One of the hallmarks of aging is the decreased capacity to adapt to changes in the environment. In a constant, controlled environment, it is often difficult to distin guish the functioning of the young organism from that of the old. However, when stresses are applied-temperature stresses, dietary stresses, infection, emotional stresses-the differences are more apparent. Frequently, the response ofthe old is delayed and may never reach the same mag'nitude as the young. These responses, in most cases, are mediated by the neuroendocrine system, which communicates via hormones, neurotransmitters, and related substances. Thus, it is important to understand the age-related changes that take place in the secretion and act ion of these substances and how these changes relate to the well-being of the whole organism. Indeed, the "neuroendocrine theory of aging" proposes that almost all of the characteristics of aging can be accounted for by dysfunction of the neuroendocrine system. A book on endocrine function and aging is particularly relevant at this time. With the advent of the techniques of molecular biology, there has bee an explo sion of knowledge concerning hormone secretion and action. Hormones, pro hormones, hormone receptors, and "second messenger" mediators rapidly are being cloned and sequenced. Such knowledge gives us important insights into the molecular workings of these substances as well as into the genetic hasis of endo crine dysfunction. These new tools are now being applied to the problem of age related changes in endocrine function."

Glucagon III complements "Glucagon I" and "II" published in 1983 in this series as "Vols. 66/I" and "II." These three volumes truly represent a "glucagon encyclopedia" and as such have no competitors in the scientific literature worldwide. In this volume, the most recent data on glucagon molecular biology are reviewed together with clinically relevant information on the role of glucagon in the pathophysiology of diabetes, the place of glucagon in medical imaging or in emergency medicine. Chapters are devoted to newly identified members of the glucagon family such as glucagon-like peptide-1 (GLP-1) and oxyntomodulin. Glucagon III is a comprehensive review of all information published on this important hormone since 1983 and is "the" reference book on the subject.

an adequate oxygen supply is vital for the undisturbed development of the fetus and its functions. This book gives a synopsis of the ruling influence that oxygen has in multiple regulation sytems in the mother and especially in the fetus. The authors consider oxygen as a manipulated variable or as a corrective element during normal pregnancy, during delivery and during acute and chronic oxygen deficiency. Furthermore, they deal with the consequences that oxygen deficiency has on the fetus.

Alcohol abuse, alcohol intolerance, alcohol dependence and other alcohol-related disabilities are some of the most challenging public health problems facing our modern-day society. The purpose of this comprehensive monograph is to review the available knowledge concerning the pharmacogenetic basis of alcohol sensitivity and its physiolgical implications and to synthesize the bulk of existing knowledge regarding metabolic features and biomedical disturbances related to alcoholism. The chapters cover a broad array of disciplines including an overview of historical and epidemiological aspects, biochemistry and molecular genetics of enzymes involved in alcohol metabolism, biochemical and neuropsychopharmacological effects of alcohol. Major emphasis is placed on the role of genetic factors in alcoholism. The experimental details are summarized and a comprehensive bibliography is included.

Inherited disorders of purine and pyrimidine metabolism in man lead to severe diseases. At the 2nd M}nchner Adventssymposium the state of the art as to the genetic basis, clinical aspects, and the biochemical basis has been given by leading experts in the fields concerning the following diseases: Hypoxanthine phosphoribosyltransferase deficiency (HGPRT-deficieny), adenine phosphoribosyltransferase deficiency (APRT-deficiency), hyperuricemia and gout, adenosine deaminase deficiency (ADA-deficiency, purine nucleoside phosphorylase deficiency (PNP-deficiency). All contributions of the symposium are published within this volume thus giving and overview of this most interesting field.

Biological membranes are often effected by diseases. Molecular events leading to or arising from pathological changes in the course of different diseases are as yet not clearly understood. This competent study by leading experts covers changes of the cellular environment, membranes and the metabolic functions during tissue growth and differentiation as well as aspects of abnormal organelle function in lysosomal storage diseases, peroxisomal and mitochondrial disorders, enzyme defects and regulatory defects of receptors due to oncogenes.

On starting to write the preface it occured to the editors that it might be a good idea to incorporate so me organizational thoughts. First of all, why have. we organized this book on "Glycoprotein storage diseases", an unfamiliar area of pathology unlikely to be encountered in practice? In preparing such a volume we considered that in the past ten years there has been a large amount of intensive research activity on glycoproteinoses and no detailed review has been entirely devoted to this subject. This research has led to new information about hereditary mental retardation and progressive neurologie degeneration, and as clinicians we are impressed with its clinical importance. This volume is intended to represent for the uninitiated as weH as for the expert a summary of studies on dis orders of glycoprotein catabolism written by experts in each area. Each author has written with freedom about his particular experience, describing the establishment and development of his investigations, his methods, the utility and limitations of his work and eventual sources of problems. We are grateful for their many fundamental studies and for their having generously accepted to partecipate in this book. The Editors Acknowledgements We wish to express our gratitude to our friends and colleagues G. Romeo, W.S. Sly and G. Tettamanti whose criticism and suggestions have significantly improved the quality of particular chapters or sections.

