Despite its universality in human female ageing, the menopause and its biology are not completely understood. New biologic mechanisms by which sex hormones may be detrimental or confer protection are continually being discovered. We are now starting to understand that the role of the oestrogen receptor is not identical in all tissues. Important nongenomic effects for sex hormones have also been described. Hormone replacement therapy (HRT) has produced effects on health risks: some are reduced, some are increased, and the rest remain uncertain. HRT is being used by an increasing number of women to alleviate climacteric symptoms in the perimenopausal period and to prevent osteoporosis and cardiovascular disease later. Positive effects on Alzheimer's disease and dementia on the one hand, and an increase in venous thrombosis on the other, are currently being reported by several groups. Both the preventive benefits and the risk of breast cancer seem to be linked to long-term and current use. HRT requires further testing through specific clinical trials, currently underway in the United States, before confident recommendations may be made about the full range of benefits and risks.

The complex relationships between alcohol use and human health represent an area of increasing interest to specialists interested in preventive cardiology. The inverse relationship between alcohol consumption and the incidence of cardiovascular diseases, especially myocardial infarction and ischemic stroke, has in fact gained sound scientific support in the last few years of the 20th century. This book, based in an international symposium on the topic held in Venice, October 30-31, 1999, analyzes in depth the epidemiological association between alcohol consumption and human diseases and discusses the possible mechanisms involved in alcohol-associated protection from atherosclerotic diseases. The oxidative effects of different amounts of alcohol intake and of various alcoholic beverages in the production of these effects - subjects of considerable debate - are also analyzed. This book should be of interest to clinicians and researchers active in the areas of atherosclerosis, public health, preventive medicine, and preventive cardiology. It is intended to specifically help practising clinicians provide their patients with evidence-based answers to the most commonly asked questions regarding alcohol use.

Few topics in women's medicine today are as fraught with confusion and controversy as the question of appropriate treatment for menopausal symptoms and the prevention of negative long term health outcomes common to post-menopausal women. Cardiovascular disease (CVD), osteoporosis, and cancer - the most common causes of death, disability and impaired quality of life for women - can potentially be prevented or forestalled by dietary, behavioural and drug interventions. A better understanding of the natural history of the menopause is critical to providing better care. If women and their physicians have a better understanding of predictors of risk, they could make more informed decisions about interventions related to menopausal symptoms, CVD, osteoporosis and gynaecologic and breast cancer. Few other recently introduced medical interventions have as great a potential of affecting morbidity and mortality as does hormone replacement therapy (HRT). HRT has produced effect on health risk: some are reduced, some are raised, and some uncertain, and these data are interpreted differently by various scientific, medical and consumer groups.

The International Symposium on Prostaglandins and Related Compounds, first held in Vienna 1972, revisited the city after 24 years for the 10TH Symposium. For the many re searchers working in this multi-disciplinary field it was an opportunity to exchange their ex periences and share new data with colleagues from all around the world. This scientific exchange was largely encouraged by the unseasonably cold and rainy weather. For the first time, there was quite a large attendance from the former Communist countries. Eugene Garfield prepared a key note address delivered during the meeting (The Sci entist 1996, 12) reviewing the contribution of the Nobel Laureates U.S. von Euler, l.R. Vane, S.K. Bergstrom, and B.I. Samuelsson, discussing the relevance of the more than 40,000 pa pers in this area published since 1991. Overall, there is still a rapidly growing interest, and in particular a great variety of clinical applications of this family of compounds which were dis cussed in detail during the meeting. Beside the lectures there were 19 workshops covering nearly all the topics of key in terest. All the speakers were invited to prepare a manuscript which has resulted in the volume now in your hands. Special thanks to Dr. Patrick Wong and the new publisher of this series who helped to publish the proceedings in the usual quality and reasonable period of time. Looking forward to seeing all of you again in Florence in 1999, hopefully with much more sun."

The issue of interaction of risk factors in cardiovascular disease is timely and of clinical relevance. This book is a collection of the scientific contributions to the 4th International Symposium on Multiple Risk Factors and Cardiovascular Disease: Strategies of Prevention of Coronary Heart Disease, Cardiac Failure, and Stroke, and addresses the role of simultaneous risk factors in patients. Because patients with two or more risk factors are at very high risk for developing cardiovascular diseases, special care should be taken in the choice of appropriate therapeutic intervention.

