Advances in Compararative and Environmental Physiology helps biologists, physiologists, and biochemists keep track of the extensive literature in the field. Providing comprehensive, integrated reviews and sound, critical, and provocative summaries, this series is a "must" for all active researchers in environmental and comparative physiology. Cellular volume and osmolality in animals is a well studied topic and this specific volume in the series provides the reader with a thorough grounding in this area of physiology. Consisting of two parts, the text discusses osmolality and volume control in terms of both inorganic and organic ions which as a result gives an excellent overview to those working and interested in this field.

Introduction to Mammalian Reproduction is a welcome contribution to the fields of gametogenesis, gamete transport, fertilization, and reproduction technologies. Key topics covered include:
*formation and maturation of male gametes;
*morphology and physiology of female gametes;
*how the sperm meets the egg;
*sperm-egg fusion, egg activation, and implantation of fertilized egg;
*assisted reproduction and environmental chemicals that have an effect on formation and function of male and female gametes. This book is for both researchers and students involved in reproductive biology.

This book includes articles relating to presentations given in a variety of forms (lectures, posters, contributions to round tables, software presentations) at the 5th International Biothermokinetics Meeting held in Bordeaux-Bombannes, September 23-26, 1992. The fact that not just lectures were considered for these proceedings reflects the aims of BTK meetings to instigate discussion, promote scientific cooperation and confront as many different ideas as possible with each other (at best heretical ones). BTK conferences have expanded more and more; 130 participants came to the 1992 meeting from 20 countries. It was therefore necessary to hold the round tables in parallel sessions. It is difficult to have an unbiased feeling of what should be selected as the salient features of the meeting. As the name suggests, Biothermokinetics embraces thermodynamic and kinetic approaches to experimental and theoretical investigations of biological processes, in particular at the cellular level. This "classical" point of view is mainly represented in the chapter "Thermodynamics and Kinetics of Transport Processes and Biological Energy Transduction."

Similarities in structure and function between pigs and human beings include size, feeding patterns, digestive physiology, dietary habits, kidney structure and function, pulmo nary vascular bed structure, coronary artery distribution, propensity to obesity, respiratory rates, tidal volumes and social behaviors. Since the pig is an omnivore, it provides an adaptable model to evaluate chronic and acute exposures to xenobiotics such as alcohoL caffeine, tobacco, food additives and environmental pollutants. Swine have been used successfully as models to evaluate alcoholism, diabetes, absorption, digestion, total paren teral nutrition, organ transplantation, atherosclerosis, exercise, hypertension. hemorrhagic hypotension, melanoma, gingivitis, obstructive and reflux nephropathy. osteochondrosis. dermal healing and septic shock. A severe and worsening shortage of organs and tissues for transplantation in patients with severe organ failure has encouraged the consideration of inter species or xenotransplan tation. In developing programs toward this end, the pig generally is viewed as the preferred donor because of its size, physiology and availability. The pig harbors relatively few diseases which could be transmitted inadvertently to human patients. The ability to genetically modify swine to ameliorate the consequences of the human immune response offers a further significant advantage. Another important consideration for an animal model is that basic biologic back ground information be available for investigators to design future prospective studies."

Understanding how the brain works is undoubtedly the greatest challenge for human intelligence and one of the most ambitious goals of contemporary science. We are certainly far from this goal, but significant advancements in several fields of Neuroscience and Neurobiology are being obtained at an increasing pace. The NATO ASI School in Neurobiology, held in Erice May 2-12,1995, as the 23rd Course of the International School of Biophysics, provided an update on three basic topics: Biophysics and Molecular Biology ofIon Channels, Sensory Transduction, and Higher Order Functions. Current knowledge on these subjects was covered by formal lectures and critical discussions between lecturers and participants. This book collects original contributions from those scientists who attended the School. Many students presented their results in poster sessions, steering lively informal discussions. A selection of these contributions is also included. A major portion of the program of the School was devoted to a general overview of current trends of thought and experimental approaches in neurobiology, emphasising the importance of understanding molecular aspects of the elementary events underlying sensory transduction and processing in the nervous system, without indulging however in a pure reductionistic view of such complex phenomena. Recent studies of molecular biology and the electrophysiology of heterologously expressed ionic channels, have shed new light on the molecular mechanisms underlying ionic permeation of excitable membranes and its regulation by physical and chemical parameters.

