The development of the modern organic insecticides has contri- buted a major chapter to the history of neurotoxicants. From their roots in the organochlorines and organophosphates discovered prior to and during the Second World War, to the carbamates developed in the 1950's, and most recently to the extremely potent and promising synthetic pyrethroids, the most important organic insecticides have been those whose wite of action lies within the nervous system. In this regard, man is only mimicking nature in attacking the nervous system with lethal intent since potent neurotoxins are cornmon compo- nents of the venoms with which animals of all types defend themselves and subdue their prey. This central role of the nervous sytem as a broad target for pesticides may also be projected into the future - a prediction to which this volume is devoted. The nervous system in its diversity is likely to be of central concern to those charged with discovering novel pesticides whether they be modifications of familiar chemical groups or structurally novel neurotoxicants such as the nitromethyl- ene insecticides described here. On a second front, the ability to influence insect behavior through the nervous system will become increasingly important in pest management. Pheromones represent one obvious example of this; recent work described in this volume indi- cates that the forrnamidine pesticides may represent another.

The Permanent Commission and International Association on Occupational Health (PCIAOH) established in 1969 a Subcommittee on the Toxicology of Metals under the chairmanship of Lars Friberg. This committee, which later was named the Scientific Committee on the Toxicology of Metals, has organized a number of previous meetings that have led to publications in three major areas of metal toxicology: a preliminary meeting in Slanchev Bryag, Bulgaria in- 1971, followed by a meeting in 1972 in Buenos Aires, Argentina which produced two reports (Dukes and Friberg, 1971; Task Group on Metal Accumulation, 1973), that discussed the metabolism of metals with special reference to absorption, excretion and biological half-times. The effects and dose-response relationships of toxic metals, including a discussion of general principles, was the second major topic addressed by the Scientific Committee at a meeting in Tokyo in 1974 (Nordberg, 1976). The philosophy of this conference, as well as the previous one in Buenos Aires, was based on the concept of a "threshold dose" for the occurrence of adverse effects. In a conference held in Atlanta, USA in 1980, the scope of discussion on metal effects was broadened to include the role of metals in carcinogenesis. Thus, for the first time, the Scientific Committee took under consideration the possibility of non-threshold relationships (Belman and Nordberg, 1981). In addition, the Scientific Committee on the Toxicology of Metals organized a workshop on metal interactions in Stockholm 1977 (Nordberg et al.

The ready acceptance and wide demand for copies of the first two volumes of Chemical Mutagens: Principles and Methods Jar Their Detection have demon strated the need for wider dissemination of information on this timely and urgent subject. Therefore, it was imperative that a third volume be prepared to include more detailed discussions on techniques of some of the methods that were presented from a theoretical point of view in the first two volumes, and to update this rapidly expanding field with current findings and the new developments that have taken place in the past three years. Also included is a special chapter by Dr. Charlotte Auerbach giving the historical background of the discovery of chemical mutagenesis. Methods for recognizing mutagenic compounds in vitro are a necessary preliminary step toward arriving at satisfactory solutions for recognizing significant mutation rates in man, which must be done before our test tube methods of detection can be considered reliable. Two chapters in this volume make important contributions to this problem. Due to the increasing activity in efforts to perfect techniques for detecting chemical mutagens and their effects on man, it is planned to continue this series of volumes as necessary to keep abreast of current findings.

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.

Androgen Receptors is the most comprehensive and up to date volume on the topic, including discussions of the basic mechanisms of androgen-androgen receptor actions, their roles in the androgen-related diseases, and their potential clinical applications. Key topics covered include: -The discovery and cloning of the androgen receptor; -Androgen receptor coregulators; -Androgen related genes and their consensus DNA response elements; -Basic mechanism of action including functional analyses, cellular localization and phosphorylation studies; -Cross-talk to other signal transduction systems; -The recent connections of androgens to women's diseases, such as osteoporosis and ovarian cancer. This book is of interest to students, basic scientists, and clinicians as both a study guide and reference of research in the androgen field. It could also be used as an advanced level text in endocrinology, urology, OBGYN, or oncology.

