Matthias; (Reichenberg, DE) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030180896 Date filed: January 27, 2003 Abstract: The invention relates to a process for the production of (R)- or (S)-8-chloro-6hydroxyoctanoic acid alkyl esters of the general formula (R)-II or (S)-II, 1in which R means C.sub.1-4 alkyl, from 8-chloro-6-oxo-octanoic acid alkyl esters of the general formula I, 2in which R has the above meaning.The desired enantiomers are produced biocatalytically in an enantioselective reduction, wherein as desired the strains Mucor racemosus are used for (S)-II compounds and Geotrichum candidum for (R)-II compounds.The resultant esters may, in known manner, be converted stereospecifically into (R)-.alpha.-lipoic acid. Excerpt(s): The present invention relates to a novel biocatalytic process for the enantiose-lective reduction of prochiral 8-chloro-6-oxo-octanoic acid alkyl esters of the
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formula I as desired with the assistance of the strains Mucor racemosus or Geotrichum candidum to yield respectively the corresponding (S)- or (R)-enantiomer of the reaction products. Once the chiral centre has been formed, the further stereospecific conversion into R-.alpha.-lipoic acid may proceed in known manner (DE 195 33 881). As a racemate,.alpha.-lipoic acid is primarily used for treating diabetic neuropathy and acute and chronic liver disease. Since it is only the natural (R)-(+)-enantiomer which exhibits biological activity, asymmetric synthesis of this pure natural substance is of great importance. The compounds I are known and serve as intermediates for the large scale industrial production of racemic thioctic acid (M. W. Bullock et al., J. Am. Chem. Soc. 1954, 76, 1828). The literature describes not only chemical synthesis processes but also processes comprising biocatalytic sub-stages for the production of enantiomerically pure (R)-.alpha.-lipoic acid (review article: J. S. Yadav et al., J. Sci. Ind. Res. 1990, 49, 400). Chemical, asymmetric synthesis processes generally require costly and complicated starting compounds since, for example, the possibility of using enantioselective chemocatalysis is associated with specific electronic and steric structural features. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of skin care and/or treatment using lipoic acid Inventor(s): Perricone, Nicholas V.; (Guilford, CT) Correspondence: ST. Onge Steward Johnston & Reens, Llc; 986 Bedford Street; Stamford; CT; 06905-5619; US Patent Application Number: 20020012642 Date filed: September 24, 2001 Abstract: Methods for the prevention of sun burn and other skin damage, and treatment of sunburn and other skin damage, arising from exposure to ultraviolet or solar radiation, using lipoic acid and/or a lipoic acid derivative in a dermatologically acceptable carrier that can be topically applied to the skin areas. A fat-soluble fatty acid ester of ascorbic acid such as palmityl ascorbate and/or tocotrienol and/or an.alpha.hydroxy acid such as glycolic acid is applied with the lipoic acid and/or its derivatives in some embodiments. Excerpt(s): This is a continuation-in-part of co-pending U.S. application Ser. No. 09/272,505, filed Mar. 19, 2001, which is a continuation-in-part of U.S. application Ser. No. 08/988,117, filed Dec. 10, 1997, now abandoned, which was a continuation application of U.S. application Ser. No. 08/531,290, filed Sep. 20, 1995, which issued as U.S. Pat. No. 5,709,868 on Jan. 20, 1998. This invention relates to the topical application of compositions containing lipoic acid for the prevention and/or treatment of damage to skin, particularly for the prevention and treatment of sunburn and other sun damage. Lipoic acid was originally identified as a bacterial growth factor present in the watersoluble fraction of liver and yeast. It was found to be necessary for the oxidative decarboxylation of pyruvic acid by Streptococcus fecalis and for the growth of Tetrahymena gelii, and replaced acetate for the growth of Lactobacillus casei. It has been variously known as acetate replacing factor, protogen A, and pyruvate oxidation factor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of treating age-related vision impairment Inventor(s): Hamilton, Nathan D.; (Palo Alto, CA) Correspondence: Skinner, Sutton, Watson & Rounds; 548 California Street; Reno; NV; 89509; US Patent Application Number: 20020077349 Date filed: April 27, 2001 Abstract: Disclosed herein are methods to treat age-related vision losses. The method comprises administering a combination of a carnitine and an oxidant. Preferably the oxidant is thioctic acid. Preferably 0.12 grams to 3 grams of carnitine (particularly ALC) and 0.12 and 1.5 grams of R-.alpha.-lipoic acid are administered. Optionally, coenzyme Q and/or creatine also are administered. Preferably 10 mg to 500 mg/day of coenzyme Q10 and 1 to 30 grams/day of creatine are administered. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/706,207, now pending, which claims the benefit of U.S. Provisional Application No. 60/223,167, filed Aug. 7, 2000, and U.S. Provisional Application No. 60/163,352, filed Nov. 3, 1999. This invention is related to the prevention and amelioration of vision impairment due to aging and other causes. More specifically, this invention is related to the administration of micronutrients, such as an antioxidant, a carnitine product, and optionally coenzyme Q and/or creatine to those at risk of age-related vision loss. With age prominent changes occur in the brain and include a decrease in brain weight, gyral atrophy, ventricular dilation, and selective loss of neurons within different brain regions (Kemper, Neuroanatomical and neuropathological changes during aging and dementia. In: Martin A L, Knoefel J E (eds). GERIATRIC NEUROLOGY (2nd ed). Oxford University Press, New York City, pp. 3-67, 1994). The relevance of these changes to behavioral measurements is still largely ambiguous (e.g., Lezak, NEUROPSYCHOLOGICAL ASSESSMENT (3rd ed). Oxford University Press, New York, 1995). In addition to biological changes, environmental contexts are reflected in age-related cognitive changes (Arbuckle et al., Psychol Aging 7: 25-36, 1992). Recent studies with advanced brain imaging methods (especially PET and functional MRI) have elucidated the neuroanatomical localization of cognitive functions (e.g., Frackowiak, Trends Neurosci 17: 109-115, 1994; Moscovitch et al., Proc Natl Acad Sci USA 92: 37213725, 1995; Schacter et al., Proc Natl Acad Sci USA 93: 321-325, 1996). So far, very few of these studies have considered the effects of aging (Eustache et al., Neuropsychologia 33: 867-887, 1995; Grady et al., Science 269: 218-221, 1995). However, some associations between age-related cerebral and cognitive changes have been suggested. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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METHOD OF TREATING, PREVENTING OR INHIBITING CENTRAL NERVOUS SYSTEM INJURIES AND DISEASES Inventor(s): Koenig, Michael L.; (Silver Spring, MD), Meyerhoff, James L.; (Silver Spring, MD), Yourick, Debra L.; (Linthicum Heights, MD) Correspondence: Office OF The Staff Judge Advocate; U.S. Army Medical Research And Materiel Command; Attn: Mcmr-ja (MS. Elizabeth Arwine); 504 Scott Street; Fort Detrick; MD; 21702-5012; US Patent Application Number: 20020177558 Date filed: April 20, 2001
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Abstract: Methods of preventing, treating, or both preventing and treating CNS injury, disease, neurotoxicity or memory deficit in a subject by the administration of at least one lipoic acid compound to the subject are disclosed. Examples of CNS injuries or disease include traumatic brain injury (TBI), posttraumatic epilepsy (PTE), stroke, cerebral ischemia, neurodegenerative diseases of the brain such as Parkinson's disease, Dementia Pugilistica, Huntington's disease and Alzheimer's disease, brain injuries secondary to seizures which are induced by radiation, exposure to ionizing or iron plasma, nerve agents, cyanide, toxic concentrations of oxygen, neurotoxicity due to CNS malaria or treatment with anti-malaria agents, and other CNS traumas. Examples of lipoic acid compounds include alpha-lipoic acid (ALA), dihydrolipoic acid (DHLA), 2-(N,Ndimethylamine) ethylamido lipoate-HCL (LA-plus), the oxidized or reduced R- or Sisomers thereof, the metabolites of alpha-lipoic acid such as 6,8-bisnorlipoic acid and tetranorlipoic acid and analogs thereof. Also disclosed are pharmaceutical compositions and kits comprising at least one lipoic acid compound. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/198,958, filed Apr. 21, 2000, naming James L. Meyerhoff, Debra L. Yourick and Michael L. Koenig as inventors, which is herein incorporated by reference. 1. Field of the Invention. The invention relates to a method of treating, preventing or inhibiting central nervous system (CNS) injuries and diseases. In particular, the invention relates to a method of treating, preventing or inhibiting a CNS injury or disease in a subject by the administration of at least one lipoic acid compound to the subject. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and compositions for the improvement of insulin sensitivity, reduction of hyperglycemia, and reduction of hypercholesterolemia with chromium complexes and alpha lipoic acid Inventor(s): Greenberg, Danielle; (Waccabuc, NY), Komorowski, James R.; (Trumbull, CT) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020098247 Date filed: October 31, 2001 Abstract: A composition for improving insulin sensitivity, reducing hyperglycemia, and reducing hypercholesterolemia, the composition including at least one chromium complex and alpha-lipoic acid is disclosed. A method of improving insulin sensitivity in a subject in need thereof including administering to a subject a pharmaceutically effective dose of alpha-lipoic acid in conjunction with at least one chromium complex selected from the group consisting of chromium picolinate, chromium nicotinate, chromic tripicolinate, chromic polynicotinate, chromium chloride, chromium histidinate, and chromium yeasts is also provided. Excerpt(s): This application claims priority to Provisional Application No. 60/245,705 entitled METHODS AND COMPOSITIONS FOR THE IMPROVEMENT OF INSULIN SENSITIVITY, REDUCTION OF HYPERGLYCEMIA, AND REDUCTION OF HYPERCHOLESTEROLEMIA filed on Nov. 2, 2000. The subject matter of the aforementioned application is hereby incorporated by reference. The disclosed invention relates to compositions and methods for the improvement of insulin sensitivity, reduction of hyperglycemia, and reduction of hypercholesterolemia. Specifically,
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compositions comprising chromium complexes in combination with alpha-lipoic acid are provided. Diabetes mellitus is a chronic disorder characterized by impaired metabolism of glucose and other energy-yielding fuels, and the late development of vascular and neuropathic complications. In this group of disorders with distinct pathogenic mechanisms, hyperglycemia is the common denominator. Independent of the cause, the disease is associated with insulin deficiency, which may be total, partial, or relative when viewed in the context of coexisting insulin resistance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and compounds useful in inhibiting oxidative and/or free radical damage and in the treatment and prevention of disease Inventor(s): Hass, Martha A.; (Wynantskill, NY), Levin, Robert M.; (Albany, NY) Correspondence: Peter Rogalskyj, ESQ.; Braman & Rogalskyj, Llp; P.O. Box 352; Canandaigua; NY; 14424-0352; US Patent Application Number: 20030187059 Date filed: February 24, 2003 Abstract: Disclosed are methods for treating obstructive and ischemic bladder diseases which include administering a compound which includes a cyclic or acyclic disulfide covalently bonded to a lipid-soluble antioxidant or which include administering a reduced sulfhydryl derivative thereof. Also disclosed are compounds that include a benzopyran moiety which is directly or indirectly covalently bonded to a cyclic or acyclic disulfide, as well as reduced sulfhydryl derivatives of such compounds. Methods for making such compounds and reduced sulfhydryl derivatives using tocopherol and lipoic acid starting materials are also disclosed, as are methods for inhibiting oxidative and/or free radical damage in a subject's cells, nerve membranes, sarcoplasmic reticula, mitochondrial membranes, and/or muscle plasma membranes and methods for treating and/or preventing obstructive and ischemic bladder diseases, conditions involving hypoxia, ischemia, and/or reoxygenation injury. Excerpt(s): The present application claims the benefit of U.S. Provisional Patent Application Serial No. 60/359,080, filed Feb. 22, 2002, and U.S. Provisional Patent Application Serial No. 60/387,943, filed Jun. 12, 2002, each of which provisional patent applications is hereby incorporated by reference. The present invention relates, in part, to methods and compounds that are useful in inhibiting oxidative and/or free radical damage and in the treatment and prevention of disease, particularly, obstructive and ischemic bladder diseases and other diseases involving ischemia, hypoxia, and reoxygenation injury. Bladder dysfunction secondary to benign prostatic hyperplasia ("BPH") is a major affliction associated with human aging (Girman et al., "Epidemiology of Benign Prostatic Hyperplasia," pp. 116-126 in Lepor, ed., Prostatic Disease, Philadelphia, Pa.: W. B. Saunders Co. (2000); Barry et al., "The Natural History of Benign Prostatic Hyperplasia," pp. 106-115 in Lepor, ed., Prostatic Disease, Philadelphia, Pa.: W. B. Saunders Co. (2000); and Boyle et al., "Epidemiology and Natural History," pp 19-68 in Chatelain et al., Benign Prostatic Hyperplasia (5th International Consultation on Benign Prostatic Hyperplasia), Plymouth, U.K.: Plymbridge Distributors, Ltd. (2001)). It is clear that bladder dysfunction secondary to BPH is a slow progressive disease. In many cases, medical treatment is not sought until the dysfunction is relatively severe. This is primarily a function of the insidious nature of the disease. It is well known that bladder function can remain relatively "normal" for many years during the progression of BPH. This is because the bladder can compensate for the progressive increase in
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urethral resistance (mediated by prostate growth) by bladder hypertrophy (an increase in bladder wall thickness and mass). During this compensated period of functioning, there are changes in micturition pressure and flow characteristics, these changes are not severe and, therefore, do not require medical attention. It is not until the patient shifts to decompensated function that severe alterations occur, and the patient seeks medical attention. These clinical changes leave the patient susceptible to subsequent renal injury and frequent urinary infections in addition to the considerable discomfort experienced prior to and during urination. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multiple antioxidant micronutrients Inventor(s): Haase, Gerald M.; (Greenwood Village, CO), Prasad, Kedar N.; (Denver, CO) Correspondence: Ostrolenk, Faber, Gerb & Soffen, Llp; 1180 Avenue OF The Americas; New York; NY; 10036-8403; US Patent Application Number: 20030147996 Date filed: August 28, 2002 Abstract: A method for optimizing the health of humans according to their age and sex is disclosed wherein the method comprises administering to said humans a daily dose of a multiple antioxidant micronutrient composition comprising vitamin A (palmitate), beta-carotene (from natural d. salina), vitamin C (calcium ascorbate), vitamin D-3 (cholecalciferol), natural source vitamin E including both d-alpha tocopherol and dalpha tocopheryl acid succinate, thiamine mononitrate, riboflavin, niacinamide ascorbate, d-calcium pantothenate, pyridoxine hydrochloride, cyanocobalamin, folic acid (folacin), d-biotin, selenium (l-seleno methionine), chromium picolinate, zinc glycinate, calcium citrate, and magnesium citrate.For persons over the age of about 51, the composition preferably further comprises one or more of co-enzyme Q.sub.10, Nacetyl cysteine, and alpha lipoic acid. Preferably, also, vitamin D is added for women over the age of about 36. Excerpt(s): We claim the benefit under Title 35, United States Code,.sctn.120 of U.S. Provisional Application No. 60/315,523, filed Aug. 29, 2001, entitled MULTIPLE ANTIOXIDANT MICRONUTRIENTS FOR OPTIMAL HEALTH. In the beginning, the earth's atmosphere had no oxygen. Anaerobic organisms, which can live without oxygen, were thriving. About 2.5 billion years ago, blue-green algae in the ocean acquired the ability to split water into hydrogen and oxygen and this chemical reaction initiated the release of oxygen into the atmosphere. The increased levels of atmospheric oxygen caused extinction of many anaerobic organisms owing to oxygen's toxicity. This important biological event also led to the evolution of multicellular organisms, including humans, who utilize oxygen for survival. The content of oxygen in the air gradually increased to the current amounts of about 21 percent in dry air and about 34 percent in water. The use of oxygen by any organism generates free radicals that are toxic. Therefore, during this period of atmospheric oxygenation, organisms must have struggled to survive the sudden exposure to oxygen toxicity. There must have been enormous rearranging of nucleotides in genes to produce specific proteins that could protect organisms against the damage produced by free radicals. This process eventually led to the production of three antioxidant enzymes. Superoxide dismutase (SOD) requires manganese, copper, or zinc for its biological activity. Mn-SOD is present in mitochondria, whereas Cu-SOD and Zn-SOD are present in the cytoplasm and