Risk factors are also discussed from the point of view of the biochemist and the pharmacologist by addressing the mechanisms underlying the onset of hypertension, hyperlipoproteinemia, hypercoagulability, and the possibility of therapeutic intervention.

This book will therefore be of value to the biochemist, pharmacologist, and clinical pharmacologist, as well as to specialists in the field of cardiovascular medicine in order to keep up-to-date with current knowledge in this fast moving field of research.

This volume represents the proceedings ofthe invited lectures ofthe first International Symposium on "Serotonin from Cell Biology to Pharmacology and Therapeutics" which was held in Florence on March 29 -Aprill, 1989. This meeting, held under the co-sponsorship of the Serotonin Club and the Fondazione Giovanni Lorenzini, represents the first attempt to bring together scientists fascinated by the complexity of the action of 5-hydroxytryptamine throughout the body and in various species. Hence this volume provides the reader with the unique overview of the sources, effects, receptors, physiological actions and pathological role of Serotonin. As such it will be of interest not only to the person devoting herorhis research efforts to the study of 5-hydroxytryptamine but also to all scholars and even clinicians wanting to know how the powerful monoamine can modulate cellular functions. To accelerate the publication of these proceedings the Editors and the publishers have selected the camera ready format and have avoided a lengthy refereeing process. Hence the scientific content of, and the opinions expressed in the chapters are the sole responsibility of the authors. The Editors Milan and Houston The Editors want to thank Mrs. H. Liepman and her staff at Kluwer for the prompt and efficient handling of the manuscripts.

The term "autoimmunity" has been used to categorize a number of different diseases of unknown etiology. The term as applied to many of these diseases would probably be interpreted best as "autoreactivity," as the clinical phenotypes are often characterized by an inflammatory-like accumulation of activated cells of the immune system at sites of obvious damage of normal cells and/or tissue. The reasons as to why an immune system should attack itself are far from clear, although the association with specific infectious diseases in genetically susceptible people remains perhaps our best lead. The input of the biotechnological revolution has enabled us to attempt to readdress many of the fundamental questions raised by clinical and serological associations with autoimmune disease. The ability to dissect the immune response to these infectious agents which are associated with autoimmune features (as well as the facility to identify new agents, e. g. HIV), in addition to the ability to clone and sequence immune response genes, has enabled a much better understanding, at least of the complexity of "autoimmunity" to be gleaned. This volume contains the chapters that summarize the plenary presentations given at The Impact of Biotechnology on AUTOIMMUNI1Y meeting in Florence, Italy in June 1993. They cover all aspects from pathogenesis to treatment. The association with infectious diseases and autoimmunity is comprehensively covered by David Isenberg who reviews major issues, such as the association of autoantibodies appearing after infectious disease and antibacterial antibodies associated with autoimmune disease.

This volume contains the Proceedings of the invited lectures of the Second International Sym posium on SEROTONIN from Cell Biology to Pharmacology and Therapeutics held in Houston, Texas September 15-18, 1992. The meeting was held under the co-sponsorship of the Serotonin Club, the Giovanni Lorenzini Medical Foundation, and the Fondazione Giovanni Lorenzini. This volume discusses the major exploration in knowledge that has occurred recently of the complex role that 5- hydroxytryptamine (serotonin) plays in health and disease. In par ticular, these Proceedings highlight major breakthroughs in molecular biology and classification of receptor subtypes that are responsible for the many actions of the monoamine. The ever increasing importance of serotonin in central regulation, whether autonomic or behavioral is represented by a large number of chapters prepared by world experts. Additionally, the role of serotonin in peripheral organs is also discussed. Hence, this volume provides the reader with a unique, up-to-date review of this exciting and novel area of science. These Proceedings obviously are of great interest, not only to the researchers directly engaged in the quest for the understanding and unraveling of the actions of the interactions with serotonin as a major neurohumoral mediator, but also to all scholars and clinicians who wish to acquire a better understanding of the functioning of the brain and of peripheral organs. Since this volume was constructed as a compilation of invited lectures, the scientific content and the opinions expressed in the chapters are the sole responsibility of the authors."

