It was an extraordinary pleasure for me, as the secretary general, to organise, with my collaborators, this Second International Symposium on Antibiotic Resistance in the Castle of Smolenice in Czechoslovakia. We all appreciated many offers all participants must have spent to attend this Symposium and we were glad to do our best to prepare this meeting in a suitable and convenient way. We gathered in Smolenice Castle after the significant International Congress on Che motherapy in September 1973 in Athens. We had the chance of getting acquainted, on that world-wide forum, with the latest information about bacterial resistance to anti biotics. It was possible at that Congress to outline main topics of interest in the field of bacterial resistance to antibiotics which then have been placed on the programme of the subsequent Smolenice Symposium. Undoubtedly, enzymatic mechanisms by which bacteria can inactivate older and newer antibacterial drugs and which can be transmitted and spread among bacterial strains, have both medical as well as theoretical priority. Dealing specially with Pseudomonas aeruginosa is highly urgent at present from the clinical, hygienical and genetical point of view. We have realised that antibiotics have ceased to be "magic bullets" which hit the microorganisms without discrimination. Today we urgently consider the question what should be done in the area of "antibiotic policy" to preserve the effectiveness of antibiotics for the future.

Metallomics and the Cell provides in an authoritative and timely manner in 16 stimulating chapters, written by 37 internationally recognized experts from 9 nations, and supported by more than 3000 references, several tables, and 110 illustrations, mostly in color, a most up-to-date view of the "metallomes" which, as defined in the "omics" world, describe the entire set of biomolecules that interact with or are affected by each metal ion. The most relevant tools for visualizing metal ions in the cell and the most suitable bioinformatic tools for browsing genomes to identify metal-binding proteins are also presented. Thus, MILS-12 is of relevance for structural and systems biology, inorganic biological chemistry, genetics, medicine, diagnostics, as well as teaching, etc.

B. R. Buckley and H. Heaney: Mechanistic Investigations of Copper(I)- Catalyzed Alkyne-Azide Cycloaddition Reactions.- J. D. Crowley and D. A. McMorran: "Click-Triazole" Coordination Chemistry: Exploiting 1,4-Disubstituted-1,2,3-Triazoles as Ligands.- S. Lee and A. H. Flood: Binding Anions in Rigid and Reconfigurable Triazole Receptors.- M. Watkinson: Click Triazoles as Chemosensors.- H.-F. Chow, C.-M. Lo and Y. Chen: Triazole-Based Polymer Gels.- T. Zheng, S. H. Rouhanifard, A. S. Jalloh, P. Wu: Click Triazoles for Bioconjugation.- S. Mignani, Y. Zhou, T. Lecourt and L. Micouin: Recent Developments in the Synthesis 1,4,5-Trisubstituted Triazoles.

The biological activity of mycotoxins ranges from weak and/or sometimes positive effects, such as antibacterial activity (see penicillin derivatives derived from Penicillium strains) to strong mutagenic (e. g. aflatoxins, patulin), carcinogenic (e. g. aflatoxins), teratogenic, neurotoxic (e. g. ochratoxins), nephrotoxic (e. g. fumonisins, citrinin), hepatotoxic, and immunotoxic (e. g. ochratoxins, diketopiperazines) activity. Nowadays, many laboratories around the world are specialized in the detection of mycotoxins in food products and contaminated material found in housing. In this volume, a focus on the most important classes of mycotoxins is provided and their chemistry of the last ten years is discussed. In each Section, the individual biological impact is outlined. Sections are arranged according to mycotoxin classes (e. g. aflatoxins) and/or structural classes (e. g. resorcinyl lactones, diketopiperazines). The biology of mycotoxins is also described.

Enhancing Medication Adherence: The Public Health Dilemma is a comprehensive guide to medication adherence for the healthcare professional. Clinicians and pharmacists alike can benefit from key opinion leader and author Hayden Bosworth s text as he explains the details and causes behind medication nonadherence as well as methods on how healthcare providers can determine if a patient is nonadherent. Additionally, Bosworth discusses various studies, which assess adherence, adherence-related technology, best practices for clinicians and pharmacists, and future directions and recommendations in the field."