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nucleus of the cell. All three can destroy free radicals and hydrogen peroxide. Another enzyme, catalase, requires iron for its biological activity and it destroys H.sub.2O.sub.2 in cells. Human tissue also contains glutathione peroxidase which requires selenium for its biological activity. It is also responsible for removing hydrogen peroxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel antioxidants Inventor(s): Avery, Mitchell Allen; (Oxford, MS), Pershadsingh, Harrihar A.; (Bakersfield, CA) Correspondence: Harrihar A. Pershadsingh; 404 Windsor Park Drive; Bakersfield; CA; 93311; US Patent Application Number: 20020048798 Date filed: March 14, 2001 Abstract: This invention comprises administering to a human or animal in need of treatment an effective amount of an antioxidant lipoic acid derivative and/or pharmaceutically acceptable salts and solvates thereof for the treatment or prevention of pathological (inflammatory, proliferative and degenerative diseases, e.g. diabetes mellitus, atherosclerosis, Alzheimer's disease and chronic viral diseases) and nonpathological (e.g. skin aging and wrinkle formation) conditions caused by oxidative damage. Methods of synthesizing novel antioxidant lipoic acid derivatives and their use in preventing or treating diseases or conditions caused by oxidative stress and other free radical mediated conditions are described. Another aspect of this invention is the use of these antioxidant compositions for the protection of skin from damage caused by ultraviolet radiation and dessication, and to provide improved skin feel by desquamating, cleansing and clarifying the skin. The compositions described in this invention increase cellular viability of epidermal cells, promote cytoprotection, and decrease the production of inflammatory mediators such as inflammatory cytokines in these cells. The antioxidant compositions are incorporated into sunscreen products, soap, moisturizing lotions, skin toners, and other skin care products. Excerpt(s): U.S. Provisional Application No. 60/189514 was filed for this invention on Mar. 15, 2000 for which the inventors claim domestic priority.alpha.-lipoic acid (thioctic acid, 1,2-dithiacyclopentane-3-valeri- c acid, 1,2-dithiolane-3-pentanoic acid) is widely distributed in plants and animals in the form of the R-enantiomer; it acts as coenzyme in many enzymatic reactions, constitutes a growth factor for a number of bacteria and protozoa and is used in death-head fungus poisoning. Lipoic acid (1,2-dithiolane-3pentanoic acid) is a naturally occurring compound. It is a component of mitochondrial multienzyme complexes which dehydrogenates.alpha.-keto acids (e.g. pyruvate). In pathological conditions, lipoic acid is applied in the treatment of diabetic polyneuropathy, liver cirrhosis and metal intoxications. Particularly in diabetic polyneuropathy, the antioxidant activity of lipoic acid is considered to contribute to its therapeutic effect. One aspect of this invention relates to the uses of optical isomers of the novel lipoic acid-related thiazolidinedione and phenyl acetic acid derivatives of the instant invention. In the case of the purely optical isomers of.alpha.-lipoic acid (R- and Sform, i.e. R-.alpha.-lipoic acid and S-.alpha.-lipoic acid), unlike the racemate (Biewenga et al. "An overview of lipoate chemistry." In: Lipoic Acid in Health and Disease. (Fuchs J, Packer L, Zimmer G, eds.), Marcel Dekker, Inc. 1997, pp 1-32), the R-enantiomer mainly has an anti-inflammatory activity, for example, being stronger by a factor of 10 than that of the racemate (Ulrich et al. U.S. Pat. No. 5,728,735 Mar. 17, 1998), and has
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been shown to have superior insulin-sensitizing activity and to confer improved cardiac function (Zimmer G et al. J Mol Cell Cardiol. 27:1895-903 (1995)) and ameliorate diabetic peripheral and autonomic neuropathy (Ziegler D, Gries F A. Diabetes. 46 Suppl 2:S62-6 (1997)). In contrast, the S-enantiomer has been shown to be more effective as an antinociceptive agent. The anti-nociceptive (analgesic) activity of the S-enantiomer is for example stronger by a factor of 5 to 6 than that of the racemate (Ulrich et al. U.S. Pat. No. 5,728,735 Mar. 17, 1998). Accordingly, the R- and S-enantiomers of the novel lipoic acidrelated thiazolidinedione and phenyl acetic acid derivatives are considered to have superior efficacy in the treatment of specific diseases. For example, a particular stereoisomer, e.g. R-(+)-.alpha.-lipoic stereoisomeric thiazolidinedione derivative is expected to have superior anti-inflammatory activity whereas the corresponding optical isomers are expected to provide greater efficacy in the treatment of other diseases. In addition, the.alpha.-lipoic acid racemate and R and S isomeric forms display antiinflammatory, anti-nociceptive (analgesic) and cytoprotective properties. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel lipoic acid heterocyclic or benzene derivatives, preparation and use thereof as medicines Inventor(s): Auguet, Michel; (Palaiseau, FR), Harnett, Jeremiah; (Gif-Sur-Yvette, FR) Correspondence: Bierman Muserlian & Lucas; 600 Third Avenue; New York; NY; 10016; US Patent Application Number: 20030105107 Date filed: September 10, 2002 Abstract: A subject of the invention is new heterocyclic or benzenic derivatives comprising a lateral chain derived from lipoic acid, which have an inhibitory activity on NO-synthase enzymes producing nitrogen monoxide NO and/or are agents allowing the regeneration of antioxidants or entities trapping the reactive oxygen species (ROS) and which intervene in a more general manner in the redox status of thiol groups. A subject of the invention is also their preparation methods, the pharmaceutical preparations containing them and their use for therapeutic purposes, in particular their use as inhibitors of NO-synthases and/or as agents which intervene in a more general manner in the redox status of thiol groups. Excerpt(s): A subject of the present invention is new heterocyclic or benzenic derivatives comprising a lateral chain derived from lipoic acid, which have an inhibitory activity on NO-synthase enzymes producing nitrogen monoxide NO and/or are agents which allow the regeneration of antioxidants or entities which trap the reactive oxygen species (ROS) and which intervene in a more general fashion in the redox status of thiol groups. These antioxidants or entities which trap the reactive oxygen species can be of natural origin, such as for example vitamin E or glutathione, or of synthetic origin such as certain products which trap the ROS or products having both an inhibitory activity on NO-synthase enzymes and an activity which traps the ROS. Examples of such products of synthetic origin can in particular be found in the PCT Patent Applications WO 96/09653, WO 98/42696 and WO 98/58934. Therefore, the invention relates in particular to the derivatives corresponding to general formula (I) defined below, their preparation processes, the pharmaceutical preparations containing them and their use for therapeutic purposes, in particular their use as NO-synthase inhibitors and/or as agents which allow the regeneration of antioxidants or entities which trap the ROS's and which intervene in a more general fashion in the redox status of thiol groups. cardiovascular
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and cerebrovascular disorders including for example atherosclerosis, migraine, arterial hypertension, septic shock, ischemic or hemorragic cardiac or cerebral infarctions, ischemias and thromboses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
NUTRACEUTICAL COMPOSITION Inventor(s): Cartwright, Rudolph; (Odessa, TX), Hendricks, Leo Edward; (Washington, DC) Correspondence: Kenyon & Kenyon; One Broadway; New York; NY; 10004; US Patent Application Number: 20030091552 Date filed: November 13, 2001 Abstract: Provided is a nutraceutical composition including a tripeptoid component, a flavonoid component, guanidine hydrochloride,.alpha.-lipoic acid, an amino acid component, a brazilin component, catalase, and, optionally, vitamin E ans selenium. The composition is effective to maintain normal blood sugar levels and normal levels of nonenzymatic protein glycosylation in a human. Excerpt(s): The present invention relates to a nutraceutical composition and a method for maintaining normal levels of blood sugar and normal levels of non-enzymatic protein glycosylation. U.S. Pat. No. 5,156,852 teaches that a composition containing both selenium and vitamin E is useful in treating macular degeneration. U.S. Pat. No. 5,405,613 teaches vitamin and mineral compositions that include bioflavonoids for restoring energetic balance or intensity. Administration of glutathione in combination with vitamin E and selenium has been taught to reduce hematological toxicities in patients undergoing radiation therapy. See U.S. Pat. No. 5,639,482. U.S. Pat. No. 5,976,568 teaches that the bioflavonoid quercetin can inhibit the enzyme cyclooxygenase and U.S. Pat. No. 6,190,678 teaches a personal care product (skin cleaner) containing, inter alia, brazilin, rutin, glutathione, and.alpha.-lipoic acid. Vitamin E and.alpha.-lipoic acid are taught as components of a multicomponent supplement, that also includes aspirin and magnesium salts, for the treatment and control of diabetes. See U.S. Pat. No. 5,976,568. Applicant is the first to recognize that a bioflavonoid such as quercetin or rutin can be combined with brazilin,.alpha.-lipoic acid, and other substances to produce a composition that, when administered to a mammal, is effective to promote normal levels of non-enzymatic protein glycosylation in that mammal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nutritional supplements for aged pets Inventor(s): Hamilton, Nathan D.; (San Francisco, CA) Correspondence: Barbara J. Luther, Chartered; 18124 Wedge Parkway, #516; Reno; NV; 89511; US Patent Application Number: 20010043983 Date filed: January 25, 2001 Abstract: Disclosed herein are compositions to meet the needs of aged pets and other animals. Pet foods, pet treats and pet supplements with anti-aging effects are disclosed whose compositions include the R-.alpha.-lipoic acid in the amount of 0.10 grams to 1.5
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grams and L-carnitine in the amount of 0.10 grams to 3 grams in addition to the usual composition. Optionally, coenzyme Q can be added in an amount of at least 1 mg/day. Optionally, creatine can be added in an amount of at least 0.2 grams/day. These additional components fight age-related declines in mitochondrial function, which result in less energy and other signs of aging. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/178,073, filed Jan. 25, 2000, and U.S. Provisional Application No. 60/223,586, filed Aug. 7, 2000. The present invention is generally directed to pet food and dietary supplements. More specifically, the present invention relates to the addition of the combination of lipoic acid and carnitine to these compositions. Optional additional ingredients are coenzyme Q and creatine. Many pet foods contain nutrition for a specific stage of the pet's life. Stages of a pet's life are broken down as follows: kitten or puppy is up to 1 year, adult cat or dog is one to six years, and a senior cat or dog is over six years old. However, different animals age at different rates. Cats are often considered older or senior, at seven to eight years of age and geriatric or very old at 10 to 12 years. Dogs often are considered older between 7.5 and 13.5 years of age. Dogs often are considered older when they reach half of their life expectancy, which corresponds to about five years for larger dogs and seven years for smaller dogs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
PERFORMANCE-ENHANCING DIETARY SUPPLEMENT Inventor(s): BARNES, DAVID J; (WILDWOOD, MO), DALEY, CHRISTINE A; (COLUMBIA, IL), HASTINGS, CARL W; (GLENCOE, MO) Correspondence: Marshall, O'toole, Gerstein, Murray & Borun; 600 Sears Tower, 233 Wacker Drive; Chicago; IL; 60606-6402; US Patent Application Number: 20010041187 Date filed: October 20, 1998 Abstract: A dietary supplement for enhancing physical performance of human subjects is disclosed. The supplement in dry, finely-divided form includes as a major ingredient a soy protein isolate containing at least 80% protein on a moisture-free basis with lesser amounts of carbohydrate, free form amino acids, medium chain triglycerides, creatine monohydrate, l-carnitine, grape seed extract, coenzyme Q10, piper nigrum extract, and alpha lipoic acid. In a preferred embodiment, the supplement also includes minor amounts of conjugated linoleic acid and phosphatidylserine/phosphatidylcholine complex. Excerpt(s): Soy protein is known to be the only plant protein equal in quality to protein derived from milk, meat or eggs. The most concentrated source of soy protein is soy protein isolate which, preferably, is manufactured by water extraction (rather than alcohol extraction) of defatted and dehulled soybeans and therefore retains its natural isoflavones. On a Protein Digestability Corrected Amino Acid Score (PDCAAS) of 1.0, soy protein isolate is highly digestible and meets or exceeds the essential amino acid requirements for children and adults. Such an isolate contains naturally high levels of branched chain amino acids to provide an energy source during physical activity, it having been reported that during the first 20 minutes of strenuous sports activity muscle glycogen serves as the primary energy source but that after 20 minutes bioavailable fatty acids and branched chain amino acids become the primary energy sources. Isolated soy protein is therefore known to be a highly desirable energy source for athletes that also
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helps to reduce muscle fatigue and enhance muscle recovery. In addition, isolated soy protein is known to contain naturally high levels of arginine which stimulates the release of anabolic hormones to promote muscle formation, enhances wound healing, helps to maintain a strong and healthy immune system, and is believed to be beneficial in reducing stress. Such isolated soy protein is also a good source of naturally occurring iron, a fact of considerable importance for athletes who are highly susceptible to "sports anemia" resulting from loss of iron occurring in sweat and urine. There is compelling evidence from both animal and human studies that, compared to animal protein, soy protein also reduces elevated levels of LDL-cholestrol. A meta-analysis of 38 clinical studies reported in 29 scientific articles has provided quantitative data showing that consumption of soy protein rather than animal protein significantly decreases blood concentrations of total cholestrol, LDLcholestrol, and triglycerides in humans. Anderson J. W., Johnstone B. M. and Cook-Newell M. E., NEJM 1995; 333:276-282. Such studies provide motivation for recommending the increased consumption of soy protein, particularly isolated soy protein, as part of an integrated dietary approach to the control of hypercholesterolemia. It is therefore believed that the intake of protein isolates may be advantageous to athletes and others concerned about the risk of developing coronary heart disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmacological inducement of the fed mode for enhanced drug administration to the stomach Inventor(s): Berner, Bret; (El Granada, CA), Markey, Micheline; (Santa Cruz, CA), Shell, John W.; (Hillsborough, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030044466 Date filed: September 4, 2002 Abstract: Drugs intended for absorption in the stomach or upper intestinal tract are administered in oral drug delivery systems in conjunction with any of various substances that have been discovered to function as potent agents for inducing the fed mode. By inducing the onset of the fed mode, these agents cause the stomach to prolong its retention of the drug delivery system, which is either large enough to be retained in the stomach during the fed mode or swells or expands to such a size upon ingestion. The fed mode inducing agents include the following compounds and their salts: glycine and glycylglycine, xylitol and related sugar alcohols, sodium and other metal docusates,.beta.-casomorphins,.alpha.-lipoic acid and similarly structured acids, 2,2diaryl-4-(4'-aryl-4'-hydroxypipendino)butyramides, arginine, Trp-Trp, alkylpyridinium halides, dihydroxybenzoic acids, and potent sweeteners such as aspartame, aspartic acid, acesulfame, and stevioside. Excerpt(s): This invention is in the general field of pharmacology, and relates in particular to oral dosage formulations that deliver drugs by controlled release in the stomach for a prolonged period of time. Many drugs have their greatest therapeutic effect when released in the stomach, particularly when the release is prolonged in a continuous, controlled manner. Drugs delivered in this manner cause less side effects and provide their therapeutic effects without the need for repeated dosages, or with a low dosage frequency. Localization of the drug delivery in the stomach is an advantage for the treatment of local disorders of the stomach such as esophageal reflux disease, for