Health Effects of Ambient Air Pollution provides the reader with an overview of the health effects of air pollution in human subjects. The majority of the book is devoted to the discussion of the health effects of common widespread air pollutants regulated by the U.S. Environmental Protection Agency through national ambient air quality standards. The book reviews the sources and fate of common air pollutants in ambient air and researches the adverse effects of these outdoor and indoor air pollutants in 'in vivo' cell systems, animals, and humans. Research for the book was conducted in controlled laboratory studies and epidemiologic studies. Special emphasis throughout Health Effects of Ambient Air Pollution is placed on the effects of air pollution in subjects with asthma.

Pulmonary Immunotoxicology is a comprehensive exploration of the effects of various inhaled materials upon the immune system of the respiratory tract. It will be useful to investigators in the field of pulmonary toxicology and immunotoxicology, and to those involved in administration and regulation of matters related to inhaled materials. It can also serve as a textbook for a course in pulmonary immunotoxicology at graduate or advanced undergraduate level. Pulmonary Immunotoxicology comprises four sections. The first provides basic background concepts essential for understanding pulmonary immunotoxicology, including discussions of the normal structure and function of the respiratory system, its basic immunology, and the manner by which inhaled particles and gases are removed from the air and deposited upon respiratory tract surfaces. The second section provides an overview of the major types of pathological consequences which can arise from immunomodulation within the respiratory tract, including hypersensitivity and asthma, inflammation and fibrosis, as well as immunosuppression and autoimmunity. The third section, which comprises the largest portion of the book, deals specifically with major classes of airborne agents that are known to alter the immune function of the respiratory tract. These are arranged into major classes: organic agents, metals, gases, particles, biologics, and complex mixtures. The fourth and final section of the book explores the area of risk assessment, including discussions of the basic concepts of risk assessment as they apply specifically to immunotoxicologic effects upon the lungs, and the use of biomarkers as indices of potential pulmonary immunotoxic responses to inhaled materials.

Humans are exposed daily to low concentrations of metals that are released into the environment by both natural and industrial processes. Environmental Metal Pollutants, Reactive Oxygen Intermediaries and Genotoxicity: Molecular Approaches to Determine Mechanisms of Toxicity examines concerns about the acute and/or chronic exposure of humans to concentrations of these metals that are below the threshold levels established by various federal regulatory agencies. Some of these metals are accumulated in various tissues and over time this may result in the accumulation of a significant body burden. This could increase the risk of developing a variety of diseases later in life, at a time when thresholds for such effects may already be reduced by the processes of aging. Such possibilities could only further compromise the quality of life in the elderly population and could contribute to the rising cost of health care in this country. Studies that have been conducted to determine the possible risks associated with exposure to relatively non-toxic concentrations of environmental metals have been hampered by a lack of appropriate models and a lack of funding. It has also been difficult for researchers to demonstrate a correlation between the exposure of humans or animals to low concentrations of environmental pollutants and disease. This book examines recent technological advances in the areas of molecular biology, biochemistry, and computer-enhanced image analyses that provide researchers with the tools to begin elucidating the genotoxic effects of environmental metal pollutants and the mechanisms by which these metals cause DNA damage. Environmental Metal Pollutants, Reactive Oxygen Intermediaries and Genotoxicity: Molecular Approaches to Determine Mechanisms of Toxicity presents data that demonstrate that certain environmental metal pollutants are genotoxic. The authors describe the role of reactive oxygen intermediates in causing the DNA damage induced by environmental metal pollutants and discuss their possible role in human disease.

Voltage-gated calcium channels are critical regulators of cytoplasmic levels of calcium, the universal signaling ion. As such, calcium channels trigger a wide range of cellular functions, from muscle contraction to neurotransmitter secretion, and are important players in human disease. Prominent in the nervous, cardiovascular, and endocrine systems, members of the calcium channel family are targets for existing antihypertensive and anticonvulsant drugs. In addition, they are emerging targets for drugs to treat an extraordinarily diverse group of disorders, including pain, cerebral ischemia, cardiac arrhythmia, and migraine. This book reviews the compounds that target individual calcium channel subtypes and the cellular and behavioral functions governed by each different channel. It contains information for basic scientists using calcium channel antagonists as experimental tools, for behavioralists studying animal models of human disease, and for pharmaceutical scientists interested in creating the next generation of calcium channel-targeted drugs. Several factors make an entire book on calcium channel pharmacology timely.

