Twenty years after its discovery, recombinant human leptin has been approved by the Food and Drug Administration for the treatment of patients with lipodystrophy. Beginning with a synthesis of the vast body of work on its discovery, dissection of mechanisms, and effects in experimental models , the focus of this book shifts to a consideration of the regulation and role of leptin in humans. The emphasis on human-level data is a unique feature of this book. The results of numerous studies indicate that leptin is indeed a regulated human hormone. Leptin provides a detailed account of the myriad physiological, hormonal, metabolic, immunological, mitogenic and inflammatory modulators and targets of leptin in a single volume. Next follows a comprehensive presentation of the therapeutic trials of recombinant leptin in patients with congenital leptin deficiency, lipodystrophy, hypothalamic amenorrhea, and other emerging areas, including leptin supplementation in leptin-replete subjects, leptin substitution for insulin in diabetic models, and novel combination regimens of leptin and other biogenic peptides. Unanswered questions and future directions in leptin research are highlighted in the Foreword by Dr. Jeffrey Friedman and throughout the volume. Identifying such questions helps direct research that could deepen understanding of the complex regulation of leptin under physiological and pathological conditions, a critical prerequisite to its rational deployment in the treatment of human disorders.

The scientific advances in the physiology and pathophysiology of adipose tissue over the last two decades have been considerable. Today, the cellular and molecular mechanisms of adipogenesis are well known. In addition, adipose tissue is now recognized as a real endocrine organ that produces hormones such as the leptin acting to regulate food intake and energy balance in the central nervous system, a finding that has completely revolutionized the paradigm of energy homeostasis. Other adipokines have now been described and these molecules are taking on increasing importance in physiology and pathophysiology. Moreover, numerous works have shown that in obesity, but also in cases of lipodystophy, adipose tissue was the site of a local low-grade inflammation that involves immune cells such as macrophages and certain populations of lymphocytes. This new information is an important step in the pathophysiology of both obesity and related metabolic and cardiovascular complications. Finally, it is a unique and original work focusing on adipose tissue, covering biology and pathology by investigating aspects of molecular and cellular biology, general, metabolic, genetic and genomic biochemistry.

The role of oxidative stress in human disease has become an area of intense interest. Free radicals, a normal product of metabolism, exist in all aerobic cells in balance with biochemical antioxidants. Environmental stress increases the levels of free radicals drastically, thereby disturbing the equilibrium between free radical production and the antioxidant capability causing oxidative stress. Over the years, ROS has been implicated in the pathologies of various diseases like cancer, neurological disorder, cardiovascular diseases rheumatoid arthritis, diabetes etc. This book provides an in depth critical state-of-art reviews from established investigators on free radicals, ROS associated pathogenesis of human diseases, biomarkers of oxidative damage, antioxidants, phytonutrients and other related health concerns of modern society. The present book is aimed at graduate students, researchers in academia, industry and clinicians with the interest in redox biology. Special attention has been devoted to the topic of ROS signalling, oxidative stress induced human pathologies & antioxidative therapies. The book consists of four parts in specified topics based on the current literatures for the better understanding of the readers with respect to their subject-wise interests. The first section of the book provides an overview about the ROS production and their measuring tools and techniques followed by the mechanisms involved in the oxidative stress in the second section. The third section describes the involvement of oxidative stress in different human diseases and the last section focuses on the different strategies to ameliorate oxidative stress induced stress.

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.

Food research (and funding) is becoming more and more focused on health. While researchers and product developers have made great strides in food engineering, there needs to be increased focus on what happens when the food is actually digested. How is the food absorbed? Do the benefits remain? Digestion is a complex topic, and this will be the first book aimed at food researchers. Authored by a physiologist and a food engineer, the book will be a welcome addition to the literature.

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.

This is the first comprehensive volume on Dipeptidyl Aminopeptidases that can be marketed to a wide variety of disciplines, as well as to a variety of clinicians. Leading experts in the field contribute to this state-of-the-art view on these enzymes. This book comes at a time when our understanding of their function is growing ever more rapidly and therapeutic options have become imminent.