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the eradication of ulcer-causing bacteria in the gastric mucosa, and for the treatment of disorders that require sustained antacid action. Sustained release in the stomach is also useful for therapeutic agents that the stomach does not readily absorb, since sustained release prolongs the contact time of the agent in the stomach or in the upper part of the small intestine, which is where absorption occurs and contact time is limited. Under normal or average conditions, for example, material passes through the small intestine in as little as 1 to 3 hours. For drugs that are absorbed almost exclusively in the small intestine, such as captopril and the cephalosporins, this short contact time limits the bioavailability of these drugs, particularly when the drugs are administered in a controlled-release dosage form. The passage of matter through the stomach can be delayed in the normal digestive process by the physiological condition that is variously referred to as the digestive mode, the postprandial mode, or the "fed mode" (the latter term is used in the remainder of this specification for convenience). When the stomach is not in this mode, it is in the interdigestive or "fasting" mode. The difference between the two modes lies in the pattern of gastroduodenal motor activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Preparation of dihydroxycarboxylic esters in the absence of solvents Inventor(s): Erhardt, Melanie; (Lambsheim, DE), Klatt, Martin Jochen; (Bad Durkheim, DE), Niebel, Markus; (Mannheim, DE) Correspondence: Herbert B. Keil; Keil & Weinkauf; 1350 Connecticut AVE., N.W.; Washington; DC; 20036; US Patent Application Number: 20030109720 Date filed: December 2, 2002 Abstract: A description is given of a process for preparing dihydroxycarboxylic esters and of an overall process for preparing R-(+)-.alpha.-lipoic acid. Excerpt(s): The present invention relates to a process for preparing dihydroxycarboxylic esters and an overall process for preparing R-(+)-.alpha.-lipoic acid. Dihydroxycarboxylic esters are valuable intermediates and synthesis building blocks in organic chemistry. In particular, (6S)-6,8-dihydroxyoctanoic esters serve as intermediates for the synthesis of enantiomerically pure R-(+)-.alpha.-lipoic acid. EP 487 986 discloses preparing (6S)-6,8-dihydroxyoctanoic esters by reducing the corresponding (3S)-3-hydroxyoctanedioic diesters with complex hydrides in the presence of aprotic solvents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Process for the production of r(+) alpha-lipoic acid Inventor(s): Falabella, Giovanna; (Milano, IT), Nardi, Antonio; (Paderno Dugnano, IT), Salvi, Annibale; (Milano, IT), Villani, Flavio; (Parma, IT) Correspondence: Joseph M Noto; Nixon Peabody; Clinton Square; PO Box 31051; Rochester; NY; 14603-1051; US Patent Application Number: 20030187279 Date filed: April 9, 2003
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Abstract: Process for the synthesis of R(+).alpha.-lipoic acid comprising the following stages: a) Salifying of racemic thioctic acid with R(+).alpha.-methylbenzylamine; b) separation by filtration of the crystallized diastereoisomeric salt of R(+).alpha.-lipoic acid-R(+).alpha.-methylbenzylamine; c) purification by re-crystallization of the diastereoisomeric salt of R(+).alpha.-lipoic acid-R(+).alpha.-methylbenzylamine, in which the re-crystallization solvent consists of a mixture of non-polar/polar solvents; d) separation of the diastereoisomeric salt to obtain R(+).alpha.-lipoic acid by reaction of said salt with acids selected from the group consisting of aliphatic hydroxy-carboxylic acids having 3 to 6 carbon atoms and aqueous phosphoric acid. Excerpt(s): The present invention relates to a process of synthesis of R(+).alpha.-lipoic acid through the formation of diastereoisomeric salts of racemic thioctic acid with optic isomers of.alpha.-methylbenzylamine. It is well known from the state of the art about the process of resolution of racemic mixtures, or racemates, i.e. the splitting of a racemate into the enantiomers constituting it. The racemate is first transformed into a mixture of diastereoisomers by reaction with an optically active substance. The diastereoisomers thus obtained, characterized by different physical properties among which solubility, are generally separated by fractioned crystallization. The enantiomers of the starting racemic mixture are obtained from said separated diastereoisomers by simple chemical reactions of separation of said diastereoisomers. U.S. Pat. No. 5,281,722 describes diastereoisomeric salts obtained from pure enatiomers of.alpha.-lipoic acid by reaction with optic isomers of.alpha.-methylbenzylamine. The state of the art describes methods for the preparation of said diastereoisomeric salts and their use as intermediate products in the resolution of a racemic mixture of thioctic acid in both optically active enantiomeric forms R(+) and S(-) of.alpha.-lipoic acid. The process of resolution of racemic thioctic acid has a low yield, in particular for the separation of the R(+).alpha.lipoic enantiomer (see Examples 7 and 8 of U.S. Pat. No. 5,281,722). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of acne using alkanolamine compositions Inventor(s): Perricone, Nicholas V.; (Guilford, CT) Correspondence: Mary M. Krinsky, PH. D., J.D.; Patent Attorney; 79 Trumbull Street; New Haven; CT; 06511; US Patent Application Number: 20030021855 Date filed: February 27, 2002 Abstract: Acne is treated or prevented by the topical application of compositions containing an alkanolamine such as dimethylaminoethanol, tyrosine, and a sulfur ingredient such as lipoic acid or glutathione. Adjunct ingredients such as fatty acid esters of ascorbic acid, e.g., ascorbyl palmitate and.alpha.-hydroxy acids may be included in the formulations. Compositions of the invention may be used alone, or, in many preferable embodiments, in combination with conventional acne medications such as anti-acne products containing salicylic acid, benzoyl peroxide, or a retinoid. In these embodiments, alkanolamine compositions of the invention are applied to affected skin areas first, and then a conventional acne medication is applied. This maximizes the efficacy of the treatment while minimizing skin irritation caused by conventional medications. Excerpt(s): This is a continuation-in-part of co-pending U.S. patent application Ser. No. 09/900,680, filed Jul. 6, 2001. This invention relates to improved compositions and
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methods for the treatment and prevention of acne, and the promotion of clear skin. This invention relates primarily to methods and compositions for the treatment of acne vulgaris. Acne is the most common pustular condition of the skin, disfiguring afflicted persons with inflammatory and noninflammatory lesions (including pustules, papules and comedones) during the active phase, and with atrophic scars afterwards. It occurs most commonly in teenagers, but is not confined to adolescents, as increasing numbers of persons aged >20 years are seeking advice on treatment for acne (Brogden, R. N., and Goa, K. L., Drugs, 1997, 53: 511-519; this reference and others cited below are hereby incorporated herein in their entireties by reference). Although acne is generally considered to be self-limiting, its social effects can be substantial, and it may have its most severe effects on the psyche (ibid.). In about 60% of teenagers, disease severity and embarrassment are sufficient for them to self-medicate with proprietary preparations and/or seek medical advice. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of cancer using lipoic acid in combination with ascorbic acid Inventor(s): Casciari, Joseph J.; (Newton, KS), Riordan, Neil H.; (Wichita, KS) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20020037917 Date filed: September 18, 2001 Abstract: Lipoic acid and/or its water soluble salt is used to treat cancer, alone or in combination with ascorbic acid (vitamin C). Alone or in combination, it was shown to be effective on in vitro tumors and mouse tumors. The agents can be administered safely, and have been used effectively in case studies. Excerpt(s): This is a Continuation of U.S. application Ser. No. 09/359, 498, filed Jul. 23, 1999, which is a Divisional of U.S. application Ser. No. 09/249,872, filed Feb. 16, 1999. This invention relates generally to methods of cancer therapy and particularly the use lipoic acid as a therapeutic agent administered in combination with ascorbic acid. Ascorbate has been shown to be selectively toxic toward tumor cells, but at doses that are too high to be achieved clinically. Both lipoic acid and its water-soluble sodium salt enhance the efficacy of sodium ascorbate against three-dimensional in vitro tumors and in mouse tumors. These agents can be administered safely to patients, and in preliminary trials have been shown to stabilize or resolve disease. The most common methods currently in use for the treatment of cancer include surgery, radiation therapy, and chemotherapy. While these therapies are successful for some forms of the disease, they are far from universally successful in curing cancer. Moreover, traditional therapeutic regiments often cause adverse side effects such as nausea, vomiting, cardiac toxicity, bone marrow suppression, and secondary cancer. Vitamin C (ascorbic acid, ascorbate) has been proposed as an alternative to chemotherapy or as an adjuvant to lessen side effects associated with it. (For the purposes of this application, a reference to ascorbic acid includes the anionic component, ascorbate whether as an acid or one of the pharmaceutically acceptable salt thereof, most notably including sodium ascorbate and calcium ascorbate, any of which are included in a reference to "ascorbic acid" or "ascorbate"). Ascorbic acid has been thought by some to improve immune response and to prevent tumor spreading by strengthening extracellular matrix, but these theories have not as yet been conclusively proven. Clinical trials with ascorbate at doses on the order of 10 g/day were successful in some cases, but not in others. At very high doses,
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ascorbic acid is preferentially toxic to tumor cells. This preferential toxicity is understood to relate to the ascorbate mediated production of hydrogen peroxide, which is more toxic to tumor cells due to the lower levels of catalase typically present in tumor cells as compared to normal cells. High dose intravenous ascorbate has thus been suggested for the treatment of cancer, as described in U.S. Pat. No. 5,639,787. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of lipid metabolic disorders using 5-(1,2-dithiolan-3-yl) valeric acid (alphalipoic acid) or its physiologically compatible salts Inventor(s): Alken, Rudolf-Giesbert; (Zepernick, DE), Fries, Gerhard; (Wahlitz, DE), Koegst, Dieter; (Wahlitz, DE) Correspondence: Kriegsman & Kriegsman; 665 Franklin Street; Framingham; MA; 01702; US Patent Application Number: 20020042444 Date filed: October 9, 2001 Abstract: Lipid metabolic disorders, such as hyperlipidemia or hyperlipoproteinemia can be treated by administering to an afflicted individual an effective amount of 5-(1,2dithiolan-3-yl) valeric acid (.alpha.-lipoic acid) or one of its physiologically acceptable salts. Pharmaceutical compositions containing (.alpha.-lipoic acid) and methods for making such compositions also are disclosed. Excerpt(s): The invention concerns the use of 5-(1,2-dithiolan-3-yl) valeric acide (.alpha.lipoic acid) or its physiologically compatible salts for the treatment of disturbances of lipid metabolism. Arteriosclerosis, after heart disease and cancer, is one of the primary causes of death in humans. A risk factor for the disease of arteriosclerosis is an increased quantity of serum lipids and lipoproteins, so that a decrease in the level of serum lipids and lipoproteins is important for therapy. An object of the present invention is thus to make available an active ingredient, which is suitable for the treatment of disturbances of lipid metabolism. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of rosacea using lipoic acid Inventor(s): Perricone, Nicholas V.; (Guilford, CT) Correspondence: ST. Onge Steward Johnston & Reens, Llc; 986 Bedford Street; Stamford; CT; 06905-5619; US Patent Application Number: 20020013361 Date filed: September 14, 2001 Abstract: Rosacea is treated by application of a composition containing lipoic acid and/or a lipoic acid derivative such as dihydrolipoic acid, a lipoic or dihydrolipoic acid ester, a lipoic or dihydrolipoic acid amide, a lipoic or dihydrolipoic acid salt, and mixtures of any of these. Preferred compositions further comprise.alpha.-hydroxy acids or acid derivatives such as glycolic and/or lactic acid. Other embodiments also contain fatty acid esters of ascorbic acid such as ascorbyl palmitate, and/or tocotrienol.
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Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/415,792, filed Oct. 8, 1999, which is a continuation-in-part of U.S. application Ser. No. 08/971,820, filed Nov. 17, 1997, now issued as U.S. Pat. No. 5,965,618. This invention relates primarily to methods and compositions for the treatment of rosacea. Rosacea is a chronic inflammatory disorder affecting the blood vessels and pilosebaceous units of the face in middle-aged individuals, afflicting as many as 13 million Americans. Patients with rosacea have papules and pustules superimposed on diffuse erythema and telangiectasia (visible blood vessels) over the central portion of the face. Hence, the clinical features are facial redness, swelling, papules, pustules, and telangiectasias. An important component of the patients' history is often easy flushing and blushing of the face, and this is often accentuated when alcohol, caffeine-containing, or hot spicy foods are ingested. Hyperplasia of the sebaceous glands, connective tissue, and vascular bed of the nose sometimes causes rhinophyma, or a large, red, bulbous nose in addition to the other signs. Ocular complications occur in a small but significant number of rosacea patients; these include blepharitis, chalazion, conjunctivitis, and keratinitis. Progressive keratinitis can lead to scarring and blindness. Rosacea and the eye complications are usually responsive to tetracycline, but the antibiotic must be continued for life (at the lowest dose that suppresses the condition) because rosacea recurs when therapy is interrupted. In addition to the undesirability of the more prevalent use of antibiotics in general, a disadvantage to such treatments are the possible side effects associated with long-term use of oral antibiotics, such as nausea, gastrointestinal upset, phototoxicity, enhanced susceptibility to yeast infection, and interactions with other medications. Oral antibiotics may also lessen the effectiveness of oral contraceptives. High-potency topical corticosteroid preparations may induce or aggravate pre-existing rosacea and should not be used for long periods of time on the face. Instead, topical metronidazole is sometimes prescribed for reducing skin redness and the number of pimples on the face of patients with rosacea. Laser therapy has been used to reduce the telangiectasia and redness in some cases. (See Wilkin J K: Rosacea: Pathophysiology and Treatment. Archives of Dermatology, 1994, 130 :359-362; this and subsequent references are expressly incorporated herein by reference.) It would be desirable to have alternate treatments for rosacea. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of alpha-lipoic acid for producing cosmetic or dermatological preparations for regenerating stressed skin, in particular aged skin Inventor(s): Blatt, Thomas; (Hamburg, DE), Kruse, Inge; (Hamburg, DE), Mummert, Christopher; (Bienenbuttel, DE), Mundt, Claudia; (Bremen, DE), Schonrock, Uwe; (Nahe, DE), Stab, Franz; (Echem, DE) Correspondence: Alston & Bird Llp; Bank OF America Plaza; 101 South Tryon Street, Suite 4000; Charlotte; NC; 28280-4000; US Patent Application Number: 20030091605 Date filed: March 6, 2002 Abstract: Use of.alpha.-lipoic acid for producing cosmetic or dermatological preparations for regenerating stressed skin, in particular aged skin. Excerpt(s): The present invention relates to the use of.alpha.-lipoic acid for producing cosmetic or dermatological preparations for regenerating stressed skin, in particular aged skin. Cosmetic skin care is primarily understood as meaning strengthening or restoring the natural function of the skin as a barrier against environmental influences
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(for example, dirt, chemicals, microorganisms) and against the loss of endogenous substances (for example, water, natural fats, electrolytes). If this function is disturbed, it will come to an increased resorption of toxic or allergenic substances, or an attack of microorganisms, and consequently to toxic or allergenic skin reactions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of lipoic acid for improving the bioavailability of mineral salts Inventor(s): Klatt, Martin Jochen; (Bad Durkheim, DE), Kramer, Klaus; (Landau, DE) Correspondence: Herbert B. Keil; Keil & Weinkauf; 1101 Connecticut AVE., N.W.; Washington; DC; 20036; US Patent Application Number: 20020028796 Date filed: July 5, 2001 Abstract: The use of.alpha.-lipoic acid or.alpha.-dihydrolipoic acid for increasing the bioavailability of mineral salts, the use of.alpha.-lipoic acid or.alpha.-dihydrolipoic acid in combination with metal salts, in particular the use of metal.alpha.-lipoates, metal.alpha.-dihydrolipoates or metal-.alpha.-lipoic acid complexes, in particular in mineral preparations or drugs and the metal.alpha.-lipoates, metal.alpha.dihydrolipoates or metal-.alpha.-lipoic acid complexes themselves are described. Excerpt(s): The present invention relates to the use of.alpha.-lipoic acid or.alpha.dihydrolipoic acid for increasing the bioavailability of mineral salts, the use of.alpha.lipoic acid or.alpha.-dihydrolipoic acid in combination with metal salts, in particular the use of metal.alpha.-lipoates, metal.alpha.-dihydrolipoates or metal-.alpha.-lipoic acid complexes, in particular in mineral preparations or drugs and the metal.alpha.-lipoates, metal.alpha.-dihydrolipoates or metal-.alpha.-lipoic acid complexes themselves. Minerals are the constituents of plant and animal tissues which remain as ash in combustion. Depending on the content of the individual elements, minerals are classified as major elements, for example Ca, P, K, Cl, Na, Mg, or as trace elements, for example Fe, Zn, Cu, Mn, V, Se, Mn, I, Sn, Ni, Mo, Cr, Co. The metallic minerals are absorbed by human or animal organisms as cations, generally as mineral salts together with inorganic anions. The essential metallic minerals having a known biological function in the organism have very varied functions in the organism, for example as electrolytes, constituents of enzymes or as building blocks of certain bodily substances. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with lipoic acid, 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 “lipoic acid” (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 lipoic acid.
