Macromolecular (specifically peptide-based) drugs could potentially be highly effective medicines. However they have a relatively short duration of action and variable therapeutic index. An example of such a peptide is Glucagon-like Peptide I which could potentially be used as a revolutionary drug for diabetes. This is because it stimulates insulin only when the blood glucose level is high thereby reducing the risk of hypoglycemia (a significant disadvantage of using insulin is that an insulin overdose is the single most potent cause of life-threatening hypoglycemia). However it's short duration of action (half-life of 2 minutes in plasma) precludes its therapeutic use. In this volume, the use of novel therapeutics like GLP1 as an alternative to tradition insulin-based drugs in diabetes is described. Application of Peptide-Based Prodrug Chemistry in Drug Development elucidates the traditional concept of prodrugs as "specialized non-toxic protective groups used in a transient manner to alter or to eliminate certain limiting properties in the parent small molecule" (IUPAC definition). It goes on to provide insight into how prodrugs of peptides (with GLP1 as an example) could be appropriately used to extend the biological half life, broaden the therapeutic index of macromolecules and improve the pharmacodynamics of such drugs. Author explains the logic behind designing peptide prodrugs, synthetic procedures and bioassays to examine the conversion of the prodrug to the drug under therapeutic conditions. The prodrugs described slowly convert to the parent drug at physiological conditions of 37C and pH 7.2 driven by their inherent chemical instability without the need of any enzymatic cleavage. The diketopiperazine and diketomorpholine (DKP and DMP) strategies for prodrug conversion are demonstrated in detail with special emphasis on the chemical flexibility that it offers to develop prodrugs with variable time actions. This book will be of useful to chemists, biochemists, medicinal chemists, biologists and people in the medical profession (doctors). It may be used in undergraduate classes but will certainly help post-graduate students and advanced professionals. The author is grateful to Prof. Richard DiMarchi (Standiford H. Cox Professor of Chemistry and the Linda & Jack Gill Chair in Biomolecular Sciences at Indiana University) for valuable suggestions. The foreword for the book has been written by Prof. Jean Martinez, (Legion d'Honneur awarded by the French Republic; Professor of Chemistry and Medicinal Chemistry of the University of Montpellier, France; and Chairman of European Peptide Society, 2002-2010).

The evolution ofdata about the HIV-Associated Lipodystrophy Syndrome has been rapid. The syndrome itself is complex and controversial. Although great progress has been made in understanding epidemiology and etiology of the syndrome, much about the syndrome remains mysterious. It was our intention to assist HIV providers with a framework for understanding the status and complexities ofthe field. Each author was requested to provide an evidence-based discussion of a topic for which they have expertise. While it is impossible that such a volume be completely comprehensive, we believe that the approach of this book will allow the reader to develop a relatively complete snapshot of the syndrome. We also believe that the reader of this volume will be able to confront the emerging literature on the HIV-associated lipodystrophy syndrome with a critical eye and that the volume will provide a context in which to place additional data as they are published.

Despite the advent of insulin for clinical use in 1922, our ability to control hypergly cemia and prevent the long term sequelae ofthe disease remains limited. Thus normalization of the milieu interieur with physiologic responses of insulin and metabolites remains an elusive but critically important goal. The developing endocrine pancreas provides a model system that speaks to many challenges of the transplantation biologist. Thus the attempt to of vascularization, growth and development, immunologic toler recapitulate the ontogeny ance, and glucose responsive insulin secretory capacity of fetal islet tissue provides a tantalizing possibility to replace insulin secreting tissue in persons with diabetes. Studies of this tissue are also important because of the implications such investigations have for genetic and molecular biological approaches to restoring insulin secretion as well as for providing clues to enhancing the growth and repair of islets that have been the target of autoimmune disease. Investigators in the area offetal islet transplantation comprise a small group scattered throughout the world scientific community. Therefore it seemed important to provide a forum where these scientists could gather, share ideas, and achieve consensus such that progress in this rapidly evolving area could be facilitated. The conference would have remained a dream if the support of the Okla Basil Meade, Jr. family had not made it manifest."

