This book evolved from a graduate course on applications of statistical thermody- namics to biochemical systems. Most of the published papers and books on this subject used in the course were written by experimentalists who adopted the phenomenological approach to describe and interpret their results. Two outstanding papers that impressed me deeply were the c1assical papers by Monod, Changeux, and Jacob (1963) and Monod, Wyman, and Changeux (1965), where the allosteric model for regulatory enzymes was introduced. Reading through them I feIt as if they were revealing one of the c1everest and most intricate tricks of nature to regulate biochemical processes. In 1985 I was glad to see T. L. HilI's volume entitled Cooperativity Theory in Biochemistry, Steady State and Equilibrium Systems. This was the fIrst book to systematically develop the molecular or statistical mechanical approach to binding systems. HilI demonstrated how and why the molecular approach is so advanta- geous relative to the prevalent phenomenological approach of that time. On page 58 he wrote the following (my italics): The naturalness of Gibbs' grand partition function for binding problems in biology is evidenced by the rediscovery of what is essentially the grand partition function for this particular type of problem by various physical biochentists, including E. Q. Adams, G.

This book describes some of the most exciting developments for the discovery of new drugs, such as Fragment-based methods. It contains the latest developments in technologies that can be used to obtain the 3-D structures. This book includes experimental approaches using X-ray crystallography and NMR for Fragment-based screening as well as other biophysical methods for studying protein/ligand interactions.

Nanobiotechnology is one of the key technologies of the 21st century. It is a combination of nanoscience and biotechnology and covers areas ranging from gene transfer and nanoencapsulation to food technology. Nanocarriers are a leading nanobiotechnology tool with the ability to provide protection, site-specific delivery, enhanced bioavailability and controlled release of pharmaceuticals, genetic material, imaging agents, nutraceuticals and cosmetics to name a few. For this reason, the study of nanocarriers, their properties and applications has attracted a great deal of interest over recent years. Designed as an advanced survey of the field, this book describes the key research parameters of nanocarrier technologies including their preparation methods, evaluation of their safety and efficiency, their interaction with biologicals and their application in biotechnology, drug delivery, gene therapy and food technology areas.

Understanding the molecular basis of complex biological processes has been a major goal of biological chemistry from early on. Inflammation is one such entity, and recent years have seen exciting progress in the under- standing of molecular interactions; there has been a long way from dolor, rubor, calor, and tumor as a fundamental description of the phenomenon to current knowledge, e.g., on the control of the respiratory burst of the granulocyte, the atomic details of protease regulation, or the interaction of cytokines. We were glad to have been given the opportunity by the Gesellschaft fUr Biologische Chemie to call upon experts in this bustling field of research for this Colloquium. The sessions were organized in the order of increasing complexity, starting with the key phenomena of the inflamma- tory response and its modulation by cytokines to intravascular events and shock and sepsis; thus, the current attempts to apply basic knowledge on mediators of inflammation to the clinical situation were also considered. In-depth chapters presenting the state of the art in these areas are collected in this book, and we thank the authors for their efforts. We also thank the Chairmen of the sessions, Profs. C. Sorg (Munster), D. Roos (Amsterdam), S. Bhakdi (Mainz), H. J. Muller-Eberhard (Hamburg), H. G. Schwick (Marburg), K. Resch (Hannover), W. Schaper (Bad Nauheim), D. Keppler (Heidelberg), and O. Trentz (Zurich) for their input, and it is a great pleasure to acknowledge the support by Drs.

Leading experts survey the currently available technologies designed to improve the delivery of today's cancer chemotherapeutic agents. The authors review both the theoretical and practical considerations governing conventional and nonconventional methods of drug administration, and identify promising opportunities for product development. In their outline and discussion of the use of novel formulation technologies-including synthetic polymers and biomaterials for prolonged or sustained drug release to achieve potentially greater therapeutic effect-they profile those technologies that have resulted in a number of approved and late-stage clinical products.

Expert researchers and physician/clinicians describe in detail the newest and most commonly used technologies today in this rapidly advancing field. The authors provide readily reproducible methods for assessing the functional consequences of a certain polymorphism, evaluate the variety of genotyping platforms currently available, and discuss the management of pharmacogenomic information. Highlights include techniques for making a snapshot of the allele-specific variation in human gene expression, genome wide analysis of allele-specific expression using oligo microarrays, in vivo assays with HaploChIP, SNP genotyping in DNA pools, and PharmGKB, the pharmacogenetics and pharmacogenomics knowledge base. The methodologies for genotyping include denaturing high-performance liquid chromarography, pyrosequencing, kinetic-fluorescence detection, mass spectrometry, and TaqMan assay for insertion/deletions.