Responding to the dramatic scientific and technological developments in the agro-food sector and to the enormous public concern about novel food production and novel food ingredients this volume focusses on defining, classifying and reassessing the quality of food towards human nutritional needs aimed at health. It is designed for all those actively involved in the food sector and for interested lay persons and responsible consumers interested in getting information about the driving forces of the present and future food market, the food industry, and the food policy and the consumer association.

Dyslipidemia affects almost half of American adults and is the most prevalent manageable risk factor for atherosclerosis. Lipid disorders often co-occur with other prevalent conditions such as diabetes and kidney disease; they are also often a concern with certain medication regimens (such as anti-retroviral and certain anti-psychotic agents). Proper treatment of dyslipidemia can reduce the risk of peripheral arterial disease, revascularization procedures, nonfatal myocardial infarction, stroke, and cardiac death. However, only 20% of adults meet the national guidelines for cholesterol control. As part of the Oxford American Cardiology Library, this practical handbook is designed to serve as a concise yet authoritative resource on diagnosing and treating dyslipidemia. The book is tailored to the needs of busy health care professionals treating patients in various clinical settings, and focuses on presenting essential information to clinicians who are at the forefront of the diagnosis and management of dyslipidemia. Featuring evidence-based, concise yet comprehensive discussion of key clinical concepts in addition to numerous figures, tables and illustrations, this pocket-sized handbook will serve as an invaluable guide to healthcare professionals. Features: * Authored by a renowned international group of experts on dyslipidemia. * Chapters include vignettes to enhance clinical relevance.

Mitochondrial diseases are often hard to diagnose. From the time they were first researched without animal models, patients of mitochondrial diseases were of equal interest to both clinical and basic scientists. With the new research done, this book includes updates on the normal structure, function, and molecular biology of the mitochondrial respiratory chain, information on traditional diagnostical methodologies, and an overview of the diagnostic promise of new technologies. The hypermetabolism of Luft disease, although only seen twice, is also studied. There are critical reviews of symptoms and signs associated with syndromes, as well as updates on the genetic defects of either the mitochondrial or the nuclear genome responsible for many disorders.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

The aim of this volume is to underline that promoting physical activity is crucial to preventing illness and maintaining our health, thus leading to a reduction in healthcare costs. Over the last decade studies have shown that physical exercise plays an important role in maintaining an individual's psycho-physical balance. Physical activity therefore helps in tackling today's major health challenges, including diabetes, high blood pressure, and cardiorespiratory diseases.

This timely book provides an overview of topics related to obesity. These include associated health risks, childhood obesity, genetics, evaluation, treatment, behavioral strategies, and successes and failures in preventing obesity. The volume covers evaluation guidelines, different approaches to treatment, including diet, exercise, behavior, drugs, and surgery to deal with the current world-wide obesity epidemic.

Research into the paraoxonase (PON) multigene family has really only blossomed in the last 10 years. Before this time only PON1 was known and research was restricted to toxicologists investigating the metabolism of organophosphate insecticides and nerve gases and a few mad scientists searching for natural substrates.

Since this time two new members PON2 and PON3 have been discovered, all 3 PONs have been shown to act as antioxidants and the PON family has taken centre stage as major players in the development of a wide variety of diseases such as cardiovascular disease, diabetes mellitus, rheumatism, Alzheimer and many more while remaining important in determining organophosphate toxicity.

In September 2006 the 2nd International Conference on Paraoxonases took place in Hajduszoboszlo, Hungary, bringing together the world's foremost experts in the field. The current book is a distillation of the plenary lectures which took place at the meeting, resulting in a comprehensive up to date, state of the art review of current paraoxonase research."

