The world is beset by a pandemic of obesity and type 2 diabetes and the need for new drugs is startlingly clear; recent years have seen a huge increase in research activity to fill this gap. The development of new drugs for diabetes and obesity must be founded upon a sound appreciation of the pathophysiology of these common disorders. The dual defects of insulin resistance and impaired insulin secretion are fundamental to the pathogenesis and progression of obesity-associated type 2 diabetes. There is a need to explain how new drugs can counter insulin resistance and insulin deficiency to a broad range of professionals, from clinical scientists active in early (and later) phase drug development to specialist physicians and increasingly primary care doctors who must tailor drug regimens to the individual patient. Clinical research methods for measuring insulin action and insulin secretion have become well-established in proof-of-mechanism studies; however, selection of the best techniques is by no means straightforward. The purpose of the book is to aid the selection of the most appropriate techniques for assessing insulin action, insulin secretion and body composition in humans (with particular reference to new drugs) in phase 1 and 2 studies and aid the understanding of drug effects and non-drug treatment strategies on key biochemical-hormonal defects of obesity and type 2 diabetes. The book will assume a working knowledge of human physiology relating to glucose metabolism and will be of interest to biomedical scientists, pharmacologists, academics involved in metabolic research and clinicians practicing in these specialties.

This is a timely and informative updated edition for all health care providers challenged with helping patients manage weight. Similar to the well-reviewed first edition, this updated title is directed toward individuals who wish to read further about targeted topics, rather than find an introduction to the field. This second edition again provides insights into recent scientific advances in obesity research and provides the most up-to-date instruction about current treatment issues and strategies for both adults and children. While several of the chapters are no longer relevant from the first edition, other topics have emerged as interesting and current. This edition will keep the two-section format of Physiology and Pathophysiology and Clinical Management, but it increases the first section to 10 chapters and reduces the second section to 12 chapters. The plan is to keep this edition in the range of about 350 to 400, maximum, printed pages. The volume is again divided into two parts. Part 1 covers new discoveries in the physiological control of body weight, as well as the pathophysiology of obesity. Expert authors discuss pathways that control food intake, energy expenditure and peripheral nutrient metabolism, including a look at the emerging evidence of the role of adipose tissue as an endocrine organ. Part 2 covers all the key issues central to clinical management, including recent developments in the epidemiology of obesity, assessment of the obese patient, behavioral strategies in weight management, dietary modification as a weight management strategy, physical activity as a weight management strategy, weight loss drugs, surgical approaches to obesity and other important clinical topics. An essential, practical text that sorts, synthesizes and interprets the latest information on obesity-related topics, this second edition will be an essential resource for clinical endocrinologists and other health care providers across a broad spectrum of specialties.

This book provides the reader with a multidisciplinary approach that is state of the art and reflects input from the European Neuroendocrine Tumor Society and the North American Neuroendocrine Tumor Society. In particular, the text focuses on the pathophysiology of neuroendocrine tumors and includes a comprehensive review of the most recent developments in understanding the complex hormone and receptor signaling that is important for the future development of potent pharmacological treatments. The volume reviews the pathological grading and staging systems providing useful clinical information for the treating clinician as well as a useful reference for pathologists. The clinical management of neuroendocrine tumors is reviewed enabling the treating physician to understand the diagnostic approaches to differentiating the various types of neuroendocrine tumors. In addition, the treatments are reviewed in great detail and include novel radiological, surgical, and chemotherapeutic approaches. The reader will utilize this book as both a comprehensive and quick reference guide through the use of diagnostic and treatment algorithms. Written by international experts in their particular field of study, Management of Pancreatic Neuroendocrine Tumors will be of great value to medical oncologists, endocrinologists, gastroenterologists, pathologists, surgeons, and diagnostic and interventional radiologists.

Nuclear Receptors focuses on the structural analysis of nuclear receptors from the initial work using isolated protein domains to the more recent exciting developments investigating the conformational shape of full-length receptor complexes. The book also reviews the structure of key nuclear receptor co-regulatory proteins. It brings together, for the first time, a comprehensive review of nuclear receptor structure and the importance of receptor conformation underpinning allosteric regulation by different ligands (hormone, drugs, DNA response elements, protein-protein interactions) and receptor activity. The nuclear receptor superfamily, including receptors for steroid hormones and non-steroid ligands, are pivotal to normal physiology, regulating processes as diverse as reproduction, metabolism, the immune system and brain development. The first members of the family were cloned over 25 years ago, which heralded in the idea of a superfamily of intracellular receptor proteins that bound small molecule ligands: classical steroid hormones, vitamins, fatty acids and other products of metabolism. These signals are then transmitted through multiprotein receptor-DNA complexes, leading to the regulation of target genes, often in a cell-selective manner. The cloning of the receptor cDNAs also ushered in an era of unparalleled analysis of the mechanisms of action of these ligand-activated transcription factors.