Since its inception in 1973, The International Society on Oxygen Transport to Tissue (ISOTT) has provided a unique forum to facilitate and encourage scientific interaction and debate. Welcoming scientists and clinicians from a broad spectrum of disciplines, each with their own particular skills and expertise, ISOTT unites them under the common theme of oxygen transport. The successful blend of scientific presentations and informal discussion which characterizes ISOTT is epitomized best by the many fundamental discoveries and technical advancements which it has spawned. The breadth and strengths of The Society's scientific base promotes the rapid progression of ideas from theoretical concepts to rigorous scientific testing and often, ultimately to the clinical arena. Each publication of the ISOTT proceedings has been recognized by Science Citation Index listing and the papers frequently establish scientific precedents and become considered as standard works in their respective fields. The 21st ISOTT Meeting was held in San Diego from August 14th through August 18th, 1993. The San Diego Meeting attracted about 150 registrants and 40 accompanying persons. Ten state-of-the-art lectures were presented by international experts in ~ transport and there were in addition two symposia -one dealing with assessment of tissue hypoxia and the other with functional heterogeneity in different organ systems. There were 100 free communications, consisting of posters accompanied by an abbreviated oral summary. All manuscripts were reviewed by the Editors for form and content, but as is customary for the ISOTT proceedings, rigorous scientific peer review was not undertaken.

The aimoftheHypospadiasand Genital Symposium, held at theUniversityof California,SanFrancisco,wastoprovideaforumforauthoritativeinvestigatorswhoare activelyinvolvedinthevariousdisciplineswhichdefinetheleadingedgesofhypospadias and genital research. It is important for such investigators to continue to meet for the purpose of discussing the latest developments in their individual fields, to analyze the significanceofcurrent research, to discuss new tactics for unresolved problems and to develop new theories andapproaches asneeded. The two day conference on hypospadiasandgenitaldevelopment research was organizedintothreesections: 1)HumanStudies;2)MechanismofGenitalDevelopment; and 3) Endocrine Disruptors and Sexual Dimorphism in the Animal Kingdom. Each sessionwasintroducedbyanexpertmoderatorfollowedtheinvitedspeakerswithtimefor extensiveinteractionbetweeninvestigators. Thisbookdocumentstheproceedingsofthe HypospadiasandGenitalDevelopmentSymposium. Iwould especially like to thank Kari Gaudette for editorial assistants, Cynthia Ashe, Selcuk Yucel, Antonio Souza and the administrative staffinthe Departmentof Urology. Ihopeyoufindthisresourceuseful. Laurence S. Baskin,M. D. ProgramChair ChiefPediatricUrology UCSF vii ACKNOWLEDGEMENTS Supportforthissymposiumisgratefullyacknowledged TheNationalInstituteofHealthGrant#R13DK*HDS997 UCSFDepartmentofUrology AmericanUrologicAssociation CONTENTS Introduction...1 SECTIONI. HUMANSTUDIES EpidemiologyofHypospadias...*...*...25 J. DavidErickson EndocrineEvaluationofHypospadias...31 G. HyunandT. Kolon EndocrineAbnormalitiesinBoyswithHypospadias...45 R. I. Silver GeneticandClinicalStudiesonHypospadias...***...**...*...73 A. Nordenskjold SECTIONII. MECHANISMOFGENITALDEVELOPMENT DevelopmentofthePenileUrethra. . 87 G. CunhaandL. Baskin AnatomicalStudiesoftheMouseGenitalTubercle...103 L. Baskin,W. Liu,J. Bastacky,andS. Yucel AnatomicalStudiesoftheFibroblastGrowthFactor-l0Mutant,Sonic HedgeHogMutant,andAndrogenReceptorMutantMouseGenital Tubercle...*. **. . 123 S. Yllcel,W. Liu,DCordero,A. Donjacour,G. Cunha,andL. Baskin DevelopmentalGeneticsofHypospadias...149 M. Cohn xiii xiv Contents DevelopmentoftheMouseExternalGenitalia: UniqueModelof Organogenesis...159 K. Suzuki, K. Shiota,Y. Zhang,L. Lei,andG. Yamada NewConceptsontheDevelopmentoCtheVagina...173 E. Shapiro. H. Huang,andX. R. Wu SECTIONIII. ENDOCRINEDISRUPTORSANDSEXUAL DIMORPHISMINTHEANIMALKINGDOM EndocrineDisruptionOverview: AreMalesatRisk? 189 T. Colburn EndocrineDisruptionandHypospadias...203 G. Steinhardt Toxicant-InducedHypospadiasintheMaleRat * 217 L. E. Gray. . I. Ostby,J. Fun,C. Wolf,C. Lambright,V. Wilson, and N. Noreiga MasculinizationofFemaleMammals: LessonsfromNature...243 N. J. PI:H'candS. Glickman Index...255 SectionI Introduction HYPOSPADIAS LaurenceS. Baskin* M. D. ,FAAP 1.

The Association Internationale de Recherche sur la Circulation Osseuse, A.R.C.O., was founded in London in December 1989 by a small group of doctors, surgeons and researchers in basic sciences who had been involved for many years in the study of bone circulation and its disorders. They had met several times in Toulouse, during the International Symposia on Bone Circulation held there since 1973 and they wished to carry their contacts further. In founding A.R.C.O., they established as their primary aims the encouragement and furtherance of research, organisation of meetings and promotion of knowledge on the subject. At the present time, the Association has over a hundred members from more than bone tissue twenty countries in Europe, America and Asia. All have the conviction that and its pathology can only be truly known and studied if one has an understanding of its vascular system and the way its circulation functions. This concept, apparently beyond question, has not yet been adopted by all physicians and scientists who are interested in bone. From time to time, one comes across teaching programmes on bone patho logy which make no mention of bone circulation.

It is two years since a general meeting of the Gesellschaft fur Biologische Chemie first requested us to organize the 21 st Mosbach Colloquium on mammalian reproduction, and one year since we received final authorization to do so. The present volume contains the papers read at the Colloquium, but the discussions have been omitted because writing and proof reading them would have delayed the appearance of this volume for an unjustifiable long time. Besides, in most cases the discussion was of a relatively specific nature and we did not consider it essential, bearing in mind that the purpose of the Mosbach Col loquia is to provide advanced further education for the non specialist. One of us has referred to this and to the topical structure of the 21 st Colloquium in the introductory and final remarks. Helpful suggestions for organizing the program were made by some of the invited speakers, but the first important impulses VON BERSWORDT-WALLRABE, Dr. ELGER, Dr. came from Dr. GERHARDS, Dr. NEUMANN, and Dr. UFER to whom we here wish express our thanks. Thanks are also due to those whose donations, some of which were very generous, made it financially possible to organize the Colloquium. HEINZ GIBIAN July 1970 ERNST JURGEN PLOTZ Contents Introduction. H. GIBIAN (Berlin) 1 General Outline about Reproductive Physiology and its Developmental Background. A. JOST (Paris) .. 4 The Significance of Hormones in Mammalian Sex Differentia tion as Evidenced by Experiments with Synthetic Andro gens and Antiandrogens. W. ELGER, F. NEUMANN, H.

I had the good fortune to first meet Gerald Kuchling in 1985 when attending a conference held at the CNRS research centre, the Centre d'Etudes Biologiques des Animaux Sauvages (CEBAS), which is a wonderful scientific field station tucked away in the Foret de Chize, not far from the southwest town of Niort in France. The topic of the meeting, which included many invited overseas scientists, was "Physiological Regulations as Adaptive Mechanisms", and it was superbly organised by Ivan Assenmacher and Jean Boissin who together edited the impor- tant volume of papers published from the meeting. My stay in Chize was, unfor- tunately, cut short as the wife of a very close colleague died on the night of the first day of the meeting and I had to return to Paris to assist with the funeral -but not before I had the chance to meet and talk with Gerald. He was presenting some of his work on a terrestrial tortoise (or turtle depending upon one's origins) - Testudo hermanni - a species that is now extremely rare in France but still relatively abundant in the then Yugoslavia. Gerald had been working in Yugoslavia, collecting blood samples from both males and females in an attempt to decipher details of its reproductive biology.