As the worldwide prevalence of morbid obesity among adolescents continues to rise, recent years have seen a large increase in the performance of adolescent bariatric surgery. While surgical intervention often becomes necessary when conservative weight-loss therapies have failed, no standards regarding the post-operative regimen and long-term management of adolescent patients have been established. Thus, the treatment of obesity and its co-morbidities requires a multidisciplinary approach, taking into account epidemiological, clinical, nutritional, and genetic aspects of morbid obesity in the pediatric age group. This volume discusses both conventional therapy and surgical options for morbid obesity in the pediatric age group. In the first part, obesity-related diseases, genetics, and psychological factors are analyzed. The second part focuses on current bariatric surgery procedures, including dietary restrictions and guidelines to prevent nutritional deficiencies common after surgery. Therefore, the book will prove an invaluable resource for pediatricians, surgeons, nutritionists, dieticians, and all other health professionals who treat adolescent obesity.

Research over the years has demonstrated that free radicals mediated oxidative stress lies at the helm of almost all patho-physiological phenomena. These findings emphasize on the need to understand the underlying molecular mechanism(s) and their critical role in the pathogenesis. This book aims to focus on these areas to provide readers a comprehensive outlook about the major redox sensitive pathways and networks involved in various disease conditions. In the first chapter of the book, basic information about the oxidative stress, its generation, its biomarkers and its role in body are discussed. In the next three chapters, the role of oxidative stress in various pathologies ranging from neurological disorders, to cardiovascular diseases, cancers, metabolic diseases and ageing have been described. Chapter 5 cumulatively describes the most important molecular signaling pathways that are affected by reactive oxygen species (ROS). These are the mechanisms which are common denominators in various pathological states. In the next part of the book, various antioxidant strategies to target and mitigate ROS have been discussed with details on the mechanisms. Selenium, being the research focus and interest of the authors for years, the role of selenium as an antioxidant as part of selenoproteins has been included in the book. Finally, the book culminates with authors' perspective on the future of the redox biology field. Throughout the book, efforts have been made to use simplified language and suitable figures for ease to understand the contents. Although the authors have tried to touch on all the different aspects of oxidative stress in detail, the fact that it is a continuously growing field with updates coming every day, there might be some areas which might not be described in depth. This book is designed for students, young scientists to get acquainted with the redox biology. Overall, this book is a reference to understand the redox regulation of cellular signaling pathways involved in pathogenesis.

Fabry disease is an X-linked inborn error of metabolism wherein deficiency of a lysosomal enzyme results in systemic deposition of glycosphingolipids. Storage deposition, and hence pathological disease, occurs preferentially in renal glomerular and tubular epithelial cells, myocardial cells, heart valve fibrocytes, neurons of dorsal root ganglia, and in endothelial smooth muscle cells of blood vessels. Thus, Fabry disease is a multi-system disorder, albeit with considerable phenotypic heterogeneity in onset and in severity; however, it is progressive, exhibits extensive morbidity, and is life-threatening. Within the past two decades, there has been a radical change in the natural course Fabry disease by virtue of the availability of specific enzyme replacement therapy. Moreover, there has been a concerted effort to better understand the underlying pathology and equally to identify patients prior to the onset of irreversible end-organ damage. It is to be hoped that the future for patients with Fabry disease can be viewed with greater, albeit guarded, optimism. This state-of-the-art textbook attempts to bridge the span of pre-clinical studies, clinical finding, and management options in a readable but comprehensive manner for the medical practitioner as well as the interested non-medical reader.

This book focuses on predictive, preventative and personalized medicine (PPPM) and how it is related to the healthcare of rare diseases. Readers will discover how advanced rare diseases healthcare provides an excellent proof-of-principles for the personalisation of healthcare systems on a global scale. These chapters look at national plans on rare diseases, at biobanking, gene identification in rare diseases, mitochondrial diseases, rare cancers and virus gene therapy, amongst other topics. There is a chapter dedicated to personalized medicine for hereditary deafness and another exploring the complexity of genotype-phenotype correlations. Specific diseases such as Fabry's, Gauchers and mitochondrial cytopathies are highlighted and we look at enzyme replacement therapy in lysosomal storage diseases. This work is part of a series, produced with the involvement of the European Association for Predictive, Preventive and Personalised Medicine. The series focusses on the concept of an integrative medical approach by PPPM. This volume is dedicated to all aspects related to the prediction, prevention and personalised treatments of rare diseases, and in doing so it explores developments relevant to all medical branches. The authors cover ethical considerations, the creation of a robust platform for professional communication, synergies with patient organisations, doctor-patient collaboration and a new philosophy of integrative medicine by PPPM. This volume serves as a reference source for scientific and medical centres in the field and can be used both at medical curricula and graduate level in the life sciences. Those who place a special emphasis on healthcare promotion and innovations intended to combat rare diseases, save the affected lives and enhance life quality will all find this book of great value."