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.

Beginning with the Escherichia coli ? protein, or bacterial DNA topoisomerase I, an ever-increasing number of enzymes have been identified that catalyze changes in the linkage of DNA strands. DNA topoisomerases are ubiquitous in nature and have been shown to play critical roles in most p- cesses involving DNA, including DNA replication, transcription, and rec- bination. These enzymes further constitute the cellular targets of a number of clinically important antibacterial and anticancer agents. Thus, further studies of DNA topology and DNA topoisomerases are critical to advance our und- standing of the basic biological processes required for cell cycle progression, cell division, genomic stability, and development. In addition, these studies will continue to provide critical insights into the cytotoxic action of drugs that target DNA topoisomerases. Such mechanistic studies have already played an important role in the development and clinical application of antimicrobial and chemotherapeutic agents. The two volumes of DNA Topoisomerase Protocols are designed to help new and established researchers investigate all aspects of DNA topology and the function of these enzymes. The chapters are written by prominent investigators in the field and provide detailed background information and st- by-step experimental protocols. The topics covered in Part I: DNA Topology and Enzymes, range from detailed methods to analyze various aspects of DNA structure, from linking number, knotting/unknotting, site-specific recombi- tion, and decatenation to the overexpression and purification of bacterial and eukaryotic DNA topoisomerases from a variety of cell systems and tissues.

This work is the first monograph devoted solely to "Bombax ceiba," popularly known as the Red Silk Cotton Tree. Consisting of seven chapters, it covers all relevant aspects of this plant, from its historical and spiritual importance, to its botanical characterization, pharmacognostical details and ethnobiological uses, to its scientific validation in various animal and human studies. Each part of the tree is of medicinal value and possesses many novel chemical constituents such as shamimicin, bombasin, bombamalone, bombamaloside etc. along with other bioactive secondary metabolites. The book presents the chemical structures of the most important constituents and highlights various pharmacological activities, predominantly antioxidant, anti-inflammatory, anti-mutagenic, hypoglycemic, hypotensive, hepatoprotective and fibrinolytic, which may prove to be a source for the development of a novel phyto-pharmaceutical agent to treat diabetes, heart disease and cancer. In addition, separate chapters deal with the commercial and ecological significance of "B. ceiba," as well as a case study on its conservation. Numerous color illustrations are included to identify the plant and to justify its nickname, the Little Bird s Cafeteria . "

Drug Metabolism: Current Concepts provides a comprehensive understanding of the processes that take place following ingestion of a medicinal agent or xenobiotic, with an emphasis on the crucial role of metabolism (biotransformation). How a sound knowledge of these phenomena is incorporated into the design of effective new drug candidates is also explained. The user-friendly text focuses on concepts rather than extraneous details and is supported by many illustrated examples of biotransformations as well as frequent references to current critical reviews and articles highlighting the nature of research objectives in this vibrant area of medicinal development. The final topic on strategies for drug design relies on the background provided by the rest of the book. This book is ideally suited as an advanced text for courses in drug metabolism for students of medicine, pharmacy, pharmacology, biochemistry; and for courses in drug design and drug delivery for students of medicinal chemistry. It is also appropriate for professional seminars or courses that relate to the fate of a drug in the body, drug interactions, adverse reactions and drug design.