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You can also use this procedure to view pending patent applications concerning lipoic acid. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON LIPOIC ACID Overview This chapter provides bibliographic book references relating to lipoic acid. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on lipoic acid 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: 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 “lipoic acid” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “lipoic acid” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “lipoic acid” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
All About Alpha-Lipoic Acid (Frequently Asked Questions) by Cynthis M., MD Watson, et al; ISBN: 0895299356; http://www.amazon.com/exec/obidos/ASIN/0895299356/icongroupinterna
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Alpha Lipoic Acid Breakthrough: The Superb Antioxidant That May Slow Aging, Repair Liver Damage, and Reduce the Risk of Cancer, Heart Disease, and Diabetes by Burt Berkson, et al (1998); ISBN: 0761514570; http://www.amazon.com/exec/obidos/ASIN/0761514570/icongroupinterna
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Alpha Lipoic Acid: Nature's Ultimate Antioxidant by Allan E. Sosin, et al (1998); ISBN: 157566366X; http://www.amazon.com/exec/obidos/ASIN/157566366X/icongroupinterna
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Alpha Lipoic Acid: Nuture's Supreme Antioxidant by Rita Elkins (1998); ISBN: 1580540198; http://www.amazon.com/exec/obidos/ASIN/1580540198/icongroupinterna
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Lipoic Acid in Health and Disease by Jurgen Fuchs (Editor), et al; ISBN: 0824700937; http://www.amazon.com/exec/obidos/ASIN/0824700937/icongroupinterna
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Lipoic Acid: The Metabolic Antioxidant by Richard A. Passwater, Don R. Bensen (Editor); ISBN: 0879837209; http://www.amazon.com/exec/obidos/ASIN/0879837209/icongroupinterna
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Lipoic Acid: The Unique Antioxidant by Ray Sahelian, Edward Byrd; ISBN: 1890694029; http://www.amazon.com/exec/obidos/ASIN/1890694029/icongroupinterna
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The Antioxidant Miracle: Put Lipoic Acid, Pycogenol, and Vitamins E and C to Work for You by Lester Packer (Author), Carol Colman (Author); ISBN: 0471353116; http://www.amazon.com/exec/obidos/ASIN/0471353116/icongroupinterna
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The Potato Antioxidant: Alpha Lipoic Acid: A Health Learning Handbook by Beth M. Ley; ISBN: 0964270366; http://www.amazon.com/exec/obidos/ASIN/0964270366/icongroupinterna
Chapters on Lipoic Acid In order to find chapters that specifically relate to lipoic acid, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and lipoic acid using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “lipoic acid” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on lipoic acid: •
Diabetic Polyneuropathy Source: in Veves, A.; Giurini, J.M.; LoGerfo, F.W. Diabetic Foot: Medical and Surgical Management. Totowa, NJ: The Humana Press, Inc. 2002. p.75-98. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail:
[email protected] PRICE: $135.00, plus shipping and handling. ISBN: 0896039250. Summary: Polyneuropathy is one of the most common complications of diabetes and the most common form of neuropathy (nerve disease) in the developed world. Diabetic polyneuropathy encompasses several neuropathic syndromes, the most common of which is distal symmetrical neuropathy, the main initiating factor for foot ulceration. This chapter on diabetic polyneuropathy is from a textbook on the medical and surgical care of foot problems in people with diabetes. The author discusses the classification of polyneuropathy; symmetrical neuropathies, including distal symmetrical neuropathy, and acute painful neuropathies; asymmetrical neuropathies, include proximal motor neuropathy, cranial mononeuropathies, truncal radiculopathy, and pressure palsies (notably carpal tunnel syndrome); the pathogenesis of distal symmetrical neuropathy, including chronic hyperglycemia (high blood glucose levels), oxidative stress, increased polyol pathway flux, nonenzymatic glycation, neurotrophic factors, protein kinase C activation, and vascular factors; autonomic neuropathy, including cardiovascular, gastrointestinal (gastroparesis), abnormal sweating, and abnormalities of bladder function; the management of diabetic neuropathy through glycemic control, tricyclic
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compounds, anticonvulsants, topical capsaicin, intravenous lignocaine and oral mexiletine, and alpha lipoic acid; and the management of disabling painful neuropathy that is nonresponsive to pharmacological (drug) treatment. 3 figures. 6 tables. 101 references.
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CHAPTER 8. PERIODICALS AND NEWS ON LIPOIC ACID Overview In this chapter, we suggest a number of news sources and present various periodicals that cover lipoic acid.
News Services and Press Releases One of the simplest ways of tracking press releases on lipoic acid 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 “lipoic acid” (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 lipoic acid. 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 “lipoic acid” (or synonyms). The following was recently listed in this archive for lipoic acid: •
Listeria needs host-derived lipoic acid for growth and virulence Source: Reuters Medical News Date: October 20, 2003
•
Alpha-lipoic acid effective in rat model of hypertension, insulin resistance Source: Reuters Medical News Date: February 27, 2002
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Alpha-Lipoic Acid May Help In Mushroom Poisoning Source: Reuters Medical News Date: February 06, 1998 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 “lipoic acid” (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 “lipoic acid” (or synonyms). If you know the name of a company that is relevant to lipoic acid, 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 “lipoic acid” (or synonyms).
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Academic Periodicals covering Lipoic Acid Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lipoic acid. In addition to these sources, you can search for articles covering lipoic acid 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 Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
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
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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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
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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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.12 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:13 •
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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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/
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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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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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/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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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
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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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
12
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). 13 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “lipoic acid” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “lipoic acid” (or synonyms) into the “For these words:” box. The following is a sample result: •
Thioctic Acid Contact: AIDS Project Los Angeles, 3550 Wilshire Blvd Ste 300, Los Angeles, CA, 900102404, (213) 201-1600, http://www.apla.org. Summary: In this article, the author explores the potential value of thioctic acid, or lipoic acid, for the treatment of liver damage in HIV/AIDS patients. He explains that thioctic acid is a non-toxic micronutrient, incorporated by nutritional biochemists as a member of the B vitamin family, and biologically active in minute amounts. The principle physiological function of thioctic acid appears to be its action as a coenzyme in different metabolic reactions. The author states thioctic acid has been prescribed by physicians as a liver protective agent for alcoholics, and in cases of idiopathic liver enzyme elevation, viral hepatitis, and residual drug-induced liver injury. He refers to research showing thioctic acid to be effective for chemical hypersensitivity syndrome, diabetic neuropathy, peripheral neuropathy, heavy metal toxicity, and elevated liver enzymes. He believes thioctic acid has important implications for people with AIDS by serving to lower elevated liver enzyme levels brought on by some of their medications. Those taking thioctic acid on their own are cautioned to inform their physicians, since it will affect liver enzyme tests sometimes used to determine dosages of medications. The paper includes information on availability and prophylactic and therapeutic dosage forms.
The NLM Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. 14 15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).
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Type “lipoic acid” (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 1723 10 377 5 0 2115
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “lipoic acid” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists19 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.20 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.21 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/. 16
Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
17
The HSTAT URL is http://hstat.nlm.nih.gov/.
18
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. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20
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. 21 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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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Lipoic Acid In the following section, we will discuss databases and references which relate to the Genome Project and lipoic acid. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “lipoic acid” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for lipoic acid: •
Lipoic Acid Synthase Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607031 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
•
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases:
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3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “lipoic acid” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. 23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html.
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The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “lipoic acid” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
24
Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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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 lipoic acid 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 lipoic acid. 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 lipoic acid. 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 “lipoic acid”:
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Other guides Cancer Alternative Therapy http://www.nlm.nih.gov/medlineplus/canceralternativetherapy.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Ovarian Cysts http://www.nlm.nih.gov/medlineplus/ovariancysts.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 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 lipoic acid. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lipoic acid. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lipoic acid. 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 lipoic acid. 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 “lipoic acid” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “lipoic acid”. 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 “lipoic acid” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
150 Lipoic Acid
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 “lipoic acid” (or a synonym) into the search box, and click “Submit Query.”
151
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.25
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
25
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
152 Lipoic Acid
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)26: •
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/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
154 Lipoic Acid
•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
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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/
156 Lipoic Acid
•
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
157
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
159
LIPOIC ACID DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-Methoxytryptamine: Serotonin derivative proposed as potentiator for hypnotics and sedatives. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abrasion: 1. The wearing away of a substance or structure (such as the skin or the teeth) through some unusual or abnormal mechanical process. 2. An area of body surface denuded of skin or mucous membrane by some unusual or abnormal mechanical process. [EU] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acyl Carrier Protein: Consists of a polypeptide chain and 4'-phosphopantetheine linked to a serine residue by a phosphodiester bond. Acyl groups are bound as thiol esters to the pantothenyl group. Acyl carrier protein is involved in every step of fatty acid synthesis by
160 Lipoic Acid
the cytoplasmic system. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] 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] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH] Aldose Reductase Inhibitor: A class of drugs being studied as a way to prevent eye and
Dictionary 161
nerve damage in people with diabetes. Aldose reductase is an enzyme that is normally present in the eye and in many other parts of the body. It helps change glucose (sugar) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Drugs that prevent or slow (inhibit) the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergens: Antigen-type substances (hypersensitivity, immediate). [NIH]
that
produce
immediate
hypersensitivity
Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] 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] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH]
162 Lipoic Acid
Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, 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] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [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]
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Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Animal Welfare: The protection of animals in laboratories or other specific environments and the promotion of their health through better nutrition, housing, and care. This may be carried out through legislation or regulation. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anode: Electrode held at a positive potential with respect to a cathode. [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 supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage
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causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphlogistic: An agent that counteracts inflammation and fever. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Aqueous fluid: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the
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walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartame: Flavoring agent sweeter than sugar, metabolized as phenylalanine and aspartic acid. [NIH] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that
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produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [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] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] 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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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]
Benign prostatic hyperplasia: A benign (noncancerous) condition in which an overgrowth of prostate tissue pushes against the urethra and the bladder, blocking the flow of urine.
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Also called benign prostatic hypertrophy or BPH. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Benzoyl Peroxide: A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy. It is used also as a bleach in the food industry. [NIH] Beta Rays: A stream of positive or negative electrons ejected with high energy from a disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and
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protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blepharitis: Inflammation of the eyelids. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood 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 Proteins: Proteins that are present in blood serum, including serum albumin, blood coagulation factors, and many other types of proteins. [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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Blushing: Involuntary reddening, especially of the face, associated with feelings of embarrassment, confusion, or shame. [NIH] Body Fluids: Liquid components of living organisms. [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] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH]
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Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Injuries: Acute and chronic injuries to the brain, including the cerebral hemispheres, cerebellum, and brain stem. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with diffuse axonal injury or coma, posttraumatic. Localized injuries may be associated with neurobehavioral manifestations; hemiparesis, or other focal neurologic deficits. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [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] Buthionine sulfoximine: A drug that may help prevent resistance to some anticancer drugs. [NIH]
Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH]
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Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carbon Monoxide Poisoning: Toxic asphyxiation due to the displacement of oxygen from oxyhemoglobin by carbon monoxide. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which
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can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carpal Tunnel Syndrome: A median nerve injury inside the carpal tunnel that results in symptoms of pain, numbness, tingling, clumsiness, and a lack of sweating, which can be caused by work with certain hand and wrist postures. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cefotaxime: Semisynthetic broad-spectrum cephalosporin. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other 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 Degranulation: The process of losing secretory granules (secretory vesicles). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by exocytosis. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral 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] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU]
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Cerebrovascular Disorders: A broad category of disorders characterized by impairment of blood flow in the arteries and veins which supply the brain. These include cerebral infarction; brain ischemia; hypoxia, brain; intracranial embolism and thrombosis; intracranial arteriovenous malformations; and vasculitis, central nervous system. In common usage, the term cerebrovascular disorders is not limited to conditions that affect the cerebrum, but refers to vascular disorders of the entire brain including the diencephalon; brain stem; and cerebellum. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chalazion: A non-neoplastic cyst of the meibomian glands of the eyelid. [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] Chelating Agents: Organic chemicals that form two or more coordination bonds with a central metal ion. Heterocyclic rings are formed with the central metal atom as part of the ring. Some biological systems form metal chelates, e.g., the iron-binding porphyrin group of hemoglobin and the magnesium-binding chlorophyll of plants. (From Hawley's Condensed Chemical Dictionary, 12th ed) They are used chemically to remove ions from solutions, medicinally against microorganisms, to treat metal poisoning, and in chemotherapy protocols. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chelation Therapy: Therapy of heavy metal poisoning using agents which sequester the metal from organs or tissues and bind it firmly within the ring structure of a new compound which can be eliminated from the body. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Cholecalciferol: An antirachitic oil-soluble vitamin. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes,
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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] 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] Chromic: Catgut sterilized and impregnated with chromium trioxide. [NIH] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Arteries: Three groups of arteries found in the eye which supply the iris, pupil, sclera, conjunctiva, and the muscles of the iris. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citric Acid Cycle: A series of reactions involving oxidation of a two-carbon acetyl unit to carbon dioxide and water with the production of high-energy phosphate bonds by means of tricarboxylic acid intermediate. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH]
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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognition Disorders: Disturbances in the mental process related to thinking, reasoning, and judgment. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comedo: A plug of keratin and sebum within the dilated orifice of a hair follicle, frequently containing the bacteria Propionibacterium acnes, Staphylococcus albus, and Pityrosporon ovale; called also blackhead. [EU] Comet Assay: A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail"
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formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage. [NIH] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [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, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH]
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Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constrict: Tighten; narrow. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH]
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Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Cumulative Trauma Disorders: Harmful and painful condition caused by overuse or overexertion of some part of the musculoskeletal system, often resulting from work-related physical activities. It is characterized by inflammation, pain, or dysfunction of the involved joints, bones, ligaments, and nerves. [NIH] Curative: Tending to overcome disease and promote recovery. [EU]
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Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompression: Decompression external to the body, most often the slow lessening of
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external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Decompression Sickness: A condition occurring as a result of exposure to a rapid fall in ambient pressure. Gases, nitrogen in particular, come out of solution and form bubbles in body fluid and blood. These gas bubbles accumulate in joint spaces and the peripheral circulation impairing tissue oxygenation causing disorientation, severe pain, and potentially death. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [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] Deprenyl: Substance that blocks the breakdown of dopamine, thus preserving its availability in the striatum. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH]
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Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] 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] Diffuse Axonal Injury: A relatively common sequela of blunt head injury, characterized by a global disruption of axons throughout the brain. Associated clinical features may include neurobehavioral manifestations; persistent vegetative state; dementia; and other disorders. [NIH]
Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU]
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Dissection: Cutting up of an organism for study. [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] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Docetaxel: An anticancer drug that belongs to the family of drugs called mitotic inhibitors. [NIH]
Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the 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
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effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysgeusia: A condition characterized by alterations of the sense of taste which may range from mild to severe, including gross distortions of taste quality. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH]
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Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH]
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Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1) activation by ions (activators); 2) activation by cofactors (coenzymes); and 3) conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. [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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] 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.
