This third installment of The Year in Diabetes and Obesity review series includes reviews with a special focus on metabolic syndrome and health. NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit http://ordering.onlinelibrary.wiley.com/subs.asp?ref=1749-6632&doi=10.1111/(ISSN)1749-6632. ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to Annals online and discounts on print volumes. Please visit http://www.nyas.org/MemberCenter/Join.aspx for more information about becoming a member.

The 6th triennial meeting of the International Study Group for Tryp- tophan Research (ISTRY) was held May 9-12, 1989 in Baltimore, Maryland (USA). From the wide variety of topics and disciplines represented, as documented in this volume, it is clear that tryptophan research and ISTRY are alive and well. ISTRY traces its or1g1ns to at a tryptophan symposium organized in 1971 by H. Schievelbein at Hohenried near Munich (Germany). Up to that time there had been occasional international tryptophan conferences at irregular inter- vals. A number of participants at the Hohenried meeting felt that an inter- national tryptophan organization should be formed to organize regular meet- ings and to foster collaboration and information exchange on tryptophan-re- lated topics. Thanks mainly to the founding work of H. Schievelbein and W. Kochen, an executive committee was elected and ISTRY was born. The inaugural meeting in 1974 was held in Padova (Italy) to honor L. Musajo, one of the foremost pioneers in tryptophan studies. This first ISTRY meeting was suc- cessfully organized by L. Musajo, G. Allegri, A. De Antoni, and C. Costa, and was critical in assuring the viability of the new organization. Subsequent meetings were held in 1977 in Madison, Wisconsin (USA), organized by R.R. Brown, D.P. Rose, and W.E. Knox, honoring C.P. Berg; 1980 in Kyoto (Japan), organized by O. Hayaishi, R. Kido, Y. Ishimura, T. Deguchi, T. Hino, T.

Most of us spend at least two-thirds of our lives either sitting or standing. It is somewhat surprising, therefore, to find not a single book devoted to disorders caused by derangements of the normal physiological adjustments to changes in posture. In fact, until very recently, medical students have not even been advised to measure the blood pressure and heart rate in the upright posture as part of the routine physical examination. Although Bradbury and Eggleston first described orthostatic hypotension as a consequence of autonomic insufficiency in 1925, interest in orthostatic disorders has been slow to develop in the subsequent years. It is well known that the change from recumbency to the standing posture stimulates neurological, endocrine, and cardiovascular adjustments that ensure maintenance of a normal circulation despite the effects of gravitational forces. The mechanisms of these physiological responses to orthostasis have been stud ied by many investigators. Some of the defects to which antigravitational com pensatory mechanisms are subject, such as postural hypotension resulting from autonomic failure, have been studied intensively and have become part of the general knowledge of most medical practitioners. Other orthostatic disorders such as various other postural abnormalities of blood pressure control, and orthostatic edema-have received far less attention and have been unable to compete with the more dramatic and life-threatening ailments of humankind for a place in our standard medical texts. These disorders often give rise to distressing symptoms and may lead to severe impairment of health.

Diabetes. Its Medical and Cultural History covers the history of scientific inquiry into this affliction from antiquity to the discovery of insulin (1921) with concurrent consideration of the history of the patient and the cultural historical background. The reprints of medical historical studies discuss general relationships as well as specific details and exceptional research achievements of the past. Included in the bibliography of primary sources are the most important historical contributions in diabetic research and diabetic therapy with the author's name and information on the place of publication. The bibliography of secondary literature consolidates international studies from the past century to the present on the history of the theory of diabetes and therapeutic approaches. Illustrations and literary texts document cultural historical relationships. In index of persons and items facilitates use of this work which is intended to provide a stimulus for the physician, medical historian, medical student, general historian as well as diabetics themselves.