Im Juni 1979 hatte in Dusseldorf ein Symposion uber Diuretika stattgefunden. Behandelt wurden experimentelle und klinische Ergebnisse mit Diuretika, unter anderem mit Diucomb. Ziel des Symposions war, Untersuchungsergebnisse zu referieren und diskutieren. Teilnehmer waren Wissenschaft ler aus der Schweiz, Osterreich, Grossbritannien, USA und der Bundesrepublik Deutschland. Das Material dieses Symposions wurde uberarbeitet, Diskussionen durch einen Redaktionsstab gestrafft. Wir danken Frau J. BOROS fur wertvolle technische Assistenz. Der Springer-Verlag hat uns wiederum sach kundig beraten und ist in grosszugiger Weise unseren Wunschen entgegengekommen Die Herausgeber Inhaltsverzeichnis Einleitung. F. KRUCK . . . . . . . . . . . . . 1 1. Wirkungsmechanismen. Moderation: K. GREEFF . 3 Plasma Concentrations and Comparative Bioavailability of Bemetizide and Triamterene in Combination. L. F. CHASSEAUD . . . . . . . . 5 Pharmakokinetik von Diuretika bei eingeschrankter Nierenfunktion. H. KNAUF und E. MUTSCHLER 14 Diskussion 24 Neue Daten zur Toxizitat von Diuretika. F. LEUSCHNER 26 Diskussion 29 2. Renale Wirkungen. Moderation: O. KRAuPP. . . . . . . . . . . . 33 Die Wirkungsweise diuretischer Substanzen in Abhangigkeit von ihrer re- len Behandlung. P. DEETJEN . . . . . . . . . . . . . . . . . . . 35 Effects of Diuretics on Renal Potassium and Hydrogen Ion Transport. G. GIEBISCH and M. HROPOT . . . . . . . . . . . . . . . . . . . 42 Wirkungen von Diuretika auf den transzellularen Elektrolyttransport der Niere. M. WIEDERHOLT und L. L. HANsEN 53 Diskussion 60 Interaktion zwischen Diuretika und renalem Prostaglandinsystem. H. J. KRAMER, B. STINNESBECK, W. PRIOR und R. DUSING 64 71 Diskussion Untersuchungen zum Wirkungsmechanismus von Acetazolamid und SITS auf den Bikarbonattransport im proximalen Tubulus der Rattenniere."

Sulfonium compounds have been known to the organic chemist for almost 90 years. During most of this period they remained curiosities, well suited for didactic purposes to illustrate certain similarities to ether adducts and to organic ammonium compounds. Their exploration remained largely in the academic realm, because no unusual practical applications were found in spite of a steady increase in the attention paid to them. An event that occasionally puts a class of compounds into the center of interest is the recognition of its occurrence in nature and of special biological significance. The first natural sulfonium compound was discovered less than 20 years ago, somewhat by chance rather than as the climax of some coveted biochemical problem. Gradually, however, the unique role of sulfonium compounds, especially of S-adenosyl- methionine, in enzymatic group transfer reactions such as trans- methylation was recognized, and the recent upsurge of interest has been exceptional. The present review is directed toward an interpretation of the properties and functions of biological sulfonium compounds with frequent reference to their structural chemistry. The data presented here may suggest novel or improved analytical techniques and new interpretations of the mechanism of group transfer. Furthermore, a stimulus may be derived for the design of sulfonium compound analogues. The availability of competitive analogues of biochemical key compounds has aided in the understanding of the function of virtually all metabolic intermediates, prosthetic groups of enzymes, vitamins, amino acids, and other compounds. The pattern will be similar in sulfonium biochemistry.

Volumes 18 and 19 of "Progress in Drug Research" differed from the earlier volumes insofar as they were concerned almost exclusively with problems in the field of Tropical Medicine. The editor and publishers believed that in this way some contribution could be made to the solution of some of the many problems with which the developing countries are burdened. The 20th volume, however, is in the customary form; it contains 17 contributions from various areas of drug research and therapy. Whereas the articles concentrate on a short representation of the progress which has already been made, nevertheless reference is also made to the many unsolved problems within the particular areas. The editor hopes that the 20th volume will not only represent a comprehensive review but will also be of some use in focusing further investigations on problems of medicine that have still not been overcome. The editor would also like to take this opportunity of expressing his gratitude to Dr. A. Naffor carefully working over the manuscripts and correcting proofs. Thanks are also due to the publishers and the printers, Druckerei Birkhauser, especially Dr. A. Birkhauser, Th. Birkhauser and C. Einsele, for their painstaking work on the printing and lay-out of the volume. August 1976 Dr. E. JUCKER Sandoz AG, Basel Vorwort Die Bande 18 und 19 der "Fortschritte der Arzneimitte1forschung" wichen insofern von den vorhergehenden Banden ab, a1s sie fast ausschliess1ich Prob1eme der Tropenkninkheiten behandelten.

Novel drugs are being developed which interact with the programmed cell death (apoptotic) machinery in cancer cells, thereby causing these cells to commit suicide and to be removed from the body. Research is also directed to investigate why the cancer cells sometimes lose the ability to undergo apoptosis after a certain period of time and methods are being developed to reactivate this cell death process. This book is intended for workers in the field and clinicians as a useful guide of the state of affairs in this exciting field which may offer more effective possibilities for treatment of cancer patients.