Non-vesicular intracellular cholesterol transport is an important mechanism for maintaining membrane cholesterol homeostasis. Recent reports of studies directed at soluble cholesterol transport proteins indicate that aberrant expression of the START proteins may contribute to disease states associated with disorders in cholesterol homeostasis. This is an exciting new direction in the field and the purpose of this book will be to highlight the current research directed at potential roles for the START family in diabetes, cancer and atherogenesis. This book also provides a personal and historical perspective of the discovery-to-publication journey that the authors had for their particular START domain family member. The goal will be to provide perspectives to graduate students, post-doctoral fellows and endocrinology fellows on the research discovery process.

This highly illustrated book, complete with comprehensive clinical references and annotated images, will serve as a leading text to educate head and neck surgeons, endocrinologists, and radiologists on the basics and nuances of thyroid and parathyroid ultrasound. It emphasizes the use of ultrasound as an office-based modality by clinicians and radiologists who actively care for this special set of patients. This text uniquely combines the collaboration between a clinician/surgeon and radiologist who share their extensive experience in head and neck ultrasound.

The increasing prevalence of morbid obesity has led the World Health Organization to coin the descriptive term "globesity" to reflect the worldwide nature of the problem. Providing health care to these patients, especially when surgery is required, can be extremely challenging owing to the specific needs in respect of logistics, facilities, and professional expertise. Appropriate care has to date often been unachievable and unaffordable outside of established bariatric centers, but such centers themselves usually have insufficient capacity and resources to cope with the demand among the general population. This book therefore provides a wealth of guidance and helpful tips and tricks on how to deal with obese patients within a general surgery setting. Importantly, it highlights the need for global rethinking on public health as regards resource allocation and patterns and standards of care, with the ultimate goal of improving outcomes through greater affordability.

Studies on Diabetes examines how increased oxidative and nitrosative stress - one of the leading causes of diabetes complications - pathologically affects multiple tissues in the body. The volume editors and chapter authors are leading investigators in the field of basic and clinical research in diabetes and vascular disease. Their contributions represent a wealth of knowledge on and research into how diabetes triggers metabolic abnormalities that lead to hyperactivation of cellular and mitochondrial pathways that ultimately result in oxidative and nitrosative stress that left un-neutralized, results in tissue damage. Each chapter provides the reader with invaluable insight to the complicated mechanisms responsible for diabetes complications and vascular disease. Potential treatments for diabetes complications from animal models to the patient will also be discussed. This is essential reading for researchers and clinicians in endocrinology, diabetes, vascular disease and oxidative stress.

Primary Aldosteronism (PA) is a disease caused by the overproduction of aldosterone hormone from the adrenal glands. PA causes hypertension and the majority with this disease are undiagnosed for PA. There are new insights into this matter by using biochemistry as well as advanced radiology. In 2011, a breakthrough in the genetic derangements came, identifying a mutated potassium channel gene - KCNJ5 - in about 40% of PA with adenoma. Chapters in this book include a history of the disorder, epidemiology, genetics derangements, the KCNJ5 mutations and phenotype and more.

The purpose of the The Active Female: Health Issues Throughout the Lifespan, 2nd Edition is twofold: (1) to increase the awareness of wellness and fitness issues for active females and their family members; and (2) to provide an avenue for medical practitioners, allied health professionals, health educators, and certified individuals in sports medicine to gain critical, updated knowledge of a field specific to active females. Part I of the book offers a foundation to help the reader understand the interrelationship among body image concerns, the female reproductive cycle, and musculoskeletal anatomy/physiology of females that makes their health risks and concerns unique. Reproductive health is discussed by a prominent researcher in reproduction/endocrinology. An overview of the Female Athlete Triad which is a syndrome of three interrelated conditions (isordered eating, menstrual disturbances and bone loss) is presented in Part II. Physicians and certified professionals in sports medicine discuss the individual components of the triad, relating not only to the athletic female but also to the recreationally active woman throughout the lifespan. In Part III, Prevention and management of common musculoskeletal injuries is addressed by a female orthopedic surgeon who sub-specializes in treating female athletes. Finally, appropriate exercise and nutritional guidelines for active females are discussed in Parts IV-V of the book by certified professionals and licensed physicians in sports medicine. An invaluable addition to the literature, The Active Female: Health Issues Throughout the Lifespan, 2nd Edition will be of great interest to physicians, allied health care practitioners, medical/other wellness educators, and students who are interested in advancing women's health issues. Sports medicine specialists, family practitioners, gynecologists, team physicians, residents in sports medicine, athletic trainers, health educators, nurses, physicians assistants, physical therapists, sport psychologists, counselors, athletic trainers, and other members of the sports medicine team should also find this title of significant interest.

