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.

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.

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."

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.

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.

Das Buch enthalt Kapitel uber: M. B. Bottorff, W. E. Evans, Memphis, TN, USA: "Uberwachung der Medikament-Konzentration"E. Truscheit, I. Hillebrand, B. Junge, L. Muller, W. Puls, D. D. Schmidt, Wuppertal, FRG: "Inhibitoren der mikrobiellen " "alpha-Glucosidase: Chemie, Biochemie und potentielle " "therapeutische Anwendungen"H. Will, Berlin-Buch, GDR: "Plasminogen-Aktivatoren: Molekuleigenschaften, biologische " "Zellfunktion und klinische Anwendung""

The cells of the immune system generate a large variety of binding sites which differ in their binding specificities and can therefore react specifically with a large variety of ligands. These binding sites are part of receptor molecules, enabling the system to react to the universe of antigens. The classical antigen receptor is the antibody molecule, and accord ingly the first session of this colloquium deals with a classical sub ject, namely antibody structure. Dramatic recent advances in this field make it possible to interrelate primary and three-dimensional struc ture both to each other and to function, i.e. the binding of antigen and possible reactions occurring in the antibody molecule upon antigen binding. The latter point is of particular interest since it may be relevant not only for effector functions of antibodies such as the binding of complement, but also for the triggering of a lymphocyte through its antibody receptor for antigen."

Combining two separate textbooks entitled Essentials of Human Physiology for Pharmacy and Essentials of Pathophysiology for Pharmacy into one cohesive volume, this new book seamlessly integrates material related to normal human physiology and pathophysiology into each chapter. Chapters include: Study objectives at the beginning of each chapter; Summary tables, flow charts, diagrams, and key definitions; Real life case studies to emphasize clinical application and stimulate student critical thinking; An emphasis on the rationale for drug therapy; Simple, straightforward language. Written by authors with extensive teaching experience in the areas, Essentials of Human Physiology and Pathophysiology for Pharmacy and Allied Health is a concise learning instrument that will guide students in pharmacy and allied health programs.

From beach encounters, aquaculture perils, and processed-food poisoning to snake bites and biological warfare, natural toxins seem never to be far from the public's sight. A better understanding of toxins in terms of their origin, structure, structure-function relation ships, mechanism of action, and detection and diagnosis is of utmost importance to human and animal food safety, nutrition, and health. In addition, it is now clear that many of the toxins can be used as scientific tools to explore the molecular mechanism of several biological processes, be it a mechanism involved in the function of membrane channels, exocytosis, or cytotoxicity. Several of the natural toxins have also been approved as therapeutic drugs, which has made them of interest to several pharmaceutical companies. For example, botulinum neurotoxins, which have been used in studies in the field of neurobiology, have also been used directly as therapeutic drugs against several neuromus cular diseases, such as strabismus and blepherospasm. Toxins in combination with modem biotechnological approaches are also being investigated for their potential use against certain deadly medical problems. For example, a combination of plant toxin ricin and antibodies is being developed for the treatment of tumors. The great potential of natural toxins has attracted scientists of varying backgrounds-pure chemists to cancer biologists-to the study of fundamental aspects of the actions of these toxins."

Bereits 3 Jahre nach dem ersten Adriamycin-symposium und 2 Jahre nach der Veroffentlichung der Referate jener Tagung erschien es angezeigt, Wissenschaftler aus aller Welt erneut zusammenzurufen, um tiber die inzwischen gewonnenen Erfahrungen mit Adriamycin zu berichten. Nachdem in einer ersten Phase die Wirkung dieses Chemotherapeutikums ftir die systemischen Krebserlaankungen erkannt und erforscht war, konnte in vielen kontrollierten Studien an bedeutenden, mit der Krebs- forschung befassten 1nstituten in aller Welt nachgewiesen werden, dass Adriamycin heute auch in der Bekampfung solider Tmnoren zu einem wich- tigen, in der Krebs-Therapie wirksamen Pharmakon gezahlt werden muss. Die Vortrage dieses Symposiums unterstreichen die wichtige Rolle die- ser ftir die moderne cytostatische Therapie bedeutsamen Substanz. Der Sinn dieser Tagung ist, auch ftir die Zukunft neue Anregungen ftir For- schung und internationa.le Zusammenarbei t beim Kampf gegen den Krebs zum Wohle des Patienten zu gewinnen. D. Schmahl Die Veroffentlichung der Referate des zweiten Adriamycin-Symposiums sollte moglichst rasch erfolgen und in kurzer Zeit dem interessier- ten und onkologisch tatigen Arzt zur Verftigung stehen. Deshalb haben wir uns entschlossen, auf ein Sachregister und ein ausftihrliches Li- teraturverzeichnis in diesem Buche zu verzichten, was dankenswerter- weise unter diesen Voraussetzungen vom Springer Verlag akzeptiert wurde. Allen Vortragenden und allen Beteiligten bei der Durchftihrung des Symposiums mochten wir an dieser Stelle unseren besonderen Dank sagen.

In the first years of the existence of this series of monographs, during the so-called "Golden Age" of drug research, the majority of the pa pers published were mainly concerned with the traditional domains of drug research, namely chemistry, pharmacology, toxicology and pre clinical investigations. The series' aim was to give coverage to impor tant areas of research, to introduce new active substances with thera peutic potential and to call attention to unsolved problems. This objective has not changed. The table of contents of the present volume makes evident, however, that the search for new medicines has become increasingly complex, and additional, new disciplines have entered the research arena. The series now includes reviews on bio chemical, biological, immunological, physiological and medicinal aspects of drug research. Researchers actively engaged in the various scientific fields forming the entity of drug research can benefit from the wealth of knowledge and experience of the respective authors, and will be assisted in their endeavour to discover new pharmaceutical agents. Those simply wanting to keep abreast of new developments in the complex, multi-discipline science can turn to the "Progress in Drug Research" volumes as an almost encyclopaedic source of information without having to consult the innumerable original publications. Volume 32 contains 12 reviews, a subject index, an index for the close to 400 articles published in the series so far, and an author and titles index for all 32 volumes."

In 1970 I gave up the chairmanship of the Department of Pharmacology at Stanford University Schoel of Medicine to devote full time to basic and clinical research on problems of drug addiction. In 1971 I developed the method of radioligand binding that led to the important characterization of opioid receptors in several laboratories. The extraordinary specificity of these receptors for morphine and related opiates suggested the likelihood that there were naturally occurring morphine-like molecules in the brain and other tissues. The systematic search for these molecules culminated in 1979 in the discovery, by my group, ofthe dynorphin peptides-one of the three families of opioid peptides, the first of which (the enkephalin family) had been discovered in Aberdeen, Scotland, in 1975. I also became involved in clinical research on the pharmacologic treatment of heroin addicts, for which I established the first large methadone mainte nance treatment program in California. My basic and clinical research experience convinced me that an institution encompassing laboratory research, studies on normal human volunteers, and treatment research, under a single roof, could expedite progress in understanding the drug addictions. That concept was transformed into reality by the founding, in 1974, of the Addiction Research Foundation of Palo Alto, California. The funds for construction of a laboratory were provided by a generous grant from the Drug Abuse Council (a consortium of several foundations), the president of which was Thomas L. Bryant."

MTDSC provides a step-change increase in the power of calorimetry to characterize virtually all polymer systems including curing systems, blends and semicrystalline polymers. It enables hidden transitions to be revealed, miscibility to be accurately assessed, and phases and interfaces in complex blends to be quantified. It also enables crystallinity in complex systems to be measured and provides new insights into melting behaviour. All of this is achieved by a simple modification of conventional DSC.

In 1992 a new calorimetric technique was introduced that superimposed a small modulation on top of the conventional linear temperature program typically used in differential scanning calorimetry. This was combined with a method of data analysis that enabled the sample s response to the linear component of the temperature program to be separated from its response to the periodic component. In this way, for the first time, a signal equivalent to that of conventional DSC was obtained simultaneously with a measure of the sample s heat capacity from the modulation. The new information this provided sparked a revolution in scanning calorimetry by enabling new insights to be gained into almost all aspects of polymer characteristics.

This book provides both a basic and advanced treatment of the theory of the technique followed by a detailed exposition of its application to reacting systems, blends and semicrystalline polymers by the leaders in all of these fields. It is an essential text for anybody interested in calorimetry or polymer characterization, especially if they have found that conventional DSC cannot help them with their problems.

1 R. Satchi-Fainaro, R. Duncan, C.M. Barnes: Polymer Therapeutics for Cancer: Current Status and Future Challenges.- 2 N. Nishiyama, K. Kataoka: Nanostructured Devices Based on Block Copolymer Assemblies for Drug Delivery: Designing Structures for Enhanced Drug Function.- 3 H. Maeda, K. Greish, J. Fang: The EPR Effect and Polymeric Drugs: A Paradigm Shift for Cancer Chemotherapy in the 21st Century.- 4 J.S. Ellis, S. Allen, Y.T. A. Chim, C.J. Roberts, S.J.B. Tendler, M.C. Davies: Molecular-Scale Studies on Biopolymers Using Atomic Force Microscopy.- 5 A.V. Kabanov, E.V. Batrakova, S. Sherman, V.Y. Alakhov: Polymer Genomics.-

"Drug Metabolism and Pharmacokinetics Quick Guide" covers a number of aspects of drug assessment at drug discovery and development stages, topics such as pharmacokinetics, absorption, metabolism, enzyme kinetics, drug transporters, drug interactions, drug-like properties, assays and in silico calculations. It covers key concepts, with useful tables on physiological parameters (eg. blood flow to organs in x-species, expression and localization of enzymes and transporters), chemical structure, nomenclature, and moieties leading to bioactivation (with examples). Overall it includes a number of key topics useful at the drug discovery stage, which would serve as a quick reference with several examples from the literature to illustrate the concept.

Protein and peptide therapeutics currently represent eight of the top 100 prescription pharmaceuticals in the U.S., and biotechnology products are projected to account for 15% of the total US. prescription drug market by 2003. Of the protein and peptide products now on the market, many are administered as daily injections, though several are deliveredby noninvasive routes. For example, desmopressin is delivered as a nasal spray, and deoxyribonuclease I is administered by inhalation. Although cyclosporin A is orally active, as yet there are no general means to confer oral bioava- ability to peptides and proteins. A major advance in delivery ofpeptides was achieved with the introduction of a monthly injectable, biodegradable microsphere formulation of LHRH. Despite the enormous success of biotechnology products to date, much effort continues to be focused on the development of more convenient and noninvasive routes of administration for those products that require f- quent and prolonged dosing. Here we present an overview of the te- nologies, both developed and emerging, which are applicable to protein delivery. In addition, chapters 11 through 13 detail case studies on physical methods for delivery ofinsulin and growth hormone

Cell Culture Methods for in vitro Toxicology introduces the reader to a range of techniques involved in the use of in vitro cell culture in toxicological studies. It deals with major cell types studied in the field of toxicology and will be useful for anyone wishing to start work with animal cell cultures or to refresh their knowledge relating to in vitro cell models. Fundamental chapters deal with the general biology of cytotoxicity and cell immortalisation these are key issues for in vitro systems addressing the 3Rs' principle. Up-to-date overviews deal with the use of cells from liver, brain and intestine. In addition, biochemical analysis of cell responses, biotransformation pathways in cells and recombinant approaches to the early detection of cell stress are also covered in detail. Prominent features of in vitro technologies also include regulation, biosafety and standardisation. Dedicated chapters deal with these issues in a practical way in order to lead the reader to the right source of information. This book provides an up-to-date, informative and practical review of cell culture methods for in vitro toxicology. It will be of equal benefit to students and experienced toxicologists with little experience of in vitro cell culture.

The use of various pharmaceutical carriers to enhance the in vivo efficiency of many drugs and drug administration protocols has been well established during the last decade in both pharmaceutical research and clinical setting. Surface modification of pharmaceutical nanocarriers, such as liposome, micelles, na- capsules, polymeric nanoparticles, solid lipid particles, and niosomes, is normally used to control their biological properties in a desirable fashion and to simulta- ously make them perform various therapeutically or diagnostically important functions. The most important results of such modification include an increased stability and half-life of drug carriers in the circulation, required biodistribution, passive or active targeting into the required pathological zone, responsiveness to local physiological stimuli, and ability to serve as contrast agents for various imaging modalities (gamma-scintigraphy, magnetic resonance imaging, computed tomography, ultra-sonography). Frequent surface modifiers (used separately or simultaneously) include soluble synthetic polymers (to achieve carrier longevity); specific ligands, such as antibodies, peptides, folate, transferrin, and sugar moieties (to achieve targeting effect); pH- or temperature-sensitive lipids or polymers (to impart stimuli sensitivity); chelating compounds, such as EDTA, DTPA, and deferoxamine (to add a heavy metal-based diagnostic/contrast moiety onto a drug carrier). Certainly, new or modified pharmaceutical carriers (nanocarriers) as well as their use for the delivery of various drugs and genes are still described in many publications.

In the literature, several terms are used synonymously to name the topic of this book: chem-, chemi-, or chemo-informatics. A widely recognized de- nition of this discipline is the one by Frank Brown from 1998 (1) who defined chemoinformatics as the combination of "all the information resources that a scientist needs to optimize the properties of a ligand to become a drug. " In Brown's definition, two aspects play a fundamentally important role: de- sion support by computational means and drug discovery, which distinguishes it from the term "chemical informatics" that was introduced at least ten years earlier and described as the application of information technology to ch- istry (not with a specific focus on drug discovery). In addition, there is of course "chemometrics," which is generally understood as the application of statistical methods to chemical data and the derivation of relevant statistical models and descriptors (2). The pharmaceutical focus of many developments and efforts in this area-and the current popularity of gene-to-drug or si- lar paradigms-is further reflected by the recent introduction of such terms as "discovery informatics" (3), which takes into account that gaining kno- edge from chemical data alone is not sufficient to be ultimately successful in drug discovery. Such insights are well in accord with other views that the boundaries between bio- and chemoinformatics are fluid and that these d- ciplines should be closely combined or merged to significantly impact b- technology or pharmaceutical research (4).

A collection of powerful new techniques for oligonucleotide synthesis and for the use of modified oligonucleotides in biotechnology. Among the protocol highlights are a novel two-step process that yields a high purity, less costly, DNA, the synthesis of phosphorothioates using new sulfur transfer agents, the synthesis of LNA, peptide conjugation methods to improve cellular delivery and cell-specific targeting, and triple helix formation. The applications include using molecular beacons to monitor the PCR amplification process, nuclease footprinting to study the sequence-selective binding of small molecules of DNA, nucleic acid libraries, and the use of small interference RNA (siRNA) as an inhibitor of gene expression.

A comprehensive collection of readily reproducible methods for studying receptors in silico, in vitro, and in vivo. These cutting-edge techniques cover mining from curated databases, identifying novel receptors by high throughput screening, molecular methods to identify mRNA encoding receptors, radioligand binding assays and their analysis, quantitative autoradiography, and imaging receptors by positron emission tomography (PET). Highlights include phenotypic characterization of receptors in knockout mice, imaging receptors using green fluorescent protein and fluorescent resonance energy transfer, and quantitative analysis of receptor mRNA by TaqMan PCR. These book equips the researcher with techniques for exploring the unprecedented number of new receptor systems now emerging and the so-called "orphan" receptors whose activating ligand has not been identified.