List of Contributors xviii An Aging Humankind: New Realities E. Dicgalusy Does Menopause Increase the Risk of Coronary Heart Disease? M.V. Huisrnan Chronic Low-Grade Metabolic Acidosis in Normal Adult Humans: Pathophysiology and Consequences L. Frassetto, R.C. Morris, Jr., K. Todd, and A. Sebastian The Menopause, Sex Hormones, and Rheumatic Disease G. Hall Novel Mechanisms of Estrogen Action J.-A. Gustafsson The Action of Ovarian Steroid Hormones on Tissues and Organs M.J. Legato Nongenomic Mechanisms of Sex Hormones J.H.H. Thijssen Action of Specific Estrogens on Vascular Cells C.S. Wingrove and J.C. Stevenson Direct Actions of Estrogen on Vascular Cells Ameliorates Response to hjury D. W. Losordo ix Newer Progestogens G. Samsioe IV. 11. Cardiovascular Disease: Risk Factors Related to Thrombosis G. de Gaetano, M.B. Donati, and L. Iacoviello Estrogen Effect upon Coronary Vasculature G.M.C. Rosano, F. Leonardo, and G. Panina Estrogen and Endothelial Function A. Virdis, L. Ghiadoni, I. Sudano, S. Pinto, S. Taddei, and A. Salvetti Action of Specific Estrogens on the Coronary Artery: Effects on Lipoproteins, Coagulation, and Fibrinolysis J.M. Sullivan Coronary Heart Disease in Women: Status 1998 N. K. Wenger Introduction to Osteoporosis C. Christiansen Genetics of Osteoporosis L. Masi, L. Gennari, A. Falchetti, and M.L. Brandi The Clinical Management of Osteoporosis S.E. Papapou los VI.

Peroxisome Proliferator Activated Receptors (PPARs) attract great attention in light of the wide spectrum of genes of biological and medical relevance identified as under their control. As a consequence, our knowledge of the role of these receptors in physiology and pathology continues to grow at a fast pace and PPARs have become an interesting target for the treatment of many pathological conditions, including diabetes and atherosclerosis. This volume provides an authoritative view of the current clinical and scientific developments within this evolving area of study.

Patients with two or more risk factors have a very high risk of developing cardiovascular disease. It follows that the strategy for the intervention of multiple risk factors is in fact of paramount relevance in detecting patients at high risk of cardiovascular disease requiring therapeutic intervention. The text also discusses risk factors from the point of view of biochemists and pharmacologists by addressing the mechanisms underlying the onset of hypertension, hyperlipoproteinaemia, hypercoagulability and the possibility of therapeutic intervention.

The 4th International Symposium on Women's Health and Menopause, organized by the Giovanni Lorenzini Medical Foundation (Milan, Italy and Houston, Texas) focused on the new strategies to improve the quality of life of post-menopausal women. This volume illustrates the findings of this conference and includes information on the age-related degenerative processes occurring after menopause including cardiovascular disease, cancer, fractures and dementia.

The 11th international Conference on ADVANCES IN PROSTAGLANDIN AND LEUKOTRIENE RESEARCH: BASICSCIENCEANDNEWCLlNICALApPLlCA TIONS was held, as in the past, in Florence, Italy, on June 4-8, 2000. A selection of lectures presented at the meeting is included in this volume, which continues the tradition of covering both basic and clinical aspects of prostaglandin and leukotriene research. At this meeting particular emphasis was given to the lipid mediator circuits of lipoxin and leukotrienes and to the expression ofthe COX2 gene. The plenary lectures by C.N. Serhan (Boston, Massachusetts, U.S.A.) and H.R. Herschman (Los Angeles, California, U.S.A.) were devoted to these areas, while S. Narumiya (Kyoto, Japan) and J.M. Drazen (Boston, Massachusetts, U.S.A.) presented the latest advances in the fields ofprostanoid receptors and the genetics of asthma. Specific sessions focused on vascular physiopathology, cell differentiation and cancer, and the cardiovascular system. Lipoxygenases were discussed in detail at the molecular and cellular levels and attention was given to signal transduction pathways for leukotrienes and prostanoids. K.F. Austen (Boston, Massachusetts, U.S.A.) and T. Izumi (Tokyo, Japan) clarified the role and regulation ofLTC synthase ofleukotriene biosynthesis. Other important sessions 4 described regulation and control of nitric oxide, cannabimimetic eicosanoids, and the roles of eicosanoids in neuroscience. Applied clinical sessions devoted to the respiratory system and inflammation, including cyclooxygenase pathways, concluded the meeting.