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.

Carl Edward Sagan's (1934-1996) one of the famous quotation was "Who are we? We find that we live on an insignificant planet of a humdrum star lost in a galaxy tucked away in some forgotten corner of a universe in which there are far more galaxies than people." From past to date, well-known molecules, enzymes, proteins, lipids and carbohydrates are studied in the pathogenesis of several diseases both as a diagnostic/prognostic biomarker and therapeutic agent. The underlying mechanism of unexplained diseases and failure of therapies are frequently studied with well-known biomarkers, but remain unclear in many cases. As Dr. Sagan said other keys are still waiting to be known in some forgotten corner of a body universe, we find strength to propose that one of them can be the growth factor with cytokine activity named "Midkine" This book summarizes the extensive up-to-date literature overeview with the lastest work of experts about midkine in a detailed format that conveys its role as both a pathologic factor and therapeutic agent.

Six decades after the serendipitous discovery of chlorpromazine as an antipsychotic and four decades after the launch of clozapine, the first atypical or second generation antipsychotic, psychopharmacology has arrived at an important crossroad. It is clear that pharmacological research and pharmaceutical development must now focus on complementary or even alternative mechanisms of action to address unmet medical needs, i.e. poorly treated domains of schizophrenia, improved acceptance by patients, better adherence to medication, safety in psychoses in demented patients, and avoiding cardiac and metabolic adverse effects. The first completely novel mechanisms evolving from our insights into the pathophysiology of psychotic disorders, especially the role of glutamatergic mechanisms in schizophrenia, are now under development, and further principles are on the horizon. This situation, in many respects similar to that when the initial second-generation antipsychotics became available, can be rewarding for all. Preclinical and clinical researchers now have the opportunity to confirm their hypotheses and the pharmaceutical industry may be able to develop really novel classes of therapeutics. When we were approached by the publishers of the Handbook of Experimental Pharmacology to prepare a new volume on antipsychotics, our intention was to capture both, the accumulated preclinical and clinical knowledge about current antipsychotics as well as prospects for new and potentially more specific antischizophrenia principles. These efforts should be based on the pathophysiology of the diseases and the affected neurotransmitter systems. Since preclinical research on antipsychotic compounds is only reliable when intimately linked through translational aspects to clinical results, we decided to include clinical science as well. It turned out that that this endeavor could not be covered by a single volume. We thank the editorial board and the publishers for supporting our decision to prepare two volumes: Current Antipsychotics and Novel Antischizophrenia Treatments. These topics cannot really be separated from one another and should be seen as a composite entity despite the somewhat arbitrary separation of contributions into two volumes. The continuing challenges of developing improved and safer antipsychotic medications remain of concern and are discussed in the first volume. The new opportunities for the field to develop and license adjunctive treatments for the negative symptoms and cognitive deficits that are treated inadequately by existing compounds have been incentivized recently and provide the focus for the second volume. We hope these collective contributions will facilitate the development of improved treatments for the full range of symptomatology seen in the group of schizophrenias and other major psychotic disorders. Gerhard Gross, Ludwigshafen, Germany Mark A. Geyer, La Jolla, CA This volume will try to put current therapy - achievements, shortcomings, remaining medical needs - and emerging new targets into the context of increasing knowledge regarding the genetic and neurodevelopmental contributions to the pathophysiology of schizophrenia. Some of the chapters will also deal with respective experimental and clinical methodology, biomarkers, and translational aspects of drug development. Non-schizophrenia indications will be covered to some extent, but not exhaustively.

Thin-layer chromatography (TLC) is widely used particularly for pharmaceutical and food analysis. While there are a number of books on the qualitative identification of chemical substances by TLC, the unique focus here is on quantitative analysis. The authors describe all steps of the analytical procedure, beginning with the basics and equipment for quantitative TLC followed by sample pretreatment and sample application, development and staining, scanning, and finally statistical and chemometric data evaluation and validation. An important feature is the coverage of effect-directed biological detection methods. Chapters are organized in a modular fashion facilitating the easy location of information about individual procedural steps.