Mels Sluyser is the Editor of the journals APOPTOSIS and ANTI-CANCER DRUGS. He brings together a collection of papers written by the world 's leading experts in these fields.

Over the last several years it has become apparent to most researchers that interdisciplinary research is the key to success in the sciences' future. The present book exemplifies such interdisciplinary work. Thus, some new derivatives have been prepared by chemists and consecutively analyzed by physicists in order to better understand their physical-chemical properties for future tests to be performed by pharmacists. The book consists of an introductory section and other eight chapters. First, the fundamentals of infrared, Raman and surface-enhanced Raman spectroscopy and those of the theoretical methods employed for the vibrational prediction modes are highlighted. The SERS investigations illustrated in the following chapters are focused on different kinds of drugs: tranquilizers and sedatives, anti-inflammatory drugs, vitamins, drugs with anti-bacterial properties, etc. Since there is an increased interest in designing highly effective and controllable SERS-active substrates, a few newly developed substrates that could contribute to a deeper understanding and knowledge of the adsorption behavior of various types of molecules of pharmaceutical and medical interest are also presented.

Today, the basic mood of researchers and clinical investigators, both at the center and on the periphery of interferon studies, is optimistic regarding the future of interferons as therapeutic substances. Many also feel these polypeptides will prove invaluable probes in unraveling certain fundamental biochemical processes which control the life cycle and developmental pattern of many human cells. In contrast, only a year or two ago, this optimism had given way to an attitude almost of disenchantment as public and scientific expectations were raised steeply, then rapidly waned, as it turns out, prematurely. Both the mUltiple actions of interferons (a virtual cascade of biochemical reactions may be induced, as documented herein) and the high visibility of interferon research provided by the millions of dollars invested both by national health agencies and by multinational pharmaceutical companies, contributed to an upsweep in public attention to drug development probably unprecedented in this century. Virtually every oncologist, it would seem, was plagued by requests for the experimental agent, although they already had therapies of more proven value. As recently as 1980, even though interferon had achieved success against certain cancers and certain viral diseases, the variability in clinical results was seemingly ever present and little evidence emerged to suggest interferons could cure advanced diseases. Why then the resurgence of an optimistic mood? There are almost always many elements which contribute to happiness, and this is certainly true of the broad frontier of interferon and its place in biochemical research and treatment.

Before the late 1970s, interest in caffeine among both the general public and the scientific community was at a relatively low level for many years, even though it was recognized that caffeine was an al most universal component of the diet. The National Coffee Associa tion was supporting a continuing program of research, some re search was being conducted by a few of the largest companies selling coffee, and an occasional university researcher became inter ested in caffeine and conducted experiments, often on effects of caf feine in very high concentration in vitro on skeletal muscle fibres or on dividing cells. Since 1978, however, there has been a mighty up surge in both public and scientific interest in caffeine. It is interest ing to note that this was prompted not by discovery of hitherto un known effects or hazards of caffeine, but by the actions of a regulatory agency, the Food & Drug Administration (FDA) of the U. S. Public Health Service. The U. S. Congress passed new laws on foods and drugs in 1958. One of the provisions was for testing of food additives to assess risk to health. As it was clearly impracticable to require immediate test ing of all additives already in use, a list was drawn up of some hun dreds of additives that were generally recognized as safe (GRAS)."

Ten years have elapsed since the publication in 1978 of Vol. 49 of the Handbook of Experimental Pharmacology [41], a toOO-page survey of the data then available on Ergot Alkaloids and Related Compounds. A booklet published in 1979 presented the in formation on one of these compounds, namely co-dergocrine (Hydergine@), as extracted from the Handbook and updated to take the latest developments into account [42]. Co-dergocrine had at the time been on the market for 30 years and had given rise to over 2000 papers, so that one might have felt justified in thinking that its scientific history had virtually come to an end. It has now become obvious that such a view would have been wide of the mark. Research on the pharmacology and clinical pharmacology of co-dergocrine has remained as active as ever. The resulting obsolescence of the 1979 booklet made necessary the preparation of the present version. Like its predecessor, it is intended as an inventory of findings and facts rather than a work dealing with their interpretation.