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[NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxins: Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or
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foot. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [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
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chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flavodoxin: A low-molecular-weight (16,000) iron-free flavoprotein containing one molecule of flavin mononucleotide (FMN) and isolated from bacteria grown on an irondeficient medium. It can replace ferredoxin in all the electron-transfer functions in which the latter is known to serve in bacterial cells. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Flushing: A transient reddening of the face that may be due to fever, certain drugs, exertion, stress, or a disease process. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructosamine: An amino sugar formed when glucose non-enzymatically reacts with the Nterminal amino group of proteins. The fructose moiety is dervied from glucose by the "classical" Amadori rearrangement. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has
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calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastroparesis: Nerve or muscle damage in the stomach. Causes slow digestion and emptying, vomiting, nausea, or bloating. Also called delayed gastric emptying. [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] 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
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order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Geriatric: Pertaining to the treatment of the aged. [EU] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]
Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid
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(glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
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] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Glycylglycine: N-Glycylglycine. The simplest of all peptides. It functions as a gammaglutamyl acceptor. [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] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia,
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30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] 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] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] 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] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as
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antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [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] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hesperidin: Predominant flavonoid in lemons and sweet oranges. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [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]
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Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxy Acids: Organic compounds containing both the hydroxyl and carboxyl radicals. [NIH]
Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotics and Sedatives: Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. [NIH]
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Hypoglycemia: Abnormally low blood sugar [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [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] Impotence: The inability to perform sexual intercourse. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood
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cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [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]
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Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Embolism: The sudden obstruction of a blood vessel by an embolus. [NIH] Intracranial Embolism and Thrombosis: Embolism or thrombosis involving blood vessels which supply intracranial structures. Emboli may originate from extracranial or intracranial sources. Thrombosis may occur in arterial or venous structures. [NIH] Intrahepatic: Within the liver. [NIH] Intrahepatic bile ducts: The bile ducts that pass through and drain bile from the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented
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epithelium. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. [NIH] Isothiuronium: Proposed topical anti-inflammatory agent that may release histamine if given intradermally. [NIH] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually
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by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [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] Lenticular: 1. Pertaining to or shaped like a lens. 2. Pertaining to the crystalline lens. 3. Pertaining to the lenticular nucleus. [EU] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH]
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Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipoamide Dehydrogenase: A flavoprotein that catalyzes the reduction of lipoamide by NADH to yield dihydrolipoamide and NAD+. The enzyme is a component of the multienzyme pyruvate dehydrogenase complex and 2-oxoglutarate dehydrogenase complex. EC 1.8.1.4. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Enzyme Tests: Blood tests that look at how well the liver and biliary system are working. Also called liver function tests. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobule: A small lobe or subdivision of a lobe. [NIH] Loc: A brain region associated with object recognition. [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] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU]
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Lumen: The cavity or channel within a tube or tubular organ. [EU] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports
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the lower teeth. [NIH] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mannans: Polysaccharides consisting of mannose units. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] 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] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meglumine: 1-Deoxy-1-(methylamino)-D-glucitol. A derivative of sorbitol in which the hydroxyl group in position 1 is replaced by a methylamino group. Often used in conjunction with iodinated organic compounds as contrast medium. [NIH] Meibomian: A series of simple, branched, alveolar, sebaceous glands, located in the tarso of the eyelids, whose ducts empty into the eyelid margins in line with and lateral to the lacrimal puncta. [NIH] Meibomian Glands: The sebaceous glands situated on the inner surface of the eyelids between the tarsal plates and conjunctiva. [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] 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]
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Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic Clearance Rate: Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [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] Micelles: Electrically charged colloidal particles or ions consisting of oriented molecules; aggregates of a number of molecules held loosely together by secondary bonds. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular
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animals, lower algae, lower fungi, bacteria. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Micturition: The passage of urine; urination. [EU] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milk Thistle: The plant Silybum marianum in the family Asteraceae containing the bioflavonoid complex silymarin. For centuries this has been used traditionally to treat liver disease. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [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] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH]
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Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Mononeuropathies: Disease or trauma involving a single peripheral nerve in isolation, or out of proportion to evidence of diffuse peripheral nerve dysfunction. Mononeuropathy multiplex refers to a condition characterized by multiple isolated nerve injuries. Mononeuropathies may result from a wide variety of causes, includingischemia; traumatic injury; compression; connective tissue diseases; cumulative trauma disorders; and other conditions. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multienzyme Complexes: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates; may involve simply a transfer of water molecules of hydrogen atoms or be associated with large supramolecular structures such as mitochondria or ribosomes. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Muscle Fatigue: A state arrived at through prolonged and strong contraction of a muscle. Studies in athletes during prolonged submaximal exercise have shown that muscle fatigue increases in almost direct proportion to the rate of muscle glycogen depletion. Muscle fatigue in short-term maximal exercise is associated with oxygen lack and an increased level of blood and muscle lactic acid, and an accompanying increase in hydrogen-ion concentration in the exercised muscle. [NIH]
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Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] N-acetyl: Analgesic agent. [NIH] N-acetyl cysteine: An antioxidant drug that may keep cancer cells from developing or reduce the risk of growth of existing cancer. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH]
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Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Nervousness: Excessive excitability and irritability, with mental and physical unrest. [EU] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurobehavioral Manifestations: Signs and symptoms of higher cortical dysfunction caused by organic conditions. These include certain behavioral alterations and impairments of skills involved in the acquisition, processing, and utilization of knowledge or information. [NIH]
Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but
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often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU]
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Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] 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] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic nerve head: The circular area (disc) where the optic nerve connects to the retina. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the
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increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] 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] Palsies: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] 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] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Particle Accelerators: Devices which accelerate electrically charged atomic or subatomic particles, such as electrons, protons or ions, to high velocities so they have high kinetic energy. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
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Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal (or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Peroxisome Proliferators: A class of nongenotoxic carcinogens that induce the production of hepatic peroxisomes and induce hepatic neoplasms after long-term administration. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] 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]
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Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH]
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Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together 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] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]
Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] 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] 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] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU]
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Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [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] Proenzyme: 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] Progeny: The offspring produced in any generation. [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] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH]
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Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [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] Prostatic Hyperplasia: Enlargement or overgrowth of the prostate gland as a result of an increase in the number of its constituent cells. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] 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] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosine: An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the cerebroside. [NIH] Psychotomimetic: Psychosis miming. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right
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ventricle and conveying unaerated blood to the lungs. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyruvate Carboxylase: A biotin-dependent enzyme belonging to the ligase family that catalyzes the addition of carbon dioxide to pyruvate. It is occurs in both plants and animals. Deficiency of this enzyme causes severe psychomotor retardation and lactic acidosis in infants. EC 6.4.1.1. [NIH] Pyruvate Dehydrogenase Complex: An organized assembly of three kinds of enzymes; catalyzes the oxidative decarboxylation of pyruvate. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radicular: Having the character of or relating to a radicle or root. [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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH]
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Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme,
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and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] 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 Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH]
