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.

The aim of this book is to return to the biomimicry and medicinal potential that inspired many of the early supramolecular chemists and to set it in the context of current advances in the field. Following an overview of supramolecular chemistry, the first section considers the efforts made to synthesize artificial systems that mimic biological entities. The second section addresses the application of supramolecular principles to molecular diagnostics with a particular emphasis on the 'receptor-relayreporter' motif. Many of the examples chosen have clinical importance. The third section takes the clinical diagnostic theme further and demonstrates the therapeutic applications of supramolecular chemistry through photodynamic therapy, drug delivery, and the potential for synthetic peptides to form antibiotic tubes. The short epilogue considers the potential for supramolecular solutions to be found for further challenges in biomimetic and therapeutic chemistry.

This book updates clinicians on the most recent data regarding the medical management of patients of acute coronary syndrome (ACS), providing useful information and expert opinion on the large trials, international guidelines, and clinical practice. It reinforces the need for rapid intervention with pharmacologic therapies to treat and prevent coronary thromboembolism, and to prepare the patient for revascularization procedures, especially percutaneous coronary intervention. Pharmacological Treatment of Acute Coronary Syndromes describes conventional treatment - including anti-ischemic, antiplatelet and anticoagulant therapy - and discusses the clinical use of newer treatment options: the potent new P2Y12 platelet receptor inhibitors with the recently recommended ticagrelor and prasugrel, and new oral anticoagulant agents showing promise for acute management and secondary prevention in ACS. Triple therapy, while not initiated in the acute setting, may impact on future surgical and medical emergencies and their management. Also covered are the various recommendations for each of the antiplatelet and anticoagulant agents in terms of patient selection, pretreatment and timing of therapy, making this book an essential read for a wide range of health professionals.

Sex matters! Are there differences between the sexes when it comes to brain function and the behaviours that result? This volume attempts to answer this fundamental question. If the answer is 'yes' then this should impact upon our approach to treating mental illness in humans, and to modelling it in animals, as we look for aetiological and pharmacological solutions.

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."

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).

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".

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."

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."

(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.