Bone Drugs in Pediatrics brings together in one place the evidence for the use of certain drugs in the treatment and prevention of bone loss in children, as well as the reservations still present in the pediatric community regarding their use. Beginning with a discussion of developmental pharmacokinetics and drug development for pediatric diseases where bone loss occurs, such as osteogenesis imperfecta, the physiology of pediatric bone and how best to monitor the safety and efficacy of these drugs is presented. The pros and cons of utilizing the drugs themselves - such as bisphosphonates, antiresorptives and anabolic agents - within the pediatric population are carefully considered, with an eye toward safe and effective integration. The potential use of drugs in future treatment is also highlighted. On the whole, Bone Drugs in Pediatrics is a cogent presentation of the ongoing debate surrounding the potential for pharmacological interventions in pediatric bone loss.

Endocrinology, and diabetes care in particular, is a dynamic field where clinicians must translate new evidence into clinical practice at a rapid pace. Designed in an engaging, case-based format, Endocrinology and Diabetes: A Problem Oriented Approach offers a wide range of thought-provoking case studies that reflect contemporary, challenging, hands-on clinical care. Further, by providing a list of specific clinical problems, this format offers the reader a more convenient and pointed way to solve precise clinical problems in a timely manner. Developed by a renowned, international group of experts, this comprehensive title covers the most common clinical problems in endocrinology and diabetes and should be of great interest to endocrinologists, diabetologists, internal medicine physicians, family physicians, fellows, and residents.

This book tackles the problem of overshoot and undershoot in blood glucose levels caused by delay in the effects of carbohydrate consumption and insulin administration. The ideas presented here will be very important in maintaining the welfare of insulin-dependent diabetics and avoiding the damaging effects of unpredicted swings in blood glucose - accurate prediction enables the implementation of counter-measures. The glucose prediction algorithms described are also a key and critical ingredient of automated insulin delivery systems, the so-called "artificial pancreas". The authors address the topic of blood-glucose prediction from medical, scientific and technological points of view. Simulation studies are utilized for complementary analysis but the primary focus of this book is on real applications, using clinical data from diabetic subjects. The text details the current state of the art by surveying prediction algorithms, and then moves beyond it with the most recent advances in data-based modeling of glucose metabolism. The topic of performance evaluation is discussed and the relationship of clinical and technological needs and goals examined with regard to their implications for medical devices employing prediction algorithms. Practical and theoretical questions associated with such devices and their solutions are highlighted. This book shows researchers interested in biomedical device technology and control researchers working with predictive algorithms how incorporation of predictive algorithms into the next generation of portable glucose measurement can make treatment of diabetes safer and more efficient.

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.

Defining and understanding cellular and molecular mechanisms that are relevant to women's health has become a critical area of scientific pursuit. Until recently, very little effort has been place on defining or understanding critical differences between women and men that may be critical to the overall health of the woman. In 1990, the National Institutes of Health recognized this gap in knowledge resulting in the creation of the Office of Research on Women's Health. One of the purposes of this office was to advance the understanding of health issues from the women's perspective from both a basic and clinical scientific perspective. From a scientific evolution of understanding, the existence of this office is new and thus there has not been enough time for new information to integrate itself in our current scientific thought process. This book will seek to capture and disseminate our current understanding of scientific advancements relevant to women's health and provide the information to a broad audience. The purpose of this work is to discuss recent advancements in basic science across three areas of concern for women's health. In addition, the book will provide "translational" chapters that attempt to place the basic science work in context within our current understanding of the human. Although it is well acknowledge that gender differences exist across organ function which translates into differences in whole body function, until recently little effort has been made to define basic mechanisms within various tissues within the woman. This work will focus on recent scientific findings that are relevant to women's health and to provide novel and relevant information to interested scientists and clinicians.

The sustained skin research efforts over the past decades has led to the accumulation of a significant collection of information on skin structure and physiology as well as on the pathogenesis of cutaneous diseases. In Molecular Dermatology: Methods and Protocols, leading experts in the field provide a collection of state-of-the-art reliable protocols covering a wide spectrum of techniques and experimental models, specific molecular assays and disease models, as well as overviews of diagnostic and research areas relevant to molecular dermatology. As a volume in the highly successful Methods in Molecular Biology (TM) series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and authoritative, Molecular Dermatology: Methods and Protocols emphasizes the vital importance of skin research and collects the methodologies necessary to aid scientists in moving forward in this valuable field.