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Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] 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] Rheumatic Heart Disease: Disease of the heart resulting from rheumatic fever and characterized by inflammatory changes in the myocardium or scarring of the valves. [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] Rhinophyma: A manifestation of severe Acne rosacea resulting in significant enlargement of the nose and occurring primarily in men. It is caused by hypertrophy of the sebaceous glands and surrounding connective tissue. The nose is reddened and marked with numerous telangiectasias. [NIH] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickettsia: A genus of gram-negative, aerobic, rod-shaped bacteria often surrounded by a protein microcapsular layer and slime layer. The natural cycle of its organisms generally involves a vertebrate and an invertebrate host. Species of the genus are the etiological agents of human diseases, such as typhus. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]
Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [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] Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH]
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Salivary glands: Glands in the mouth that produce saliva. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] 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] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Selenium Compounds: Inorganic compounds that contain selenium as an integral part of the molecule. [NIH] Selenomethionine: Diagnostic aid in pancreas function determination. [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] Senescence: The bodily and mental state associated with advancing age. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU]
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Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shame: An emotional attitude excited by realization of a shortcoming or impropriety. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Silymarin: A mixture of flavonoids extracted from seeds of the milk thistle, Silybum marianum. It consists primarily of three isomers: silicristin, silidianin, and silybin, its major component. Silymarin displays antioxidant and membrane stabilizing activity. It protects various tissues and organs against chemical injury, and shows potential as an antihepatoxic agent. [NIH]
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Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skin Care: Maintenance of the hygienic state of the skin under optimal conditions of cleanliness and comfort. Effective in skin care are proper washing, bathing, cleansing, and the use of soaps, detergents, oils, etc. In various disease states, therapeutic and protective solutions and ointments are useful. The care of the skin is particularly important in various occupations, in exposure to sunlight, in neonates, and in decubitus ulcer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solar radiation: Sunbathing as a therapeutic measure. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH]
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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] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [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] Spinous: Like a spine or thorn in shape; having spines. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat, scaly cells. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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]
Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or
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tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] 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]
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Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] 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] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH]
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Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thylakoids: Membranous cisternae of the chloroplast containing photosynthetic pigments, reaction centers, and the electron-transport chain. Each thylakoid consists of a flattened sac of membrane enclosing a narrow intra-thylakoid space (Lackie and Dow, Dictionary of Cell Biology, 2nd ed). Individual thylakoids are interconnected and tend to stack to form aggregates called grana. They are found in cyanobacteria and all plants. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] 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] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and
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pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trifluoroacetic Acid: A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Truncal: The bilateral dissection of the abdominal branches of the vagus nerve. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the
228 Lipoic Acid
appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] 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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vanadium: Vanadium. A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which
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constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] 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]
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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] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] 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] 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] Zygote: The fertilized ovum. [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]
231
INDEX 5 5-Methoxytryptamine, 48, 159 A Abdominal, 159, 160, 203, 210, 227 Abrasion, 95, 159 Acatalasia, 159, 171 Acceptor, 159, 191, 200, 210, 227 Acetylcholine, 159, 173, 208 Acetylcholinesterase, 5, 159 Acetylcysteine, 19, 159 Acidosis, 37, 38, 92, 159, 216 Acne, 89, 90, 120, 121, 159, 167, 219 Acne Vulgaris, 90, 121, 159 Acremonium, 159, 172 Actin, 19, 159 Acyl, 23, 50, 159 Acyl Carrier Protein, 50, 159 Adaptability, 160, 172 Adenosine, 105, 160, 169, 212 Adipocytes, 50, 51, 160, 177 Adjuvant, 17, 121, 160, 189 Adrenal Cortex, 160, 178, 218 Adverse Effect, 4, 160, 221 Aerobic, 12, 99, 107, 160, 204, 219 Affinity, 24, 46, 160, 165, 200, 207, 222 Agar, 52, 160, 178, 195, 212 Age of Onset, 160, 228 Agonist, 23, 160, 182 Albumin, 23, 72, 92, 160, 213 Albuminuria, 27, 33, 160 Aldose Reductase Inhibitor, 26, 160 Alertness, 161, 169 Algorithms, 161, 167 Alimentary, 161, 210 Alkaline, 80, 159, 161, 162, 170, 176 Alkaloid, 161, 170, 175 Allergens, 72, 161 Allylamine, 161 Alpha Particles, 161, 216 Alternative medicine, 132, 161 Alveolar Process, 161, 218 Amebiasis, 161, 203 Ameliorating, 91, 161 Amine, 106, 161, 193 Amino Acid Sequence, 161, 163, 189 Ammonia, 161, 162, 191, 224, 228 Amphetamine, 76, 162, 181 Amylase, 72, 162
Amyloid, 5, 15, 162 Anabolic, 118, 162, 181 Anaerobic, 16, 92, 113, 162 Anaesthesia, 162, 196 Anal, 162, 187 Analgesic, 80, 85, 97, 103, 115, 162, 206 Analogous, 80, 162, 213, 227 Analysis of Variance, 4, 162 Anaphylatoxins, 162, 176 Anatomical, 162, 177, 181, 195, 220 Androgens, 160, 162, 178 Anemia, 106, 118, 143, 162, 169, 188, 201 Aneurysm, 162, 229 Angiogenesis, 162, 202 Angiography, 23, 163 Animal model, 7, 8, 9, 19, 23, 50, 163 Animal Welfare, 20, 163 Anionic, 121, 163 Anions, 124, 160, 163, 197, 221, 224 Anode, 163 Anorexia, 101, 163 Antagonism, 163, 169 Anterior Cerebral Artery, 163, 172 Antiallergic, 163, 178 Antibacterial, 163, 223 Antibiotic, 90, 123, 163, 169, 179, 182, 211, 223, 225 Antibodies, 23, 106, 163, 165, 192, 193, 195, 201, 213 Antibody, 32, 160, 163, 176, 185, 192, 194, 195, 196, 202, 205, 216, 223 Anticoagulant, 163, 215 Anticonvulsant, 163, 203 Antigen, 160, 161, 163, 176, 194, 195, 196, 202 Antigen-Antibody Complex, 163, 176 Anti-infective, 164, 193, 197, 222 Anti-inflammatory, 12, 22, 84, 85, 114, 164, 165, 171, 178, 190, 198 Anti-Inflammatory Agents, 12, 164, 165, 171, 178 Antineoplastic, 164, 178, 182 Antiphlogistic, 73, 164 Antiviral, 67, 159, 164 Anxiety, 76, 164, 194 Apolipoproteins, 164, 200 Apoptosis, 8, 18, 19, 28, 36, 40, 58, 95, 104, 164, 171
232 Lipoic Acid
Aqueous, 80, 83, 87, 92, 120, 164, 166, 174, 179, 184, 193, 199 Aqueous fluid, 87, 164 Arachidonic Acid, 21, 164, 199, 215 Arginine, 21, 118, 162, 164, 208, 227 Aromatic, 7, 106, 164, 170, 212 Arterial, 23, 99, 116, 161, 164, 165, 169, 170, 172, 173, 190, 194, 197, 215, 225 Arteries, 99, 106, 164, 165, 168, 169, 172, 173, 174, 178, 198, 200, 203, 206, 226 Arterioles, 21, 87, 92, 99, 164, 165, 168, 170, 204 Arteriolosclerosis, 164, 165 Arteriosclerosis, 62, 91, 100, 122, 164, 194 Arteriovenous, 165, 173, 204 Articular, 165, 209 Ascorbic Acid, 5, 18, 22, 31, 48, 50, 56, 90, 98, 99, 103, 109, 120, 121, 122, 165, 194 Aspartame, 118, 165 Aspartate, 104, 165 Aspartic, 118, 165, 186 Aspartic Acid, 118, 165 Aspirin, 75, 116, 165 Assay, 5, 10, 16, 18, 35, 36, 165, 176 Astringents, 165, 203 Astrocytes, 7, 165, 190, 205, 207 Ataxia, 31, 143, 165, 225 Atherogenic, 13, 165 Atmospheric Pressure, 91, 165 Atrophy, 110, 143, 165, 207 Auditory, 20, 88, 165, 228 Autoantibodies, 41, 165, 166 Autoantigens, 43, 165, 166 Autoimmune disease, 23, 166 Autonomic, 27, 35, 51, 115, 128, 159, 166, 211, 223 Autonomic Neuropathy, 27, 35, 115, 128, 166 Axillary, 166, 169 Axillary Artery, 166, 169 Axons, 17, 166, 180, 181, 209, 218, 223 B Bacteriophage, 166, 212, 227 Bacterium, 19, 166, 177 Basal Ganglia, 165, 166 Basal Ganglia Diseases, 165, 166 Base, 103, 166, 180, 189, 191, 198, 225 Basement Membrane, 166, 186 Basophils, 166, 172, 191, 199 Benign, 81, 82, 112, 164, 166, 192, 207, 216 Benign prostatic hyperplasia, 112, 166 Benzene, 115, 167, 198
Benzoic Acid, 49, 105, 106, 167 Benzoyl Peroxide, 90, 120, 167 Beta Rays, 167, 183 Beta-pleated, 162, 167 Bilateral, 167, 227 Bile, 167, 189, 193, 197, 200, 214, 225 Bile Acids, 167, 225 Bile Ducts, 167, 197, 214 Biliary, 23, 41, 167, 200 Bilirubin, 160, 167 Bioavailability, 119, 124, 167 Bioavailable, 117, 167 Biochemical reactions, 167, 225 Biomarkers, 5, 167 Biopsy, 167, 211 Biosynthesis, 6, 13, 24, 47, 50, 56, 164, 167, 200, 215, 221 Biotechnology, 24, 25, 132, 139, 142, 143, 144, 167 Biotin, 6, 13, 47, 53, 60, 98, 100, 105, 106, 113, 168, 216 Biotransformation, 168 Bladder, 106, 112, 128, 166, 168, 215, 228 Blepharitis, 123, 168 Bloating, 168, 189 Blood Coagulation, 168, 170, 226 Blood Coagulation Factors, 168 Blood Glucose, 128, 168, 192, 196 Blood pressure, 58, 99, 168, 170, 171, 190, 194, 195, 205, 211, 222 Blood Proteins, 92, 168 Blot, 15, 168 Blushing, 123, 168 Body Fluids, 167, 168, 183, 188, 208, 222, 228 Bone Marrow, 121, 167, 168, 195, 201, 222 Boron, 105, 168 Boron Neutron Capture Therapy, 168 Bowel, 162, 168, 169, 181, 197, 199 Bowel Movement, 169, 181 Brachial, 6, 23, 169, 202 Brachial Artery, 6, 169 Brachytherapy, 169, 197, 216 Bradykinin, 169, 208, 213 Brain Injuries, 111, 169 Brain Ischemia, 169, 173 Brain Stem, 169, 172, 173 Branch, 155, 169, 183, 201, 211, 222, 225, 226 Breakdown, 76, 105, 169, 172, 180, 181, 189, 209 Broad-spectrum, 57, 169, 171, 172
Index 233
Buccal, 169, 223 Burns, 89, 98, 167, 169 Burns, Electric, 169 Buthionine sulfoximine, 29, 169 C Cadmium, 51, 169 Cadmium Poisoning, 169 Caffeine, 76, 123, 169, 216 Calcification, 164, 170 Calcium, 7, 8, 21, 99, 105, 113, 121, 169, 170, 174, 176, 202, 206, 221 Caloric intake, 76, 170 Capillary, 31, 43, 92, 169, 170, 219, 229 Capillary Fragility, 170, 219 Capsaicin, 129, 170 Capsules, 170, 182, 187, 189 Captopril, 119, 170 Carbohydrate, 72, 98, 117, 170, 178, 190, 191 Carbon Dioxide, 107, 170, 174, 179, 187, 216, 218, 229 Carbon Monoxide Poisoning, 81, 170 Carboxy, 170 Carboxylic Acids, 80, 120, 170 Carcinogen, 17, 170, 203 Carcinogenesis, 7, 170, 173 Carcinogenic, 167, 170, 196, 214 Cardiac, 20, 27, 35, 59, 115, 116, 121, 161, 169, 170, 185, 186, 189, 199, 206, 218 Cardiovascular, 7, 21, 57, 99, 101, 115, 128, 162, 166, 170, 171, 199 Cardiovascular disease, 7, 21, 57, 99, 101, 170 Cardiovascular System, 99, 166, 171 Carotene, 113, 171, 218 Carotenoids, 79, 100, 171 Carpal Tunnel Syndrome, 62, 128, 171 Caspase, 40, 171 Catabolism, 13, 171 Catalase, 8, 21, 88, 114, 116, 122, 159, 171 Cataract, 29, 84, 86, 96, 171 Cathode, 163, 167, 171, 183 Cations, 49, 124, 171, 197 Caudal, 171, 181, 213 Causal, 171, 192 Cause of Death, 9, 18, 21, 99, 171 Cefotaxime, 52, 171 Celecoxib, 12, 171 Cell Adhesion, 29, 171 Cell Cycle, 28, 171, 174 Cell Death, 7, 23, 36, 104, 164, 171, 207 Cell Degranulation, 20, 172
Cell Differentiation, 172, 221 Cell Division, 143, 166, 171, 172, 204, 212 Cell membrane, 10, 32, 88, 89, 172, 180, 186, 198, 212 Cell proliferation, 165, 172, 221 Cell Respiration, 172, 204, 218 Cell Size, 172, 188 Cellular metabolism, 17, 172 Cellulose, 172, 189, 212 Cephalosporins, 119, 172 Cerebellar, 165, 172, 217 Cerebellum, 169, 172, 173, 217 Cerebral Arteries, 172, 204 Cerebral hemispheres, 166, 169, 172, 173 Cerebral Infarction, 116, 172, 173 Cerebrovascular, 99, 116, 166, 171, 172, 173, 225 Cerebrovascular Disorders, 99, 116, 173, 225 Cerebrum, 172, 173, 228 Chalazion, 123, 173 Character, 17, 173, 180, 216 Chelating Agents, 18, 173 Chelation, 7, 26, 173 Chelation Therapy, 7, 173 Chemopreventive, 84, 173 Chemotactic Factors, 89, 173, 176 Chemotaxis, 90, 173 Chemotherapy, 121, 173 Chlorophyll, 173, 189 Chloroplasts, 6, 173 Cholecalciferol, 113, 173 Cholesterol, 10, 13, 68, 99, 106, 167, 173, 174, 178, 194, 200, 220 Cholesterol Esters, 173, 200 Choline, 46, 89, 105, 106, 108, 159, 173 Choroid, 174, 218 Chromatin, 164, 174, 185 Chromic, 111, 174 Chromium, 41, 60, 75, 76, 78, 98, 100, 105, 111, 112, 113, 174 Chromosomal, 24, 174, 219 Chromosome, 174, 177, 192, 200, 228 Chronic Fatigue Syndrome, 98, 174 Chronic renal, 174, 213 Chylomicrons, 174, 200 Cicatrix, 174, 198 Ciliary, 87, 164, 174 Ciliary Arteries, 87, 174 Ciliary processes, 164, 174 CIS, 174, 218 Cisplatin, 30, 57, 174
234 Lipoic Acid
Citric Acid, 76, 94, 174 Citric Acid Cycle, 76, 174 Citrus, 105, 165, 174 Clear cell carcinoma, 174, 180 Cleave, 14, 174 Clinical Medicine, 175, 214 Clinical study, 175, 177 Clinical trial, 4, 8, 10, 11, 15, 19, 28, 67, 68, 121, 139, 175, 177, 217 Cloning, 24, 50, 167, 175, 199 Coal, 167, 175 Coca, 175 Cocaine, 76, 175 Cofactor, 12, 14, 15, 17, 46, 73, 77, 81, 102, 175, 215, 226 Cognition, 81, 175 Cognition Disorders, 81, 175 Collagen, 12, 89, 166, 175, 186, 187, 189, 198, 202, 213, 214 Collapse, 11, 169, 175 Colloidal, 160, 175, 183, 203, 221 Combinatorial, 4, 175 Comedo, 90, 175 Comet Assay, 18, 175 Commensal, 90, 176 Complement, 89, 162, 176, 190, 213 Complementary and alternative medicine, 55, 64, 176 Complementary medicine, 11, 55, 176 Complete remission, 176, 217 Computational Biology, 139, 142, 176 Conduction, 21, 39, 61, 176 Cones, 176, 218 Confusion, 168, 176, 181 Congestion, 177, 185 Congestive heart failure, 101, 177 Conjugated, 7, 98, 117, 167, 177, 179 Conjugation, 23, 49, 168, 177 Conjunctiva, 174, 177, 202 Conjunctivitis, 123, 177 Connective Tissue, 59, 123, 165, 168, 175, 177, 187, 189, 190, 191, 198, 201, 203, 205, 219 Connective Tissue Cells, 177 Consciousness, 162, 177, 180, 182, 218 Constrict, 92, 177 Constriction, 92, 177, 198, 229 Constriction, Pathologic, 177, 229 Consumption, 12, 19, 98, 118, 177, 210 Contraindications, ii, 177 Control group, 11, 17, 177 Controlled clinical trial, 6, 177
