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.

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.

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.

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.

Even a brief scan of the table of contents of the present volume is enough to disclose the diversity of research interests and opinions in the field of lipidology. It is precisely this diversity that is the strength of our field and that was showcased by the XII International Symposium of DRUGS AFFECTING LIPID METABOLISM (DALM). The papers published here from these proceedings may be divided into three categories: those that define-and refine---our understanding ofthe clinical benefit of aggressive lipid management, those that develop our knowledge of ris!. assessment, and those that discuss the genetic, bio~hemical, and biophysical mechanisms underlying the pathology of coronary heart disease. On the clinical front, further analysis of the results of the Scandinavian Simvastatin Survival Study (4S) has indicated the cost-effectiveness of therapy in patients with established coronary heart disease. The West of Scotland Coronary Prevention Study (WOSCOPS), whose methodology was described at the DALM XII symposium, has demonstrated in a mostly primary-prevention population what 4S demonstrated for secondary prevention the year before: aggressive lipid-regulating therapy reduces coronary heart disease morbidity and mortality rates without concurrently increasing mortality from noncardiovascular causes. In the future, important considerations will be to develop protocols that maximize benefit in groups underrepresented in traditional clinical research for example, women and the elderly-and to improve compliance to existing treatment regimens. Furthermore, antioxidant, omega-3 fatty acid, and gene therapies warrant further investigation.

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.

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."

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.