This book reports the text of the lectures of the 6th International Conference on Sodium Calcium Exchange held in Lacco Ameno in the Island of Ischia in the Gulf of Naples, Italy, from October 1 to October 5, 2011. The present book uncovers the most striking new findings on NCX that emerged since the previous Conference on Sodium Calcium Exchange, such as the structural dissection of the molecular determinants of Ca2+ sensitivity of the exchanger, the epigenetic regulation of ncx1 gene, the molecular identification of the mitochondrial Sodium Calcium Exchanger, and the discovery of NCX in unexpected anatomical locations such as the female reproductive tract. The book is organized into 11 parts covering NCX structural aspects, genetic and epigenetic regulation, regulatory mechanisms, subcellular localization in mitochondria, involvement in neurodegenerative diseases and in immune regulation, and the role of the cardiovascular and endocrine systems, as well as diabetes in physiology and pathophysiology. Selected chapters of the book are also devoted to the interaction of NCKX and other ion channels and transporters with NCX, like ASICs, TRPM, and NHE.

This book pursues a multidisciplinary approach, presenting chapters with updated information on various aspects of treatment for patients with neuroendocrine tumors. Authors have been selected from expert centers in Europe and the United States. The goal of this book is to comprehensively summarize recent data and provide inspiring ideas to optimize the care of patients with neuroendocrine tumors. Neuroendocrine tumors are fascinating multifaceted diseases that can primarily localize in many organs with various presentations. These tumors are rare but their increasing incidence renders likely that physicians caring for cancers may have either already faced or may be certainly exposed to diagnose and/or treat a patient with neuroendocrine tumors. Over the last years, novel therapeutic options have emerged for neuroendocrine tumors, profoundly challenging practices that had previously been the standards for decades. These include - but are not limited to - somatostatin analogues, targeted therapies such as tyrosine kinase and mTOR inhibitors, antiangiogenic compounds, but also peptide-receptor targeted therapy or radioembolization. This changing field has generated novel treatment algorithms to guide medical decisions. To better understand and handle the multidisciplinary approaches that are required for optimizing the care of neuroendocrine tumor patients, physicians are now looking for references from experts and comprehensive reviews summarizing current knowledge on treatments for patients with neuroendocrine tumors.

Darwinian medicine looks at the ecological and evolutionary roots of disease. A disease is an interaction between a genome and its biotic or abiotic environment and therefore a disease is essentially an ecological process. Good understanding of ecology and a Darwinian way of thinking can give us novel and useful perspectives on health and disease. If we understand the disease process better, we can certainly prevent, control as well as treat diseases in a better way. Although the thought that the origins of obesity and type 2 diabetes (T2D) might lie in our hunter gatherer adaptations is not new, research over the last decade makes us rethink many of the classical concepts. Brain and behavior is increasingly being recognized as central to all the endocrine, metabolic and immunological changes that earmark type 2 diabetes and other metabolic syndrome disorders. A major change in paradigm appears to be on the horizon and the proposed book intends to speed up the paradigm shift by raising important questions, pointing out flaws and inadequacies in the prevalent paradigm and stimulating radical rethinking which would redirect and refine the line of research as well as bring some fundamental changes in drug discovery and clinical practice.

This book offers a complete overview on non colorectal non neuroendocrine (NCRNNE) liver metastases and describes in detail the currently available therapies. Each chapter focuses on the treatment of metastases from a particular primary malignancy and also provides valuable information on incidence, natural history and diagnosis. NCRNNE liver metastases are rare entities compared with colorectal and neuroendocrine metastases, for which the treatments are well codified. While more publications have appeared on the topic in recent years, an in-depth study has to date been lacking. Furthermore, most published series are insufficiently comparable as they comprise patients with NCRNNE hepatic metastases from a variety of primary malignancies and consequently overlook differences in tumor behavior, frequency of isolated hepatic metastases, response to neoadjuvant or adjuvant therapy and interval between diagnosis of the primary tumor and the liver metastases. This book, with its more specific approach, will serve not only as an up-to-date guide to diagnosis and treatment but also as a reference on which to base future studies.

