The Sixth International Conference on Miniaturized Chemical and Biochemical Analysis Systems, known as /JTAS2002, will be fully dedicated to the latest scientific and technological developments in the field of miniaturized devices and systems for realizing not only chemical and biochemical analysis but also synthesis. The first /JTAS meeting was held in Enschede in 1994 with approximately 160 participants, bringing together the scientists with background in analytical and biochemistry with those with Micro Electro Mechanical Systems (MEMS) in one workshop. We are grateful to Piet Bergveld and Albert van den Berg of MESA Research Institute of the University of Twente for their great efforts to arrange this exciting first meeting. The policy of the meeting was succeeded by late Prof. Dr. Michael Widmer in the second meeting, /JTAS'96 held in Basel with 275 participants. The first two meetings were held as informal workshops. From the third workshop, /JTAS'98 (420 participants) held in Banff, the workshop had become a worldwide conference. Participants continued to increase in /JTAS2000 (about 500 participants) held in Enschede and /JTAS2001 (about 700 participants) held in Monterey. The number of submitted papers also dramatically increased in this period from 130 in 1998, 230 in 2000 to nearly 400 in 2001. From 2001, /JTAS became an annual symposium. The steering committee meeting held in Monterey, confrrmed the policy of former /JTAS that quality rather than quantity would be the key-point and that the parallel-session format throughout the 3.

Pharmacy Practice discusses the many factors impinging on daily practice and the place of pharmacy in the delivery of health care. The book goes beyond simply considering how pharmacy is practised and draws on a diverse range of disciplines, including sociology, social policy, psychology, anthropology, history and health economics, with each contributor bringing a unique perspective and insight into that practice. In this fully updated edition, the content and presentation have been thoroughly revised and new material added to reflect the many changes that have occurred in the last edition, particularly in pharmacy and health policy and professional regulation and development. The book provides the background and context for issues currently impacting professional practice and which will determine how pharmacy will develop in the future.

1. 1. General 1. 1. 1. Biaryls-Structural and Biosynthetic Variety The biaryl axis is the joint central structural element of a broad variety of structurally (in particular stereochemically) and biosynthetically inter- esting as well as pharmacologically promising natural products. The increasing importance of this challenging class of secondary metabolites, its widespread occurrence, its pharmacological implications, and, in particular, the phenomenon of axial chirality, have so far been largely underestimated, if not neglected. This is reflected by the fact that there is as yet no true comprehensive review on naturally occurring biaryls in the literature. By this article, we do not intend to provide such a fully comprehensive review, but still want to draw the attention of the scientific community on the manifold rewarding facets of this exciting class of natural products, which is rapidly growing now, with more and more sophisticated analytical and synthetic tools becoming available. Natural biaryls occur far more frequently than initially assumed, among them constitutionally symmetric, simple dimeric monoterpenoid biphenyls like I (I) (see Fig. 1), binaphthalenes like (-)-gossypol (2) (2), bianthraquinones like skyrin (3) (3-7), and biaryls with annelated heterocyclic rings like bismurrayafoline-B (4) (8) and desertorin A (Sa) (9, 10), which is-although built up from a single monomeric precursor -constitutionally unsymmetric.

Volume 23 includes six contributions as well as the Index for volumes 16-23. The key-word Index, like those of volumes II and IS, provides the reader with a simple cross-reference to all fields of possible interest, making this series of monographs even more useful as an encyclopaedic reference work. The scientific articles treat various topical areas of drug research, reviewing developments and indicating unsolved problems. The editor hopes to have provided the reader with a useful orientation and reference work. Experience over the last few years has shown that a more rapid publica- tion of the individual volumes better meets the wishes of readers by keeping pace with the speed of modem research. The present volume, as well as its predecessor, has broken the tradition of 500-600-page volumes in the hope of better satisfying the needs of the readers of this series. Finally, thanks are due to all those who have provided helpful criticism of past volumes, thereby providing valuable advice regarding the form of future volumes, and to Dr. A. Niif for his careful revision of the manu- scripts and correction of the proofs. Thanks are also due to the publish- ers and printers Birkhiiuser, in particular Messrs. Th. Birkhiiuser and C. Einsele. July 1979 Dr. E. Jucker Sandoz Ltd., Basel Vorwort Der 23. Band umfasst sechs Beitrage nebst dem Index der Bande 16-23.

In 1998, we published the data compilation PROTEIN STABILITY AND FOLDING which covered the data from the early beginnings of thermodynamic studies of protein folding until 1996. Since then, the amount of available thermodynamic data has increased nearly twice. The data constitute very important additions to the information on the protein folding problem, the construction of mutant protein, and the practical application of proteins in various fields. The Supplement covers the period 1997-1999 and is designed to make the vast amount of present data accessible to multidisciplinary research where chemistry, physics, biology, and medicine are involved and also biotechnology, pharmaceutical and food research. At the same time the data could be helpful to identify problems unsolved so far, and to avoid unnecessary duplication of scientific work. The structure of the Supplement is the same as in the previous data compilation. However, some additional data characterizing protein-denaturant interaction and protein unfolding by trifluoroethanol have been added. In that context, some previous data have been reconsidered. The author wishes to thank everyone who provided data, ideas, or even unpublished results. Furthermore, support by the Deutsche Forschungsgemeinschaft (INK 16 BI-I) is gratefully acknowledged. Finally, I would like to thank the staff of Springer Verlag for their efforts and for excellent assistance during the production of the data collections.

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."

Today's drug research is an extremely complex process which, apart from chemistry, pharmacology, toxicology and preclinical trials, in cludes a variety of sciences such as biotechnology, biochemistry, im munology, physics, biology and even computer sciences. The Table of Contents of the present volume demonstrates this situation and makes it evident that the individual researcher cannot possibly hope to keep abreast of all aspects of modern drug research. In this re spect, the series of monographs "Progress in Drug Research" pro vides valuable help and assistance. Those who simply wish to remain informed of the latest trends and developments in drug research can use the 34 volumes so far available as a source of almost encyclo pedic character. 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 they will be assisted in their endeavour to discover new pharmaceutical agents. Moreover, the extensive bibliographies of the individual reviews provide an invaluable overview of the literature most pertinent to today's drug research. I should like to thank all the authors for their willingness to prepare the reviews and for sharing their insights and experience with the readers. Thanks are also due to Mrs L. Koechlin, H.-P. Thiir and A. Gomm of Birkhauser Publishers for their valuable help in the pre paration of this volume."

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).

Shunsuke Hirotsu "Coexistence of Phases and the Nature of First-Order Transition in Poly-N-isopropylacrylamide Gels," Masayuki Tokita "Friction between Polymer Networks of Gels and Solvent," Masahiro Irie "Stimuli-Responsive Poly(N-isopropyl- acrylamide), Photo- and Chemicals-Induced Phases Transitions Edward Cussler, Karen Wang, John Burban"Hydrogels as Separation Agents," Stevin Gehrke "Synthesis, Equilibrium Swelling, Kinetics Permeability and Applications of Environmentally Responsive Gels," Pedro Verdugo "Polymer Gel Phase Transition in Condensation- Decondensation of Secretory Products," Etsuo Kokufuta "Novel Applications for Stimulus-Sensitive Polymer Gels in the Preparation of Functional Immobilized Biocatalysts," Teruo Okano "Molecular Design of Temperature-Responsive Polymers as Intelligent Materials," Atsushi Suzuki "Phase Transition in Gels of Sub-Millimeter Size Induced by Interaction with Stimuli," Makoto Suzuki, O. Hirasa "An Approach to Artificial Muscle by Polymer Gels due to Micro-Phase Separation."

Finally - a book that covers all aspects of the illicit use of cocaine, amphetamines, ecstasy and/or designer drugs such as GHB, written by two experts in their field. The use of these drugs remains a continuous threat in health and medical care delivery, and this book will be an essential asset to the physician who may have to face the evaluation of patients whose use of these drugs compromises an effective treatment plan for other health issues. The book has been conceived to fill the void in existing physician reference materials, and provides a comprehensive review of the theoretical knowledge and scope of pharmacotherapy in individuals who are hooked on a psychoactive substance. While detailed scientific information is obtainable in other major articles, the book's straightforward format and style, along with its illustrations, will make for easy reading as emphasis is put on information specifically related to drugs that occur most abused in today's society. The information provided is based on clinical practice rather than pure experimental data, which will give the physician more effective tools useful in their daily practice. Many mechanisms of action of abuse are described in detail and references are provided to direct the reader to further sources for additional information. As a special feature, the book incorporates uncluttered tables and charts, which result in immediate clarification of the mode of action on the central nervous system and the reason for misuse, thus avoiding usual long and fatiguing text in common reference books. The book aims to give the reader a clear and concise plan on what to do when being faced with an overdose situation. A well-organized Table of Contents rapidly leads the reader from general pharmacological issues to the specific overdose syndrome and its management. Additionally, significant emphasis is placed on the practical do's and don'ts for physicians, with special reference to the predictive signs of aberrant drug-related behavior and the identification of the drug diverter by using urine drug screening.

Established as a classic text on nuclear chemistry and pharmacy, Fundamentals of Nuclear Pharmacy has been thoroughly revised with new information added covering innovations in imaging technology and clinical applications in the field. The Sixth Edition also eliminates outdated information from previous editions on radiopharmaceuticals now discontinued from the market. Dr. Gopal B. Saha's books have continually been praised for their clarity and accuracy while setting new standards for making complex theoretical concepts readily understandable to the reader. Like past editions, this book is intended to be used as a textbook on nuclear chemistry and pharmacy for nuclear medicine residents and students and as a reference book for nuclear medicine physicians and radiologists. New sections in the Sixth Edition include: * PET/CT and SPECT/CT * Digital Imaging * Exploratory IND * Nanoparticle Imaging * Treatment of liver cancer with 90Y-TheraSpheres and 90Y-SIR-Spheres * Treatment of Non-Hodgkin's lymphoma with 131I-Bexxar

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.

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.

The specific topic, Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants New Perspectives In ParkinsonS Disease Therapy, was chosen in light of accumulating neurobiological evidence indicating that, in addition to exogenous neurotoxins (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP]), endogenous compounds may play an important role in the most common neurodegenerative disorders (e.g., Parkinsons disease). Two groups of amine related compounds, which appeared chemically like MPTP, were detected in human brain and cerebrospinal fluid (CSF): "ss"-carbolines (BCs) and tetrahydroisoquinolines (TIQs). These are heterocyclic compounds formed endogenously from phenylalanine/tyrosine (TIQs) and tryptophan, tryptamine, and 5-hydroxytryptamine (BCs), respectively and exert a wide spectrum of psychopharmacological and behavioral effects. The TIQs and BCs may bind to their own high affinity sites on neuronal membranes associated with or located close to the receptors of neurotransmitters. Research on TIQs and BCs is stimulated also by their possible role in pathological conditions, especially parkinsonism and alcoholism. Recently, clinical interest has been spurred by their role as neuroprotective, and even neurorestorative, anticonvulsant and antiaddictive, substances.

In this book we are going to summarize, for the first time, the results from behavioral, neurochemical and molecular experiments, which demonstrate a wide spectrum of TIQs and BCs effects - from their rather mild neurotoxic actions to the important neuroprotective and antiaddictive properties.

Additionally, the recent results of experimental studies "in vivo" have allowed a much better understanding and simultaneous comparison of the neurochemical and molecular mechanisms underlying the neuroprotective and neurotoxic actions of endogenous TIQs and BCs and have pointed to the possibility of their therapeutic applications in neurodegenerative diseases such as Parkinson's disease."

Biologics have revolutionised the treatment of many severe conditions, delivering exceptional clinical results but also producing exceptionally high prices. As patents expire, copies and price competition are expected throughout the world. However, due to the intrinsic heterogeneity and molecular complexity of biologic medicinal products, their copies cannot simply be authorized under the "generic rule" valid for small chemical entities. In response, a dedicated regulation was issued in the European Union. It is based on the concept of "biological medicinal products similar to a biological reference product", or "biosimilars". This book analyses the context of biotechnological production and addresses the European legal framework for biosimilar market approval. It highlights post-market authorisation issues, such as Risk Management Plans and substitution of products, and outlines some other issues, such as cost management and international nomenclature. This book is primarily intended for hospital-based physicians and pharmacists. It will also be a valuable resource for all actors from all countries who want to better understand the emergence of these new medicinal products within the European context.

In the late 1980s, Peptide Societies were established in Europe, the United States, and Japan, and more recently, in the Asian and the Pacific Rim regions including Australia, China, and Korea. At the time of the establishment of the American, European and Japanese Peptide Societies, the International Liaison Organizing Committee representing these Peptide Societies, along with the Australian Peptide Society, began discussions for holding international confer ences which would supercede or be held in lieu of the numerous individual meetings, held by the peptide societies of each individual country or region. The representative of the Chinese Peptide Society participated in these discus sion in the International Liaison Organizing Committee at the meeting of the American Peptide Symposium in Nashville, in June 1997. After lengthy discus sions over several years, we agreed to organize and host the International Peptide Symposium in Japan. The First International Peptide Symposium (IPS'97) was held on November 30-December 5, 1997, in Kyoto, and was co sponsored by four Peptide Societies. The attendance at this Symposium was 550 participants, including representatives from 32 different countries. We were very pleased with this outcome and anticipate an even larger attendance for forthcoming Symposia in future years. The revolution and advances in science and technology during the past two decades has caused traditional peptide chemistry to expand to peptide science, spreading from physical science to biology, pharmacology, and medicine.

A comprehensive treatment of the characterisation techniques used in investigating inorganic and organic molecules that interact with biomolecules is presented to the reader in a clear fashion. The work consists of two parts: (i) synthetic aspects of metallointercalators along with targeting and improving transport and (ii) the various techniques that are used for probing their interactions, such as; DNA-NMR, PGSE-NMR, DNA ESI-MS, Linear and Circular Dichroism, Fluorescence Spectroscopy, Confocal Microscopy, Viscosity, TGA and dialysis, Microarrays, biological analysis. Chapters are devoted to the synthesis and the techniques used to study the interactions of inorganic complexes with biomolecules. Considerably detailed examples are used to help illustrate the application of these techniques. This book is a useful resource for an array of inorganic and organic advanced undergraduate and graduate courses and for researchers in drug discovery.