Contents: V. Zingel, C. Leschke and W. Schunack: Developments in research on histamine (H1) receptor agonists / P.D. Hoeprich: Antifungal chemotherapy / G. de Stevens: The diversity of heterocyclic compounds and their biological activities / R.M. Schultz: Newer antifolate compounds in cancer therapy / P.K. Mehrotra, S. Batra and A.P. Bhadun: Non-steroidal agents for regulation of the menstrual cycle / A.K. Saxena and M. Saxena: Developments in anti-convulsant drugs

Bioactive Spin Labels focusses on nitroxyl radicals, their chemistry, biological activity and their application as paramagnetic contrast agents in biomedical research. New EPR techniques for in-vivo studies utilizing nitroxyl radical reagents are described. Recent results on stable nitroxyl radicals as anticancer, antishock, antiaggregant and antischemic drugs are summarized.

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.

La composition particuliere des lipides des Bacteries justifie pleinement la redaction de la presente revue; en effet, les Bacteries elaborent des lipides dont la composition est tres differente de celle des lipides des autres organismes, que ce soient des Champignons, des Algues ou des Animaux superieurs. L'interet porte actuellement a 1'etude des lipides bacteriens est egalement justifie par 1'importance biologique de certaines fractions lipidiques. Le domaine que nous allons resumer est d' ailleurs encore peu developpe; a part des etudes nombreuses et tres detaillees sur les lipides des Myco- bacteries et sur ceux du Bacille diphterique, nous ne possMons que des renseignements sporadiques concernant ceux d'autres especes bacteriennes. R. ]. ANDERSON, a qui nous devons la plus grande partie de nos connaissances sur les lipides des Mycobacteries, a publie dans Ie volume III de la presente collection, une revue intitulee {

These proceedings contain the papers presented at the Bayer-Symposium V which was held in Grosse Ledder on October 16-21, 1973 and which was simultaneously the Second International Research Conference on Proteinase Inhibitors. The cordial atmosphere, the frank discussions and the profitable exchange of ideas during the First International Research Conference on Proteinase Inhibitors which was held on November 4--6, 1970 in Munich were a stimulant for us to consider holding a Second Conference especially as the steadily increasing research activities in this and related fields called for a new assessment of recent efforts in proteinase inhibitor research. In the three years since the First Conference was held, this field has developed particularly in the areas of molecular aspects of protein-protein interactions and in the extension to inhibitors of nonserine proteinases and peptidases. In planning this meeting the Organizing Committee was faced with the problem of selecting a limited number of participants and we decided that it was appropriate and necessary to focus in detail on the chemistry of proteinase inhibitors, their interac tions with a variety of enzymes and also to invite more general papers to survey the physiological and clinical aspects of the subject which we felt would be of importance in the future.

This report on Future Trends in Inflammation IV records another of the multidisciplinary meetings organized by the European Biological Research Association. The organizers wish to record their thanks to all the participants and delegates who made this such an enjoyable meeting. Our thanks are due to a number of members of the pharmaceutical industry who so kindly donated funds. These funds were used to provide grants for young research workers to attend this meeting. Many people have kindly given their time and help to make this congress possible. It is impossible to list them by name, but we are profoundly grateful. We were dubious at the outset as to whether to hold this meeting in a period when many other meetings are being organized on inflammation. The enthusiastic attendance proves that we were right in going ahead. The next international meeting will be held in France in 1983. For further details please contact: Professor J. P. Giroud Department of Pharmacology, Hopital Cochin 75014 Paris, France D. A. Willoughby J. P. Giroud xxxiii Section I Future Trends CHAIRMAN: L. Chedid CO-CHAIRMAN: Dame Honor Fell 1 The participation of mononucleur phagocytes in immune based inflammatory processes with special reference to their secretory responses P. DAVIES AND R. J.

Volume XXV of the Handbook of Experimental Pharmacology series entitled "Bradykinin, Kallidin, and Kallikrein" was published in 1970. My aim in editing this volume of the series is not to replace, but to update the 1970 edition. During the decade preceding the publication of Vol. XXV, the existence of kinins and kallikreins gained acceptance, the protein components of the system were purified and characterized and the peptides were synthesized. Even after these accomplish ments, interest in the subject has not abated, but has increased substantially. We have learned a great deal about the role that components of the kallikrein-kinin system play in other systems and about the immensely complex and intricate inter actions in blood. Directly or indirectly, kallikrein and kinins affect the coagulation of blood, the activation of complement, and the generation of angiotensin. Kinins release or modulate the actions of other agents, including prostaglandins, histamine, and catecholamines. Inhibitors of kallikrein or kininase II are employed, for example, in extracorporeal circulation or in hypertension. Kallikrein, kinins, and kininases, present in urine, were described first in 1925 and 1954, but have been ignored for decades. These substances are now studied extensively because of their possible role in blood pressure regulation. The evidence that kinins have a metabolic function is also increasing. The abundance of active components of the system in genital organs suggests a role in the fertilization process. The book is organized into chapters which bear upon these issues.

