For many years now, our understanding of the somatotrophic and reproduc tive axes has evolved essentially independently, both fields of study reaching a highly advanced, although far from complete, level of under standing. Along the way, however, it became apparent that in some circumstances the reproductive and somatotrophic axes may be inter dependent. Inklings to this effect were at times feeble and at other times more convincing. Among those inklings are the clinical recognition by pediatric endocrinologists of the apparent association between isolated GH deficiency and delayed puberty, as well as of the apparent permissive, pUberty-promoting property of GH. Equally important is a body of experi mental studies establishing the ovary of multiple species as a site of GH reception and action. Arguing against an essential role for GH in the reproductive process is the observation that individuals who have GH resistance of the Laron variety are fertile arid that isolated GH deficiency does not constitute an absolute barrier to the attainment of sexual maturation and fertility. The intraovarian insulin-like growth factor (IGF) hypothesis proposes that IGFs may serve as amplifiers of gonadotropin action. Although the dependence of intraovarian IGFs on systemic GH action has never been unequivocally demonstrated, that leap of faith has often been made. The intraovarian IGF hypothesis serves as the rationale for the adjunctive use of GH in the induction of ovulation."

The beautiful town of Cavtat near Dubvronic, Yugoslavia was the site of the twelfth meeting of the International Foundation for Biochemical Endocrinology. It was sponsored by the Serbian Academy for Sciences and Arts and by the Foundation. The Croatia Hotel in Cavtat was a splendid place for a meeting. The presentation of the subject matter relating to "Neuroendocrine Correlates of Stress" was interesting and informa tive. The topics included many forms of stress, their mediators and responses. They included: releasing factors; neurotransmitters in the hypothalamus; role of noradrenal ine; the reaction of the hypothalamo-pituitary-adrenocortical axis to stress; immunological stress; thermal stress; immobil ization stress; peptides in shock; stress-induced prolactin; stress and acupuncture; stress and behavior; spinal cord transection and stress; electroconvulsive stress; neuroendocrine cells and stress; protein kinase as a signal transducer; the effects of constant 1 ight and darkness on the pineal; sleep, stress and ovarian function; and finally, hormonal response to exercise. Subsequently, the papers presented were rewritten for inclusion in this monograph. The Chairmen for the sessions at Cavtat were K. McKerns and Stefan Manolov, V. Chong-Li and L. Rakic, S. Feldman and R. Mil in, M. Lee and V. Liposits. The next meeting of the Foundation will be held in Edinburgh near the end of September, 1985. The topic will be "Neuroendocrine Molecular Biology" with Professor George Fink as Honorary Chairman of the local organizing committee."

Lipids and Women's Health is an up-to-date critical review of pertinent scientific and clinical issues connected with lipid disorders in women. Topics discussed include the public health significance of cardiovascular disease in women, lipoprotein and lipid metabolism, effects of estrogens and progestins on lipid metabolism, metabolic changes of menopause, and the paradox of obesity, a curable disease that is rarely cured, as well as those conceptual advances in our understanding of diabetes mellitus that have clarified diagnosis and may have improved treatment. The relationship of diet and lipid intake to the development of breast and uterine cancer; dietary and drug treatment of lipid disorders; effects of exercise, smoking, and stress; and repercussions of lipid disorders on the family are explored. The volume should prove of use to gynecologists, internists, family practitioners, and pediatricians, as well as to all other professionals with a major concern for the health of female patients.

A central concept in the evolutionary theory of senescence is the idea that ageing results from life-history trade-offs. In particular, the disposable soma theory suggests that longevity is determined through the setting of longevity assurance mechanisms so as to provide an optimal compromise between investments in somatic maintenance (including stress resistance) and in reproduction. Comparative studies among mammalian species confirm that cells from long-lived species appear to have a greater intrinsic capacity to withstand stresses than cells from short-lived species. Childbearing at older ages has become increasingly common in modern societies because of demographic changes, medical progress and personal choice. While the detrimental effects of late reproduction on infant mortality and genetic diseases have been well documented, little is known about the possible postponed detrimental effects of late parenting.