Controlled study, 11, 31, 177 Convulsions, 163, 177, 207 Coordination, 172, 173, 177 Cornea, 164, 178, 220 Coronary, 13, 22, 62, 99, 118, 170, 178, 203, 206 Coronary heart disease, 13, 99, 118, 170, 178 Coronary Thrombosis, 178, 203, 206 Cortex, 15, 165, 172, 178, 184, 204, 217 Cortical, 46, 178, 186, 207, 220, 225 Corticosteroid, 123, 178 Cortisol, 160, 178 Cranial, 128, 172, 178, 192, 209, 211, 228 Creatine, 76, 77, 81, 82, 84, 102, 110, 117, 178 Creatinine, 178 Crystallization, 120, 178 Culture Media, 160, 178 Cultured cells, 13, 178 Cumulative Trauma Disorders, 178, 205 Curative, 178, 208, 225 Cyanide, 111, 179 Cyclic, 106, 112, 169, 179, 192, 208 Cyst, 173, 179 Cysteine, 8, 19, 22, 41, 60, 81, 82, 95, 99, 100, 102, 105, 108, 159, 179, 224 Cystine, 39, 72, 96, 179 Cytochrome, 48, 179, 210 Cytokine, 11, 179 Cytoplasm, 113, 164, 166, 172, 179, 185, 191 Cytoprotection, 114, 179 Cytoskeleton, 19, 179 Cytotoxic, 18, 99, 104, 170, 179, 216, 221 Cytotoxicity, 18, 32, 47, 161, 174, 179 D Dairy Products, 179, 220 Databases, Bibliographic, 139, 179 Daunorubicin, 179, 182 De novo, 39, 81, 102, 179 Decarboxylation, 73, 80, 81, 87, 97, 102, 103, 109, 179, 193, 216 Decompression, 91, 179, 180 Decompression Sickness, 91, 180 Decubitus, 180, 222 Decubitus Ulcer, 180, 222 Defense Mechanisms, 84, 107, 180 Degenerative, 8, 16, 79, 82, 84, 86, 96, 99, 114, 180, 190, 193, 201, 209, 219 Dehydration, 75, 180 Deletion, 164, 180
Index 235
Dementia, 4, 10, 82, 110, 111, 180, 181 Dendrites, 180, 207 Density, 5, 15, 43, 180, 188, 200, 209, 222 Dentate Gyrus, 180, 193 Depolarization, 180, 221 Deprenyl, 37, 49, 180 DES, 52, 162, 180 Detergents, 180, 222 Detoxification, 50, 181 Deuterium, 16, 181, 193 Dextroamphetamine, 76, 162, 181, 203 Diabetes Mellitus, 5, 33, 41, 59, 62, 65, 93, 114, 181, 190, 192 Diagnostic procedure, 71, 132, 181 Dialyzer, 181, 192 Diastolic, 181, 194 Diencephalon, 173, 181 Diffuse Axonal Injury, 169, 181 Digestion, 72, 161, 167, 168, 181, 189, 197, 200, 223 Digestive system, 69, 181 Digestive tract, 166, 181, 222 Dihydrotestosterone, 181, 217 Dihydroxy, 181, 219 Dilatation, 162, 181, 214, 229 Dilatation, Pathologic, 181, 229 Dilation, 6, 110, 169, 181, 229 Dimethyl, 111, 181 Diploid, 181, 212 Direct, iii, 5, 28, 33, 47, 51, 82, 88, 105, 175, 181, 182, 190, 205, 217 Disease Progression, 10, 181, 229 Disorientation, 176, 180, 181 Dissection, 182, 227 Dissociation, 160, 182, 197 Distal, 17, 39, 128, 182, 211, 215 Diuresis, 169, 182 Docetaxel, 30, 57, 182 Domesticated, 182, 192 Dopamine, 162, 175, 180, 181, 182, 205, 212 Dorsal, 17, 182, 213, 223 Dorsum, 182 Dosage Forms, 140, 182 Dose-dependent, 77, 182 Doxorubicin, 47, 182 Drug Delivery Systems, 118, 182 Drug Interactions, 182 Drug Tolerance, 182, 226 Duct, 90, 183, 219, 224 Duodenum, 167, 183, 189, 223 Dyes, 162, 166, 183, 188 Dysgeusia, 37, 183
Dysplasia, 143, 183 Dystrophy, 143, 183 E Edema, 92, 183, 199, 206 Effector, 159, 176, 183 Efficacy, 4, 5, 7, 9, 11, 31, 78, 95, 115, 120, 121, 183 Elasticity, 99, 164, 183, 222 Elastin, 175, 183, 186 Elective, 25, 42, 183 Electrolysis, 163, 171, 183 Electrolyte, 178, 183, 188, 204, 208, 214, 222 Electrons, 99, 164, 166, 167, 171, 183, 197, 209, 210, 216 Electrophoresis, 31, 33, 47, 175, 183, 195 Electrophysiological, 11, 183 Elementary Particles, 183, 208, 215 Embolus, 183, 196, 197 Embryo, 172, 184, 196, 213, 214 Emulsion, 184, 188 Encephalitis, 184 Encephalomyelitis, 46, 56, 184 Encephalopathy, 8, 184 Endemic, 184, 201, 223 Endocrine Glands, 184 Endothelial cell, 5, 13, 19, 21, 26, 28, 33, 34, 38, 44, 49, 89, 184, 226 Endothelium, 5, 21, 31, 184, 208 Endothelium, Lymphatic, 184 Endothelium, Vascular, 184 Endothelium-derived, 184, 208 Endotoxin, 13, 184 End-stage renal, 75, 174, 184, 213 Energetic, 85, 116, 184 Enteropeptidase, 184, 227 Entorhinal Cortex, 184, 193 Environmental Exposure, 185, 209 Environmental Health, 138, 140, 185 Enzymatic, 6, 8, 13, 14, 16, 17, 85, 103, 114, 116, 170, 171, 176, 185, 193, 218 Enzyme Activation, 14, 185 Eosinophils, 172, 185, 191, 199 Epidermal, 89, 114, 185, 198, 202 Epidermal Growth Factor, 89, 185 Epidermis, 185, 194, 198, 214, 216 Epigastric, 51, 185, 210 Epinephrine, 182, 185, 228 Epithelial, 20, 46, 82, 185, 193 Epithelial Cells, 46, 82, 185, 193 Epithelium, 90, 166, 184, 185, 189, 197 Epitope, 23, 185
236 Lipoic Acid
Erythema, 84, 90, 123, 185, 224 Erythrocytes, 29, 38, 42, 48, 162, 168, 185, 192, 217 Esophageal, 118, 185 Esophagus, 181, 185, 217, 223 Essential Tremor, 143, 186 Ethanol, 186, 187 Excipient, 101, 186 Excitability, 186, 207 Excitation, 186, 188 Excitatory, 186, 190, 191, 208 Excitatory Amino Acids, 186, 208 Exhaustion, 163, 186, 201 Exocytosis, 172, 186 Exogenous, 16, 21, 101, 168, 170, 186, 227, 228 Exotoxins, 108, 186 External-beam radiation, 186, 216 Extracellular, 18, 22, 35, 121, 162, 165, 177, 186, 187, 202, 207, 222 Extracellular Matrix, 121, 177, 186, 187, 202 Extracellular Matrix Proteins, 186, 202 Extracellular Space, 186 Extraction, 117, 186 Extravascular, 87, 186 Extremity, 186, 202, 220 F Facial, 123, 187 Family Planning, 139, 187 Fatigue, 174, 187, 192, 205 Fatty acids, 25, 48, 76, 117, 160, 170, 187, 215, 222, 226 Fermentation, 83, 187 Fetus, 187, 214 Fibrin, 89, 168, 187, 225, 226 Fibrinogen, 187, 213, 225 Fibroblasts, 18, 89, 177, 187 Fibronectin, 89, 187 Fibrosis, 143, 161, 187, 220 Filler, 78, 187 Filtration, 120, 187 Fistula, 187, 189 Fixation, 6, 187 Flavodoxin, 14, 188 Flow Cytometry, 10, 188 Fluid Therapy, 188, 208 Fluorescence, 5, 188 Fluorescent Dyes, 188 Flushing, 123, 188 Folate, 105, 188 Fold, 75, 188, 203
Folic Acid, 75, 100, 106, 113, 188 Foot Ulcer, 128, 188 Forearm, 23, 168, 188, 202 Fovea, 187, 188 Frontal Lobe, 163, 172, 188 Fructosamine, 41, 188 Fructose, 47, 58, 72, 188 Fungi, 177, 189, 191, 204, 230 Fungistatic, 167, 189 Fungus, 85, 114, 172, 189 G Gallbladder, 159, 167, 181, 189 Gamma Rays, 189, 216 Ganglia, 17, 159, 166, 189, 207, 211, 223 Gas, 162, 170, 180, 189, 193, 208, 224, 229 Gasoline, 167, 189 Gastric, 119, 171, 182, 185, 189, 193 Gastric Emptying, 189 Gastric Mucosa, 119, 189 Gastroduodenal, 119, 189 Gastrointestinal, 20, 81, 101, 123, 128, 169, 185, 186, 189, 199, 201, 224, 228 Gastrointestinal tract, 81, 186, 189, 199, 228 Gastroparesis, 128, 189 Gelatin, 178, 189, 191, 225 Gene, 12, 13, 14, 15, 16, 58, 66, 88, 144, 145, 167, 189, 190, 194, 199, 209 Gene Expression, 12, 15, 58, 66, 144, 189 Genetic Code, 189, 208 Genetic Engineering, 167, 175, 190 Genetics, 15, 23, 177, 190 Genital, 166, 174, 190 Geriatric, 117, 190 Giardiasis, 190, 203 Gland, 90, 106, 160, 190, 201, 210, 212, 215, 220, 223, 224, 226 Gliosis, 7, 190 Glomerular, 59, 190 Glomerulus, 190 Glucocorticoids, 160, 178, 190 Gluconeogenesis, 13, 190 Glucose Intolerance, 181, 190 Glucose tolerance, 75, 190 Glucose Tolerance Test, 190 Glutamate, 97, 104, 190, 191 Glutamic Acid, 99, 188, 190, 191, 214 Glutamine, 40, 41, 60, 191 Glutathione Peroxidase, 114, 191, 220 Glycine, 24, 49, 57, 77, 99, 118, 167, 191, 221 Glycogen, 98, 117, 190, 191, 205
Index 237
Glycols, 191, 194 Glycolysis, 107, 191 Glycoprotein, 187, 191, 205, 226 Glycosylation, 38, 116, 191 Glycylglycine, 118, 191 Governing Board, 191, 214 Graft, 191, 193, 195, 206 Graft Rejection, 191, 195 Gram-negative, 191, 219 Granulation Tissue, 89, 191 Granulocytes, 191, 221, 230 Grasses, 188, 191 Guanidine, 116, 191 Guanylate Cyclase, 192, 208 Guinea Pigs, 22, 192 H Habitual, 173, 192 Hair follicles, 192, 230 Haploid, 192, 212 Haptens, 160, 192 Headache, 169, 192 Health Promotion, 7, 192 Heart attack, 171, 192 Heart failure, 192 Heme, 167, 179, 192 Hemiparesis, 169, 192 Hemodialysis, 41, 181, 192, 199 Hemoglobin, 92, 162, 173, 185, 192, 198, 199 Hemoglobin A, 173, 192 Hemoglobinuria, 143, 192 Hemolysis, 29, 192 Hemorrhage, 192, 193, 206, 224 Hepatic, 34, 160, 190, 193, 200, 205, 211 Hepatitis, 26, 37, 43, 46, 49, 56, 62, 148, 193, 229 Hepatocytes, 51, 56, 193 Hereditary, 193, 207, 218 Heredity, 159, 189, 190, 193 Hesperidin, 105, 193 Heterogeneity, 160, 193 Hippocampus, 15, 180, 193, 224 Histamine, 162, 193, 194, 198 Histidine, 42, 193 Histology, 90, 193 Homeostasis, 6, 8, 13, 21, 40, 56, 193 Hormonal, 165, 178, 193 Hormone, 178, 180, 185, 193, 196, 197, 213, 219, 221, 225, 226 Host, 31, 131, 166, 176, 193, 195, 199, 219, 229 Humoral, 82, 191, 193
Humour, 193 Hydrogen Peroxide, 84, 99, 114, 122, 171, 191, 193, 200, 224 Hydrolysis, 87, 159, 165, 168, 174, 194, 212, 213, 215, 227 Hydrophilic, 80, 180, 194 Hydrophobic, 180, 194, 200 Hydroxides, 194 Hydroxy Acids, 120, 122, 194 Hydroxyl Radical, 18, 35, 41, 60, 99, 194 Hydroxylation, 41, 60, 194 Hydroxylysine, 175, 194 Hydroxyproline, 175, 194 Hygienic, 194, 222 Hyperaemia, 177, 194 Hypercholesterolemia, 6, 67, 100, 111, 118, 194 Hyperglycemia, 111, 128, 194 Hyperlipidemia, 91, 98, 122, 194 Hyperlipoproteinemia, 91, 122, 194 Hyperpigmentation, 84, 194 Hypersensitivity, 90, 140, 161, 194, 199, 219 Hypersensitivity, Immediate, 161, 194 Hypertension, 47, 51, 58, 86, 87, 98, 99, 101, 116, 131, 164, 171, 192, 194 Hyperthyroidism, 101, 194 Hypertriglyceridemia, 98, 194 Hypertrophy, 113, 167, 194, 219 Hypnotics and Sedatives, 159, 194 Hypoglycemia, 4, 195 Hypotension, 99, 177, 195 Hypoxia, 92, 112, 169, 173, 195, 225 I Id, 53, 61, 148, 154, 156, 195 Idiopathic, 37, 140, 195 Imidazole, 168, 193, 195 Immune response, 23, 82, 121, 160, 163, 166, 178, 191, 192, 195, 224, 229 Immune system, 11, 20, 118, 195, 199, 201, 211, 228, 230 Immunity, 34, 195, 209 Immunization, 195 Immunodeficiency, 67, 143, 195 Immunodiffusion, 160, 195 Immunoelectrophoresis, 160, 195 Immunologic, 173, 195, 216 Immunology, 19, 33, 41, 160, 188, 195 Immunosuppressive, 195 Immunosuppressive therapy, 195 Immunotherapy, 72, 195
238 Lipoic Acid
Impairment, 5, 10, 15, 21, 50, 110, 165, 173, 195, 203 Implant radiation, 195, 197, 216 Impotence, 96, 195 In vitro, 4, 6, 7, 8, 11, 13, 16, 18, 19, 22, 23, 32, 46, 47, 57, 72, 121, 195 In vivo, 8, 9, 10, 13, 16, 22, 37, 49, 59, 195, 209, 226 Incubated, 11, 195 Indicative, 127, 196, 211, 228 Induction, 11, 18, 19, 162, 196 Infarction, 99, 169, 172, 196, 218 Infusion, 23, 73, 77, 89, 196, 206 Ingestion, 88, 118, 169, 190, 196, 213 Inhalation, 196, 213 Initiation, 13, 196 Inlay, 196, 218 Innervation, 196, 202, 211, 220, 226 Inorganic, 124, 174, 194, 196, 213, 220 Inositol, 105, 106, 196 Insight, 50, 196 Insomnia, 76, 196 Insulin, 12, 30, 33, 41, 50, 51, 65, 76, 77, 78, 86, 93, 98, 111, 115, 131, 190, 196, 219, 228 Insulin-dependent diabetes mellitus, 196 Intermittent, 17, 188, 197 Internal radiation, 197, 216 Intervertebral, 197, 216 Intestinal, 20, 99, 118, 171, 184, 190, 197, 201 Intestine, 119, 168, 197, 199, 203 Intoxication, 197, 228 Intracellular, 5, 7, 13, 16, 19, 22, 28, 36, 76, 82, 83, 97, 169, 196, 197, 208, 214, 219, 220, 221 Intracranial Embolism, 173, 197 Intracranial Embolism and Thrombosis, 173, 197 Intrahepatic, 23, 197 Intrahepatic bile ducts, 23, 197 Intramuscular, 77, 197, 210 Intramuscular injection, 77, 197 Intraocular, 87, 197 Intraocular pressure, 87, 197 Intravascular, 87, 92, 197 Intravenous, 92, 122, 129, 196, 197, 210 Intrinsic, 94, 160, 166, 197 Involuntary, 166, 168, 186, 197, 206, 217 Iodine, 105, 197 Ion Channels, 165, 197, 207 Ionization, 197
Ionizing, 111, 161, 185, 197, 202, 216 Ions, 104, 166, 173, 182, 183, 185, 191, 193, 197, 203, 204, 210 Iris, 174, 178, 197, 216 Ischemia, 9, 18, 21, 50, 59, 88, 91, 92, 97, 111, 112, 165, 169, 180, 198, 206, 207, 218 Ischemic stroke, 18, 198 Isoflavones, 117, 198 Isoleucine, 83, 198 Isothiuronium, 87, 198 Isotonic, 105, 198, 204 J Joint, 100, 165, 180, 198, 209, 224 K Kb, 138, 198 Keloid, 89, 198 Keratin, 175, 198, 220 Keratinocytes, 89, 198 Keto, 33, 36, 38, 42, 48, 52, 73, 80, 81, 93, 97, 102, 103, 114, 198 Kidney Disease, 69, 138, 143, 160, 198 Kidney Failure, 184, 198 Kidney stone, 199, 228 Kinetic, 197, 199, 210 L Labile, 176, 199 Large Intestine, 181, 197, 199, 217, 222 Latency, 8, 199 Laxative, 160, 199, 222 Lens, 26, 46, 84, 164, 171, 199, 229 Lenticular, 86, 199 Leprosy, 188, 199 Lesion, 9, 13, 90, 188, 190, 199, 200, 228 Lethal, 57, 179, 199 Leucine, 83, 199 Leukemia, 7, 47, 143, 182, 199 Leukocytes, 9, 166, 168, 173, 185, 191, 199 Leukotrienes, 164, 199 Library Services, 154, 199 Lidocaine, 199, 203 Life Expectancy, 117, 199 Ligament, 199, 215 Ligase, 199, 216 Ligation, 25, 200 Linkages, 192, 200 Lip, 24, 200 Lipid, 5, 8, 10, 22, 37, 38, 57, 61, 91, 92, 112, 122, 164, 174, 196, 198, 200, 210, 227 Lipid Peroxidation, 5, 37, 38, 57, 200, 210 Lipoamide Dehydrogenase, 36, 56, 200 Lipophilic, 80, 92, 200 Lipopolysaccharide, 13, 191, 200
Index 239
Lipoprotein, 5, 43, 191, 200 Liver Cirrhosis, 114, 200 Liver Enzyme Tests, 140, 200 Lobe, 163, 172, 200 Lobule, 90, 200 Loc, 77, 200 Localization, 110, 118, 200 Localized, 169, 187, 196, 200, 205, 212, 228 Locomotion, 200, 212 Lovastatin, 11, 19, 200 Low-density lipoprotein, 37, 48, 100, 200 Lumbar, 200, 220, 226 Lumen, 20, 184, 201 Lycopene, 105, 201 Lymph, 20, 166, 184, 193, 201, 224 Lymph node, 20, 166, 201 Lymphatic, 184, 196, 201, 203, 213, 222 Lymphatic system, 201, 222 Lymphocyte, 11, 28, 163, 201, 202 Lymphoid, 163, 191, 201 Lymphoma, 143, 201 Lysine, 16, 23, 37, 49, 105, 194, 201, 227 M Macula, 188, 201 Macula Lutea, 201 Macular Degeneration, 84, 86, 116, 201 Malabsorption, 143, 201 Malaria, 111, 201 Malaria, Falciparum, 201 Malaria, Vivax, 201 Malignant, 82, 143, 164, 201, 207, 216 Malnutrition, 101, 160, 165, 201, 206 Malondialdehyde, 5, 201 Mandible, 161, 201, 218 Man-made, 95, 202 Mannans, 189, 202 Matrix metalloproteinase, 18, 202 Meat, 3, 47, 77, 117, 202, 220 Medial, 164, 202, 209, 226 Median Nerve, 171, 202 Mediator, 88, 202 MEDLINE, 139, 142, 143, 202 Megaloblastic, 188, 202 Meglumine, 77, 202 Meibomian, 173, 202 Meibomian Glands, 173, 202 Melanin, 90, 197, 202, 212, 228 Melanocytes, 194, 202 Melanoma, 84, 143, 168, 202 Membrane, 8, 35, 88, 104, 159, 165, 172, 173, 174, 176, 177, 180, 181, 186, 191,
197, 202, 205, 209, 212, 218, 221, 226, 227, 229 Memory, 5, 10, 25, 50, 82, 97, 98, 99, 111, 163, 180, 202 Meninges, 172, 203 Mental Disorders, 69, 203, 215 Mercury, 39, 60, 188, 203 Mesenchymal, 185, 203 Mesenteric, 20, 203 Mesentery, 203 Meta-Analysis, 118, 203 Metabolic Clearance Rate, 77, 203 Metabolic disorder, 74, 91, 98, 122, 203 Metabolite, 8, 88, 168, 181, 200, 203 Metastasis, 202, 203, 207 Methamphetamine, 76, 203 Methionine, 14, 16, 108, 113, 181, 203, 224 Metronidazole, 123, 203 Mexiletine, 129, 203 MI, 88, 157, 203 Micelles, 92, 203 Microbe, 203, 226 Microcirculation, 34, 200, 204 Micronutrients, 7, 82, 110, 113, 204 Microorganism, 83, 175, 204, 229 Microscopy, 20, 43, 166, 204 Micturition, 113, 204 Middle Cerebral Artery, 9, 204 Migration, 46, 56, 204, 207 Milk Thistle, 108, 204, 221 Mineralocorticoids, 160, 178, 204 Mitochondria, 8, 12, 25, 47, 52, 76, 113, 204, 205, 206, 209 Mitochondrial Swelling, 204, 207 Mitosis, 164, 204 Mitotic, 182, 204 Mitotic inhibitors, 182, 204 Modification, 12, 43, 66, 73, 74, 97, 190, 204, 216 Modulator, 29, 204 Molecular, 6, 7, 10, 11, 14, 15, 18, 24, 33, 37, 38, 40, 46, 49, 50, 51, 77, 103, 107, 139, 141, 142, 162, 167, 176, 180, 187, 188, 191, 204, 224, 227 Molecular Structure, 204, 227 Monitor, 178, 205, 208 Monoamine, 162, 181, 205 Monoamine Oxidase, 162, 181, 205 Monoclonal, 205, 216 Monocyte, 13, 205 Mononeuropathies, 128, 205 Mononuclear, 30, 42, 205