Many of the reactions and compounds involved in metabolism are almost iden tical in the different groups of living organisms. They are known as primary me tabolic reactions and primary metabolic products. In addition, however, a wide variety of biochemical pathways are characteristic of only a few species of organ isms, of single "chemical races", or even of a certain stage of differentiation of specialized cells. Such pathways are collectively referred to as "secondary metab olism", and the compounds formed are called "secondary products". Secondary products are frequently revealed by their color, smell, or taste. They are responsi ble for the flavor of most foodstuffs and beverages and for the color and fragrance of flowers and fruits. Many of them are part of the materia medica, e. g. , alka loids, cardiac glycosides, antibiotics, or compounds acting as hormones. Others are used in the industry, e. g. , rubber, tannins, and cellulose. This book treats the organization and significance of biosynthesis, storage, transformation, and degradation of the most important groups of secondary pro ducts in microorgimisms, plants, arid animals. It shows that the formation of sec ondary products is a common characteristic of specialized cells brought about by the action of special enzymes encoded by specific genetic material.

G. Sandford: Perfluoroheteroaromatic Chemistry: Multifunctional Systems from Perfluorinated Heterocycles by Nucleophilic Aromatic Substitution Processes.- A. A. Gakh: Monofluorinated Heterocycles.- R. Dembinski Y. Li D. Gundapuneni A. Decker: Synthesis of beta-Halofurans.- Y. Shermolovich S. Pazenok: Synthesis of halogenated 5- and 6-membered sulfur- and Sulfur, Nitrogen Containing Heterocycles.- S. Minakata Y. Takeda J. Hayakawa: Heterocyclic Reagents Containing Nitrogen-Halogen Bond: Recent Applications.- Michael Schnurch: Recent Progress on the Halogen Dance Reaction on Heterocycles.- T. Kosjek E. Heath: Halogenated Heterocycles as Pharmaceuticals.- E. Heath T. Kosjek: Sources, Occurrence and Fate of Halogenated Heterocyclic Pharmaceuticals in the Environment.- J. Iskra: Green Methods in Halogenation of Heterocycles."

How do firms jointly develop open information infrastructures? To answer this question, this book draws on the results of a longitudinal research project covering the development of the pharmaceutical distribution industry in China from 2004 to 2012, focusing on the emergence and subsequent evolution of industry-wide information infrastructures. How do firms delimit areas of proprietary innovation in open innovation projects? How do firms coordinate, initiate, negotiate and implement the development of innovative infrastructures? How do processes and practices within firms enable and constrain such collective efforts? - This book provides answers to these questions and draws conclusions regarding the challenges and new capabilities that firms will need in a world in which participation in the building of open information infrastructures becomes a necessary task for commercial organizations.

This book approaches the subject from a mechanistic perspective that pitches the language at a level that is understandable to those entering the field and who are not familiar with its common phrases or complex terms. It provides a simple encapsulation of concepts and expands on them. In each chapter the basic concept is explained as simply and clearly as possible without a great deal of detail, then in subsequent sections additional material, exceptions to the general rule, examples, etc., is introduced and built up. Such material was generously supplemented with diagrams; conceptually elegant line diagrams in two or three colors. The artwork was well thought out and able to condense the scientific principles into a novel and visually exciting form. The diagrams encourage browsing or draw the reader to salient points. In addition, the technique of highlighting key concepts in a separate box is used throughout each chapter.