The study of biogenic amines, which from the beginning of modern pharma- cology has always attracted the enthusiastic attention of research workers and has led to some of the most brilliant and illuminating experimental results in biology, has been unexpectedly extended in the last fifteen years. 'With the discovery of 5. hydroxytryptamine (enteramine, serotonin), in fact, the vast field of indole- alkylamines has been opened up for research. In a decade of intensive and dedicated work, an immense amount of experi- mental data has been collected, the significance of which, having rapidly overrun the limits of pharmacology, physiology, and biochemistry, has spread into all fields of biology and medicine, as previously occurred with choline esters, catechol- amines and imidazolealkylamines. Thus, the study of indolealkylamines, espe- cially that of their metabolism, has led not only to explanation of the mechanism of action, formerly largely obscure, of some important drugs, to clarification of the pathogenesis of some morbid syndromes and to a parallel flourishing of research on other biogenic amines, but also to surprising achievements in the field of therapeutics. The discovery of monoamineoxidase and dopadecarboxylase inhibitors, and of drugs which block the storage of biogenic amines in the body depots are among the most striking results of research on the indolealkylamines.

This volume is an important advancement in the application ofpharmacokinetic (PK) and pharmacodynamic (PO) principles to . drug development. The series of topics presented deal with the application of these tools to everyday decisions that a pharmaceutical scientist encounters. The ability to integrate these topics using PK and PO methods has optimized drug development pathways in the clinic. New technologies in the areas of in vitro assays that are more predictive of human absorption and metabolism and advancement in bioanalytical assays are leading the way to minimize drug failures in later, more expensive clinical development programs. of Pharmacokinetics and pharmacodynamics have become an important component understanding the drug action on the body and is becoming increasingly important in drug labeling due to it's potential for predicting drug behavior in populations that may be difficult to study in adequate numbers during drug development. The ability to correlate drug exposure to effect and model it during the drug development value chain provides valuable insight into optimizing the next steps to derive maximum information from each study. These principles and modeling techniques have resulted in an expanded and integrated view of PK and PO and have led to the expectations that we may be able to optimally design clinical trials and eventually lead us to identifying the optimal therapy for the patient, while minimizing cost and speeding up drug development. There is wide utility for the book both as a text and as a reference.

Burgeoning research into marine natural products during the past two decades has in no small measure been due to an heightened and world-wide interest in the ocean, to the development of new sophisticated computer-driven instrumentation, and to major advances in separation science. Organic chemists have been fully aware that processes in living systems occur in an aqueous medium. Nevertheless, the chemists who have specialized in the study of small molecules have found it expedient to use organic rather than aqueous solvents for the isolation and manipulation of secondary metabolites. The emergence of new chromatographic techniques, the promise of rewarding results, not to mention the relevance of polar molecules to life itself, have contributed to a new awareness of the importance of organic chemistry in an aqueous medium. The first chapter in Volume 2 of Bioorganic Marine Chemistry reflects the growing interest and concern with water-soluble com pounds. Quinn, who pioneered the separation of such molecules, has contributed a review which closely links techniques with results and is based on practical experience. The second chapter, by Stonik and Elyakov, examines the vast chemical literature of the phylum Echinodermata - over one fourth of it in difficulty accessible Russian language publications. The Soviet authors evaluate the data for their suitability as chemotaxonomic markers."

This is the first comprehensive work to review blood platelet biochemistry, physiology, pharmacology, and function. It provides up-to-date information on how platelets function, the biochemical mechanisms that modulate their physiology and function, as well as the pharmacology of platelet inhibitory drugs.

Leading scientists offer detailed profiles of ten protein drugs currently in development. The case histories of these important new compounds are described from the perspective of their formulation, characterization, and stability. This ready reference also features recent data and an abundance of previously unpublished information. The in-depth coverage includes a highly useful compendium of degradation sites occurring in over 70 proteins. An invaluable aid in the rapid identification of potential 'hot spots' in proteins, this accessible compilation allows for inspection of the protein's primary structure and preparation of a hydroflex plot.