This book is divided into two main sections, and covers a broad range of issues important for health practitioners to be aware of when caring for people with co-morbid diabetes and depression. Section One of the book contains the overall ideas and the more recent developments in measuring psychological morbidity in people with diabetes. When attempting to identify people with depression or other psychological problems, it is important for practitioners to recognize the limitations of screening as well as its utility. Issues such as the basic principles regarding when and when not to screen, the cultural applicability of tools, different questionnaire formats and key concepts such as sensitivity and specificity of tools, and their positive and negative predictive value, will be considered. In particular there has been increased interest in the concept of diabetes-related distress and several tools have been developed to measure this. There are broad-based measures of distress such as the Problem Areas in Diabetes (PAID) scale, the Diabetes Adjustment Scale (DAS), The Diabetes Health Profile, The Fear of Hypoglycemia Scale, etc. There are also a range of generic quality of life tools which have been used effectively in people with diabetes; for example the Medical Outcomes Survey Short-Forms (SF36, SF12), the World Health Organisation Well-being questionnaire (WHO-5) and the EQ5-D. These tools are important because they measure aspects of psychological well-being that are specifically associated with the experience of having a long-term conditions and so have important implications for both self-care and health care practice. The potential overlap of symptoms of depression and symptoms of diabetes-related distress are considered in this section and the implications for practice discussed. Section Two covers the most commonly used tools that have been used to screen for depression. For each tool considered some information which is easily referred to by the readeris set out in a table which includes details of the authors, time of first use, country where it was first developed, some examples of the questions used, the languages it is available in, data on sensitivity/specificity. Each instrument will then be discussed in terms of its use in research as well as practice, and its applicability in different patient groups, different cultural settings and so on. Guidance on the practical use of each tool is included, and the most popular depression screening tools are focussed on.

Fresh insights into the pathogenic mechanisms by which hyperglycemia induces tissue and organ injurt are the basis for rapidly evolving promising therapies in diabetes. Especially promising as targets for intervention are products of oxidative stress, including kinins and growth factors. Improving results of renal replacement regimes now incorporating pancreatic islet transplants are able to delay and prevent end-organ damage in diabetic individuals. The evolving story of the taming of diabetes is of direct concern to nephrologists, endocrinologists, ophthalmologists, primary care physicians and medical students.

During the past 5 years, impressive progress has been made in understanding the etiopathogenesis of expeiimental and clinical diabetes. The rapid progress that has been made in the general field of immunology has made possible new understanding regarding the role of the immune system in the pathogenesis of diabetes. The other two areas in which recent progress has been made in the field of diabetes include genetics and the role of infectious agent(s) in the etiopathogenesis of diabetes. Because of these recent developments, a vast amount of data has been accumulated and published in a number of metabolic, endocrine, immunological, and general medicine journals. The purpose of this book is to consolidate all the available information and present it in its current state. In the present volume, I strive to bring together relevant contributions from leaders in the fields of immunopathology, immunobiology, and genetics. The advancing understanding has in several instances reached the point of clinical applica tion. This volume encompasses the entire scope of modem immunology of diabetes mellitus. This volume has been divided into two major parts, Experimental Diabetes and Clinical Diabetes. In the Experimental part are included chapters dealing with the structure and functions of insulin and the immune response to insulin. Spontaneous and experimentally induced models of type I diabetes mellitus are presented. The role of virus(es) in the etiology of experimental diabetes and the influence of sex on experi mental diabetes are discussed. The transplantation of pancreas and islets is reviewed in detail."

Painful Diabetic Neuropathy in Clinical Practice provides a concise, didactic and essential resource for clinicians in the management of neuropathic pain in diabetic patients. This volume opens with overviews of epidemiology, classification and clinical features, including a discussion of the negative effect of painful neuropathic symptoms on quality of life. These are followed by a chapter on diagnosis and staging, which includes approaches to history taking, clinical examination, pain assessment scales, testing and staging. The book concludes with a chapter on the various approaches in the management of neuropathic pain, including the most up-to-date guidelines on the pharmacological treatment of this condition. This concise handbook is an invaluable reference for primary care practitioners and diabetologists who wish to keep up to date with the diagnosis and management of neuropathic pain. Content Level Professional/practitioner

The use of performance-enhancing substances by athletes is not a contemporary epi demic. In fact, athletes purportedly resorted to such measures over 2000 years ago. Even at the ancient olympic games, athletes employed special diets and concoctions to enhance their performance. In ancient Rome and ancient Egypt, gladiators and athletes ingested various potions in order to improve their physical endurance. In most in stances, such early examples of substance abuse by athletes involved relatively in nocuous chemicals, and one might presume that any enhanced performance could be attributed largely to a placebo effect. Nowadays, aside from the ethical issues, these performance-enhancing substances are far more potent and hence toxic to the body. The many performance-enhancing chemicals, drugs, and hormones exert a variety of complex pharmacological actions, but all are meant in some fashion to improve phys ical ability. Their pharmacological effects ranges from imprOVed muscle strength, as in the case of anabolic steroids and growth hormone, to central nervous system stimula tion, as in the case of caffeine or amphetamine. Analgesics or other pain-killing drugs may also be used to suppress an existing injury in order that the athlete may compete."