Cocoa and chocolate are the subjects of much research in the fields of food chemistry, food technology, and health science. We now know that cocoa contains a remarkable number of bioactive compounds, and these are being tested in humans to verify their disease prevention characteristics. This state of the art text thoroughly explores the different aspects of the relationship between chocolate and health. After introductory discussion of the historical background, careful attention is devoted to technological developments designed to improve the health-giving qualities of chocolate and biochemical and clinical trials of cocoa and its components. Various health impacts of cocoa and chocolate are thoroughly evaluated, including acute vascular effects and effects on blood pressure, blood lipids, and platelets. Psychological drivers of chocolate consumption and craving are also considered. Readers will find this book to be a rich source of essential information on cocoa and chocolate, their purported health-giving qualities, and the advances that are being made in this area.

Cocoa and chocolate are the subjects of much research in the fields of food chemistry, food technology, and health science. We now know that cocoa contains a remarkable number of bioactive compounds, and these are being tested in humans to verify their disease prevention characteristics. This state of the art text thoroughly explores the different aspects of the relationship between chocolate and health. After introductory discussion of the historical background, careful attention is devoted to technological developments designed to improve the health-giving qualities of chocolate and biochemical and clinical trials of cocoa and its components. Various health impacts of cocoa and chocolate are thoroughly evaluated, including acute vascular effects and effects on blood pressure, blood lipids, and platelets. Psychological drivers of chocolate consumption and craving are also considered. Readers will find this book to be a rich source of essential information on cocoa and chocolate, their purported health-giving qualities, and the advances that are being made in this area.

List of Contributors xviii An Aging Humankind: New Realities E. Dicgalusy Does Menopause Increase the Risk of Coronary Heart Disease? M.V. Huisrnan Chronic Low-Grade Metabolic Acidosis in Normal Adult Humans: Pathophysiology and Consequences L. Frassetto, R.C. Morris, Jr., K. Todd, and A. Sebastian The Menopause, Sex Hormones, and Rheumatic Disease G. Hall Novel Mechanisms of Estrogen Action J.-A. Gustafsson The Action of Ovarian Steroid Hormones on Tissues and Organs M.J. Legato Nongenomic Mechanisms of Sex Hormones J.H.H. Thijssen Action of Specific Estrogens on Vascular Cells C.S. Wingrove and J.C. Stevenson Direct Actions of Estrogen on Vascular Cells Ameliorates Response to hjury D. W. Losordo ix Newer Progestogens G. Samsioe IV. 11. Cardiovascular Disease: Risk Factors Related to Thrombosis G. de Gaetano, M.B. Donati, and L. Iacoviello Estrogen Effect upon Coronary Vasculature G.M.C. Rosano, F. Leonardo, and G. Panina Estrogen and Endothelial Function A. Virdis, L. Ghiadoni, I. Sudano, S. Pinto, S. Taddei, and A. Salvetti Action of Specific Estrogens on the Coronary Artery: Effects on Lipoproteins, Coagulation, and Fibrinolysis J.M. Sullivan Coronary Heart Disease in Women: Status 1998 N. K. Wenger Introduction to Osteoporosis C. Christiansen Genetics of Osteoporosis L. Masi, L. Gennari, A. Falchetti, and M.L. Brandi The Clinical Management of Osteoporosis S.E. Papapou los VI.

The International Symposium on Prostaglandins and Related Compounds, first held in Vienna 1972, revisited the city after 24 years for the 10TH Symposium. For the many re searchers working in this multi-disciplinary field it was an opportunity to exchange their ex periences and share new data with colleagues from all around the world. This scientific exchange was largely encouraged by the unseasonably cold and rainy weather. For the first time, there was quite a large attendance from the former Communist countries. Eugene Garfield prepared a key note address delivered during the meeting (The Sci entist 1996, 12) reviewing the contribution of the Nobel Laureates U.S. von Euler, l.R. Vane, S.K. Bergstrom, and B.I. Samuelsson, discussing the relevance of the more than 40,000 pa pers in this area published since 1991. Overall, there is still a rapidly growing interest, and in particular a great variety of clinical applications of this family of compounds which were dis cussed in detail during the meeting. Beside the lectures there were 19 workshops covering nearly all the topics of key in terest. All the speakers were invited to prepare a manuscript which has resulted in the volume now in your hands. Special thanks to Dr. Patrick Wong and the new publisher of this series who helped to publish the proceedings in the usual quality and reasonable period of time. Looking forward to seeing all of you again in Florence in 1999, hopefully with much more sun."

J. Folch-Pi Director of Scientific Research, McLean Hospital, Belmont, Mass., U.S.A. The development of the central nervous system is possibly the most significant aspect of the growth of a mammal from embryo to adulthood. The central nervous system is obviously the main repository not only of the species' inherited functional characteristics but also of the process of individuation. Whatever "engrams" constitute the basis of individual characteristics are laid down mainly in the central nervous system, and especially the brain, during its growth. The chemical aspect of this process IS clearly of great importance and the significance of its study should be self evident. Nevertheless, it is only one aspect of a parel lei series of morphological, physiological, biochemical and psychological events which take place as an integrated process, the final result of which is the transformation of the post-embryonic nervous system into the functioning adult system. It is imperative, therefore, that any study or description of the chemical events during the development of the CNS should be undertaken in ful I awareness of the concomitant morphological, physiological and psychological events. It is only against this multidiscipl inary informational framework that the chemical events during 2 J. FOLCH-PI development can be correctly interpreted and acquire their ful I significance. With this in mind, the introduction to this volume may best serve its purpose by describing briefly the morphological and physiological events that accompany the chemical aspect of development.

Although the importance of calcium (Ca2+) in the maintenance of cardiac contractility was recognized as early as 1880, the critical role of the ion in the contractile process in skeletal, cardiac, and smooth muscle has only been established within the last three decades. As the complexity of the pharmacological actions of the Ca2+ channel inhibitors grows, there is a continued need to further clarify the inhibitors, both chemically and functionally. This volume provides an update of the field based on the work presented at the 5th International Symposium on Calcium Antagonists: Pharmacology and Clinical Research. It reviews the current state of the growing area of molecular biology of Ca2+ channels. In the cardiovascular area, in addition to the well-established clinical uses of Ca2+ channel inhibitors, exciting new work pointing to an application in atherosclerosis is described. The book also includes important uses of Ca2+ antagonists in novel areas of interest such as the gastrointestinal tract, renal protection and multi-drug resistance.

Despite its universality in human female aging, the menopause and its biology are not completely understood. New biologic mechanisms by which sex hormones may be detrimental or confer protection are continually being discovered. We are now starting to understand that the role of the estrogen receptor is not identical in all tissues. Important nongenomic effects for sex hormones have also been described. Hormone replacement therapy (HRT) has produced effects on health risks: some are reduced, some are increased, and the rest remain uncertain. HRT is being used by an increasing number of women to alleviate climacteric symptoms in the perimenopausal period and to prevent osteoporosis and cardiovascular disease later. Positive effects on Alzheimer's disease and dementia on the one hand, and an increase in venous thrombosis on the other, are currently being reported by several groups. Both the preventive benefits and the risk of breast cancer seem to be linked to long-term and current use. HRT requires further testing through specific clinical trials, currently underway in the United States, before confident recommendations may be made about the full range of benefits and risks.

This volume contains the Proceedings of the invited lectures of the Second International Sym posium on SEROTONIN from Cell Biology to Pharmacology and Therapeutics held in Houston, Texas September 15-18, 1992. The meeting was held under the co-sponsorship of the Serotonin Club, the Giovanni Lorenzini Medical Foundation, and the Fondazione Giovanni Lorenzini. This volume discusses the major exploration in knowledge that has occurred recently of the complex role that 5- hydroxytryptamine (serotonin) plays in health and disease. In par ticular, these Proceedings highlight major breakthroughs in molecular biology and classification of receptor subtypes that are responsible for the many actions of the monoamine. The ever increasing importance of serotonin in central regulation, whether autonomic or behavioral is represented by a large number of chapters prepared by world experts. Additionally, the role of serotonin in peripheral organs is also discussed. Hence, this volume provides the reader with a unique, up-to-date review of this exciting and novel area of science. These Proceedings obviously are of great interest, not only to the researchers directly engaged in the quest for the understanding and unraveling of the actions of the interactions with serotonin as a major neurohumoral mediator, but also to all scholars and clinicians who wish to acquire a better understanding of the functioning of the brain and of peripheral organs. Since this volume was constructed as a compilation of invited lectures, the scientific content and the opinions expressed in the chapters are the sole responsibility of the authors.

Few topics in women's medicine today are as fraught with confusion and controversy as the question of appropriate treatment for menopausal symptoms and the prevention of negative long term health outcomes common to post-menopausal women. Cardiovascular disease (CVD), osteoporosis, and cancer -- the most common causes of death, disability and impaired quality of life for women -- can potentially be prevented or forestalled by dietary, behavioral, and drug interventions. A better understanding of the natural history of the menopause is critical to providing better care. If women and their physicians have a better understanding of predictors of risk, they could make more informed decisions about interventions related to menopausal symptoms, CVD, osteoporosis and gynecologic and breast cancer. Few other recently introduced medical interventions have as great a potential of affecting morbidity and mortality as does hormone replacement therapy (HRT). HRT has produced effect on health risk: some are reduced, some are raised, and some uncertain, and these data are interpreted differently by various scientific, medical and consumer groups.

The term "autoimmunity" has been used to categorize a number of different diseases of unknown etiology. The term as applied to many of these diseases would probably be interpreted best as "autoreactivity," as the clinical phenotypes are often characterized by an inflammatory-like accumulation of activated cells of the immune system at sites of obvious damage of normal cells and/or tissue. The reasons as to why an immune system should attack itself are far from clear, although the association with specific infectious diseases in genetically susceptible people remains perhaps our best lead. The input of the biotechnological revolution has enabled us to attempt to readdress many of the fundamental questions raised by clinical and serological associations with autoimmune disease. The ability to dissect the immune response to these infectious agents which are associated with autoimmune features (as well as the facility to identify new agents, e. g. HIV), in addition to the ability to clone and sequence immune response genes, has enabled a much better understanding, at least of the complexity of "autoimmunity" to be gleaned. This volume contains the chapters that summarize the plenary presentations given at The Impact of Biotechnology on AUTOIMMUNI1Y meeting in Florence, Italy in June 1993. They cover all aspects from pathogenesis to treatment. The association with infectious diseases and autoimmunity is comprehensively covered by David Isenberg who reviews major issues, such as the association of autoantibodies appearing after infectious disease and antibacterial antibodies associated with autoimmune disease.

This volume is a collection of the most significant contributions to the 4th International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE: STRATEGIES OF PREVENTION OF CORONARY HEART DISEASE, CARDIAC F AlLURE, AND STROKE held in Washington, D. C. in April 1997. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological, clinical, and biological evidence that individuals from industrialized countries often possess two or more risk factors which synergistically increase the global risk profile. This has become more evident in recent years with the increase in life expectancy of populations in the industrialized countries. The evidence that a combination of risk factors confers a very high risk of developing cardiovascular diseases, is of pivotal interest in the process of detection of patients who will benefit the most from pharmacological treatment. Many recent epidemiological data identifying the intrinsic and environmental factors contributing to the development of atherosclerosis are discussed. These results, in parallel with basic and clinical research, underline atherosclerosis as a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure rheologic forces, carbohydrate tolerance, and thrombogenic factors, including fibrinogen, tissue factor, PAl-I, and homocysteine. Furthennore, the risk associated with anyone of these risk factors varies widely depending on the level of the associated atherogenic risk factors. Hyper cholesterolemia and hypertriglyceridemia, for instance, are more common than would be expected by chance among hypertensive patients.

This volume, based on the International Congress Creatine: From Basic Science to Clinical Application, held in Milan on June 4, 1999, outlines the physiological role of creatine in the human body as well as its possible role in different pathological conditions. Creatine is already used as a dietary supplement to augment muscle performance in healthy individuals and inpatients with immobilizing diseases, such as complex fractures. There is also an increasing interest in its administration in a growing number of clinical conditions. A specific deficit of endogenous synthesis of creatine which responds to high dosage exogenous supplementation has been described. In cardiac failure and in chronic obstructive pulmonary disease, creatine improves the contractility of the muscular system. Promising effects of this substance have also been described in animal models of neurodegenerative disorders, such as amyotrophic lateral sclerosis, and in some mitochondrial cytopathies. This volume is of obvious interest to basic scientists working on the physiology of creatine and to clinicians interested in its medical indications.