The traditional concept of a neuroendocrine mechanism for regulation of growth hormone (GH) secretion is based in large part on the work of Roger Guillemin. The work of Dr. Guillemin, who was awarded the 1977 Nobel Prize in Physiology and Medicine, supported the view that quantita tive change in GH secretion was the net result of pituitary stimulation and inhibition by the hypothalamic neurohormones, GH releasing hormone (GHRH), and somatostatin (somatotropin release inhibiting factor; SRIF), respectively. During the 1970s, another endocrine research pioneer, Dr. Cyril Bowers, discovered that structural modification of enkephalin re sulted in a family of peptides with GH releasing properties. These com pounds, simply called GH releasing peptide (GHRP), were originally thought to mimic GHRH. However, upon subsequent investigation they were found to supplement the activity of the natural hormone through a different mechanism. Nearly two decades after their discovery, the differ ences between GHRP and GHRH have been described by many different laboratories throughout the world. The complementary GH secretagogues have different binding sites, second messengers, and effects on gene expres sion. Based on these differences, it has been suggested that expansion of the original two hormone mechanisms for GH regulation to include a third molecule may be appropriate, even though the naturally occurring ana logue of GHRP has not yet been identified. Despite our lack of knowledge concerning the natural product mimicked by GHRP, clinical development of the new family of GH secretagogues for diagnostic and therapeutic purposes has begun in earnest."

In the words of Disraeli, "To be conscious that you are ignorant of the facts is a great step to knowledge. " For most of us, the conscious awareness of relative ignorance is an uncomfortable aspect of daily life. New data appear in such inexorable profusion that the necessity for continuous retooling has joined death and taxes as an inescapable component of our destinies. Perhaps it is this "consciousness of ignorance" that accounts for the success of the preceding volumes of this new series. The Year in Metabolism and The Year in Endocrinology series were introduced with the avowed intention of "providing an efficient and enjoyable bridge between those who are creating new knowledge at the bedside and the professional consciousness of those for whom such knowledge is ultimately intended. " That objective seems particularly appropriate at a time when the award of the 1977 Nobel Prize in Medicine or Physiology to Guillemin, Schally, and Yalow has served to emphasize the epoch-making advances that have characterized the recent course of endocrinology and me bolism. For the 1977 volume of The Year in Metabolism, the previous formula has been preserved. The same internationally recognized authorities again have contributed commentaries about the progress in their areas of expertise. They have been joined by Drs. Jack W. Coburn, David L. Hartenbower, and Charles R. Kleeman, who have provided a new section on Divalent Ion Metabolism.

"Fertility Preservation in Males: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this practical reference guide provides an update on options for fertility preservation in men, while also discussing important related epidemiologic, ethical, medico-legal, psychological, and social aspects. Using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms, the chapters all conform to a uniform structure, including step by step protocol of laboratory procedures, key issues in commentary and a list of references. The result is a unique resource for reproductive endocrinologists, urologists, embryologists, reproductive scientists, and oncologists."

A growing majority of women in the western hemisphere have been delaying initiation of childbearing to later in life. Consequently, more than ever before, women in their late 30s to early 40s are attempting their first pregnancy. Since the incidence of most cancers increases with age, delayed childbearing results in more female cancer survivors interested in fertility preservation." Fertility Preservation in Females: Emerging Technologies and Clinical Applications" contains a selection of the valuable chapters and protocols of Seli and Agarwal s previously published hardcover text "Fertility Preservation: Emerging Technologies and Clinical Applications." Newly available in this convenient and affordable softcover format, this unique and practical reference guide for reproductive endocrinologists, gynecologists, embryologists, reproductive scientists, and oncologists provides strategies for fertility preservation in women, using a format that combines concise scientific background with practical methodological information and easy-to-grasp algorithms."

Cell biology has made an appreciable impact on the evaluation of physiological and pathophysiological processes leading to a more detailed understanding of the signaling mechanisms by which cells communicate in vivo and in vitro and modify adaptively. By using cell culture models in addition to animal experiments we are now able to better define the overall and the selective potential of drugs. This book is designed to give information on the advantages and limitations and on new aspects and the meaning of cell culture models in pharmaceutical research.