The ciliopathies are a group of rare diseases that often affect multiple systems within the body, and are caused by defects in the function or structure of cilia. When cilia go wrong, there are profound consequences; these are discussed in detail for the first time in Ciliopathies: a reference for clinicians. The book provides a clinical overview and reference to this newly emergent group of disorders ranging from Alstroem syndrome to putative ciliopathic disorders. Each chapter provides an in-depth discussion on a specific disorder, including the latest scientific research together with a description of its features, and practical guidelines on diagnosis. The authors also examine the evidence for dysfunction of cilia in cancer and more common disorders. Ciliopathies: a reference for clinicians will appeal to those involved in the care of patients with ciliopathies, including specialists in the fields of nephrology, diabetes, cardiology, and ophthalmology, and non-clinical researchers interested in cilia biology.

This book will enlighten on some of the recent progress in diabetic care and therapy. Diabetes mellitus is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because of the inability of cells to respond to the insulin that is produced. According to the recent report of World Health Organization, 346 million people worldwide are suffering from diabetes, and in 2004, approximately 3.4 million people died as a result of high blood sugar. This book explores applying both classical and modern approaches to the management of diabetes by focusing on a holistic approach. Great attention has been focused on global trends in diabetes, epidemiology of diabetes, inhibitors in diabetes and diabetes therapy, vitamins and diabetes, and the role of dietary fats in diabetes in this book. Topics include: * diabetic foot ulcers and therapeutic footwear * Withania coagulans. Dunal as an antidiabetic herb * the pharmacological interventions for diabetic cardiomyopathy * the use of saliva as a noninvasive tool to monitor glycemic control in diabetic patients * a cutting-edge biomedical device for continuous in vivo glucose monitoring * the temporal effect of repeated stress in the pathophysiology of T2DM * nanosensor technology for glucose detection The editors and authors emphasize a holistic approach toward the diagnosis, treatment, and management of diabetes by joining hands with experts from various disciplines Medical students and doctors of modern medicine, Ayurveda, homeopathy, etc., medical reserachers, researchers in the area of diabetes, pharma professionals.

The central nervous system controls vital functions by ef?ciently coordinating peripheral and central cascades of signals and networks in an orchestrated manner. Historically, the brain was considered to be insulin independent. These earlier views have been challenged by ?ndings demonstrating that insulin exerts multiple actions in the brain, regulating vital biological processes such as life span, neuronal survival, cognition, reproduction, feeding behavior, energy balance, and glucose and fat metabolism, and that inef?cient central action of insulin contributes to the development of severe pathologies (Banks et al. 2000; Gerozissis 2003, 2004, 2008; Lustman and Clouse 2005; Okamoto et al. 2001; Park 2002; Perrin et al. 2004; Pocai et al. 2005; Reger et al. 2008; Schwartz and Porte, 2005; Schubert et al. 2004; van der Heide et al. 2005; Woods et al. 1979; Wrighten et al. 2008). Insulin and speci?c insulin receptors are widely distributed in the networks of the central nervous system related mainly to feeding or cognition (Baskin et al. 1983; Bruning et al. 2000; Gerozissis 2003, 2008; Havrankova et al. 1978a, b; Schechter et al. 1996; Schulingkamp et al. 2000; Schwartz et al. 1992; Zhao et al. 2004). Insulin receptors located in the synapses of neurons and in astrocytes are present in high concentrations in the cerebral cortex, olfactory bulb, hippocampus, amygdala, cerebellum and hypothalamus (Abbott et al., 1999; Havrankova et al.

Fundamental to survival of living organisms is their ability to react appropri ately to their environment. Cannon (1929) recognized that "back of internal homeostatic mechanisms are powerful motivating agencies-appetites and hunger and thirst." Almost all observed behavior may be viewed as activity required to meet some physical or emotional need. "The higher in the scale of living things, the more numerous, the more perfect, and the more compli cated do these regulatory agencies become." This statement by Fredricq (1885) regarding internal mechanisms is at least as valid for behavior. Adrenal medullary secretion in preparation of "fight or flight" may be con sidered the first described behavioral neuroendocrine response. The conse quences of more prolonged stress on pituitary-adrenal cortical function and the subsequent unfolding of the means by which the brain controls the secre tion of the anterior and posterior pituitary glands led to the birth of neuroen docrinology. During the last decade, neuroendocrinology has taken a remarkable turn. Peptides which were believed at first to be involved solely in control of the pituitary by the hypothalamus were found in other areas of the brain. Other peptides were encountered in brain by their activity in competing for the high affinity binding of drugs to their receptors, and still others, first found in peripheral organs, were discovered also in brain. Perhaps even more amaz ing was the discovery that one or another of these peptides influence almost every aspect of behavior."

