Since the late 1950's when proton n. m. r. spectroscopy was first used in organic natural products studies the technique has increasingly con of this important area of chemistry. tributed to the rapid advancement Although the potential utility of 13C n. m. r. was recognized very early, essentially no application of 13C n. m. r. appeared in the literature prior to 1966 and 95% of the existing data are less than five years old. The initially slow growth had its cause in inadequate instrumentation, insufficient sensitivity being the main obstacle. This situation drastically changed with the advent and commercial availability of broadband ex citation and Fourier transform methods, giving natural-abundance 13C n. m. r. and its numerous chemical applications a tremendous impetus. Today BC spectra can be recorded on sample quantities down to the submilligram level, which until recently even withstood proton n. m. r. Paralleling the development of experimental techniques considerable progress has also been made on an understanding of spectral parameters, in particular their stereochemical implications on natural products. Although the large majority of data present up to now deals with known structures, an adequate basis now exists which allows the chemist to use the technique for tackling real problems on unknown molecules."

Toyiochi Tanaka, Mitsuhiro Shibayama, "Phase Transitions and related Phenomena of Polymer Gels", Akira Onuki "Theory of Phase Transition in Polymer Gels", Alexei Khokhlov, Sergei Starodybtzev, Valentina Vasilevskaya "Conformational Transitions in Polymer Gels: Theory and Experiment", Michal Ilavsky " Effect on Phase Transition on Swellingand Mechanical Behavior of Synthetic Hydrogels", Shozaburo Saito , M. Konno, H. Inomata "Volume Phase Transition of N-Alkylacrylamide Gels", Ronald Siegel "Hydrophobic Weak Polyelectrolyte Gels: Studies of Swelling Equilibria and Kinetics".

The Fifth Chinese Peptide Symposium, hosted by Lanzhou University, was held at Lanzhou, China July 14-17, 1998, with 156 participants, including 30 scientists from abroad, representing nine countries. The four-day conference was both intense and spiritually rewarding. Our goal for CPS-98 was to provide a forum for the exchange of knowledge, cooperation and friendship between the international and Chinese scientific communities, and we believe this goal was met. The symposium consisted of 8 sessions with 42 oral and 90 poster presentations, including synthetic methods, molecular diversity and peptide libraries, structure and conformation of peptides and proteins, bioactive peptides, peptide immunology, De Novo design and synthesis of proteins and peptides, ligand-receptor interactions, the chemistry-biology-interface and challenging problems in peptides. The enthusiastic cooperation and excellent contributions were gratifying and the active response of the invited speakers contributed to the success of the symposium. The presentations were of excellent caliber and represented the most current and significant aspects of peptide science. Dr. Kit Lam of the University of Arizona and Dr. Yun-Hua Ye of Peking University were the recipients of "The Cathay Award" sponsored by the H. H. Liu Education Foundation, offered for their seminal contribution in peptide science and the Chinese Peptide Symposium. Four outstanding young scientists were selected by the organizing committee to receive awards sponsored by Haikou Nanhai Pharmaceutical Industry Co. Ltd. (Zhong He Group).

High-throughput screening and combinatorial chemistry are two of the most potent weapons ever to have been used in the discovery of new drugs. At a stroke, it seems to be possible to synthesise more molecules in a month than have previously been made in the whole of the distinguished history of organic chemistry, Furthermore, all the molecules can be screened in the same short period. However, like any weapons of immense power, these techniques must be used with care, to achieve maximum impact. The costs of implementing and running high-throughput screening and combinatorial chemistry are high, as large dedicated facilities must be built and staffed. In addition, the sheer number of chemical leads generated may overwhelm the lead optimisation teams in a hail of friendly fire. Mother nature has not entirely surrendered, as the number of building blocks that could be used to build libraries would require more atoms than there are in the universe. In addition, the progress made by the Human Genome Project has uncovered many proteins with different functions but related binding sites, creating issues of selectivity. Advances in the new field of pharmacogenomics will produce more of these challenges. There is a real need to make hi- throughput screening and combinatorial chemistry into 'smart' weapons, so that their power is not dissipated. That is the challenge for modellers, computational chemists, cheminformaticians and IT experts. In this book, we have broken down this grand challenge into key tasks.