A definitive review in the field of magnesium research, this book brings together the proceedings of the 11th International Magnesium Symposium in Osaka, Japan from October 22-26, 2006. Written by authorities in the area, the book provides a thorough overview of progress in the area of magnesium research. The author is one of the world's foremost magnesium researchers and reviewers, and the book provides essential reading for researchers in magnesium.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

It is fourteen years since insulin was last reviewed in The Handbook of Ex perimental Pharmacology, in volume 32. The present endeavor is more modest in scope. Volume 32 appeared in two separate parts, each having its own subeditors, and together the two parts covered nearly all areas of insulin pharmacology. Such comprehensiveness seemed impractical in a new volume. The amount of in formation related to insulin that is now available simply would not fit in a reasonable amount of space. Furthermore, for better or worse, scientists have be come so specialized that a volume providing such broad coverage seemed likely in its totality to be of interest or value to very few individuals. We therefore decided to limit the present volume to the following areas: insulin chemistry and structure, insulin biosynthesis and secretion, insulin receptor, and insulin action at the cellular level. We felt these areas formed a coherent unit. We also felt, perhaps as much because of our own interests and perspectives as any objective reality, that these were the areas in which recent progress has been most dramatic, and yet, paradoxically and tantalizingly, these were the areas in which most has yet to be learned. Even with this limited scope, there are some major gaps in coverage. Regrettably, two important areas, the beta cell ATP-sensitive potassium channel and the glucose transporter, were among these. Nevertheless, the authors who con tributed have done an excellent job, and we would like to thank them for their diligence.

There has been much popular and scientific interest in the fields of nu trition and aging in recent years. As the importance of proper nutrition in children and young adults becomes more fully understood, it is natural to wonder if proper nutrition could playa similar role in later life. Recent research has indicated that nutrition can potentially intervene in the ag ing process in at least two ways. First, studies in animals and humans have shown that nutrition can be used to improve functional status, which, in turn, is related to perceived quality of life. Second, nutritional manipu lation has been used to extend maximal life span in laboratory animals. How these interesting findings apply to the human situation remains to be explored. The purpose of this book is twofold. The first is to present recent ad vances in our basic knowledge of how nutrition and aging interact with each other. The second is to discuss some applications of this knowledge to the care of the elderly patient. The interaction between aging and nutrition is complex because each may act on the other in either a synergistic or antagonistic fashion. Aging may alter the nutritional status of the elderly by affecting the way nu trients are absorbed and utilized by the body. Aging may also influence food intake and, therefore, nutritional status by decreasing the palatabil ity of food. The environment of the elderly may change so they are less likely to eat well-balanced meals."

As I read this unique volume on diabetes and pregnancy edited by Lois Jovanovic, I was struck by two themes that run throughout these collected chapters. First, this volume provides an excellent assessment of past problems, present management, and future challenges presented by dia betes in pregnancy. Orury's unique, longitudinal experience with diabetes iIi pregnancy provides the reader with an important overview, as does Coetzee's discussion of gestational diabetes. Current problems-deter mining the etiology and prevention of congenital malformations in infants of diabetic mothers (10M), assessment of antepartum fetal condition, management of pregnant patients with diabetic retinopathy, recognition of thyroid dysfunction in the pregnant diabetic woman, and understanding the multitude of metabolic sequelae observed in the 10M-are thoroughly reviewed. Finally, important considerations for future treatment and ther apy such as the adaptation of the fetal pancreas to the disordered intra uterine environment often seen in maternal diabetes, the use of fetal pan creatic tissue for transplantation, the application of exercise in the management of the pregnant woman with diabetes, and the long-term con sequences for the 10M provide an exciting glimpse into the future. The second important theme that emerges is the critical role the problem of diabetes in pregnancy has played in our understanding of maternal and fetal physiology. Clinical observations supported by basic research have emphasized the role of fetal fuels in teratogenesis.

In the years since the initial discovery that blood from diabetic patients contains increased amounts of a posttranslationally gluco sylated form of hemoglobin (hemoglobin Ale)' an impressive number of studies have clarified and expanded the use of glycohemoglobin levels to assess disease status. Many other structural proteins have been shown to undergo similar changes, including proteins from tissues most commonly affected in diabetes (e.g., lens, aorta, peripheral nerve, basement membrane). Thus, the nonenzymatic glycosylation of hemoglobin emerges as an invaluable model for the pathogenesis of certain chronic diabetes complications. In addition to reviewing a wealth of investigative possibilities in the area of these chronic complications-including eye, kidney, nerve, and vascular disease-Dr. Cohen indicates how enhanced nonenzymatic glycosylation in uncontrolled diabetes underscores the pressing need for maintenance of long-term euglycemia. Dr. Cohen is an endocrinologist and diabetes specialist whose research activities have largely focused on the chemistry and metabo lism of the basement membrane in diabetes. This superb monograph on nonenzymatic glycosylation clearly shows the major trends of her past and present research and clinical activities. This book is beautifully written and a pleasure to read. It provides great insight into the mechanisms of the pathogenesis of the oom- vii viii Foreword cations of diabetes and should be of immense value not only to basic and clinical investigators, but also to internists, diabetologists, and endocrinologists in clinical practice."