Invertebrate animals represent a diversity of solutions to life's challenges. Success in a wide range of environments has been achieved by an almost bewildering range of invertebrate body forms. These body forms are reflected in the wonderful diversity of their nervous systems. Despite this apparent diversity, studies of the development of invertebrates and vertebrates are yielding common themes at the molecular level. Likewise, the phenome non of neural regeneration is based upon properties intrinsic to neurons and responses to a remarkably conserved chemical lan guage. This monograph focuses on the diversity and commonal ity of responses to neural injury. The rough and tumble of life may frequently damage some part of the body, particularly the appendages or sensory sys tems. The nervous system is usually involved in repair of other body systems and often may itself require repair. Some animals are particularly successful in regenerating the nervous system or body parts. We particularly marvel at these feats of regeneration because we human beings are not particularly successful, despite our relatively long life and the advantages that would seem to accrue from such repair. It is no wonder that we would hope to learn the secrets of the more successful animals and strive to emulate them Mechanisms of neural regeneration are often more acces sible in invertebrates than in vertebrates because questions of specificity are more easily addressed using the identifiable neu rons of the relatively simpler nervous systems of some inverte brates."

During the past decade there has been a dramatic expansion of our knowledge on phospholipases in general, and phospholipase A2 (PLA2) in particular. Progress in this field has been evident on many fronts, with novel information rapidly accumulating in the literature regarding the chemistry and molecular biology of this enzyme and its role in many important physiological processes. These include cellular signal transduction via the G-protein cycle, and in the generation of many cellular mediators, such as the platelet activating factor (PAF) and the eicosanoids that participate in the initiation and propagation of inflammation, to mention a few. This symposium was organized to obtain an overview of current investigations on this enzyme from the standpoint of its chemistry, molecular biology and physiology. Another important focus of this symposium concerns the regulation of PLA2, including endogenous and synthetic inhibitors and activators of this enzyme. To review these important areas in PLA2 research we invited scientists who made significant contributions in this field. The papers in this volume are organized to emphasize the recent advances in several areas of investigation, including: (I) the structure and mechanism of action of PLA2, (2) mechanism of activation of PLA2, (3) molecular biology, physiology and endogenous inhibitors of this enzyme and finally, (4) clinical investigations emphasizing the pathophysiological role of this enzyme in human diseases. The first article in this volume is by Dr.

I have spent less time in the arid zone in the last few years than I did during the 1960's, 1970's and early 1980's. This results from a progression through age and a career structure which gradually shifted the emphasis of my work from being essentially field-oriented to essentially office-hound. When, therefore, I was asked by John Cloudsley-Thompson to undertake the writing of this hook I hesitated for two reasons. One reason was that, although I now had access to good library facilities and kept up with the literature on the arid zones and their fauna, I was not sure that a sedentary and pleasant life in a temperate highland island in tropieal Africa would provide a mental attitude suitable to writing a hook which related to areas where life is usually nomadie and often extremely disagreeable. The other reason was that I was uncertain whether I could devote the time necessary to researehing and writing the hook on top of my professional (which now specifical ly excluded research in the arid zones and on camels) and social (new-found and time-consuming) commitments. In the event I accepted and the fates were kind to me. By some peculiar combination of circumstances I was given the opportunity to spend a considerable part of the first half of 1988 in some of the driest areas of the globe. I had already visited all of the locations used for the construction of Fig. 2."

The research field of somatosensory processing in mammals has experienced revolutionary changes in recent years. Accumulation of basic and clinical data has greatly accelerated, and new phenomena have emerged. With the aid of new, refined methods, molecular and cellular changes have been described, underlying the signal transduction-transmission between the internal/external environment and the central nervous system have been described. The discovery of the interaction between the nervous and the immune system has, for example changed our view on the development of inflammatory diseases, while the cloning of genes encoding different trophic factors has boosted studies revealing profound changes in the regeneration of neurons, and induction of changes in phenotype. The study of the pre-and postsynaptic modulation of transmitter release, and the examination of the combined effects of amino acid and peptide transmitters has become recently possible by using cultured cell lines and in vitro techniques. Although it is in embryonic state, computational properties of single DRG cells under normal and pathological conditions are being investigated. Results soon or later will have a great impact on pain research and consequently ultimately in clinical pain management. This brief introduction indicates how our knowledge of the somatosensory system has increased dramatically recently. However, many investigators cultivate only a very specific field in the growing area of somatosensory research and find it difficult to integrate a more universal knowledge of their work.

Experimental approaches to auditory research make use of validated animal models to determine what can be generalized from one species to another. This volume brings together our current understanding of the auditory systems of fish and amphibians. To address broader comparative issues, this book treats both fish and amphibians together, to overcome the differing theoretical and experimental paradigms that underlie most work on these groups.