Part 3 of the Handbook of Experimental Pharmacology (Concepts in Biochem ical Pharmacology) applies the principles enunciated in Parts 1 and 2 to clinical pharmacology and toxicology. The major objective is to elucidate the many factors that determine the relationships between pharmacokinetic aspects of the disposition and metabolism of drugs and their therapeutic or toxic actions in man. Because of the more restricted information obtainable in human studies, this volume reflects the editors' bias that an understanding of pharmacokinetics is fundamental for assessing pharmacologic or toxicologic effects of drugs in humans. The first chapter is a unique primer on when to apply and how to use pharmaco kinetic tools in human pharmacology. The second chapter explains the general assumptions underlying pharmacokinetic approaches both in simple terms for the novice and in mathematical form for the more sophisticated reader. Several chapters on determinants of drug concentration and activity discuss drug absorption, drug latentiation, drugs acting through metabolites, entero hepatic drug circulation, influence of route of drug administration on response, genetic variations in drug disposition and response, age differences in absorption, distribution and excretion of drugs, and pathologic and physiologic factors affecting absorption, distribution and excretion of drugs and drug response. The focus of these chapters is data obtained in human, rather than animal, studies. Most of the chapters contain new material never summarized previously."

A major vehicle for the transition of carrier-mediated drug delivery from a theoretical/experimental status to one with practical uses has been the NATO Advanced Studies Institute series "Targeting of Drugs." Three previous ASls of the series 1-3], also held in Cape Sounion, dealt with carriers of natural and synthetic origin, their preparation and drug incorporation as well as a wide range of applications. This book contains the proceedings of the 4th NATO ASI "Targeting of Drugs: Anatomical and Physiological Considerations" held in Cape Sounion, Greece during 20 June - 1 July 1987. Historically, carrier systems have been chosen on the basis of selective affinity for target sites. For instance, monoclonal antibodies bind selectively to antigens on the surface of cells and the same applies to ligands such as certain glycoproteins which bind to cell receptors. Colloidal carriers on the other hand, are "passively" targeted to the reticuloendothelial system. However, effective drug delivery depends not only on demonstration of affinity of the carrier system for its target but also, and perhaps crucially, on the way(s) by which the carrier-drug entity interacts with the interposed biological milieu. The book deals in depth with a number of biological milieus as travelled space for carriers en route to their destination, difficulties arising from unfavorable milieu-carrier interactions and ways to circumvent such difficulties. It also identifies, when possible, situations where proposed uses would or would not be realistic and provides perspectives for future goals.

Themulticomponentnatureofbiologicalmembranesandtheirintra- andextracel- lar interactions make direct investigations on the membrane structure and processes nearly impossible. Clearly, a better understanding of the membrane properties and the mechanisms determining membrane protein functions is crucial to the imp- mentation of biosensors, bioreactors and novel platforms for medical therapy. For this reason, the interest in model systems suitable for the construction and study of complex lipid/protein membrane architectures has increased steadily over the years. The classical portfolio of model membranes used for biophysical and - terfacial studies of lipid (bi)layers and lipid/protein composites includes Langmuir monolayers assembled at the water/air interface, (uni- and multi-lamellar) vesicles in bulk (liposomal) dispersion, bimolecular lipid membranes (BLMs), and various types of solid-supported membranes. All these have speci?c advantages but also suffer from serious drawbacksthat limit their technical applications. Polymer m- branes comprised of entirely synthetic or hybrid (synthetic polymer/biopolymer) block copolymersappeared to be an attractive alternative to the lipid-based models. Generally, the synthetic block copolymer membranes are thicker and more stable and the versatility of polymer chemistry allows the adoption of relevant properties for a wide range of applications. This volume provides a vast overview of the physico-chemical and synthetic - pectsofarti?cial membranes. Numerousmembranemodelsaredescribed,including their properties(i. e. swelling, drying,lateral mobility,stability, electrical conduct- ity, etc. ), advantages, and drawbacks. The potential applications of these models are discussed and supported by real examples. Chapter 1 summarizesmethodsfor the stabilizationof arti?cial lipid membranes.