Written by a qualified veterinarian, this is a complete and comprehensive guide to health care for cats and dogs, providing invaluable advice on essential aspects of care, such as diet and vaccinations, as well as a guide to holistic treatments. The first part of the book describes the main lifestyle choices every dog and cat owner makes, whether or not they are aware of them: settling in a new puppy or kitten, vaccination, neutering, diet, finding the right veterinarian, and caring for the ageing animal. The second part describes the main holistic modalities and their relevance when animals become sick. What they are, how they work, when they are useful, and how to find a practitioner. Also includes chapters on osteopathy, homeopathy, acupuncture, Bach's flower remedies, and herbal medicine. The third part of the book discusses a range of common health problems in dogs and cats, both from a conventional veterinary point of view and from an holistic perspective, and aims to help the owner understand the condition they are facing, as well as providing tips on how to supplement their veterinarian's advice and treatment.

This book has its origin in my experience as a teacher of pharmacokinetics in many universities in four different continents. It was not my intention to write a popular book; what distinguishes this one from many others on the same subject is its large use of algebra and calculus. For this I make no apologies; in fact a serious study of pharmacokinetics without the help of mathematics is, in my opinion, impossible. The exact definition of many pharmacokinetic quantities, even the most common, and the correct use of many equations, even the most simple, requires the constant use of mathematical language. On the other hand I have made a considerable effort to use only elementary algebra and elementary calculus, as commonly taught in most introductory university courses. For the few exceptions, when less common mathematical concepts were needed, I have supplied the necessary explanations in four appendices. The first three chapters are a general introduction to the scientific method. Chapters 4 to 12 show different specific methods to deal with pharmacokinetic pr- lems. There is considerable overlap among those chapters; this is intentional and its p- pose is to convince the reader that every problem can be solved in more than one way, including ways that were not mentioned in this book and that intelligent readers can find for their own pleasure. Chapters 13 to 17 show how different parameters of importance in pharmacokinetics can be exactly defined and measured.

This publication contains the proceedings of a seminar held in Toulouse, France, on 10th, 11th and 12th June 1980, under the auspices of the Commission of the European Communities, Directorate General for Agriculture, Division for the Coordination of Agricultural Research, as part of a programme of research on beef production. The seminar was intended to bring together available experience on the utilisation of hereditary muscular hypertrophy for meat production in the member states of the European Communities. Although the phenomenon of double muscling has been exploited in various countries, particularly France, Italy and Belgium, different breeds are used and different methods of exploitation employed. An attempt was therefore made to bring together the collective experience of participants. Contributions ranged from those on the inheritance of muscular hypertrophy to alternative production systems and from fundamental studies of muscle growth to practical ways of selling the additional musrile found in animals with muscular hypertrophy. The collection of assembled papers and discussions thus represents one of the most extensive reviews of the subject that has been attempted.

At the end of September 1984 Dr. M. Velickovi and Prof. H. Prechtl with the help of the International Cerebral Palsy Society organized an international conference on "New develop ments in the assessment of early brain damage" in Bled, Yugo slavia. I was invited as a speaker at this conference and I went there, curious, but without too much knowledge about the central theme: cerebral palsy. During the conference and a satellite meeting I became impressed by the quality of various contributions and also by the great variety of problems related to the etiology, early diagnosis, management and psychosocial aspects of cerebral palsy. Today, in many areas of biology and medicine, progress seems to require concentration on a very narrow field. As a consequence many conferences are highly specialized and most (young) scientists rightly consider this as most useful for their own work. On the other hand the care of patients and counselling of parents and other close relatives require a multidisciplinary approach. Also, advances in the study of complicated un resolved medical biological pr'oblems are often made unex pectedly by using ideas, theories, approaches or methods from other disciplines."