Many organisms have evolved the ability to enter into and revive from a dormant state. They can survive for long periods in this state (often even months to years), yet can become responsive again within minutes or hours. This is often, but not necessarily, associated with desiccation. Preserving one's body and reviving it in future generations is a dream of mankind. To date, however, we have failed to learn how cells, tissues or entire organisms can be made dormant or be effectively revived at ambient temperatures. In this book studies on organisms, ranging from aquatic cyanobacteria that produce akinetes to hibernating mammals, are presented, and reveal common but also divergent physiological and molecular pathways for surviving in a dormant form or for tolerating harsh environments. Attempting to learn the functions associated with dormancy and how they are regulated is one of the great future challenges. Its relevance to the preservation of cells and tissues is one of the key concerns of this book.

The field of olfactory research and chemical communication is in the early stages of revolutionary change, and many aspects of this revolution are reflected in the chapters in this book. Thus, it should serve admirably as an up-to-date reference. First, a wide range of vertebrate groups and species are represented. Second, there are excellent reviews of specific topics and theoretical approaches to communication by odors, including chapters on signal specialization and evolution in mammals, the evolution of hormonal pheromones in fish, alarm pheromones in fish, chemical repellents, the chemical signals involved in endocrine responses in mice, and the controversy over human pheromones. Third, there are exciting new findings presented in numerous specific topic areas, such as the chemis try of pheromones in a wide range of species (salamanders to elephants), the chemistry of proteins that control the release of pheromones, the molecular biology and physiology of detection, coding and response to odor signals, the effects of experience on sensitivity to odors, the role of genes of the immune system in odor production and in human mate choice, the function and perception of scent over-marks, the recognition of individuals and kin by odors, the influence of odors on predator-prey interactions, and the use of odors to help control pests. This book is an offshoot of the Eighth International Symposium on Chemical Sig nals in Vertebrates, held at Cornell University in Ithaca, New York, July 20-25, 1997, hosted and organized by Bob Johnston.

It has been great fun to write this book, even though it has taken longer than planned, and occasionally been exasperating. The most difficult problem was deciding what to exclude among so many interesting things, because the available material usually exceeded the space. Because a book like this covers so many aspects, each component must be limited. This book is intended for graduate and undergraduate students as well as professional scientists who want to work with animal flight or to gain some insight into flight mechanics, aerodynamics, energetics, physiology, morpho logy, ecology and evolution. My aim has not been to give the whole mathe matical explanation of flight, but to provide an outline and summary of the main theories for the understanding of how aerofoils respond to an airflow. I also hope to give the reader some insight into how flight morphology and the various wing shapes have evolved and are adapted to different ecological niches and habitats."

A number of remarkable recent breakthroughs have made the study of nitric oxide one of the most exciting fields in physiology and pathophysiology. This authoritative edited volume reviews the progress to date and opens perspectives to novel diagnostic and therapeutic strategies. The contributors are leading authorites, in most cases the investigators who have pioneered the ideas explored in the book.

In the past few years there has been the increased recognition that the effects of oxidative stress are not limited to the damage of cellular constituents. There is now evidence that reactive oxygen species (ROS) can alter cell function by acting upon the intermediates, or second messengers, in signal transductions. Such effects on signaling mechanisms probably account for the role of oxidative stress in inflammation, aging, and cancer. This volume brings together internationally recognized researchers in both the major areas covered by the book, oxidative stress and signal transduction. The work is organized in three sections. The first deals with the immediate cellular responses to oxidative stress and the production of second messengers. The second details the connection between second messengers and the gene. The third part looks more closely at the level of the gene.

The fourth Oxford Conference entitled "Control of Breathing: A Model ing Perspective" was held in September of 1988 at Grand Lake, Colorado. Grand Lake, also called Spirit Lake, was chosen for the fourth meet i ng so as to continue the meditative atmosphere of the previ ous meetings and to put the conference on a new higher plane (8,500 feet). The weather, as promised, exhibited its random-like rain showers. The snow report became essential for traveling the 12,000 foot passes to and from Grand Lake. Even the servi ces such as telephone and elect ri city proved to be uncertain. In all, the overall atmosphere of Spirit Lake contributed to an uninhibited free-style of presentation and interaction. All of us who attend the Oxford Conferences share a common interest in exploring respiratory control and the regulation of breathing. Modeling has become an adjunct to our exploration process. For us, models are tools that extend our ability to conceptualize just as instruments are tools that extend our ability to measure. And so these meetings attract physicians, physiologists, mathematicians and engineers who are modelers and modelers who are engineers, mathematicians, physiologists and physicians. Four of these physician-modelers have now passed away. They have been very important mentors for many of us. J. W. Bellville was my Ph.D. dissertation advisor at Stanford who introduced me to the intrigue of respiratory control. G. F. Filley was my colleague at the University of Colorado who enhanced my thinking about respiratory control. E. S.

Discovery of the mechanism for V(D)J hypermutation remains a basic goal of immunology despite the best efforts of many labo ratories. The existence of catalyzed, site-specific mutation and its exploitation for the somatic evolution of lymphocytes are re markable adaptations, yet since the discovery of hypermutation in 1970 (see cover), much hard work has generated little. Indeed, our knowledge of what is probably absolutely required for the mutator's action can be succinctly expressed: /g gene enhancers. Table 1 of Winter et a .'s chapter puts into a historical perspec tive how our notions of the mutator have changed over the years. Despite these modest gains, most of us feel that this is the best of times. Our work has not only shown us what the mutator is not, it has also, like an artist's preliminary sketch, defined the questions and experiments we must face without diminishing the potential for new biology. In short, it is great fun to toil against a significant and enigmatic problem."

Various endogenous and environmental challenges of homoiostasis have resulted in the evolution of apparently quite different mechanisms for the same or similar functions in individual representatives of the animal kingdom. One of the prominent achievements of comparative physiology over the last few decades has been the description of regula- tory features common to many studied species beyond the extreme diversity of their morphological forms. Delineation of functional princi- ples universally applicable to the physiology and biochemistry of living systems became often possible through technical advances in the devel- opment of numerous new techniques, in many cases modified and adopted from other fields of science, but also by approaching certain problems using multifactorial analysis. The advance in technology has facilitated studies of minute functional details of mechanisms, which finally lead to better understanding of generally similar functions, covered by the multiple developments of Nature as a response to an extreme variety of different conditions. Improved understanding of specific mechanisms, however, has presented new problems at the level of system integration. The importance of the integrative aspect became particularly apparent during an international symposium on 'Mecha- nisms of Systemic Regulation in Lower Vertebrates: Respiration, Circu- lation, Ion Transfer and Metabolism' (organized in 1990 by Norbert Heisler and Johannes Piiper at the Max-Planck-Institut flir experimen- telle Medizin at Gottingen/Germany).

Presented with a choice of evils, most would prefer to be blinded rather than to be unable to move, immobilized in the late stages of Parkinson's disease. Yet in everyday life, as in Neuroscience, vision holds the centre of the stage. The conscious psyche watches a private TV show all day long, while the motor system is left to get on with it "out of sight and out of mind. " Motor skills are worshipped at all levels of society, whether in golf, tennis, soccer, athletics or in musical performance; meanwhile the subconscious machinery is ignored. But scientifically there is steady advance on a wide front, as we are reminded here, from the reversal of the reflexes of the stick insects to the site of motor learning in the human cerebral cortex. As in the rest of Physiology, evolution has preserved that which has already worked well; thus general principles can often be best discerned in lower animals. No one scientist can be personally involved at all levels of analysis, but especially for the motor system a narrow view is doomed from the outset. Interaction is all; the spinal cord has surrendered its autonomy to the brain, but the brain can only control the limbs by talking to the spinal cord in a language that it can understand, determined by its pre-existing circuitry; and both receive a continuous stream of feedback from the periphery.

Ivermectin and abamectin, members of the avermectin family of compounds, were introduced to the market in the 1980's as a veterinary antiparasitic drug and agricultural pesticide, respectively. Their acceptance and commercial success have been remarkable; both are highly effective and in worldwide use. The efficacy of ivermectin in river blindness has expanded the interest in its use in human medicine. In response to the intense scientific and industrial interest in ivermectin and abamectin and the likelihood that they will be forerunners of an expanding family of drugs, this comprehensive monograph satisfies the need for a review and synthesis of current knowledge about the use of these substances in crop protection as well as in cattle, sheep, swine, horses, dogs, cats, birds, fish, reptiles, and in man. This overview presents chemical, biochemical, and microbiological data, as well as pharmacological, safety, and environmental aspects and covers practical use of the compounds as antiparasitic and pesticide agents, as well as the available safety data that have emerged from the clinical experience with human applications.