It is curious that research in endocrinology has largely ignored the testis until quite recently. There were two impor tant reasons for this neglect; first, methods of study were difficult, and second, sperinatogenesis was considered to be the concern of the urologist or cell biologist but not the endocrinologist. Since it is now almost an ethical imperative that we develop a male contraceptive, and since a host of new techniques can be brought to bear on problems of testis function, research in male reproductive biology has effloresced. In fact, it has become possible to project aseries of workshops on the testis, each dealing with discrete aspects of biochemistry, physiology and pathology. It is fitting that this first Workshop should be on Binding and Activation, since this area is one of the frontiers in endocrinol ogy. At our present rate of progress it is probable that each of the succeeding workshops will likewise bring together leaders in a rapidly developing area. The National Institute of Child Health and Human Development has the major Federal respon sibility in reproductive biology, and has therefore agreed to sponsor this and succeeding workshops. On behalf of the Institute and for those members of the Committee who have organized this meeting, I welcome you. I am quite sure that this first Workshop on the Testis will initiate aseries of important contributions to scientific thought in male reproduc tive biology. Mortimer B. Lipsett, M. D."

Tumours of the prostate are the commonest types of neoplasm in the male. Whilst the benign form is virtually a universal condition in the ageing male, malignant tumours rank amongst the top causes of cancer death. Despite the fact that the involvement of the testis in the growth of the prostate has been recognised for almost two centuries, it was not until the early 1940s that Charles Huggins' studies on the effect of orchidectomy and oestrogen therapy on prostatic cancer initiated endocrine manipulation in the management of this malignancy. During the 1960s progress in the understanding of the mechanism of hormone action, achieved through advances in molecular biology and the recognition of certain aspects of hormonal control in relation to the genome, introduced a new dimension for approaching endocrine manipulation of prostatic tumours. By the end of that decade a new scientific discipline devoted to prostate research had been born, which brought together investigators in the fields of molecular biology, biochemistry, endocrinology, immunology, urology and pathology to search for the cause and to explore methods for advancing the management of abnormal prostatic growth. Since then a wealth of scientific data has accumulated on the prostate in which endocrinology has manifested itself as the cardinal aspect to which most of the findings can be related.

This volume contains the papers presented at the Inter- national Symposium on "Cirrhosis, Hepatic Encephalopathy and Ammonium Toxicity", held in Valencia, Spain, November 27-29, 1989. Hepatic cirrhosis as well as other liver failures usual- ly lead to hepatic encephalopathy which is an important cause of death in occidental countries. However the molecular bases of the pathogenesis of hepatic encephalopathy remain unclear and several hypotheses have been proposed. Hyperammonemia is considered one of the main factors responsible for the mediation of hepatic encephalopathy. Therefore, a part of the book is devoted to the effects of hyperammonemia on cerebral function, ammonia and amino acid metabolism, brain microtobules, astrocytes and synaptic trans- mission and their possible role in the pathogenesis of hepatic encephalopathy. Carnitine has a remarkable protective effect against acute ammonium intoxication. Thus some results regarding this effect are also presented, as well as the clinical use of car- nitine. The alterations of the metabolism of ammonia and of seda- tives in liver diseases and their clinical implications are also discussed. The possible role of altered GABA-ergic neurotransmission on the pathogenesis of hepatic encephalopathy has received considerable attention recently. Results of these studies and those on benzodiazepine receptor ligands are presented as well as those on the hypothesis of the role of altered synaptic plasma membrane on the pathogenesis of hepatic encephalopathy.

This volume is devoted to the chemistry, immunology, molecular biology, and physiology of the human chorionic gonadotropin, heG. For this glycoprotein molecule the course from discovery to chemical deciphering covered about fifty years. It was in 1928 that Ascheim and Zondek reported that urine from pregnant women contains something that stimulates the ovaries of mice or rats. This provided the basis for the famous A-Z test for pregnancy and for the "rabbit test" modification introduced by Friedman. As researchers sought to find more sensitive responses to heG, they used a wide variety of species including the South African aquatic toad, Xenopus Zaevis, the terrestrial toad of South America, Bufo arinarus, and the African weaver finch, EupZeetes afra. The weaver finch feather reaction was particularly noteworthy, for it disclosed a non-gonadal response to heG/LH. In retrospect, this may have been an important evolutionary clue to the realization that the designation of the hormone as a "gonadotropin" may have been only partially descriptive of the molecule's physiological function--a concept that is gaining attention, as the papers in this 1980 volume divulge.

Diabetes is one of the oldest diseases known to mankind. It was first mentioned in the Ebers Payrus (Egypt 1500 BC) and 'honey urine' was noted by Sushrutha in India in 400 BC. By the first century of the Christian era the disease was well known, both in Roman writings and in Chinese and Japanese writings. The word 'diabetes' was first coined by the Greeks. It means a passing-through of water. They described it as a 'melting of flesh into water', meaning urine. Then in 1674 Doctor Willis discovered by heating, tasting and evaporating urine that a sweet sticky substance was in it, which, of course, was sugar. Rut sugar was not known in England in those days and honey was the only real sweet tasting substance. The Latin word 'mel' which means honey was used and the disease came to be known as diabetes mellitus - that is, the passing of honeyed urine. This is still the full name of the disease.

Proceedings of the First International Meeting of the Pancreatic Islet Study Group held in the Alicante, Spain, November 25-28 1994

THE DISCOVERY OF INSULIN, C-PEPTIDE AND PROINSULlN, SPECIES DIFFERENCES Crude insulin was extracted and isolated from dog pancreases removed 7-1 Degrees weeks after ligation of the pancreatic duct for the first time in 1921 by Banting and Best. Its lifesaving properties were subsequently documented in pancreatectomized dogs in 1922. Only about six months elapsed from its discovery until systematic collection of calf and ox pancreases and, later, porcine pancreases was established and the blood glucose lowering effect in diabetics using the crude extract from these glands proven. It was not until 1960, however, that the primary structure of all three species of insulin, lO7 human, porcine and bovine, was elucidated . It then became evident that the differences between bovine, porcine and human insulin amounted to at mosl 3 amino acids. These apparently small differences have a significant impact on the physico-chemical characteristics of the three insulins which again affect, e.g., the rate of absorption of insulin lO9 preparations from the subcutaneous tissue and their immunogenicity, i.e.

Diabetes, particularly type 2, has become increasingly more common around the world. Consequently, the effect of diabetes on the brain has achieved enormous public health importance. A surge in pre-clinical and clinical research on topics ranging from management of hyperglycemia in acute stroke to disturbances in insulin signaling in Alzheimer s disease has led to substantial progress in the field. Written by a panel of international experts, Diabetes and the Brain provides in depth reviews on the cerebral complications of diabetes, and offers introductory chapters on current insights on the pathophysiology and clinical management of diabetes, as well as neuropsychological assessment and dementia. This relevant and easily accessible book explains the cerebral complications of diabetes, with an update on diabetes for neurologists, psychiatrists, and mental health providers and researchers in general, and on stroke and dementia for those involved in research and clinical practice in diabetes."

Ghrelin is a 28-amino acid acylated peptide predominantly produced by the stomach. It displays strong GH-releasing activity mediated by the hypothalamus-pituitary GH secretagogue (GHS)-receptors specific for synthetic GHS. Ghrelin also acts on other central and peripheral receptors and enables other actions including: stimulation of lactotroph and corticotroph secretion; food-intake; gastro-entero-pancreatic functions; metabolic; cardiovascular activity; and anti-proliferative effects. This volume aims to highlight the impact and function of the hormone ghrelin and provide insight to neuroendocrinologies and researchers interested in its molecular and clinical relevance.