The selection of prolactin as the subject of the Midwest Con ference on Endocrinology was not only dictated by the recent ad vances in prolactin research but also by the long tradition in that particular area of Endocrinology in the laboratory of C.W. Turner at the University of Missouri. Therefore, it seems only appropri ate that these proceedings of the Tenth Midwest Conference on En docrinology are dedicated to the memory of this scientist, deceased in August 1975 before completion of this volume, whose pioneer in vestigations have contributed substantially to the advancement of our knowledge in many areas of Endocrinology and who played a major role in the early phases of prolactin research. This volume contains a review of the early studies in Turner's laboratory and the latest results obtained by some of the leading research workers in this area and should be a fitting memory to C.W. Turner. Some of the manuscripts printed here were prepared after the conference was held and include material of more recent origin. Much of the delay in publication was due to the length of time de voted to preparation of these manuscripts. To the other authors and participants, and to Plenum Press, we express our appreciation for their patience and cooperation. We also with to thank Mrs."

Control pre-diabetes with these 200 easy-to-follow, nutritious recipes that take 30 minutes or less and leave you feeling full, satisfied, and one step closer to a healthier life. A pre-diabetes diagnosis can be concerning, but taking action and incorporating a better diet and more activity at an early stage can help you avoid type-2 diabetes altogether. And The Everything Pre-Diabetes Cookbook is here to help on your health journey. This cookbook includes 200 healthy and easy recipes that will help you manage your pre-diabetes. You will enjoy meals like a savory stir fry, chili, pasta, and even sweet baked goods like doughnuts, all while creating positive change and improving your health. In 30 minutes or less you can devour these easy-to-make recipes that you're sure to enjoy. The first step toward a healthier life starts right here!

genic constructs. Five articles are devoted to this topic ranging from the B-cell function in transgenic animals to the various effects on diabetes complications. The section on NIDDM, comprising of 10 articles, deals both with new and existing models, their particular widely varying pathogenesis, genetic character- istics and complications. The animals reviewed include: spontaneously diabetic OLETF rats, Chinese hamsters, Goto-Kakizaki rats, db/db mice, rhesus monkeys, dogs and an article demonstrating the genetic link between the Zucker fa/fa and corpulent cp/cp obese interstrains. We wish to welcome the new members to our Editorial Board, Dr. Hubert Kolb from Dusseldorf, Dr. Alex Rabinovitch from Edmonton, Dr. Takayoshi Toyota from Sendai and Dr. Soroku Yagihashi from Hirosaki. At the same time we would like to thank Dr. Douglas L. Coleman from Bar Harbor and Dr. George Eisenbarth from Denver for their editorial contribution to the previous LAD Vol- umes who have retired from the Editorial Board. With great sadness we have to mention Dr. Otho Michaelis IV from Beltsville, MD who suddenly passed away this year. Otho, or Mike as he was called by friends, made a significant contribution in developing and metabolically defin- ing several strains of corpulent cp rats and was extremely helpful in the editor- ial work of the LAD series. His contribution will remain in a lasting memory of all researchers of animal diabetes.

We are especially grateful to Dr. Philip Corfman and his colleagues of the Population and Reproduction Grants Branch of NICHD for making this Conference possible. The format of this volume follows in general the order in which the papers were presented during the Conference. The Conference was divided into four sessions, each of which was presided over by a capable and distinguished scientist. Each of these chairmen, Drs. T. H. Hamilton, G. A. Puca, R. L. Vande Wiele and H. G. Williams-Ashman provided valuable discussion and for their services we are most appreciative. The Editors are indebted to Mr. Robert Colligan for his help in organizing and in redacting the manuscripts. A special commen dation is also extended to Ms. Mary Jane Fowler who cheerfully and efficiently typed this entire volume. Finally, we express thanks to the individual participants of the Conference for their cooperation and prompt submission of the manuscripts and to the Plenum Press for ensuring the rapid publica tion of this volume. Anthony R. Means, Ph.D. Bert W. O'Malley, M. D."

The manuscripts in this volume were contributed by the speakers invited to the Acromegaly Centennial Symposium held in San Francisco, California in July 1986. The meeting was organized to commemorate the description of acromegaly by the French physician Pierre Marie, in 1886. The members of the Scientific Committee spent many hours assisting us in ensuring an outstanding meeting. The support of Serono Symposia, USA in all phases of the planning and execution of the meeting was sincerely appreciated and was highly professional. Special recognition roust be extended to Professor Roger Guillemin of the Salk Institute, whosp interest in medical history led him to devote a great deal of time and personal expense in obtaining information about the life of Pierre Marie. Dr. GuilIemin's presentation on the life and times of Marie was an extraordinary overview of the cultural, social, and scientific backgrounds in which Marie came to describe the disease, acromegaly. Dr. Guillemin' s findings, which were presented at the main banquet in a splendid audiovisual presentation, were clearly the highlight of the meeting and will long be remembered by the attendees. We were also honored by the presence of Dr. Martine Pierre Marie Granier, the great-granddaughter of Pierre Harie. In her address at the banquet, Dr. Granier provided several delightful and intimate vignettes concerning Pierre Marie, using old family records and photographs. The Scientific Committee wishes to extend its gratitude to Dr. Granier for adding immeasurably to the historical atmosphere of the meeting.

These four volumes comprising "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at a landmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, Switzerland in February 1988. The Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of The International Committee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of Fertility and Sterility, The University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US Foundation for Studies in Reproduction Inc., and help from the World Health Organization. B. H. Vickery B. Lunenfeld June 1989 LIST OF CONTRIBUTORS TO THE SERIES H. Bartermann A. Abbondante First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" D-2300 Kiel 1, FRG Rome, ltaly M. Bartholomew P. Abel Department of Medicine/Endocrinology Department of Urology Milton S. Hershey Medical Center Hammersmith Hospital Pennsylvania State University DuCane Road PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck H.

These four volumes comprlslng "GnRH Analogues in Cancer and Human Reproduction" are a distillation of the presentations of the invited speakers at a landmark International Symposium bearing the same name, organized by one of us (B. L. ) and held in Geneva, Switzerland in February 19B8. The Symposium was truly interdisciplinary spanning gonadal hormone dependent disease including various forms of cancer and ranging to control of fertility, both pro- and conception. The international flavor can be caught from the 480 participants and 259 contributors drawn from 14 countries. The Symposium, and therefore this book, would not have been possible without the backing of The International Committee for Research in Reproduction and the sponsorship of the International Society of Gynecologic Endocrinology, The Swiss Society of Fertility and Sterility, The University of Geneva School of Medicine, The Swiss Society of Endocrinology and The US Foundation for Studies in Reproduction Inc., and help from the World Health Organization. B. H. Vickery B. Lunenfeld June 1989 xiii LIST OF CONTRIBUTORS TO THE SERIES A. Abbondante H. Bartermann First Institute of Obstetrics and Urologische Universitatsklinik Kiel Gynecology Arnold-Heller Strasse 7 University "La Sapienza" 0-2300 Kiel 1, FRG Rome, ltaly M. Bartholomew P. Abel Department of Medicine/Endocrinology Department of Urology Milton S. Hershey Medical Center Pennsylvania State University Hammersmith Hospital DuCane Road PO Box 850, Hershey, PA 17033, USA London W12 OHS, UK D. Beck H.

The mechanisms by which animals regulate the volume and composition of their body fluids has long had a particular fascination for students of biology. As a consequence, the subject can lay claim to an impressive record of ground breaking scientific achievements as well as a provocative body of philosophical speculation concerning the role of the system in the origin and evolution of life. Indeed, the entire concept of homeostasis on which so much of o r current biologic thinking is based, derives from Claude Bernard's pioneering exploration of the forces that determine the composition of this 'internal sea'. Other seminal achievements credited to this area of inquiry include the first description of a genetically transmitted human disease (familial neurogenic diabetes insipidus); the first isolation sequencing and synthesis of a peptide hormone (vasopressin and oxytocin); the first demonstration of peptide hormone synthesis by way of a larger protein precursor; the first description of resistance to the biologic actions of a hormone (nephrogenic diabetes insipidus); and the conceptual realization of the unique counter-current mechanism that permits concentration of the urine. This record of far reaching and fundamental advances has been distinguished by many fruitful inter actions between clinical and basic science."

A little over 12 years ago I wrote a small volume entitled Infertility. It seemed to me at that time that significant advances in the field called for the publication of such a volume. The following is from the preface to that volume: During the past 15 years considerable progress has been made in the field of infertility diagnosis and management. It is perhaps a paradox that much of this increased knowledge has come about because of Western medicine's preoccupation with the search for a means to control reproduction. As a result, we have achieved new insights into the physiologic mechanisms involved in reproduction, and we have found better methods for measuring physiologic changes in reproductive health and disease. To these advances can be added improvements in the utilization of endoscopic and surgical techniques, in the diagnosis and treatment of infections and endometriosis, and in the treatment of hormonal disorders. During this period, too, through workshops and conferences and in journals and texts, these latest advances have been made available to physi cians, an outstanding example being the two volumes of Progress in Infer tility, edited by Drs. Jan Behrman and Robert Kistner. As necessary as these publications are, they do not offer an overall view of infertility diag nosis and management."

Sex Hormone Replacement Therapy addresses important issues in contemporary endocrinology. Its major emphasis is on the consequences of the menopause and on androgen deficiency in the absence of overt disease of the hypothalamus and/or pituitary in men. The use of hormone therapy for the primary prevention of cardiovascular disease in post-menopausal women has become an area of major debate, and the pros and cons are examined in detail. Secondary prevention also remains controversial and is addressed in this volume. An issue of particular concern is the treatment of estrogen deficiency symptoms in women with the diagnosis of breast cancer. Whether older men with some androgen deficiency symptoms and equivocally low plasma testosterone concentrations should be treated with androgens is also a matter of great debate, as is the efficacy and safety of plant estrogens in the treatment of menopause-related complaints. Sex Hormone Replacement Therapy will be of interest to students and non-specialists, as well as a wide range of medical practitioners including endocrinologists, gynecologists, rheumatologists and cardiologists.

Is the nephrology community facilitating excess cardiovascular deaths in patients with kidney failure and anemia by treating to a subnormal hematocrit? Why have clinicians and nephrologists permitted health insurance companies and the government to decide when anemia therapy should begin in persons with progressive kidney failure? Is iron the only variable that can be manipulated to maximize response to recombinant erythropoietin? Are we using too much intravenous iron in kidney failure patients, and is oral iron supplementation worthless in sustaining iron stores during long-term erythropoietin treatment? When does left ventricular hypertrophy begin to emerge in patients with progressive renal disease and is there convincing evidence that anemia is a significant cause of LVH in this setting? Is darbepoetin alfa, a new novel, long-acting erythropoietin, really superior to recombinant erythropoietin? This book is a compilation of proceedings from a conference in Brooklyn convened to address these and other controversial and unresolved issues in renal anemia management.

The areas of experimental and clinical psychopharmacology have continued to grow in terms of the numbers of studies appearing in the literature as well as the activity generated by other disciplines that has influenced the output of behavioral pharmacology research. Psychoactive drugs have been considered for their comparative effects upon selected behaviors or for their effect upon diverse behaviors. Behavioral circum stances certainly influence not only the metabolism and action of psycho tropic drugs behaviorally, but also the disposition of these agents and/ or their metabolites in regions of the central nervous system. There can hardly be a psychopharmacology without a neuropharmacology, and the latter would seem to depend upon a neurochemistry. There would appear to be variables that exert potent influences upon the disposition and action of psychotropic drugs, that also relate quite directly to their effects upon behavior; these include drug interactions, nutritional status, environmental effects such as temperature, photic and tactile stimulation, and stress, and the basal status upon which such drug treatment is superimposed. In this volume of Current Developments in Psychopharmacology, which will be the last to appear in this format, we have sought to focus upon a series of current topical reviews that highlight representative areas of experimental and clinical research activity in psychopharmacology. In the first chapter, Dr. Lagerspetz reviews a frequently neglected aspect of psychopharmacological research-the actions of psychoactive agents upon the nervous system and behavior of non-mammalian species."

Can the art of predictive medicine anticipate the development of diabetes? And if so, what can be done about it? How early is early enough to intervene effectively? With what therapeutic modality? Why? Big babies are not an infrequent occurrence in mothers with normal carbohydrate metabolism for another 10, 20, or even 30 years. The abnor- mality present during pregnancy is now accepted as what is inherited with the diabetic predisposition, or what can be recognized as the diabetic susceptibility. It occurs before hyperglycemia, during the phase of dy- namic resistance to diabetes, during the prediabetic period. Prediabetes means before diabetes, and was applied for the first time by Mara~on in Spain, to signify the stage before hyperglycemia. Foglia in Argentina used the term in 1944 for his pancreatectomized rats. We pub- lished the first paper on humans in 1951 (Camerini-Davalos, R.A., Landabure, P., and Serantes, N., Rev Med Cordoba 39: 187).

The elucidation of the structure, function, and clinical significance of the neurohypophysis has been one of the most rewarding chapters in the history of endocrinology. Diabetes insipidus, which can be manifested by passage of 15 liters of urine a day, is one of the most dramatic disorders of the endocrine system, and can readily be managed by replacement therapy with the natural secretions of this gland, or with synthetic analogues that provide a more favorable therapeutic ratio. The neurohypophysis is the archetypical neurosecretory gland. Its secretions arise within well defined nerve cells in the hypothalamus, are transported by axoplasmic flow to nerve endings in the neural lobe, are released in response to propagated action potentials, and are regulated by neurotransmitters and osmotic signals. This gland is a model for homeostatic regulation; functional disorders of this regulation lead to well defined disorders such as the syndrome of inappropriate secretion of antidi uretic hormone (SIADH), which can be mimicked by the ectopic secretion of its hormones by tumor cells. These hormones were the first peptides to be sequenced and synthesized chemically and their structure-function relations have been characterized as well as those of any of the peptide hormones. The concept that peptide hormones generally arise as products of the processing of a larger prohormone precursor was first developed from studies of the neurohypophysis. The concept of stimulus-secretion coupling was first ap plied in neuronal tissue to the neurohypophysis.

I consider it an honor to have been asked to write the Foreword for The Diabetic Pancreas. Although I have been involved in the study of the pancreas since 1921, my interest goes back even further to the time, in 1918, that my father's sister, a nurse who had trained at the Massachusetts General Hospit.al, devel oped diabetes, lost weight, and died in diabetic coma. This sad event made a deep impression on me and was certainly pardy responsible for my choosing to join the Department of Physiology of the University of Toronto to begin a career in research into diabetes. This is not the place to describe in detail the wide-ranging research and study of the diabetic pancreas in which I have engaged in the past 56 years. Suffice it to say that I am familiar enough with the subject area to be able to predict a great future for this book. The editors have undertaken a very ambitious and worthwhile project, and their efforts have been supported and strengthened by contributors who are respected authorities in their fields, thus ensuring a successful presentation of this major work."

Despite a new title, Contemporary Metabolism, Volume 1 is actually the third volume in a continuing series and succeeds The Year in Metabolism 1975- 1976 and The Year in Metabolism 1977. As in the earlier volumes, the same internationally recognized authorities review the noteworthy recent devel opments in their areas of expertise. In many instances they also address aspects that have not been considered previously. In this volume, Dr. J. Edwin Seegmiller again updates progress in understanding disorders of purine and pyrimidine metabolism. However, particular emphasis is placed on the emerging relationships with immune mechanisms. Dr. Charles S. Lieber is joined by Dr. Enrique Baraona in a continuing review of metabolic actions of ethanol. This chapter examines effects of ethanol on protein metabolism and selected features of lipid metabolism-two areas that were not included in the earlier volumes. Dr. DeWitt S. Goodman's review of disorders oflipid and lipoprotein metabo lism builds on his previous chapters, but much additional attention is directed to a critical analysis of recent advances in epidemiology and lipoprotein structures. In collaboration with Dr. Brian L. G. Morgan, Dr. Myron Winick devotes his entire chapter to a detailed review of the impact of nutrition upon brain development-an overview that has now been rendered possible by the burgeoning recent developments in this area."

This volume in the series Developments in Medical Virology deals with viruses involved in diabetes mellitus, a syndrome with a strong genetic background that causes damage to the regulation of insulin synthesis and function. Viruses were found either to cause or to stimulate diabetes mellitus in man and in animal models. The nature of the role of viruses is described by many of the scientists who participated in the original studies. To complete the picture, chapters were included that deal with the insulin gene, the secondary structure of the proinsulin and insulin receptor polypeptides, pancreatic Langerhans islets, and clinical considerations of the disease. The aim of Developments in Medical Virology is to elucidate processes involving viruses as pathogens of cells and organisms, with special attention to human diseases. A number of volumes will be devoted to viruses affecting specific organs (e.g. brain, liver, etc.), while others will elaborate on the clinical experience in the use of antiviral drugs. The series is published in parallel with Developments in Molecular Virology, designed to present an analysis of molecular mechanisms implicated in virus infection and replicative processes. In addition, the series Developments in Veterinary Virology provides information on viruses causing diseases in animals, with special emphasis on aspects of interest to veterinarians.