Stjarne: The present review puts the emphasis on two important developments: the discovery that individual postganglionic sympathetic neurons may secrete multiple transmitter substances from different classes of vesicles and by different mechanisms, and the introduction of new techniques which may permit for the first time direct impulse by impulse analysis of transmitter secretion in individual sympathetic nerve varicosities. Illes: Exogenous and endogen opioid peptides elicit a number of effects in the organism, usually by modifying the function of transmitter and hormone systems, for example, activation of multiple opioid receptors. The effects of opioids on transmitter and hormone release have frequently been reviewed. This review gives a detailed overview on the involvement of multiple opioid receptors in these processes. Rothstein: This article gives an overview of the exchange in acidification and transepithelial salt and water transfer in nonepithelial cells. Delineating the exchanger's most important, common features, and concentrating particularly on its role in cell pH and volume regulation.

The renewal of interest in excitatory amino acids in the 1980s has altered the direction of neurobiology. L-Glutamate, widely regarded as a general perpetu- ator of nonspecific excitation, has become generally regarded as a widely dis- tributed and important neurotransmitter in the CNS. In the past three decades evidence has accumulated that excitatory amino acids are involved in many neurological diseases and that pharmacological intervention may offer pros- pects of novel and more effective therapies. Numerous studies on experimen- tal animals demonstrate that excitatory amino acid antagonists have anxio- lytic, antiepileptic and muscle relaxant effects. Particular interest has developed in the possible neuroprotective efficacy of excitatory amino acid receptor antagonists in neurological diseases such as hypoxia/ischemia, hypo- glycemia, epilepsy, and chronic neurodegenerative disorders (Huntington's, Alzheimer's, and Parkinson's disease, amyotrophic lateral sclerosis, and AIDS). Thus, the drugs changing neurotransmission mediated by excitatory amino acids possess potential therapeutic value. This volume is part of the Schering Research Foundation Workshop Series. It is the goal of the Schering Research Foundation to promote the asso- ciation between industrial and basic research. The support and the organiza- tion of highly qualified symposia belong to the armamentarium by which this purpose is fulfilled, and we are convinced that the workshop "Excitatory Amino Acids and Second Messenger Systems" has contributed to this. Gunter Stock Ursula-F.

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 heart has a very high energy demand but very little energy reserves. In order to sustain contractile function, the heart has to continually produce a large amount of ATP.The heart utilizes free fatty acids mainly and carbohydrates to some extent as substrates for making energy and any change in this energy supply can seriously compromise cardiac function.It has emerged that alterations in cardiac energy metabolism are a major contributor to the development of a number of different forms of heart disease.It is also now known that optimizing energy metabolism in the heart is a viable and important approach to treating various forms of heart disease.

"Cardiac Energy Metabolism in Health and Disease" describes the research advances that have been made in understanding what controls cardiac energy metabolism at molecular, transcriptional and physiological levels.It also describes how alterations in energy metabolism contribute to the development of heart dysfunction and how optimization of energy metabolism can be used to treat heart disease.The topics covered include a discussion of the effects of myocardial ischemia, diabetes, obesity, hypertrophy, heart failure, and genetic disorders of mitochondrial oxidative metabolism on cardiac energetics.The treatment of heart disease by optimizing energy metabolism is also discussed, which includes increasing overall energy production as well as increasing the efficiency of energy production and switching energy substrate preference of the heart. This book will be a valuable source of information to graduate students, postdoctoral fellows, and investigators in the field of experimental cardiology as well as biochemists, physiologists, pharmacologists, cardiologists, cardiovascular surgeons and other health professionals."

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.