The book provides a comprehensive account of ticks and tick-borne diseases occurring in tropical and subtropical areas. It begins with a complete up-to-date overview of the systematics of the Ixodida (Ixodidae, Argasidae and Nutalliellidae) and is followed by a review of the problem of ticks and tick-borne diseases of domestic animals world wide. This leads on to multi-disciplinary approaches to planning tick and tick-borne disease control and to contributions on calculating the economic impact of a tick species such as Amblyomma americanum on beef production systems. Heartwater fever (cowdriosis) and dermatophilosis are endemic in Africa and pose a threat to the North American mainland. The epidemiology of these two diseases is discussed in detail as is the role of frozen vaccines to control bovine babesiosis and anaplasmosis. The book also includes chapters on tick transmitted zoonoses such as Lyme borreliosis, tick typhus and ehrlichiosis. It concludes with a review of the acaricidal treatment of tick infestation.

This volume is the completion of work initially planned several years ago as a compilation of selected aspects of the biological effects of fluorides. The first portion appeared in Volume XXII (1966) of this Handbuch, under the title "Pharmacology of Fluorides, Part 1. " Inasmuch as the present volume is an integral part of the original project, justification for offering it to the scientific community remains the same as that originally set forth. This may be recapitulated as follows. The tremendous increase in the annual production of fluorides over the amounts produced thirty years ago, together with the increased diversity of their uses has correspondingly increased the hazard associated with these materials. That is to say, the possibilities of encountering their characteristic toxic effects under the conditions of their use has increased because the variety, amounts and ways of usage have increased. Their inherent toxicity, of course has not changed, but the increased hazard has led to a vast increase in the amount and scope of research reported. It is the purpose of these volumes to review selected aspects of this literature. Rochester, N. Y. , February 1970 FRANK A. SMITH Acknowledgements Even the casual reader of this volume will soon realize that contributing authors, as well as those contributing to its predecessor, Volume XX/I, have made good use of tables of data, figures and pertinent quotations from previously published work.

"He who is faithfully analysing ... epi lepsy is doing far more than studying epilepsy" Hughlings Jackson Modifying this well-known statement by Jackson, one could say today: "He who is faithfully analysing anti-epileptic drugs is doing far more than studying anti-epileptic drugs." For these drugs not only serve to prevent epileptic fits and thus advance the treatment of epilepsy, they are also effective in the treatment of cardiac arrhythmias and trigeminal neuralgia. Furthermore, clinical pharmacologists consider anti-epi leptic drugs as model drugs in pharmacokinetics and pharmocodynamics, since reliable methods are available for their determination and their effects and side effects can be defined. The methods of estimating of drugs in body fluids provide a tool that enables us to throw light on many obscure relationships in pharmaceutical treatment. Now that we can study the pharmacokinetics and interaction of drugs in man, many hypotheses based on clinical experience alone may well be eliminated or corroborated. The grow ing body of knowledge will make us more careful about the administration of drugs in combination. Now that we can study how biological parameters interfere with drug action, we may perhaps proceed to the scientific analysis of many clinical observations that suggest the importance of such factors as age, sex, menstrual cycle, pregnancy, fever, diet, stress, sport, climate, and altitude."

This volume arose from the scientific program of the XIIth International Congress of Pharmacology, held in Montreal, Canada, July 24-29, 1994. The scientific program included plenary lectures and symposia, in addition to poster presentations and colloquia. The abstracts of the Congress presentations were published as .supplement 1 of volume 72 by the Cana dian Journal of Physiology & Pharmacology. The Congress organizers sought a more expansive treatment of the Congress proceedings and appointed Dr. A. Claudio Cuello to coordinate preparation of the present volume; Dr. Brian Collier was chair of the scientific program committee and, thus, also collaborated on this work. The objective that we pursued was to produce a volume of reasonable size which would feature all of the plenary lectures and symposia from those authors who agreed to participate. To this end, we solicited mini reviews from plenary lecturers and asked symposia organizers to coordi nate a single short-review covering the individual topics within their event. Those who accepted this challenge are evident in this volume. We express our gratitude to these authors for doing so, and for exercising considerable ingenuity in completing their task within a reasonable time."

Dieser Buchtitel ist Teil des Digitalisierungsprojekts Springer Book Archives mit Publikationen, die seit den Anfangen des Verlags von 1842 erschienen sind. Der Verlag stellt mit diesem Archiv Quellen fur die historische wie auch die disziplingeschichtliche Forschung zur Verfugung, die jeweils im historischen Kontext betrachtet werden mussen. Dieser Titel erschien in der Zeit vor 1945 und wird daher in seiner zeittypischen politisch-ideologischen Ausrichtung vom Verlag nicht beworben.

The volumes of this classic series, now referred to simply as "Zechmeister" after its founder, L. Zechmeister, have appeared under the Springer imprint ever since the series' inauguration in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline.