Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view. This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.

Autoimmune diseases are common and often associated with considerable morbidity or - in diseases such as IDDM, myasthenia gravis and multiple sclerosis - mortality. In this volume, experts of international stature in basic science and clinical medicine with a common interest in understanding the normal and aberrant immune response present their experiences. It was their intention to fur- ther the understanding of potential clinical application of scientific observations and to help to comprehend the huge amount of results in autoimmunity research.

I have been privileged to witness and participate in the great growth of knowledge on chemical carcinogenesis and mutagenesis since 1939 when I entered graduate school in biochemistry at the University of Wisconsin Madison. I immediately started to work with the carcinogenic aminoazo dyes un der the direction of Professor CARL BAUMANN. In 1942 I joined a fellow graduate student, ELIZABETH CA VERT, in marriage and we soon commenced a joyous part nership in research on chemical carcinogenesis at the McArdle Laboratory for Cancer Research in the University of Wisconsin Medical School in Madison. This collaboration lasted 45 years. I am very grateful that this volume is dedi cated to the memory of Elizabeth. The important and varied topics that are reviewed here attest to the continued growth of the fields of chemical car cinogenesis and mutagenesis, including their recent and fruitful union with viral oncology. I feel very optimistic about the application of knowledge in these fields to the eventual solution of numerous problems, including the detection and estimation of the risks to humans of environmental chemical carcinogens and re lated factors.

The major cause of death in the Western world is some form of vascular disease; and principal among these forms is atherosclerotic heart disease (ASHD). Although much is known about the etiology and treatment of ASHD, there is, as yet, no specific means of prognosis of an impending coronary episode. There are, however, several indications of susceptibility to coronary disease, generally known as risk factors, the foremost of which is hyperlipidemia. Hyperlipidemia is more commonly designated as hypercholesteremia or triglyceridemia, depending upon which moiety is elevated, but since lipids are transported in the blood as members of a lipoprotein complex, the most descriptive general term would be hyperlipoproteinemia. This volume represents an effort to elucidate the origins and metabolic behavior of lipoproteins and their components, to describe aspects of the morphology, biochemistry and experimental induction of ASHD, and to describe modalities of treatment. The contributions to this book include descriptions of cholesterol synthesis and metabolism, as well as the metabolism of bile acids, the principal products of cholesterol metabolism. There are also chapters on the mechanisms of hyperlipidemia and on lipoprotein metabolism. The induction of experimental atherosclerosis and the aortic structural changes caused by this disease are discussed.

This publication comprises the reports presented at the Symposium on the Treatmenr of Burns, held in Prague on September 13-15, 1973 by the Czech Society of Plastic Surgeons under the auspices of the ISBI on the occasion of the 20th anniversary of the foundation of the Prague Burns Unit. The program of the symposium was confined to four topics which under the present state of burn treatment represent the basic range of clinical problems. They are: surgery of the burn wound, anaesthesiology and resuscitation, septicaemia and complications of the burn illness. Most of the reports presented at the Symposium are printed in this book in full, as they were submitted by the authors. Only in some cases were the editors obliged to make minor formal adjustments in the interest of the earliest possible publication of the book. We hope that, after careful study, this publication will arouse the interest of further specialists in such an intricate field as is the treatment of burns and that it will stimulate all those concerned to further work. We should like to thank all those who facilitated the publication of this book by their participation in the Symposium and by their co-operation. The Editors Welcoming Address of the President of the Symposium On behalf of the organizing committee I would like to welcome all participants in this symposium."

Volume 47 of "Progress in Drug Research" contains eight reviews and the various indexes which facilitate its use and establish the connection with the previous volumes. The articles in this volume deal with inotropic steroids, with chemokines and their involvement in a wide range of inflam matory diseases, with the subclassification and nomenclature of ul- and Uz-adrenoceptors, with Chinese traditional medicine, with drug targets in the molecular pathogenesis of asthma, with cytokines and their therapeutic application in immunosuppression and immunostimulation, with alter native medicine and with the potential use of calcium blockers in psy chiatry. These reviews and the quotations of original articles provide the reader with valuable information on several new developments in the world-wide search for new and better medicines. In 1959, when the Editor started this series of monographs, it was his intention to help disseminate informa tion on the vast and fast growing domain of drug research. Already at that time, it was not possible to follow the major individual publications in this field, and the reader was thereby provided with a tool to keep abreast of the latest developments and trends. This goal remained unchanged over the last 37 years, and I believe that the reviews in PDR are useful to the non-specialist who can obtain an overview of a particular field of drug research in a relatively short time."

The landmark description by Delay and Deniker in 1952 of chlorpromazine's effect in psychosis suddenly eclipsed all other progress in psychopharmacology over the previous centuries. Since this report 35 years ago, a vast amount of research has contributed to the major advances in treatment that have improved the lives of millions of patients who would otherwise be incapacitated by their psychiatric disorders. This research has also led to valuable new insights into the causes of mental illnesses and the mechanisms of action of therapeutic drugs. However, there is much more work to be done. Thus, it is of great value periodically to assess the present state of knowledge as a first step to charting future directions. This symposium held in Denmark in 1987 covered many critical issues in psychopharmacology. The etiology, pathogenetic mechanisms, clinical aspects, and future directions of research in schizophrenia, affective disorders, anxiety, and dementia are addressed. Several of the problems with current therapeutic agents, such as side effects and limited efficacy, are also reviewed. Preclinical strategies with existing and new animal and computer models are discussed to point the way for developing better psychopharmacologic treatments of all psychiatric disorders.

Roots of the theory and practice of ocular pharmacology may be traced to the ancient Mesopotamian code of Hammurabi and then to several papyri reflecting the clinical interests of the Egyptians. The evolution of its art and science was irregularly paced until the nineteenth century when Kohler, in 1884, proved the anesthetic effect of cocaine on the cornea, and when Fraser, Laquer, Schmiedeberg, Meyer, and others studied the pharmacology of the autonomic nervous system by way of observations of the pupil. Advances in the past few decades have been nothing short of explosive. How can the student, physician, or basic research scientist stay in touch with these electrifying studies? To help with the answer to this question, the authors set as their goal the development of increased understanding so that the student, research scientist, and ophthalmologist can cope with the latest discoveries. The authors want to narrow what appears to be an ever-increasing gap between basic science and ophthalmology. The basic aspects of pharmacology have been presented in light of the natural physiology. In this regard, while distinctions among endogenous mechanisms, drug effects, and the pathogenesis of disease are to be separately recognized, appreciation must be given to the concept that both the desirable and unwanted manifestations or functions caused by either disease or drugs must very often represent a quantitative change in normal metabolic pathways.

Volume 43 of "Progress in Drug Research" contains five reviews and the various indexes which facilitate its use and establish the connection with the previous volumes. The articles in this volume deal with high cholesterol blood levels and other dyslipidemias; search of ideal antihypertensive drugs; the natural PQlyamines and the immune system; biologically active quinazolones and with production and action of interferons. In the 35 years the PDR has existed, the Editor has enjoyed the valuable help and advice of many colleagues. Readers, the authors of the reviews, and last but not least, the reviewers have all contributed greatly to the success of this series. Although the comments received so far have generally been favorable, it is nevertheless necessary to analyze and to reassess the current position and the future direction of such a review series. So far, it has been the Editors intention to help disseminate information on the vast domain of drug research, and to provide the reader with a tool with which to keep abreast of the latest developments and trends. The reviews in PDR are useful to the non-specialist, who can obtain an overview of a particular field of drug research in a relatively short time. The specialist readers of PDR will appreciate the reviews' comprehensive bibliographies, and, in addition, they may even get fresh impulses for their own research. Finally, the readers can use the 43 volumes of PDR as an encyclopedic source of information.

Percutaneous and coronary interventions, used to treat narrow arteries of the heart caused by/found in those with coronary heart disease. This book is a detailed guide for performing percutaneous procedures and it covers in-depth the procedures that cardiologists and interested specialists must be aware of in order to use the devices proficiently

Natural product chemistry has undergone an explosive growth during the latter half of the current century. This has been brought about by a number of factors. One of these has been the growing number of sub stances from natural sources which display interesting pharmacological activities. These include antibiotics, anti-tumor agents, immunostimu lants, drugs affecting the cardiovascular and central nervous systems, analgesics etc. Another factor has been the improvements made in the technology of isolation processes which includes the development of such techniques as high pressure liquid chromatography which has al lowed the rapid isolation of substances which were previously diffi cult to obtain by classical procedures. The most important factor has been the development of new spectrosopic techniques which have opened up whole new vistas in this exciting field. Prominent in these advan ces has been the advent of powerful superconducting magnets with very stable magnetic fields, and pulse NMR in which the duration, direction and phases of pulses can be accurately controlled by means of mini computers. These have heralded the advent of two-dimensional NMR spec troscopy which has now come to be routinely employed in unravelling complex structures. No less important, though somewhat less dramatic, have been the advances made in the field of mass spectroscopy where new ionization techniques such as positive and negative fast atom bom bardment, field desorption, chemical ionization etc. have allowed the mass spectra of larger non-volatile substances to be recorded. The field of organic synthesis has seen equally rapid advances."