This volume places more emphasis on endogenous mediators of gut motility than on drugs used to treat patients with deranged motility. In this respect it resembles most other books on gastroenterology, for while only a relatively small number of drugs are really useful for a rational therapy, a tremendous amount of data is available on neural and hormonal factors regulating the motility of the alimentary canal. Moreover, it must be considered that some of the drugs which can routinely be employed to modify deranged motility of the digestive system are represented by pure or slightly modified endogenous compounds (e. g. , cholecystokinin, its C terminal octapeptide and caerulein), and it is easy to foresee that their number is destined to increase in the near future. Other drugs are simply antagonists of physiological substances acting on specific receptors (e. g. , histamine H -blockers 2 and opioid compounds). The real explosion of research in this field and the extreme specialization often connected with the use of very sophisticated techniques and methodologies would probably have required a larger number of experts to cover some very specific fields from both an anatomical (lower esophageal sphincter, stomach, pylorus, small and large intestine) and a biochemical (hormones, candidate hormones, locally active substances, neurotransmitters etc. ) point of view.

Die Entdeckung bzw. Wiederentdeckung der blutzuckersenkenden Wirkung von Sulfonylharnstoffen im Jahre 1955 durch FRANKE und FUCHS hat die For- schung sowohl uber die Physiologie der Langerhansschen Inseln als auch uber den Kohlenhydratstoffwechsel sehr angeregt. Nachdem es wahrscheinlich wurde, dass Substanzen aus der Gruppe der Sulfonylharnstoffe die Sekretion von Insulin stimulieren, wurden verschiedene Methoden zur Bestimmung von Insulin im Blut entwickelt, die wegweisend fur empfindliche Methoden zur Bestimmung anderer Peptidhormone waren, und die elektronenmikroskopischen Beobachtungen der Vorgange bei der Sekretion von Insulin aus den B-Zellen wurden zum Modell fur die Vorstellungen uber die Funktion anderer Drusen. Es gibt viele Substanzen, die die Insulin-Sekretion aus den B-Zellen beeinflus- sen, die Zucker Glucose und Mannose, die Aminosauren Arginin und Leucin, ver- schiedene kurzkettige Fettsauren, verschiedene Metaboliten des intermediaren Stoffwechsels und Hormone, wie Glucagon, Corticotropin, Secretin, Gastrin, Pankreozym und verschiedene andere. In diesem Band sollten die therapeutisch interessanten Pharmaka abgehandelt werden, zu denen vor allem die Gruppen der Sulfonylharnstoffe bzw. Sulfonamide und der Biguanide gehoren. Auf die Geschichte der Verwendung von Biguaniden zur Behandlung von Diabetikern geht BECKMANN in seinem Artikel ausfuhrlich ein, so dass sich eine Darstellung hier erubrigt. Die blutzuckersenkenden Sulfonylharnstoffe wurden 1955 sozusagen durch eine klinische Zufallsbeobachtung mit Carbutamid wieder entdeckt und fur die Therapie zuganglich gemacht, nachdem LOUBATIERES sich mit der Wirkung ahnlicher Substanzen auf den Blutzucker und auf die Langerhans'schen Inseln bereits seit Anfang der 40er Jahre ausfuhrlich experimentell beschaftigt und bereits prinzipielle Aussagen uber den Wirkungsmechanismus gemacht hatte, die auch heute noch weitgehend akzeptiert werden.

Traditional Chinese medicine has been used for thousands of years by a large population. It is currently still serving many of the health needs of the Chinese people; and still enjoying their confi dence it is practised in China in parallel with modern Western medical treatment. In addition to scientific organisations dedi cated to modern Western medicine, e. g. the Chinese Academy of Medical Sciences and various medical schools, a series of parallel institutions have been established in China to promote traditional Chinese medicine, such as the Academy of Traditional Chinese Medicine and training institutions. Almost all hospitals in China have a department of traditional medicine. Furthermore, a large number of scientific journals are dedicated to traditional Chinese medicine, covering both experimental and clinical investigations. Medicinal materials constitute a key topic in the treatment of disease according to traditional Chinese medicine. The Chinese Pharmacopoeia (1985 edition) is therefore divided into two sepa rate volumes, Volume I containing traditional Chinese medicinal materials and preparations and Volume II containing pharmaceu tics of Western medicine. The oldest Chinese review of medicinal materials, Shennong Bencao Jing (100-200 A. D. ), covered 365 herbal drugs. The clas sic compilation in this field, Bencao Gangmu (Compendium of Materia Medica), was published in 1578 by Li Shi-zhen and recorded as many as 1898 crude drugs of plant, animal and min eral origin."