These Proceedinqs of the Midwest Conference on Endocrinology and Metabolism are being published by Plenum Press for the first time. Earlier Proceedings in the series Vlere published by the University of Missouri at Columbia. The shift to an internationally recognized pub lisher reflects the considerable growth in stature that the Midwest Con ferences have undergone since their inception nine years ago. Originally concerned only with the endocrinology of the thyroid, the Conferences now explore other endocrine areas. Efforts are made to assemble a panel of speakers selected from different sub-disciplines within endocrinology for the purpose of addressing a common problem. The Ninth Conference typifi es til i s approach. The format used in recent Conferences is not unique, but is unfor tunately encountered too rarely. A few prominent scholars are invited to come together to expound their findings and concepts in considerable depth, and to participate in a discussion which, together with the for mal presentation, is published in the Proceedings. The discussion, noted for its unhurried nature, permits wide participation by the audi ence. The subject of the Ninth Conference is one which is basic and im portant not only to endocrinology but also to biology in general. Many, possibly most, life processes change in a rhythmic fashion, with similar states recurring at regular time intervals. This rhythmic property of living systems expresses itself as a recognizable and definable pattern or "time-form" in a manner equivalent to the more customary spatial form."

This volume contains the edited proceedings of the Totts Gap Colloquium on Diabetes Mellitus, DILEMMAS IN DIABETES. The Collo- quium, lasting two and a half days, was organized mainly as a dia- logue among experts in the field with different disciplinary back- grounds and, to some extent, differing points of view. The effort was to synthesize existing knowledge, reconciling disparate data and interpretation, and pointing up important areas of ignorance. Thus, the book should serve not only as a summary of recent information on diabetes, but as a reliable guide to the practicing physician as he wades through often conflicting etiologic dogmas and therapeutic practices. The Colloquium was made possible through the generous support of the Geigy Pharmaceutical Company and the conscientious and expert coordination of Mr. Oscar Swarth. The participants were: Dr. George F. Cahill, Boston, Massachusetts Dr. Harvey C. Knowles, Cincinnati, Ohio Dr. Rachmiel Levine, Duarte, California Dr. Lelio Orci, Geneva, Switzerland Dr. Norton Spritz, New York, New York Dr. Roger Unger, Dallas, Texas Dr. Robert Williams, Seattle, Washington Dr. Stewart Wolf, Galveston, Texas Dr. Arnold Lazarow and Dr. I. Arthur Mirsky were to have partici- pated, but unfortunately were ill at the time of the meeting. Others in attendance included five medical students, especially selected from medical schools in the Philadelphia/New York area.

The islets of Langerhans, the primary source of hormone production in the pancreas, have been the focus of research into the nature of diabetes for decades. In recent years, the molecular biology of this multiendocrine organ has been intensively investigated, with a corresponding increase in our understanding of the normal and pathological functioning of islet cells. Molecular Biology of the Islets of Langerhans provides a comprehensive treatment of molecular studies on the synthesis of insulin, glucagon, somatostatin and pancreatic polypeptide. In addition, this volume presents contemporary hypotheses and explanations, at the molecular level, of the defects in islet cells that may lead to diabetes. The material presented here will be essential reading for researchers in human endocrinology and, in particular, for those working in the area of diabetes research.

As widespread social transformations have been paralleled by gains in health and life expectancy through public health and other improvements, a variety of other challenges to health have emerged, particularly in lifestyle related, behaviourally mediated changes in rates of chronic disease. Hormones, Health and Behavior looks at the relationship of human biology and human society at the intersection of behavior, hormones and health. There is both scientific interest and practical urgency behind the ideas and findings presented here, as the need for a socio-ecological view of function and well-being has become more apparent. This book documents an emerging understanding of how hormones create linkage between behavior or social life and health. It will inform graduate students and researchers interested in human sciences, human development, anthropology, epidemiology, public environmental and reproductive health.

It is unclear, and really no longer relevant, whether the information explosion that we now contend with has been fostered by the growth of specialization and subspecialization in medicine, or vice versa. What is clear is that the two are mutually supportive and constitute what would be in endocrine parlance a short-loop positive feedback system. As a result, for most areas of medicine, even the subspecialist in that area has a problem in maintaining currency, the more general specialist has substan tial difficulty in doing so, and the generalist is tempted to abandon the effort altogether. Nevertheless, for all, both the internal pressures of conscience and self-esteem and the external pressures generated by peer review, recertifi cation, and subspecialty boards create the need for continuous self-educa tion. We are, therefore, in an era in which the means of dissemination of new information deserves as much creative attention as does its acquisition."

Calcium metabolism is regulated by three specific hormones: parathor- mone, calciferol metabolites, and calcitonin. Cyclic AMP also plays an important part in calcium regulation, and its concentration in urine can be taken as a measure of parathyroid function. Methods for quantitative measurement of, e.g. calcium-regulating hormones and vitamin D metabolites as well as of cAMP are absolutely necessary for safe differential diagnosis of diseases of the parathyroid like hypo- and hyperparathyroidism. In this monograph all presently available methods are summarized as to whether they can already be obtained as test kits or are still being tested. Radioimmunoassays for the various peptide fragments such as 53-84, 44-68, 28-48, and 1-34 are described, as are immunochemiluminescence methods and adenylate cyclase bioassays. The same is true for the vitamin D metabolites, where the various assays for calcidiol and calcitriol such as HPLC, protein-binding assay with second antibody separation, and double antibody RIA are dex scribed. Finally, determination of calcitonin and cAMP is discussed in detail. This is a practically and clinically oriented monograph for working in the fields of internal medicine, endocrinology, and laboratory medicine.

Following 50 years of glucocorticoid use in a clinical setting, an international body of expert scientists and physicians presents the most expansive survey of glucocorticoid pharmacology to date. This work traces the history of glucocorticoid biology from the seminal description of glucocorticoid insufficiency by Thomas Addison in the mid-19th century, up to current advances in elucidating the molecular basis of glucocorticoid action. Important discoveries are presented, as well as milestones in drug development, a survey of current clinical practice, and prospects for novel glucocorticoid-based therapeutics. Scientists and clinicians will appreciate the scope of this work, which is of special interest to workers in the fields of endocrinology, inflammation and autoimmune disease.

Embryoimplantationisaremarkableandcomplexprocess. Approachesde- velopedfromthefieldsofcellanddevelopmentalbiology,immunology, andmolecularbiologyhavegreatlyenhancedourabilitytostudythe sharedaswellasuniquefeaturesofembryo-uterineinteractions. Impres- siveandcriticalgroundworkhasbeenlaidbyalargeanddedicatedarray ofendocrinologists,reproductivebiologists,andanatomists. Thesestudies havesetthestagetoutilizesensitiveandsophisticatedtechniquestode- tectandmodulateproteinandgeneexpression. Justasthesymbiosisofmother andfetusiscriticalforthemaintenanceofpregnancy,soisthesynergyamong investigatorsfrommanydisciplines,bothinbasicandclinicalarenas,keyto unravelingthemysteriesofimplantationandplacentation. Alargegroupof contributorsinthisfieldhadtheopportunitytomeetanddiscussthestateof thisartwiththesupportofSeronoSymposiaUSA,Inc. Whileitisneverpos- sibletobringtogethereveryonewhohasplayedanimportantrole,itwas, nonetheless,bothexcitingandgratifyingtohavesomanycolleaguestogether forthisevent. Inthechaptersthatfollow,thehighlightsofthismeetingarepresented assummarizedbytheindividualpresentersofsevendifferentsessions. The topichasbeenconsideredfromthebroadsocialandethicalimplications ofmoderninvitrofertilizationandassistedreproductivetechnologiesto detailedmolecularcontrolsovereventsthatoccurduringembryonicdevel- opment,uterinepreparationforimplantation,andplacentalorganogenesis. Thesechaptersdemonstratethesignificantandrapidprogressbeingmade inthisfieldofbiologyandmedicine. Atthesametime,theyshowthat muchmoreneedstobedonetounderstandandfullyappreciatethispro- cess. Lessonslearnedfromthiseffortcanbeexpectedtocontinuetopro- videinsightsintoother,relatedfields. Ofthemanycontributorstoour understandingoftheprocessofimplantation,nonehavehadalargerim- pactthanourcolleague,AllenEnders. Dr. Endershasplayedaparamount roleindevelopingthebasicunderstandingofthecellbiologicalprocesses vii VIII Preface underlyingimplantationandplacentationinmanyspecies,includinghu- mans. Hecontinuestocontributeandguidethoughtintheseareas. The participantsofthissymposiumrecognizedDr. Enders'impressivecontribu- tionsbyholdingthiseventinhishonor. DANIELD. CARSON * Contents Preface vii Contributors xiii PartI. Development and Future ofHuman In Vitro Fertilization and Embryo Implantation I. ImplantationintheHumanasViewedbyCanonLaw, CivilLaw,andNaturalReason 3 HOWARDW. JONES, JR. , RICHARDA. MCCORMICK, AND SUSAN L. CROCKIN 2. TheImpactofMaternalAgeandOvarianAge onImplantationEfficiency...12 STEVEN SPANDORFER AND ZEV ROSENWAKS Part II. CellularAspects ofImplantation 3. VascularInvasionDuringImplantationandPlacentation 23 ALLEN C. ENDERS AND THOMASN. BLANKENSHIP 4. OxygenRegulatesHumanCytotrophoblastProliferation, Differentiation,andInvasion:Implicationsfor EndovascularInvasioninNormalPregnancy andPreeclampsia 39 OLGA GENBACEV,YAN ZHOU, MICHAEL T. McMASTER, JOHNW. LUDLOW, CAROLINEH. DAMSKY, AND SUSAN1. FISHER 5. Embryo-MaternalInteractionsafterDiapause inaMarsupial 54 MARILYNB. RENFREE AND GEOFFREY SHAW IX x Contents 6. CellularInteractionsandtheCysteineProteinases intheProcessofMouseImplantation 67 BRUCE BABIARZ, SUZANNE AFONSO, ANDLINDA ROMAGNANO Part III. HormonalRegulation 7. NovelSteroid-RegulatedMarkersofImplantation 83 INDRANIC. BAGCHI 8. MolecularSignalinginImplantation 92 SANJOYK. DAS, BIBHASHC. PARIA, AND SUDHANSU K. DEY 9. IdentificationofProgesterone-RegulatedGenes intheUterus 107 CINDEER. FUNK, BERTW. O'MALLEY, AND FRANCESCO1. DEMAYO PartIV. MolecularMarkersofReceptivity 10. MucinsProvideaBarriertoEmbryoImplantation 123 MARYM. DESOUZA, GULNARA. SURVEYOR, XINHUI ZHOU, JoANNE JULIAN, ANDDANIELD. CARSON II. PotentialInvolvementofTrophinin,Bystin, andTastininEmbryoImplantation 132 MICHIKON. FUKUDA, DAITA NADANO,NAO SUZUKJ, AND JUN NAKAYAMA 12. OsteopontininHumanEndometrium: ARoleinEndometrialReceptivityand EmbryoImplantation? 141 CHRISTOS COUTIFARJS,AKINYINKA OMIGBODUN, PIOTR ZIOLKIEWICZ, AND JOHN HOYER PartV. TrophoblastFactors 13. TheRabbitasaModelforImplantation: InVivoandInVitroStudies 151 LORENH. HOFFMAN,D. RACHEL BREINAN, AND GARETHL. BLAEUER 14. RegulationofTrophoblastEndocrineFunction: ThePlacentaDoesItsOwnThingTranscriptionally...161 JEROMEF. STRAUSSIII ANDLEE-CHUANKAo Contents XI 15. TranscriptionFactorsRegulatingtheDifferentiation oftheTrophoblastCellLineage 167 IANC. SCOTTANDJAMESC.

This volume will explore the epidemiology and the basic mechanisms of each of these prenatal phenomena, in an attempt to explain the role of the prenatal environment in promoting postnatal weight gain. This information will contribute to resolving the nature-nurture controversy. This information provides guidance to clinical practitioners involved in both prenatal and postnatal care. This volume further stimulates research into underlying mechanisms and prevention and treatment of this phenomenon.

The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidiscipli nary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of on cology."

The tenth meeting of the International Foundation for Biochemical Endocrinology was held in Geilo, Norway near the end of September, 1982. The subject matter of the conference and the monograph was on "Regulation of Target Cell Respon- siveness." The local organizing committee was Asbjjllrn Aakvaag and Vidar Hansson. The scientific sessions covered a wide range of hormone action and cell response, including: peptide hormones and target cell response, regulation of insulin responsiveness, intracellular modulation of peptide hormone response, gonado- tropins and target cell responses, hypothalamic hormone- effects and regulation, steroid receptors and cellular control, hormones and growth regulation, and hormones and gene regulation. The chairpersons for the sessions were L. Birnbauer -A. Aakvaag, S. Taylor- R. S. Horn, F. Labrie- F. Rommerts, A. R. Means - K. W. McKerns, P. F. Hall - V. Hansson K. Griffiths - K. M. Gautvik, E. J. Peck, Jr. -E. Haug, F. S. French- W. T. Schrader, and E. M. Ritzen- B. Jegou. In addition to the scientific sessions in Geilo we were all delighted to sample some of the cultural and artistic attractions of Oslo, and to travel by train from Oslo via Geilo to Bergen. The scenery and hospitality were magnifi- cant.

The tenth meeting of the International Foundation for Biochemical Endocrinology was held in Geilo, Norway near the end of September, 1982. The subject matter of the conference and the monograph was on "Regulation of Target Cell Respon- siveness." The local organizing committee was Asbj rn Aakvaag and Vidar Hansson. The scientific sessions covered a wide range of hormone action and cell response, including: peptide hormones and target cell response, regulation of insulin responsiveness, intracellular modulation of peptide hormone response, gonado- tropins and target cell responses, hypothalamic hormone- effects and regulation, steroid receptors and cellular control, hormones and growth regulation, and hormones and gene regulation. The chairpersons for the sessions were L. Birnbauer - A. Aakvaag, S. Taylor - R. S. Horn, F. Labrie - F. Rommerts, A. R. Means - K. W. McKerns, P. F. Hall - V. Hansson K. Griffiths - K. M. Gautvik, E. J. Peck, Jr. - E. Haug, F. S. French - W. T. Schrader, and E. M. Ritzen - B. Jegou. In addition to the scientific sessions in Geilo we were all delighted to sample some of the cultural and artistic attractions of Oslo, and to travel by train from Oslo via Geilo to Bergen. The scenery and hospitality were magnifi- cant.

Diabetes mellitus is rapidly increasing in prevalence throughout both developed and developing countries. The social and economic burden of this disease is estimated to cost 14 billion dollars worldwide. In the USA alone, 15 million individuals are diabetic, nearly half of them unaware of their condition. Complications of diabetes mellitus are the leading causes for blindness, limb amputation and chronic renal failure and kidney transplantation in industrialized countries. Further, diabetes mellitus per se and the metabolic derangement associated with diabetes are important risk factors for cardiovascular disease. Diabetes, as defined by an elevated fasting blood glucose level is presently subdivided in etiologically distinct groups. The most prevalent being type 2 (adult onset) diabetes characterized by insulin resistance and failure of the ~-cell to supply insulin in amounts sufficient to meet the body's needs. Type 1 (juvenile) diabetes, most commonly with an onset during childhood and adolescence, is caused by an auto-immune destruction of the pancreatic ~-cells. The causations of both type 1 and type 2 diabetes involve a combination of complex genetic traits and environmental influences. A third category are the mature onset diabetes of the young (MODY). This comparatively small group of patients (-10% of diabetes) presents relative early in life "30 years of age) compared to the more common late onset type 2 diabetes.

The Fifth Annual Washington Spring Symposium on Health Sciences attracted over 400 scientists from 20 countries. It was held at the Lisner Auditorium of the George Washington University in Washington. D.C. The theme of the meeting was neural and endocrine peptides and receptors. The meeting emphasized basic and clinical research on neural and endocrine peptides and receptors. The six plenary sessions emphasized pituitary peptides, releasing factors, brain peptides, growth factors, peripheral peptides, and clinical applications. The chapters in this volume are derived from each of these six scientific sessions plus the poster and special sessions. The Abraham White Distinguished Scientist A ward was presented to Dr. Julius Axelrod for his numerous contributions to the field of neurochemistry. He presented the keynote address, which was entitled "The Regulation of the Release of ACTH." Dr. Axelrod discussed numerous factors, such as the peptides CRF, VIP, and somatostatin, that regulate hormone secretion from pituitary cells. The Distinguished Public Service Award was presented to Senator Lowell Weicker, Jr., in recognition of his leadership and outstanding achievements in the United States Senate and for his legislative support for biomedical research and education. In the symposium banquet address, Senator Weicker stressed the need for continued federal support of biomedical science research.

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.