First published in 1986, this volume reviews the immune system of domestic ruminants, with particular emphasis on mechanisms of immunity and resistance to infectious diseases. Topics of comparative interest in other species are also covered. The cellular components of the immune system are discussed first, including ontogeny, structural organization and how they interact during the generation of immune responses. This is followed by information on specific aspects of humoral and cell-mediated immune responses, and finally a section on the relevance of various types of immune responses in protection against a number of important infectious diseases of ruminants. The papers included were presented originally at an international conference held in Nairobi, Kenya in September 1983. They provide authoritative coverage of a wide range of topics in ruminant immunology. Together, they comprise a valuable reference text for those involved in all aspects of immunological research in ruminants.

The 21st century will witness the unprecedented marketing of therapeutic drugs developed from cannabinoids and the endocannabinoid system. Cannabinoids is a timely volume, which represents a comprehensive review of the most important issues in cannabinoid research as well as those of most likely therapeutic relevance. For the first time, the multi-faceted aspects of cannabinoid chemistry, biology and medicine are presented in one volume.
Key topics of discussion:

-major families of phytocannabinoids;
-pharmacological activity of phytocannabinoids;
-interactions of phytocannabinoids with their proposed molecular target;
-components of the endocannabinoid system;
-molecular mechanisms of the endocannabinoid system;
-Physiological and pathological role of endocannabinoids;
-industrial applications of studies on the cannabinoids;
-therapeutic uses of agonists and antagonists of cannabinoids receptors. This book is a must for graduate and pre- and post-doctoral students in disciplines ranging from organic and natural product chemistry, pharmacology, biochemistry and medicine.

In some countries, especially on the European continent, there still exists a remarkable veal market. This type of meat production seems, irrespective of any economic forecasts, to remain unchallenged so long as consumers expect that restaurants should offer courses like "r6ti de veaux," "vitello a la casa" or "Kalbsschnitzel." Producers, at least since about the past 1-/2 decades, have been aware of the beneficial effect of anabolic agents in veal production. This is possible due to the lack of endogenous sexual hormones during the juvenile or prepuberal status of these animals. A discussion about the benefit / risk - evaluation in connection with the use of anabolic agents in general was promoted in recent years by the public. This concern occurred concomitantly with the detection of illegally treated veal calves and the occurrence of diethylstilbestrol (DES) residues in canned food containing veal. The aim of this paper is to summarize the present status of residue data in edible tissues and excreta in order to allow the evaluation of the risk (given in the paper of Hoffmann within this program) and to consider reasonable monitoring measures. We have to face the fact that without an efficient control system the illegal treatment of calves can not be excluded. Therefore, this paper will not only consider different compounds and formulations, but will also deal with practised routes of administration.

African swine fever (ASF) is caused by a virus that is classified as a member of the Iridovirinae family. The disease in the warthog, the natural host, in Africa was described in 1921 by R. E. Montgomery. The reservoir of the vi rus is inti cks. The i ntroduct i on of domestic pi gs into territory occupied by warthogs i nf ected wi th ASF in the 1960's has endangered the pig industry around the world. The domestic pig is highly sensitive to ASF and develops a devastating disease that kills the pig without giving the immune system a chance to defend the animal against the virus infection. The ability of ASF virus to infect and destroy cells of the reticuloendothelial system leaves a defenseless host that succumbs to an infection which may be described as an acquired immune deficiency di sease of domestic pi gs. Introduction of the virus into Iberia in the 1960's led to a series of ASF epidemics in Spain and Portugal . . and later in France, that caused heavy economic losses. Between 1976 and 1960, ASF virus made its appearance in Malta and Sardinia . . as well as in Brazil, The Dominican Republic . . Haiti, and later in Cuba. In 1985-6 . . ASF appeared in Belgium and The Netherlands.

The outbreaks of myxomatosis among rabbits in Australia in 1950 and in Europe in 1952 provided scientists with opportunities of observing the course of the interaction of a very lethal virus disease with a large population of highly susceptible mammals, i.e. with a model system to study the evolution of an infectious disease, and the effects of an infectious disease on the evolution of a mammal. This scientific account of the spread of the disease in Australia and Europe, of its effects upon rabbit numbers, and of the genetic changes that occurred in parasite and host, is of great interest to ecologists, virologists, parasitologists, mammalian zoologists, geneticists, agriculturists, and public health workers, as well as to those directly concerned with rabbit raising or control.