Der vorliegende 48. Band der Reihe "Fortschritte der Arzneimittelfor- schung" enthalt acht Beitrage, die wiederum von anerkannten Forschern verfasst wurden. Ausserdem sind auch in diesem Band ein Stichwortver- zeichnis des Bandes sowie ein Autoren-und Titelverzeichnis und ein Titel- verzeichnis aller 48 Bande enthalten. Der Leser hat dadurch die Mog- lichkeit, nicht nur den vorliegenden Band zu konsultieren, sondern auch alle bisher erschienenen Bande quasi als enzyklopadisches N achschla- gewerk zu benutzen. Da alle Beitrage umfangreiche Literaturnachweise enthalten, ist die Moglichkeit des Zugriffes auf Original-Publikationen gegeben, was dem aktiven Forscher besonders wichtig ist und seinen eige- nen Arbeiten Impulse geben kann. Die Artikel des 48. Bandes behandeln neue Entwicklungen der Genetik, der enzymatischen Herstellung von komplexen Peptiden und bringen die neuesten Erkenntnisse der Apoptose unserem Verstandnis naher. Immun- therapie bei Hirnerkrankungen und psychischen Storungen, der Einsatz vonNaturproduktenzur Vorbeugung von Krebserkrankungen, das beun- ruhigende Anwachsen der Arzneimittelresistenz, die Mannigfaltigkeit der Dopamin-Rezeptor-Wirkung und die faszinierende Darstellung einer grosseren Gruppe von neuartigen Nukleosiden als Arzneimittel runden den vorliegenden Band der "Fortschritte der Arzneimittelforschung" ab und bieten dem Leser viel Neuartiges und Interessantes.

Erik Wischerhoff, Nezha Badi, Andre Laschewsky and Jean-Francois Lutz Smart Polymer Surfaces: Concepts and Applications in Biosciences; S. Petersen, M. Gattermayer and M. Biesalski Hold on at the Right Spot: Bioactive Surfaces for the Design of Live-Cell Micropatterns; Julien Polleux Interfacing Cell Surface Receptors to Hybrid Nanopatterned Surfaces: A Molecular Approach for Dissecting the Adhesion Machinery; Abigail Pulsipher and Muhammad N. Yousaf Self-Assembled Monolayers as Dynamic Model Substrates for Cell Biology; D. Volodkin, A. Skirtach and H. Moehwald LbL Films as Reservoirs for Bioactive Molecules; R. Gentsch and H. G. Boerner Designing Three-Dimensional Materials at the Interface to Biology; Joerg C. Tiller Antimicrobial Surfaces;

Trials in the treatment of the leukemias are sometimes based on a hypothesis, as in the case of exchange transfusion [33] or the use of antimetabolites [86]. Or they are conducted empirically as the results of chance observations, as in the case of the use of the nitrogen mustards, urethane, and the Vinca alkaloids. Or they lie between the two, aiming at making use of well established biological facts: examples are the use of ACTH, cortisone and, more recently, the antibiotics. What is true for bacteria may also perhaps be true, if not for elephants, at least for the malignant cells of mammals. It was this idea that lay behind the first attempts at treating cancer and leukemia with antibiotics. The results obtained by the use of certain substances extracted from micro-organisms (actinomycin, azaserine, mito mycin, rufocromomycin), although encouraging at times, were inconsistent. The action of rubidomycin appears to cover a wider spectrum and to be more consistent and more effective. As in the case of Homer and Christopher Columbus, the honor of having given birth to rubidomycin is claimed by more than one country and town. In fact, the same product was discovered in the same year, though quite independently, by a group of French workers [184] who described it under the name of rubidomycin, and by a group of Italian workers [87] who studied it under the name of daunomycin.

Cardiac Drug Development Guide outlines, in detail, the therapeutics of cardiac medicine currently at the cutting edge of scientific research and development around the world. This volume integrates basic and clinical cardiac pharmacology by c- bining, for the first time, both classical and molecular aspects of therapeutic drug development. The chapters comprise a broad spectrum of therapeutic areas and hence involve a comprehensive discussion of molecular, biochemical, and electrophy- ological concepts based on years of in vitro as well as in vivo pharmacological st- ies. In addition, the latter part of the book includes comprehensive clinical cardiac chapters that describe important topics in molecular medicine. These chapters also discuss current clinical therapeutic trends in medicine and provide an evaluation of the efficacy of novel drugs in these areas. Cardiac Drug Development Guide has many distinctive and outstanding features that set it apart from other cardiac pharmacology books. This book introduces topics in an easily understandable format for researchers in many varying disciplines by integrating and thereby simplifying concepts not usually discussed across a broad range of cardiac disciplines and in a highly technical field. Each chapter not only introduces and describes the physiology, pharmacology, and pathophysiology of the disease, but also overviews the clinical implications of drug development, what stages these areas are currently in, and also reviews some of the methodologies involved in drug discovery and development. As a result, this book provides a comprehensive overview of the most advanced procedures in cardiac pharmacology today.

(1952), HoRNING (1956), DoNTENWILL und EDER (1959)]. Wir sahen dabei fast immer basophile Adenome mit z. T. hochgradiger Zellpolymorphie und typischen Crooke-Zellen rpit Vacuolen (Abb. 3a u. b). Die Adenome fiihrten hiiufig zu De- formierungen der Schiidelbasis. Bei diesen Adenomen konnten keine Veriinderun- gen an den endokrinen Driisen oder endokrin gesteuerten Organen nachgewiesen werden, die auf eine Mehrsekretion der vergr6Berten Hypophyse hindeuten. 1. Spezielle Hypophysenadenome Wahrend bei den bisher angefiihrten Adenomen oder Hyperplasien keine be- stimmte Differenzierung nach ihrer Sekretion bzw. Leistung vorgenommen werden konnte, wurden in den letzten Jahren besonders von FURTH (1955, 1957, 1958), FURTH und CLIFTON (1957), CLIFTON (1959) eine Reihe von verschiedenartigen Hypophysenadenomen beschrieben [Obersicht iiber diese Hypophysenade- nome, ihre Ursachen, ihre hormonelle Leistung bzw. Struktur zeigt ein Schema (Tab. 1) aus der Monographie von KwA HoNG GroG (1961)], die als mammatrope, adrenocorticotrope, thyreotrope, somatothyreotrope und amphophile Adenome bezeichnet wurden. Die Differenzierung dieser Adenome bezieht sich z. T. auf ihre spezifische Leistung, z. T. auf ihre typische Zellstruktur. RussFIELD, FRIEDLER Tabelle I. Schematische Einteilung der Hypophysentumoren bei Maus und Ratte Proliferierender Zelltyp anznnehmende Art der Experimentelle Bedingungen tatsiichlich Hormonbildung Hypophysenstimuliernng 1eoretisch erwartet beobachtet tsophiler {J-Z entgranulierter TSH (,thyro- Chirurgische Schilddriisen- Unterbrechung des basophiler trophin" usw. ) entfernung; ,Radiothy- W echselmechanismus {J-Z.

Phytochemicals from medicinal plants are receiving ever greater attention in the scientific literature, in medicine, and in the world economy in general. For example, the global value of plant-derived pharmaceuticals will reach $500 billion in the year 2000 in the OECD countries. In the developing countries, over-the-counter remedies and "ethical phytomedicines," which are standardized toxicologically and clinically defined crude drugs, are seen as a promising low cost alternatives in primary health care. The field also has benefited greatly in recent years from the interaction of the study of traditional ethnobotanical knowledge and the application of modem phytochemical analysis and biological activity studies to medicinal plants. The papers on this topic assembled in the present volume were presented at the annual meeting of the Phytochemical Society of North America, held in Mexico City, August 15-19, 1994. This meeting location was chosen at the time of entry of Mexico into the North American Free Trade Agreement as another way to celebrate the closer ties between Mexico, the United States, and Canada. The meeting site was the historic Calinda Geneve Hotel in Mexico City, a most appropriate site to host a group of phytochemists, since it was the address of Russel Marker. Marker lived at the hotel, and his famous papers on steroidal saponins from Dioscorea composita, which launched the birth control pill, bear the address of the hotel."

Pharmaceutical scientists in industry and academia will appreciate this single reference for its detailed experimental procedures for conducting biopharmaceutical studies. This well-illustrated guide allows them to establish, validate, and implement commonly used in situ and in vitro model systems. Chapters provide ready access to these methodologies for studies of the intestinal, buccal, nasal and respiratory, vaginal, ocular, and dermal epithelium as well as the endothelial and elimination barriers.

This volume attemptsto provide the formulation scientist with casehistories involving the use of therapeutic proteins and peptides that have been mar- keted or are under clinical testing. In previous volumes of this series,funda- mental theories and principles ofprotein characterization and stability were presented in depth by researchers in their fieldsofexpertise. The way from theory to practice isnot alwaysobvious and straightforward. There isa need for practical examples of how the principles and theories are put into use, specificallyin the development of a pharmaceutical product. It is our hope that this volume will fulfillsuch a need. Itisnot asimple task to choose a panel ofproteinsand peptides from the over 200 agents in human clinical trials. We have tried to collect a wide representation of molecules of different sizes-from 10 amino acids (Leu- prolide) to 1020 amino acids (Muromonab CD3). The examples include agents derived from various sources including monoclonal antibodies (Mur- omonab CD3), recombinant DNA (human and bovine growth hormones), natural source (fibrolase), and chemical synthesis (Leuprolide). Clearly this list is not intended to be encyclopedic. It isthe first time a collection of this sort has been made accessibleto the formulation scientists involved in devel- oping protein and peptide products. Although each chapter in this volume focuses primarily on the charac- terization and stability of a specific molecule, each has unique aspects.

Proteins are still gaining importance in the pharmaceutical world, where they are used to improve our arsenal of therapeutic drugs and vaccines and as diagnostic tools. Proteins are different from "traditional" low-molecular-weight drugs. As a group, they exhibit a number of biopharmaceutical and formulation problems. These problems have drawn considerable interest from both industrial and aca demic environments, forcing pharmaceutical scientists to explore a domain previ ously examined only by peptide and protein chemists. Biopharmaceutical aspects of proteins, e.g., low oral bioavailability, have been extensively investigated. Although all possible conventional routes of ad ministration have been examined for proteins, no real, generally applicable alter native to parenteral administration in order to achieve systemic effects has yet been discovered. Several of these biopharmaceutical options have been discussed in Volume 4 of this series, Biological Barriers to Protein Delivery. Proteins are composed of many amino acids, several of which are notorious for their chemical instability. Rational design of formulations that optimize the native structure and/or bioactivity of a protein is therefore of great importance when long shelf life is required, as it is for pharmaceutical products. This issue has also been examined in two prior volumes of this series: Volume 2: Stability of Protein Pharmaceuticals (Part A) and Volume 5: Stability and Characterization of Protein and Peptide Drugs.

Proceedings of a conference sponsored by the American Association of Pharmaceutical Scientists, the U.S. Food and Drug Administration, and the American Society for Clinical Pharmacology and Therapeutics, held in Arlington, Virginia, April 24-26, 1991

''A wealth of information...these two volumes will be immensely valuable to anyone having to deal with this difficult group of compounds.'' ---Biochemical Systematics and Ecology, from a review of Saponins Used in Traditional and Modern Medicine and Saponins Used in Food and Agriculture

Eine grosse Anzahl heterocyclischer Naturstoffe leitet sich vom Ring- system des Piperidins (1) ab. Als Substituenten einfach oder mehrfach substituierter Piperidinbasen finden sich Methyl-, Carboxyl-, Hydroxyl- und Aminogruppen sowie aliphatische Seitenketten unterschiedlicher Lange. Die Substitution erfolgt bevorzugt an den C-Atomen 2, 3 und 6 sowie am Heteroatom. In zahlreichen Fallen ist der Piperidinring in a- oder ss-Stellung direkt oder uber eine C-Brucke mit einem weiteren Heterocyclus verbunden, z. B. einem Piperidin-, Piperidein-, Pyridin-, Indol-, Chinolizidin- oder Furanrest. Daruber hinaus kann der Piperidin- ring zum 2,6-Dioxopiperidin (Glutarimid) oxydiert oder zum Pipendein dehydriert sein. Wahrend Naturstoffe mit Pyridinstruktur im Tier- und Pflanzenreich weit verbreitet sind und einzelnen von ihnen wie NAD oder Pyridoxal- phosphat als Coenzymen des Primarstoffwechsels besondere Bedeutung zukommt, handelt es sich bei den naturlichen Piperidinverbindungen im allgemeinen um sekundare Pflanzenstoffe (vgl. I8, I9I). Dabei sind einige wie z. B. die Pipecolinsaure (7) sporadisch auf verschiedene Pflanzen- familien verteilt. Andere Piperidinbasen wie die Conium- oder Piper- Alkaloide weisen dagegen eine ausgesprochene Artspezifitat auf. Im Gegensatz zu den meisten Pyridinalkaloiden finden sich die Piperidin- basen oft mit strukturell andersartig gebauten Alkaloiden vom Chino- lizidin- oder Trepantyp vergesellschaftet, was in den meisten Fallen durch eine enge biogenetische Verwandtschaft bedingt sein durfte.

This volume comprises the edited proceedings of the International Taurine Sympo sium held in Osaka, Japan, in June 1995, as a Satellite Symposium of the 15th Biennial of the International Society for Neurochemistry. This Taurine Symposium was the Meeting latest in a series held since 1975 at approximately two-year intervals by an informal group of international researchers. It attracted contributions from 20 countries, ranging from Armenia via Finland and Spain to the United States. Some 121 participants attended. The Symposium was organized and chaired by Junichi Azuma, University of Osaka. Other members of the Organizing Committee in Japan consisted of Kinya Kuriyama and Masao Nakagawa, both from the Kyoto Prefectural University of Medicine, and Akemichi Baba, from Osaka University. The Committee had to contend with the disaster of the Kobe earthquake, which struck on January 21. The epicenter was only around 25 miles from the meeting site, and the quake demolished the home of one Committee member. Despite this unnaturally natural handicap, the participants experienced a superbly organized meeting, one which more than maintained the high social and scientific standards established for this series. In his Welcome Message, Dr. Azuma listed a threefold objective for the Symposium: To provide a forum for the interdisciplinary exchange of information on taurine; to give an opportunity for renewing old friendships and making new friends; and to promote coopera tion among participants from around the world."

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.

Drug products are complex mixtures of drugs and excipients and, as such, their chemical and physical stability kinetics are complex. This book discusses the stability of these dosage forms with preformulation studies through to the studies on the final products. The book is intended for graduate students, researchers and professionals in the field of Pharmaceutics and Pharmaceutical Chemistry.

Proceedings of the International Conference on Dipeptidyl Aminopeptidases, held September 26-28, 2002, in Berlin, Germany. Dipeptidyl Aminopeptidases exert a potent modulatory role at an interface between immune mechanisms, metabolic responses and neuroendocrine pathways. Experimental models and clinical studies addressing the role of these enzymes and the effect of specific inhibitors pave the way to novel therapeutic concepts in immunology, rheumatology, oncology, reproductive medicine and diabetes. Leading experts in this field have contributed to this book which presents a state-of-the-art view on these enzymes, at a time when our understanding of their function is growing ever more rapidly and therapeutic options become imminent. The sections of the book focus on various topics: - Structure and function of dipeptidyl aminopeptidases, - DPP IV-like proteins, - Immune mechanisms and immune disorders, - Cancer and angiogenesis, - Diabetes and metabolism, - Therapeutic implications.