It has been a challenge for us to edit this volume of Endocrinology and Metabo lism: Progress in Research and Clinical Practice. The topic of the pathogenesis of insulin-dependent, type I diabetes mellitus is particularly appropriate for this series, since advances in this area have been made, to a large extent, by applying state-of-the-art laboratory techniques to clinical samples. Over the last several years, a number of lines of evidence have been gathered, suggesting that classic type I diabetes mellitus results from the autoimmune des truction of pancreatic beta-cells in genetically susceptible individuals. This hypothesis is particularly appealing because it offers a rational approach to the prevention of diabetes by immunosuppression. We have tried to present a balanced, authoritative summary of the information currently available to support the autoimmune hypothesis for the pathogenesis of human type I diabetes, to place this information in historical perspective, to include relevant information from animal models of type I diabetes in which more invasive experimentation is ethical, and, finally, to update the reader on the current status of attempts to intervene in the progression of diabetes with immunosuppressive drugs. New York, New York Fredda Ginsberg-Fellner Robert C. McEvoy Contents Preface.. . . .. .. .. . . . . . . . . . . . . ... . . . . . . . . . . . .. . . . . . . .. . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl . . . . . . . . . . . . . 1. The Autoimmune Hypothesis of Insulin-Dependent Diabetes: 1965 to the Present . . . . . . . . . . . . ..................... . . . . . .

In the middle of the 17th century, the great French philosopher Rene Descartes wrote (L'Homme, J. Le Gras, Paris, 1669) that a suitable stimulation of the brain results in two types of "movements": exterior movements, designed to seek desirable ends and to avoid undesirable or harmful ones and interior movements or "passions" which through the release of "animal spirits" regulate the heart, the liver, and other organs. When it appears appropriate to meet a threat with force, the passion of rage causes the release of strong spirits, whereas when avoidance appears to be the better choice, the passion of fear causes the brain to release weak spirits. We do not know what influence, if any, Descartes had on the thinking of Walter B. Cannon (Bodily Changes in Pain, Hunger, Fear and Rage, Appleton and Co. , New York, 1920), of Hans Selye (The Story of the Adaptation Syndrome, Acta, Inc. , Montreal, 1952), ofG. W. Harris or of R. Guillemin (Hypothalamic-Hypophysial Interrelationships. A Sym posium. c. c. Thomas, Springfield, 1956), but it is interesting to reflect upon the durable value of great ideas which constantly resurface even if modified by other ideas and by new techniques, as if propelled by a preordained intellectual imperative.

Adipose Tissue and Adipokines in Health and Disease presents a comprehensive survey of adipose tissue, its physiological functions, and its role in disease. This volume spans the entire range of adipose tissue studies, from basic anatomical and physiological research to epidemiology and clinical studies. The authors-distinguished researchers, clinicians and epidemiologists-have incorporated groundbreaking recent studies into traditional models of adipose tissue properties. Chapters on well-known properties of adipokines leptin and adiponectin are complemented by an introduction to a novel view of adipose tissue as a dynamic organ that regulates systemic substrate availability and metabolism, along with a variety of other discrete functions. This novel concept is expanded as the role of adipose tissue in maintaining body homeostasis and the modulation of inflammatory and metabolic responses is discussed. Worldwide trends in obesity are discussed from an evolutionary perspective and causes of the current obesity epidemic are postulated. Additionally, researchers and clinicians examine the association and potential role of adipose tissue in disease mediation and offer epidemiological evidence. This volume concludes with a thoughtful and innovative discussion of various approaches to inducing and sustaining weight loss in obese patients and the health effects of such treatments. Adipose Tissue and Adipokines in Health and Disease provides a broad and substantial foundation for understanding new developments in adipose tissue biology and successfully integrating them into new research endeavors.

JIMD Reports publishes case and short research reports in the area of inherited metabolic disorders. Case reports highlight some unusual or previously unrecorded feature relevant to the disorder, or serve as an important reminder of clinical or biochemical features of a Mendelian disorder.

Psychoneuroendocrinology is the study of the interaction between hormones, the brain and human behaviour. This is the first book to examine psychoneuroendocrinology in the context of sport and exercise, offering a comprehensive review of current research and assessment techniques and highlighting directions for future research. The book explores the links between hormones and behaviour, and draws important conclusions for how their study will aid in the understanding of the bidirectional link between sport and behaviour, central to the psychology of sport and exercise. It presents the key hormones that underpin behaviour in a sporting context, including the description of their physiologic mechanisms and behavioural effects. The book reports benchmark standards for the assessment and analysis of hormonal influences of behaviour in sport, and examines practical issues and contexts such as emotional state, overtraining and stress. Psychoneuroendocrinology in Sport and Exercise is a breakthrough text that will be of interest to all advanced students and researchers working in the psychology and physiology of sport and exercise.