G. Petursson and Rikke Hoff-J0rgensen The concept of slow viral infections was first put forward in 1954 by Dr. Bjorn Sigurdsson, an Icelandic physician who had been studying some sheep diseases which were introduced into Iceland with the importation of a foreign breed of sheep in 1933. Sigurdsson's main criteria for defining slow infec tions were a very long initial period without clinical signs lasting months or even years following infection and a rather regular protracted, progres sive course, once clinical symptoms had appeared, usually ending in serious disease or death. Sigurdsson included in this list of slow infections maedi -visna, infectious adenomatosis of sheep, scrapie in sheep, Bittner's mam mary carcinoma and Gross' leukemia in mice. All of these diseases, except scrapie, are caused by retroviruses. The characteristics of slow infections as described above are of prac tical importance for epidemiology, diagnosis and control of these diseases. For many years the slow infections remained primarily a veterinary problem, mainly affecting sheep and goats in certain countries. In recent years, how ever, the human immunodeficiency virus (HIV) causing acquired immunodefici ency syndrome (AIDS), has suddenly appeared in many countries of the world and brought the slow infection concept forcefully to the attention of the medical profession. The disease problems and the economic effects of slow infections of sheep and goats are increasingly recognized in various coun tries. For the reasons stated above we feel that this book should be useful for veterinarians and physicians alike."

Radiophannaceuticals labeled with short-lived radionuclides are utilized to unravel biochemical processes, and to diagnosis and treat diseases of the living body are-developed through extensive evaluation in ~iological models. 'fhC first attempt to compile information was a volume entitled ANIMAL MODELS IN RADIOTRACER DESIGN that was edited by William C. Eckelman and myself in 1983. The volume had a focus on the animal models that investigators were using in order to design radiotracers that displayed in vivo selectivity as measured by biodistribution and pharmacokinetic studies. A concern in the early days of nuclear medicine was species differences. Often a series of labeled compounds were evaluated in a several different animal models in order to gain confidence that the selected radiotracer would behave appropriately in humans. During the past 12 years there have been remarkable advances in molecular genetics, molecular biology, synthetic radiopharmaceutical chemistry, molecular modeling and visualization, and emission tomography. Biological models can now be selected that are better defined in terms of molecular aspects of the disease process. The development of high resolution PET and SPET for clinical applications facilitates the development of new radiopharmaceuticals by the use of models to quantitatively evaluate drug effects, and progression of disease, and hence to arrive at better diagnosis and treatments for animals and humans. With these advances there is an effective use of biological models, and the refinement of alternatives for the development of new radiophannaceuticals.

Interest in the coronaviruses has never been greater. Their economic impact is considerable as they infect humans, livestock, poultry and companion animals. Murine hepatitis virus (MHV) infection of the mouse and rat central nervous systems are the subject of intense study; these investigations are providing insights into the potential role of viruses in human neurological diseases and, more generally, into mechanisms causing neurological damage. The single-stranded, positive-sense RNA genomes of two species of these enveloped viruses (IBV and MHV) have been cloned completely and one of them (lBV) sequenced in its entirety, revealing a genome size of some 27000 nucleotides. This has made possible more incisive investigations into the nature of those polypeptides, encoded by more than half of the genome, which are likely to contribute, in the main, to RNA polymerase/replicase activity. Intriguingly, ribosomal frameshifting is exhibited within the mRNA coding for these polypeptides. The cloning/sequencing phase of coronavirology for which the 1980's will be partly remembered, has provided a sound framework for furthex: studies of the virus structural proteins and also some provocative insights relevant to these studies. The large spike glycoprotein(s), responsible for membrane fusion and bearing important antigenic sites, varies amazingly in length and composition both within as well as between coronavirus species. Receptors on host cells have been identified. The integral membrane glycoprotein (M) has been shown to use internal hydrophobic sequences to direct translocation within membranes.