The actions of honnones upon systems outside of the usual target sites for such molecules represents an area of increasing interest and growing clinical significance. This volume represents a cross-section of such actions of honnones upon several relevant sites. In the first chapter of this volume Dr. Malick discusses the current status of endorphins as analgesic agents. It is now known that a more primary level of control exists for iJ-endorphin in that a 41-amino acid pep- tide has been isolated from ovine hypothalamus; this peptide stimulates iJ-endorphin release as well as the secretion of corticotropin (Vale et al. , 1981). The analgesic properties of corticotropin and its immunoactive-like analogs are well known. so it does not come as a surprise that these two classes of analgesic peptides are regulated by a common hypothalamic con- trol peptide. It may also be of interest to observe that an increase in iJ-en- dorphin concentration in the pituitary occurs in genetically obese mice and rats, and that such obesity can be attenuated through the administration of nalaxone (Margules et al. , 1978). It has also been determined that genet- ically obese mice have a probable cholecystokinin deficiency in the cerebral cortex in that this peptide is a satiety-inducing agent (Saito, et al. , 1981). The analgesic properties of the latter have also been observed. The extra-pituitary actions of another pituitary peptide, as examined in the second chapter of this volume by Dr.

The Seventh International Congress of Mucosal Immunology held in Prague, the beautiful old capital of The Czech Republic, 16-20 August 1992, was the first to be sponsored by the Society for Mucosal Immunology, and was the largest since their inception 20 years earlier in Birmingham, Alabama. It was attended by 624 participants who gave 538 presentations, more than 10 times the numbers of the first meeting; these proceedings contain 354 papers that were submitted for publication. The political events in Europe that made it possible to hold this Congress in Prague also allowed for the first time the participation of large numbers of scientists from Eastern Europe, as weil as from Asia, and the organizers were truly gratified by this happy circumstance. It is now clear not only that mucosal immunityencompasses the huge area of mucosal surfaces and most physiological organ systems, but also that mucosal immunology extends over the whole global surface and all continents! The sheer size of the Congress and number of manuscripts unfortunately entailed some unexpected problems in editing and assembling the proceedings, partly due to the diversity of linguistic styles not represented at earlier meetings, and we apologize to the authors who have patiently awaited the publication of their contributions.

Endocrinology of Cardiovascular Function is a fitting inauguration to the Endocrine Update Series. The aim of these publications is to provide the clinician with cutting edge, yet succinct, access to the latest advances in endocrinology. Historically, our understanding of hormonal disturbances was restricted to the classical secretory glands and their targets. As Endocrinology of Cardiovascular Function so aptly indicates, endocrinology is no longer constrained by our early physiologic understanding of glandular disorder. Endocrinology of Cardiovascular Function has set the standard of excellence for the future volumes in this series. Shlomo Melmed, M.D. Series Editor, Endocrine Update Growth factors such as IGF-1 play important roles in cardiovascular cell hypertrophy and the response to acute vascular injury. From another perspective, traditional endocrine hormones, such as estrogen, have been found to participate in preventing the development of atherosclerosis in women, acting through novel mechanisms on target vascular cells. Other `endocrine' hormones, such as PTHRP and adrenomedullin, also modulate cardiovascular and renovascular dynamic states, suggesting new roles for these peptides as vasodilators. This multi-authored text is dedicated to highlighting emerging and important new information regarding the endocrinology of the cardiovascular system. Ellis R. Levin, M.D.

Diabetes continues to spread across the globe at an alarming rate, with a current count of approximately 386 million worldwide. Physicians and healthcare professionals in all specialties greatly need a concise guide for managing this disease on a daily basis.

"Diabetes Mellitus A Concise Clinical Guide" covers the basics of diagnosis, complications, therapies and prevention. Major developments in understanding diabetes and in therapeutic approaches to this disease are also featured. This book is comprised of sections originally published in the comprehensive textbook, "Principles of Diabetes Mellitus, Second Edition."

Primary care physicians and endocrinologists, as well as medical students, will find this guide an invaluable and practical reference."