Calcium Entry Blockers (CEBs) are a new class of drugs which have been pushing back the frontiers of science and medicine for almost two decades. This report reviews some of the wealth of chemical, biological and clinical data describing the discovery and development of these compounds. The scientific importance, therapeutic benefit and marketing potential of these compounds have caused an explosion of scientific literature describing their effects in many preclinical and clinical settings. The definitional characteristics of these compounds suggest a certain predictability of their biological profile but their therapeutic usefulness varies widely dependent upon their physical properties, net hemodynamic effects, duration of action and incidence of side effects. CEBs appear uniquely suited to the treatment of the underlying complexity of cardiovascular disease. The CEBs of the future may live up to the expectations of pathophysiologically based therapeutics and allow the heart and blood vessels to outlive the cells which they support. The development of CEBs is an evolving story of epic proportions and represents the cooperative efforts of individuals in all areas of science.

Beta-Rezeptorenblocker sind aus dem therapeutischen Arsenal zur Be- hand lung zahlreicher Erkrankungen nicht mehr wegzudenken. Die Be- miihung urn eine prazisere differentialtherapeutische Anwendung dieser Pharmaka-Gruppe, einschlie13lich der Erarbeitung von Dosierungsvor- schlagen und der Erkennung von therapeutischen Alternativen im Hin- blick auf Nebenwirkungen und Kontraindikationen, fUhrte eine Viel- zahl von Referenten aus dem In- und Ausland (U.S.A., England, Schweiz, Schweden) zu einem Symposion im November 1980 zusam- men. Mit dem Ziel, die praktische Anwendung von Beta-Rezeptorenblok- kern verstandlicher zu mach en und die therapeutische Sicherheit zu erh6hen, wurden zunachst pharmakologische Grundlagen und klinisch- pharmakologische Untersuchungsbefunde er6rtert. Ein wei teres wichti- ges Anliegen war es, M6glichkeiten und Grenzen, Nutzen und Risiko einer Therapie mit diesen Substanzen bei einzelnen Krankheiten aufzu- zeigen. Die Autoren der einzelnen Beitrage haben sich dankenswerterweise der Miihe unterzogen, ihre Manuskripte fUr die Publikation zu iiber- arbeiten und Anregungen und Erganzungen aus der Diskussion einzube- ziehen. Zusatzliche wichtige Gesichtspunkte aus der Diskussion wurden von den Herausgebern zusammengefaBt und sind am SchluB des Buches dargestellt. Dank und Anerkennung gebiihrt allen Mitarbeitern dieses Buches. Ferner danken wir den Damen und Herren des Springer-Verlages, ins- besondere Herrn Dr. Wieczorek und Herrn H. lakobi, fUr die ausge- zeichnete Zusammenarbeit.

The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

This volume contains a series of papers originally presented at the symposium on Water Soluble Polymers: Solution Properties and Applications, sponsored by the Division of Colloids and Surface Chemistry of the American Chemical Society. The symposium took place in Las Vegas City, Nevada on 9 to 11th September, 1997 at the 214th American Chemical Society National Meeting. Recognized experts in their - spective fields were invited to speak. There was a strong attendance from academia, g- ernment, and industrial research centers. The purpose of the symposium was to present and discuss recent developments in the solution properties of water soluble polymers and their applications in aqueous systems. Water soluble polymers find applications in a number of fields of which the following may be worth mentioning: cosmetics, detergent, oral care, industrial water treatment, g- thermal, wastewater treatment, water purification and reuse, pulp and paper production, sugar refining, and many more. Moreover, water soluble polymers play vital role in the oil industry, especially in enhanced oil recovery. Water soluble polymers are also used in ag- culture and controlled release pharmaceutical applications. Therefore, a fundamental kno- edge of solution properties of these polymers is essential for most industrial scientists. An understanding of the basic phenomena involved in the application of these polymers, such as adsorption and interaction with different substrates (i. e. , tooth enamel, hair, reverse - mosis membrane, heat exchanger surfaces, etc. ) is of vital importance in developing high performance formulations for achieving optimum efficiency of the system.

The "First International Conference on Traditional Chinese Medicine: Science, Regulation and Globalization" was held from August 30 to September 2, 2000 at the University of Maryland at College Park, Maryland. There were approximately 250 participants from the Peoples Republic of China, Taiwan, Hong Kong and the United States. This objective of this conference was to promote international collaboration for the modernization of Traditional Chinese herbal medicines (TCM) and their introduction into the global health care system. It was mainly sponsored by the Ministry of Science and Technology of the People's Republic of China and the NllI National Center for Complementary and Alternative Medicine (NCCAM). It was organized by Dr. William Tai, then director of the Institute of Global Chinese Affairs at the University of Maryland and Dr. Yuan Lin, president of Marco Polo Technologies, Bethesda, MD. This conference was conceived by Dr. Tai two years earlier recognizing that this was an appropriate time and also the unique location of the University of Maryland. Today, there is a growing recognition of the of alternative medicine in modem societies and the rapid loss of importance knowledge about traditional methods for the treatment of the multitude of human illnesses found throughout the world. TCM has been in common use in China for thousands of years; and many of its formulations are well defined.

Disturbances of haemostasis and thromboembolic disorders still constitute a great problem in clinical practice. Increasing insight into the mechanism of blood coagula tion has led to more effective therapy and prophylaxis. Particularly, the understand ing of the biochemistry of fibrinolysis has provided possibilities for the pharma cological interference of these processes, which has resulted in effective haemostatic agents and useful antithrombotic ones. The development of antifibrinolytics for interfering with pathological fibrinolytic processes is nearly complete and has led to the development of drugs essential to the therapy of hyperfibrinolytic bleeding. The search for fibrinolytics for dissolving intravascular thrombi has led to highly effective compounds. This development is still under way and promising results are hoped. Spontaneous dissolution of blood clots is a phenomenon which was described a century ago. First investigations of this process assured that there is in the organism a system capable of removing the fibrin which is formed during blood coagulation after it has fulfilled its physiological function. This fibrinolytic system is specifically adapted to the degradation of insoluble fibrin into soluble degradation products. In the past 30 years, thorough investigation of this system has clarified the fibrinolytic process, its physiological role and its meaning as a pathogenetic principle. A good knowledge of these processes is required for an understanding of the effects and side effects of fibrinolytics and antifibrinolytics, which comprise the basis of methods for the detection of fibrinolytic processes in the organism and of the control of therapy with these drugs."

Das Buch enthalt Kapitel uber: M. Azria, Basel, CH: "Calcitonin - Physiologische und Pharmakologische Aspekte"U. Niemeyer, J. Engel, P. Hilgard, M. Peukert, J. Pohl, H. Sindermann, Bielefeld, FRG: "Mafosfamid - Ein Derivat des " "4-Hydroxycyclophosphamids"S. Grunwald, G.P. Pfeifer, Frankfurt, FRG: "Enzymatische DNA Methylierung""

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 multidisciplinary 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 oncology.

Today, our world increasingly is conceived of as being molecular. An ever widening range of phenomena are described logically in terms of molecular properties and molecular interactions. The majority of known molecules are heterocyclic and heterocycles dominate the fields of biochemistry, medicinal chemistry, dyestuffs, photographic science and are of increasing importance in many others, including polymers, adhesives, and molecular engineering. Thus, the importance of heterocyclic chemistry continues to increase and this three volume work by Drs. R. R. Gupta, Mahendra Kumar and Vandana Gupta is a welcome addition to the available guides on the subject. Its scope places it in a useful niche between the single-volume texts and monographs of heterocyclic chemistry and the multivolume treatises. The authors have retained the well tried classical approach but have succeeded in placing their own individual spin on their arrangement. They have put together a well selected range from among the most important of the vast array offacts available. This factual material is ordered in a clear and logical fashion over the three volumes. The present work should be of great value to students-and practitioners of heterocyclic chemistry at all levels from the advanced undergraduate upwards. It will be of particular assistance in presenting a clear and modem view of the subject to those who use heterocycles in a variety of other fields and we wish it well.

In the beginning of this century physiology witnessed the creation of a new concept, the hormonal regulation of the work of the digestive organs. It was found that such essential functions as the flow of pancreatic juice and emptying of bile into the intestine were regulated by two hormones, secretin and cholecystokinin, respectively. Already in 1925 French authors attempted to measure the functional capacity of the exocrine pancreas by means of stimulation with secretin. The use fulness of the secretin test in this connection was definitely established by Scandinavian workers in the 1930's. In spite of the difficulties in obtaining secretin American authors succeeded in keeping the interest in the secretin test alive. The development in the 1950's of counter-current, ion exchange and chromato graphic techniques offered new possibilities in this field. The intestinal hormones were known to be relatively low molecular peptides and these could now be isolated in pure form. Thus secretin was isolated in 1961, and cholecystokinin in 1964. The newly developed methods for peptide analysis likewise soon brought us full information about the primary structure of the peptides. Gastrin, the specific stimulant of the gastric acid secretion, which was discovered in 1905 and acknowledged as a hormone in 1938, was the first of the gastrointestinal hormones for which the structure became known. This was in 1964. Synthesis soon followed. These developments are reviewed in the first chapter of the present volume."

From a logical point of view, cell division is regulated by the environment and by the ability of the cell to respond to the environmental signals. The terminology of the cell cycle, the elaborate mathematical models, and the kinetic analyses are all convenient notations and descriptions of the behavior of populations of cells. However, they tell us very little about the fundamental molecular mechanisms that control cell proliferation. Stated in other terms, what controls cell reproduction are growth factors in the environment and genes and gene products inside the cell or at its surface. This book examines the aforementioned growth factors, the study of which has made very rapid progress in the past few years. The selection of topics has been influenced by logistic considerations, but the book, as a whole, gives a broad survey of the state of the art of this exciting field. For this, thanks are due to the contributors, who have given much time to the preparation of the manuscripts and have met the deadline with a punctuality that is uncommon among biomedical scientists. I would also like to thank Ms. NORA PERRETT and the staff of Springer-Verlag for their help in editing the manuscripts and in preparing the production of the book.

Volume 27 of "Progress in Drug Research" contains 5 articles, a subject index for this volume, an alphabetic subject 4ldex for volumes 1-27, and an author and subject index for altthe volumes which have so far been published. The contributions of volume 27 are particularly concerned with fungal disease, with benzimidazole anthelmintics and with the chemistry and pharmacology of quinuclidines, azoles, and nitroimida- zoles. The authors have tried, not only to summarize the current status of particular fields of drug research, but also to provide leads for future research activity. The articles of this volume will be of special value to those actively engaged in drug research, and to those who wish to keep abrest of the latest developments influencing modem therapy. In addi- tion, it is believed that the 27 volumes of "Progress in Drug Research" now available represent a useful reference work of encyclopedic charac- ter. The editor would like to take the occasion of the publication of this volume to express his gratitude both to the authors and to the readers. The authors have willingly1undertaken'the great labor of writing signifi- cant topical contributions, hnd many readers have helped the editor with criticism and advise. With these thanks, the editor would like also to express his gratitude to the publisher, Birkhauser Verlag Basel, particu- larly to Messrs. Th. Birkhauser and C. Einsele, and their associates for the excellent cooperation.

-Encapsulation by Miniemulsion Polymerization By K. Landfester and C. K. Weiss -Enzyme-Encapsulated Layer-by-Layer Assemblies: Current Status and Challenges Toward Ultimate Nanodevices By K. Ariga, Q. Ji, and J. P. Hill -Non-LBL Assembly and Encapsulation Uses 1 of Nanoparticle-Shelled Hollow Spheres 2 By G.C. Kini, S. L. Biswal, and M. S. Wong -Polymersomes: A Synthetic Biological Approach to Encapsulation and Delivery By M. Massignani, H. Lomas, and G. Battaglia -Reaction Vessels Assembled by the Sequential Adsorption of Polymers By A.D. Price, A.P.R. Johnston, G.K. Such, and F. Caruso

Eleven years have elapsed since the appearance of the first Volume and it is with great pleasure that the Editor is now able to present Volume 14. During these eleven years various fields of drug research have undergone important, partly revolutionary, changes. A number of these have already been dealt with, so that the series PROGRESS IN DRUG RESEARCH contains a comprehensive review of a substantial part of our current knowledge. The Editor is particularly grateful for the opportunity of transmitting to those connected with the development of drugs the extensive knowledge of the Authors, who, without exception, are themselves actively engaged in research. Drug research is currently in a state of transformation: reconsideration in the light of the past and reorientation with a view to the future. To a large extent this is due to the tumultuous developments in the last 20 years, developments which are unparalleled in the history of medicine and the consequences of which cannot yet be completely evaluated. Unfortunately, however, the current situation is not devoid of its unpleasant and even tragic aspects, aspects which fall outside the research worker's sphere or influence. Those connected with drug research, be they in industry, in universities or in clinics, are aware of these problems, and, as a result of this awareness, are all the more in need of an aid which will assist them in ascertaining the current position and in fixing future goals.