240 Lipoic Acid
Morphological, 20, 184, 189, 202, 205 Morphology, 171, 205 Motion Sickness, 205, 206 Motor Activity, 119, 177, 205 Motor nerve, 21, 205 Mucolytic, 159, 205 Mucosa, 20, 189, 205, 223 Multienzyme Complexes, 14, 15, 81, 102, 114, 205 Multiple Organ Failure, 92, 205 Muscle Fatigue, 118, 205 Muscle Fibers, 206 Muscular Atrophy, 143, 206 Muscular Dystrophies, 183, 206 Myasthenia, 192, 206 Mydriatic, 181, 206 Myelin, 206, 207, 220 Myocardial infarction, 99, 178, 203, 206 Myocardial Reperfusion, 206, 218 Myocardial Reperfusion Injury, 206, 218 Myocardium, 203, 206, 219 Myotonic Dystrophy, 143, 206 N N-acetyl, 8, 11, 19, 41, 42, 60, 82, 95, 100, 105, 108, 113, 159, 206 N-acetyl cysteine, 8, 11, 42, 82, 105, 113, 206 Narcolepsy, 181, 206 Nausea, 121, 123, 182, 189, 206 NCI, 1, 68, 137, 174, 206 Necrosis, 89, 104, 164, 172, 196, 203, 206, 207, 218, 221 Need, 3, 11, 76, 86, 91, 94, 111, 114, 118, 128, 140, 149, 160, 174, 191, 202, 207, 226 Neoplasia, 143, 207 Neoplasms, 164, 168, 179, 207, 211, 216, 225 Neoplastic, 173, 201, 207 Nephropathy, 75, 86, 93, 198, 207 Nervous System, 7, 51, 78, 79, 86, 97, 106, 111, 143, 159, 162, 167, 169, 172, 173, 175, 181, 189, 190, 191, 192, 199, 202, 203, 207, 208, 209, 211, 224 Nervousness, 76, 207 Neural, 21, 37, 49, 57, 162, 193, 205, 207 Neurobehavioral Manifestations, 169, 181, 207 Neurodegenerative Diseases, 87, 111, 166, 207 Neuroglia, 190, 207 Neurologic, 9, 169, 207 Neuromuscular, 159, 207
Neuromuscular Junction, 159, 207 Neuronal, 7, 19, 38, 49, 207 Neurons, 7, 46, 79, 110, 175, 180, 186, 189, 207, 223, 225 Neuropathy, 4, 15, 17, 21, 34, 37, 39, 43, 44, 46, 57, 68, 75, 91, 109, 128, 140, 161, 166, 207, 211 Neuroprotective Agents, 79, 207 Neurotoxic, 79, 208 Neurotoxicity, 111, 208 Neurotoxins, 72, 208 Neutrons, 161, 168, 208, 216 Neutrophil, 90, 208 Niacin, 76, 100, 105, 106, 208, 227 Niacinamide, 100, 113, 208 Nitric Oxide, 5, 11, 18, 21, 22, 31, 38, 49, 51, 208 Nitrogen, 6, 7, 18, 78, 106, 115, 161, 162, 180, 186, 187, 191, 208, 227 Nuclear, 13, 41, 60, 166, 177, 183, 189, 202, 207, 208, 218 Nuclei, 161, 163, 177, 183, 190, 204, 208, 209, 215 Nucleic acid, 18, 189, 208, 216 Nucleus, 114, 163, 164, 166, 167, 174, 179, 181, 183, 185, 189, 199, 205, 208, 215, 223, 225 Nutritional Support, 100, 208 O Odour, 164, 208 Ointments, 182, 209, 222 Omega-3 fatty acid, 79, 209 Oncogene, 31, 34, 143, 209 Opacity, 171, 180, 209 Ophthalmology, 187, 209 Opsin, 209, 218 Optic Chiasm, 209 Optic Nerve, 87, 209, 218, 220 Optic nerve head, 87, 209 Organelles, 179, 202, 209, 213 Osmotic, 160, 204, 209, 221 Osteoarthritis, 101, 209 Ovary, 209, 213 Oxaliplatin, 34, 209 Oxidants, 17, 209 Oxidation, 9, 18, 25, 50, 76, 86, 94, 98, 109, 159, 164, 168, 174, 179, 191, 200, 209, 210 Oxidation-Reduction, 168, 209, 210 Oxidative Phosphorylation, 88, 210 Oxygen Consumption, 8, 210, 218 Oxygenation, 113, 180, 210
Index 241
P Palate, 210, 223 Palliative, 82, 210, 225 Palsies, 128, 210 Pancreas, 159, 167, 168, 181, 196, 210, 220, 227, 228 Pancreatic, 143, 171, 210 Pancreatic cancer, 143, 210 Papule, 90, 210 Parasitic, 210, 219 Parenteral, 77, 210 Paroxysmal, 143, 210 Partial remission, 210, 217 Particle, 202, 210, 222, 227 Particle Accelerators, 202, 210 Pathogenesis, 19, 128, 210 Pathologic, 20, 159, 164, 167, 178, 194, 211, 218 Pathologic Processes, 164, 211 Pathologies, 13, 91, 211 Pathophysiology, 18, 23, 123, 211 Pelvic, 211, 215 Penicillin, 163, 211, 228 Pepsin, 72, 211 Peptide, 184, 198, 211, 213, 215, 227 Percutaneous, 18, 211 Perfusion, 87, 92, 195, 211 Peripheral blood, 33, 42, 211 Peripheral Nervous System, 207, 210, 211, 224 Peripheral Neuropathy, 44, 140, 211 Peripheral Vascular Disease, 99, 211 Peroneal Nerve, 211, 220 Peroxide, 114, 167, 211 Peroxisome Proliferators, 8, 211 Phagocyte, 209, 211 Phallic, 187, 211 Pharmaceutical Preparations, 79, 115, 172, 186, 189, 211 Pharmaceutical Solutions, 182, 212 Pharmacokinetic, 212 Pharmacologic, 212, 227 Phenyl, 37, 49, 79, 114, 212 Phenylacetate, 11, 212 Phenylalanine, 165, 212, 228 Phospholipases, 212, 221 Phospholipids, 187, 196, 200, 212 Phosphorus, 170, 212 Phosphorylated, 175, 212 Phosphorylation, 88, 212 Physiologic, 88, 105, 160, 167, 198, 204, 212, 217, 218
Physiology, 20, 28, 33, 49, 50, 51, 57, 59, 97, 183, 212 Pigment, 167, 173, 201, 202, 212 Pigmentation, 84, 194, 212 Pilot study, 10, 59, 212 Pituitary Gland, 178, 212 Plaque, 13, 15, 99, 165, 212 Plasma cells, 163, 191, 213 Plasma protein, 160, 184, 213, 221 Plastids, 52, 209, 213 Platelet Activation, 213, 221 Platelet Aggregation, 162, 208, 213, 226 Platelet-Derived Growth Factor, 89, 213 Platelets, 89, 172, 208, 213, 225, 226 Platinum, 174, 209, 213 Platinum Compounds, 209, 213 Plethysmography, 23, 213 Plexus, 202, 213, 220 Poisoning, 15, 62, 85, 86, 93, 114, 132, 169, 173, 197, 203, 206, 213 Pollen, 72, 213, 216 Polycystic, 143, 213 Polypeptide, 159, 161, 175, 185, 187, 213, 214, 230 Posterior, 87, 162, 165, 172, 174, 182, 197, 210, 213, 220 Postoperative, 205, 213 Postprandial, 65, 98, 119, 213 Postsynaptic, 214, 221 Post-traumatic, 169, 214 Potassium, 99, 105, 204, 214, 222 Potentiate, 9, 38, 49, 214 Potentiation, 36, 214, 221 Practice Guidelines, 141, 214 Precancerous, 173, 214 Precursor, 7, 13, 15, 81, 82, 87, 99, 102, 164, 173, 182, 183, 185, 212, 214, 227, 228 Prenatal, 55, 184, 214 Prenatal Diagnosis, 55, 214 Prickle, 198, 214 Primary Biliary Cirrhosis, 32, 214 Probe, 6, 20, 192, 214 Proenzyme, 185, 214 Progeny, 177, 214 Progression, 10, 13, 15, 33, 112, 163, 214 Progressive, 7, 10, 15, 17, 88, 92, 112, 123, 164, 172, 174, 180, 182, 191, 205, 206, 207, 209, 213, 214 Progressive disease, 112, 214 Projection, 180, 209, 214, 217 Proline, 175, 194, 214 Promoter, 76, 214
242 Lipoic Acid
Prophylaxis, 91, 214 Prostaglandins, 164, 215 Prostate, 96, 113, 143, 166, 167, 215, 228 Prostatic Hyperplasia, 112, 215 Protease, 37, 48, 215 Protein C, 13, 14, 160, 161, 164, 166, 198, 200, 215, 228 Protein S, 118, 143, 144, 168, 189, 215, 225 Proteolytic, 105, 176, 184, 187, 215 Protons, 161, 193, 197, 210, 215, 216 Protozoa, 85, 114, 177, 204, 215 Proximal, 128, 182, 215 Psychiatry, 49, 187, 215 Psychic, 215, 220 Psychomotor, 215, 216 Psychosine, 10, 215 Psychotomimetic, 162, 181, 215 Public Policy, 139, 215 Publishing, 24, 215 Pulmonary, 168, 177, 199, 215, 229 Pulmonary Artery, 168, 215, 229 Pupil, 174, 178, 181, 206, 216 Purines, 216, 221 Pustular, 90, 121, 159, 216 Pyruvate Carboxylase, 37, 55, 216 Pyruvate Dehydrogenase Complex, 37, 41, 49, 107, 200, 216 Q Quality of Life, 17, 82, 216 Quercetin, 78, 116, 216 R Race, 73, 76, 80, 86, 87, 109, 120, 204, 216 Radiation therapy, 116, 121, 186, 197, 216 Radicular, 216 Radiculopathy, 128, 216 Radioactive, 193, 195, 197, 202, 208, 216 Radiolabeled, 216 Radiological, 48, 211, 216 Radiotherapy, 169, 216 Randomized, 5, 10, 11, 35, 44, 183, 217 Reactive Oxygen Species, 8, 19, 20, 22, 78, 99, 100, 107, 115, 217 Receptor, 46, 51, 104, 163, 182, 217, 221 Recombinant, 23, 217 Recombination, 177, 217 Reconstitution, 11, 14, 217 Rectum, 169, 181, 189, 199, 215, 217 Red blood cells, 106, 185, 217 Red Nucleus, 165, 217 Reductase, 6, 14, 16, 26, 35, 36, 48, 72, 73, 96, 161, 200, 217, 225
Refer, 1, 169, 176, 187, 189, 200, 201, 208, 217 Reflex, 43, 73, 217 Reflux, 118, 217 Refraction, 217, 223 Regeneration, 78, 115, 217 Regimen, 98, 183, 217 Reliability, 5, 16, 217 Remission, 17, 217 Renin, 170, 217 Renin-Angiotensin System, 170, 217 Reperfusion, 9, 18, 50, 59, 91, 92, 96, 206, 218 Reperfusion Injury, 9, 18, 50, 91, 218 Resorption, 124, 218 Respiration, 170, 205, 218 Restoration, 42, 67, 92, 206, 217, 218, 230 Resuscitation, 92, 218 Retina, 79, 174, 176, 199, 201, 207, 209, 218, 219, 229 Retinal, 79, 209, 218 Retinal Ganglion Cells, 209, 218 Retinoblastoma, 143, 218 Retinoid, 90, 120, 218 Retinol, 218 Retinopathy, 75, 161, 219 Retrovirus, 7, 219 Rheumatic Heart Disease, 99, 219 Rheumatism, 219 Rheumatoid, 96, 209, 219 Rheumatoid arthritis, 96, 219 Rhinophyma, 123, 219 Riboflavin, 76, 100, 105, 106, 113, 219 Ribose, 100, 160, 219 Rickettsia, 19, 24, 34, 219 Rickettsiae, 19, 219 Rigidity, 21, 212, 219 Risk factor, 61, 91, 100, 122, 219 Rod, 166, 219 Rosiglitazone, 12, 219 Rutin, 78, 105, 116, 216, 219 S Salicylic, 120, 219 Saline, 92, 219 Saliva, 203, 219, 220 Salivary, 181, 210, 219, 220, 224 Salivary glands, 181, 219, 220 Saturated fat, 94, 220 Sciatic Nerve, 21, 211, 220, 226 Sclera, 174, 177, 220 Sclerosis, 7, 143, 164, 220 Screening, 15, 175, 220
Index 243
Sebaceous, 90, 123, 202, 219, 220, 230 Sebaceous gland, 90, 123, 202, 219, 220, 230 Sebum, 90, 159, 175, 220 Secretion, 159, 178, 185, 190, 193, 196, 204, 220 Secretory, 172, 220 Secretory Vesicles, 172, 220 Seizures, 111, 210, 220 Selenium, 18, 25, 26, 46, 54, 56, 99, 100, 105, 108, 113, 114, 116, 220 Selenium Compounds, 18, 220 Selenomethionine, 18, 84, 95, 220 Semen, 215, 220 Senescence, 8, 220 Sensory loss, 17, 216, 220, 225 Septic, 116, 220 Sequencing, 25, 57, 221 Sequester, 173, 221 Serine, 89, 159, 221, 227 Serous, 184, 221 Serum, 17, 29, 40, 81, 92, 101, 122, 160, 162, 168, 176, 198, 200, 204, 217, 221 Serum Albumin, 40, 168, 221 Sex Determination, 143, 221 Shame, 168, 221 Shock, 17, 92, 116, 221, 227 Side effect, 4, 10, 17, 118, 121, 123, 160, 221, 226 Signal Transduction, 30, 196, 221 Signs and Symptoms, 217, 221 Silicon, 105, 221 Silicon Dioxide, 221 Silymarin, 26, 46, 56, 204, 221 Skeletal, 33, 50, 61, 162, 206, 222 Skeleton, 159, 198, 222 Skin Aging, 94, 114, 222 Skin Care, 95, 109, 114, 123, 222 Small intestine, 119, 167, 174, 183, 190, 193, 197, 222, 227 Smooth muscle, 106, 161, 162, 169, 177, 193, 194, 218, 222, 224 Soaps, 222 Social Environment, 216, 222 Sodium, 11, 19, 118, 121, 204, 222, 224 Soft tissue, 168, 222 Solar radiation, 84, 109, 222 Solid tumor, 162, 182, 222 Solvent, 80, 120, 167, 186, 209, 212, 222 Somatic, 193, 204, 211, 222, 228 Sorbitol, 161, 202, 222 Sound wave, 176, 222
Specialist, 149, 181, 222 Specificity, 160, 223 Spectrum, 84, 223 Sperm, 162, 174, 213, 223 Spinal cord, 46, 56, 91, 165, 169, 172, 173, 184, 202, 203, 207, 211, 216, 217, 220, 223 Spinal Cord Injuries, 216, 223 Spinal Nerve Roots, 216, 223 Spinous, 185, 198, 223 Sporadic, 207, 218, 223 Squamous, 90, 223 Squamous Epithelium, 90, 223 Steel, 223, 228 Steroids, 178, 223 Stimulant, 162, 169, 181, 193, 203, 223, 228 Stimulus, 186, 196, 197, 199, 217, 223, 225 Stomach, 118, 159, 181, 185, 189, 190, 193, 206, 211, 217, 222, 223 Stomatitis, 101, 223 Strand, 176, 223 Striatum, 91, 180, 224 Stroke, 9, 19, 63, 69, 96, 99, 111, 138, 171, 198, 207, 224 Subacute, 196, 224 Subclinical, 196, 220, 224 Subcutaneous, 160, 183, 210, 224 Subiculum, 193, 224 Submaxillary, 185, 224 Subspecies, 223, 224 Substance P, 203, 217, 220, 224 Substrate, 14, 24, 46, 82, 98, 224 Suction, 187, 224 Sulfur, 3, 6, 13, 14, 16, 52, 81, 83, 102, 105, 120, 186, 203, 224 Sunburn, 84, 109, 224 Superoxide, 21, 22, 84, 88, 99, 113, 224 Superoxide Dismutase, 21, 23, 224 Supplementation, 4, 5, 9, 10, 13, 32, 47, 51, 56, 57, 58, 59, 60, 61, 73, 97, 100, 101, 224 Suppression, 59, 76, 121, 178, 224 Sweat, 118, 203, 224 Sweat Glands, 224 Sympathomimetic, 162, 181, 182, 185, 203, 224 Symphysis, 215, 224 Symptomatic, 34, 44, 89, 225 Synaptic, 221, 225 Synergistic, 5, 82, 94, 98, 99, 225 Systemic, 11, 92, 168, 169, 185, 196, 216, 223, 225 Systolic, 194, 225
244 Lipoic Acid
T Taurine, 108, 225 Telangiectasia, 31, 123, 143, 225 Temporal, 193, 201, 225 Testosterone, 217, 225 Tetracycline, 123, 225 Thalamic, 165, 225 Thalamic Diseases, 165, 225 Therapeutics, 30, 107, 205, 225 Thiamine, 37, 76, 100, 105, 113, 225 Thioredoxin, 6, 35, 51, 72, 225 Threonine, 221, 225 Threshold, 186, 194, 225 Thrombin, 187, 213, 215, 225, 226 Thrombocytes, 213, 225 Thrombomodulin, 215, 226 Thromboses, 116, 226 Thrombosis, 99, 197, 215, 224, 226 Thromboxanes, 164, 226 Thrombus, 178, 196, 198, 206, 213, 226 Thylakoids, 173, 226 Thyroid, 96, 194, 197, 226, 228 Thyroid Gland, 194, 226 Thyroxine, 160, 212, 226 Tibial Nerve, 220, 226 Tin, 171, 211, 213, 226 Tissue, 15, 21, 23, 38, 49, 56, 72, 76, 89, 91, 92, 100, 104, 105, 114, 160, 162, 163, 165, 166, 167, 168, 169, 170, 173, 174, 177, 178, 180, 182, 183, 184, 186, 187, 189, 191, 195, 199, 201, 202, 203, 206, 207, 208, 211, 212, 213, 217, 218, 221, 222, 223, 226, 227, 228, 230 Tolerance, 51, 75, 160, 190, 226 Tonicity, 193, 198, 226 Topical, 18, 89, 90, 109, 120, 123, 129, 165, 186, 193, 198, 222, 226 Torsion, 196, 226 Toxicity, 12, 39, 60, 65, 107, 113, 121, 140, 182, 203, 226 Toxicokinetics, 226 Toxicology, 30, 39, 43, 47, 50, 51, 140, 226 Toxins, 7, 72, 108, 163, 184, 186, 196, 227 Trace element, 124, 168, 174, 221, 226, 227 Trachea, 226, 227 Transcriptase, 219, 227 Transduction, 221, 227 Transfection, 167, 227 Transferases, 191, 227 Translational, 66, 227 Transmitter, 104, 159, 165, 182, 186, 197, 202, 207, 227
Trauma, 79, 89, 91, 166, 169, 192, 205, 207, 225, 227 Trichomoniasis, 203, 227 Tricyclic, 17, 128, 227 Trifluoroacetic Acid, 23, 227 Triglyceride, 194, 227 Truncal, 128, 227 Trypsin, 72, 184, 214, 227, 230 Trypsin Inhibitors, 72, 227 Tryptophan, 175, 227 Tuberculosis, 177, 219, 227 Tuberous Sclerosis, 143, 227 Tumor marker, 167, 228 Type 2 diabetes, 29, 30, 35, 81, 228 Tyrosine, 7, 42, 48, 51, 89, 90, 120, 182, 228 U Ulcer, 119, 180, 191, 228 Unconscious, 180, 195, 228 Univalent, 194, 210, 228 Urea, 224, 228 Urethra, 166, 215, 228 Uric, 7, 216, 228 Urinary, 6, 113, 228 Urine, 10, 12, 32, 36, 118, 160, 166, 168, 178, 182, 185, 191, 192, 199, 204, 219, 228 V Vaccine, 160, 228 Vagina, 180, 228 Vagus Nerve, 227, 228 Valine, 83, 228 Valves, 219, 228 Vanadium, 105, 228 Vasculitis, 173, 228 Vasoconstriction, 87, 185, 228 Vasodilation, 23, 31, 229 Vasodilator, 22, 169, 182, 193, 206, 229 Vein, 19, 24, 34, 162, 165, 197, 208, 229 Venom, 72, 229 Venous, 23, 165, 172, 197, 215, 229 Venous blood, 172, 229 Ventricle, 193, 216, 225, 229 Ventricular, 110, 206, 229 Venules, 92, 168, 170, 184, 204, 229 Vertebrae, 197, 223, 229 Veterinary Medicine, 139, 229 Viral, 11, 39, 50, 114, 140, 159, 184, 219, 227, 229 Viral Hepatitis, 140, 229 Viral Load, 11, 229 Virulence, 131, 226, 229 Virus, 7, 96, 166, 190, 212, 227, 229 Visceral, 166, 228, 229
Index 245
Viscosity, 159, 229 Vitamin A, 102, 105, 116, 196, 218, 229 Vitreous Body, 218, 229 Vitro, 16, 20, 229 Vivo, 13, 22, 37, 229 Vulgaris, 90, 230 W White blood cell, 163, 196, 199, 201, 205, 208, 213, 230 Windpipe, 226, 230
Wound Healing, 89, 118, 174, 202, 230 X Xenograft, 163, 230 X-ray, 73, 171, 188, 189, 202, 208, 216, 230 Y Yeasts, 111, 189, 230 Z Zygote, 177, 230 Zymogen, 185, 214, 215, 230
246 Lipoic Acid
Index 247
248 Lipoic Acid