The commonest cause of blindness in young and middle-aged people in the Western world is diabetes mellitus. Although the mechanism underlying diabetic retinopathy is still not understood, the technology to reduce its progress exists, provided treatment is given at the appropriate time. Doctors caring for patients with diabetes should be familiar with all aspects of diabetic retinopathy as well as the other ocular complications of diabetes. They also need a basic knowledge of the special techniques used in the diagnosis and treatment of diabetic eye disease (fundus fluorescein angiography, retinal photocoagulation, vitrectomy) and to understand how these procedures affect the diabetic patient in terms of limitation of activities and time off work. To ensure the most efficient use of ophthalmic services a clear plan of referral to ophthalmologists is required. These are the concepts on which this guide is based, compiled by an ophthalmologist involved in the treatment of diabetic eye disease and a physician with a special interest in diabetes. In addition to doctors involved in the management of diabetic patients, this guide may be of value to ophthalmic opticians, medical students and nurses as a self-instruction manual. ' 7 1 Examination of the Eye Testing visual acuity Using the ophthalmoscope The normal fundus The abnormal fundus Recording the findings 9 TESTING VISUAL ACUITY Method Test one eye at a time. Test distant visual acuity. Correct the refractive error if the visual acuity is worse than 6/6.

Montreal has had a longstanding interest in somatostatin. Two years ago when the final planning began for the International Con gress of Endocrinology in Quebec City in July 1984, we seized the op portunity for having a separate Satellite Symposium on somatostatin here in Montreal. We felt that after a decade of uniformly vigorous growth in somatostatin research, the opportune moment had arrived for a review of the most significant past developments and for setting the directions for the future. Knowing the futility of trying to cover every aspect of the burgeoning somatostatin field in a two day scientific program, we opted for a detailed analysis of selected areas which were reasonably mature and of areas of greatest new activity. To attain these objectives, 27 leading international experts actively involved in their fields were invited to present an indepth review of their work in one of five major categories of somatostatin research. Thirty minutes at the end of each session were assigned for a three way, comprehensive discussion of some of the core concepts between the session moderators, the panellists and the audience. The feedback that we have received from the particip ants leaves little doubt that the meeting was a scientific and social success. This book fulfills our final commitment towards the Meeting which was to record the proceedings in a timely publication.

The discovery of hypothalamic factors that inhibited growth hormone secretion and of pancreatic factors that inhibited insulin secretion were the first clues to the existence of somatostatin. During the course of efforts to isolate growth hormone releasing factor, Krulich, McCann and Dhariwal found that hypothalamic extracts contained a potent inhibitor of growth hormone secretion. They postulated that growth hormone secretion was under a dual control system, one inhibitory and the other excitatory (I) . In studies being carried out at about the same time, Hellman and Lernmark found a factor in pancreatic extracts that inhibited insulin secretion (2). They postulated that islet cell function was regulated by local hormonal factors. With the isolation and chemical characterization of somatostatin by Brazeau and colleagues (3), and the availability of relatively large amounts of the synthetic peptide for research, it has been possible to demonstrate that both predictions were true. Subsequent work revealed that somatostatin, as initially isolated (somatostatin 14), was but one of several related peptides, part of a multigene family, with tissue specific processing. Many of the details of biosynthesis and genetic control have been worked out, and this molecule has served many workers as a model gut-brain peptide for detailed study. The peptides are widely distributed in tissues and exert an extraordinary range of effects on most glandular secretions, both internal and external.

This book includes the most significant contributions of the 3rd International Symposium on MULTIPLE RISK FACTORS IN CARDIOVASCULAR DISEASE held in Florence, Italy, July 6-9, 1994. The meeting focused on the risk factors for cardiovascular disease and their interactions. The need for this symposium is based on the epidemiological 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 the general population. The evidence that in high risk patients, a combination of risk factors often is detected, is highlighted in these Proceedings. 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 how atherosclerosis is a complex and multifactorial process involving the influences of lipids, including lipoprotein subfractions, blood pressure, rheologic forces, carbohydrate tolerance, and thrombogenic factors. Furthermore, the risk associated with anyone of these risk factors varies widely depending on level of the associated atherogenic risk factors.