Recent Advances in Prolactin Research summarizes the current knowledge of prolactin (PRL), PRL receptor, PRL-dependent signaling pathways, the role of PRL in oncogenesis and PRL crosstalk with other oncogenic factors. The chapters are written by experts in these fields and focus on identifying and reviewing timely experimental findings that provide new insights into the expanding role of PRL in the pathophysiology associated with a variety of human conditions. Prolactin is a peptide hormone that is best known for its role in lactation. Prolactin also has an influence on hematopoiesis and angiogenesis, and is involved in the regulation of blood clotting through several pathways. Although PRL was discovered more than 80 years ago, the understanding of PRL signaling and its relationship to various pathologies is still very incomplete. PRL is not only a pituitary hormone with an important role in reproduction, but PRL also acts as a cytokine, modulating a wide variety of physiological processes. For example, data gathered during the last decade have demonstrated that locally produced PRL acts as the autocrine/paracrine factor and plays a contributory role during breast oncogenesis. In fact, the scientific and clinical communities have suggested that the manipulation of the PRL axis may lead to the successful treatment of breast cancer. However, recent work has demonstrated that the role of the PRL axis is much more complex than first envisaged.

This book outlines risk assessments for 28 diseases and medical conditions including the following aspects: genetics, biochemistry, serology, past medical history, family history, co-morbidities, age, gender, ethnicity, nutrition and lifestyle. Recommendations are made for how to avoid, eliminate or mitigate risks. Preventing measures concerning chemical compound intake, lifestyle and nutrition are proposed. The unique content and approach of the book to chronic disease management make it a state-of-the-art reference work, addressing a missing component of medical care and reflecting the cutting edge of preventive medicine.

This volume presents key topics of current interest with regard to several pathophysiological conditions including (a) the basic and clinical aspects of bradykinin receptor antagonists, (b) the kallikrein-kinin pathways in hypertension and diabetes, (c) tissue kallikrein-kinin therapy for hypertension and organ damage, (d) the renal (tissue) kallikrein-kinin system in the kidney and novel potential drugs for salt-sensitive hypertension, (e) the kallikrein-kinin system in diabetes retinopathy, and (f) genetic manipulation and genetic variation of the kallikrein-kinin system and their impacts on cardiovascular and renal disease. Written by internationally reputed scientists, the book provides an essential overview of the latest developments in the field of kinin research, making it a valuable asset for endocrinologists, nephrologists, cardiologists, pharmacologists, physiologists, ophthalmologists and rheumatologists. Furthermore, it is also intended for postgraduate students in the fields of medicine, pharmacy, physiology and pharmacology, and those working at research organizations.

During vertebrate hematopoiesis many specialized cell types are formed with vastly different functions such as B cells, T cells, granulocytes, macrophages, erythrocytes and megakaryocytes. To tightly control the enormous proliferative potential of developing blood cells, an intricately balanced signaling and transcription network has evolved that ensures that the different cell types are formed at the right time and in the right numbers. Intricate regulatory mechanisms ensure that blood cells function properly and have a determined life span. Moreover, in the adaptive immune system, long-lived memory cells have evolved that ensure that when pathogens have been seen once they will never cause a problem again. In this book we will therefore make a journey from asking how more primitive organisms use the epigenetic regulatory machinery to balance growth with differentiation control towards digging deep into what controls the function of specialized cells of the human immune system. We will first discover that flies make blood but exist without blood vessels, why fish make blood cells in the kidney and which precise genetic circuitries are required for these developmental pathways. We will then learn the regulatory principles that drive the differentiation of mature blood cells from stem cells and what controls their function in mammals. In the process, we will find out what unites hematopoietic stem cells and endothelial cells. Finally, we will shed light on the molecular mechanisms that either alter hematopoietic cell differentiation or lead to the development of cells with impaired function.

It is a pleasure to introduce this new book, Clinical and Pathological Aspects of Skin Diseases in Endocrine, Metabolic, Nutritional, and Deposition Disease, edited by two of my friends and respected colleagues, Franco Rongioletti and Bruce R. Smoller. In fact, I was very ent- siastic when I learned that they were preparing this work. Although endocrine, metabolic, w, and deposition diseases are regularly included in general textbooks of dermatology and d- matopathology, one gains the general impression that these topics receive little emphasis and are mainly included for completeness. The prospect of having all of this information in one volume, lovingly described and detailed by experts in the feld, should be of great interest not only to dermatologists, pathologists, and dermatopathologists but also to internists and en- crinologists, who may well gain a different perspective on these disorders. As a derma- pathologist, I am also pleased that this project has been organized and undertaken by two distinguished authorities in cutaneous pathology. This assures a close integration of histo- thology and other laboratory techniques with the clinical aspects of these disorders, which will make it possible - perhaps for the frst time - to view these conditions in a truly comprehensive way. So I invite you, the reader, to open this volume and dig in; be prepared for an eye-catching, intellectually stimulating, and ultimately rewarding experience! Charlottesville, VA James W. Patterson v w Foreword II Dermatopathology is a bridge between Dermatology and Pathology.