Salen Metal Complexes as Catalysts for the Synthesis of Polycarbonates from Cyclic Ethers and Carbon Dioxide, by Donald J. Darensbourg.- Material Properties of Poly(Propylene Carbonates), by Gerrit. A. Luinstra and Endres Borchardt.- Poly(3-Hydroxybutyrate) from Carbon Monoxide, by Robert Reichardt and Bernhard Rieger. - Ecoflex(r) and Ecovio(r): Biodegradable, Performance-Enabling Plastics, by K. O. Siegenthaler, A. Kunkel, G. Skupin and M. Yamamoto.- Biodegradability of Poly(Vinyl Acetate) and Related Polymers, by Manfred Amann and Oliver Minge.- Recent Developments in Ring-Opening Polymerization of Lactones, by P. Lecomte and C. Jerome.- Recent Developments in Metal-Catalyzed Ring-Opening Polymerization of Lactides and Glycolides: Preparation of Polylactides, Polyglycolide, and Poly(lactide-co-glycolide), by Saikat Dutta, Wen-Chou Hung, Bor-Hunn Huang and Chu-Chieh Lin.- Bionolle (Polybutylenesuccinate), by Yasushi Ichikawa, Tatsuya Mizukoshi.- Polyurethanes from Renewable Resources, by David A. Babb.-"

After more than twenty years of use Good Laboratory Practice, or GLP, has attained a secure place in the world of testing chemicals and other "test items" with regard to their safety for humans and the environment. Gone are the days when the GLP regulations were hotly debated amongst scientists in academia and industry and were accused of stifling flexibility in, imaginative approaches to, and science-based conduct of, all kinds of studies concerned with toxic effects and other parameters important for the evaluation and assessment of products submitted for registration and permission to market. The GLP regulations have developed from rules on how to exactly document the planning, conduct and reporting of toxicity studies to a quality system for the management of a multitude of study types, from the simple determination of a physical/chemical parameter to the most complex field studies or ecotoxicology studies. At the same time the term "Good Laboratory Practice" has become somewhat of a slogan with the aim to characterise any reliably conducted laboratory work.

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.

Intensive care is a rapidly changing area of medicine, and after four years from the 2nd edition the volume editors and authors have deemed necessary to update it. In the recent years, in fact, five new randomised controlled trials and five new meta-analyses demonstrate that selective decontamination of the digestive tract [SDD] is an antimicrobial prophylaxis to prevent severe infections of not only lower airways but also of blood. Additionally, SDD has been shown to reduce inflammation including multiple organ failure and mortality. An intriguing observation is the evidence that SDD using parenteral and enteral antimicrobials reduces rather than increases antimicrobial resistance. Moreover, a new chapter on microcirculation had been added. The volume will be an invaluable tool for all those requiring in depth knowledge in the ever expanding field of infection control.

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.

The inspiration for this text was the 1988 volume by Alder and Zbinden, written before the ICH harmonization process for drug safety evaluation (or its ISO analog for device biocompatibility evaluation) had been initiated or come to force. Since then, much has changed in both the world and practice of medicine and the regulation of drugs. The intent of this volume is to provide similar guidance as to what nonclinical safety assessment tests need to be performed to move a drug into man, through development and to market approved (this intent was subsequently extended to cover the closely related medical device biotechnology, and combination product fields) in a concise, abbreviated manner for all the major world market countries.

During its short 20 year history High Performance Liquid Chro matography (HPLC) has won itself a firm place amongst the instrumental methods of analysis. HPLC has caused a revolution in biological and pharmaceutical chemistry. Approximately two thirds of the publications on HPLC are concerned with problems from this area of life science. Biotechnology, where it is necessary to isolate substances from complicated mixtures, is likely to give further impetus to the dissemination of modern liquid chromatog raphy in columns, particularly on the preparative scale. This book presents, by means of examples, the application of HPLC to various fields, as well as fundamental discussions of chromatographic methods. The quality of the analytical result is decisively dependent on the qualities of the equipment employed (by Colin, Guiochon, and Martin). Especially the demands are discussed that are placed on the components of the instrument including those for data acquisition and processing. The section on "quantitative analy sis" (by ABhauer, Ullner) covers besides the principles also the problems of ensuring the quality of the data in detail. The basic problems arising by enlarging the sample size to preparative di mensions and the requirements put on the aparatus are discussed in the section on "preparative applications" (by Wehrli)."

In most natural sciences, modeling is a widespread method of gaining new knowledge about natural and technical systems. This book analyses the concepts of 'model' and 'modeling' in different fields of research. The different methods of modeling as well as the potentials and limits of this concept are reflected and discussed. The book presents a variety of modeling techniques, from mathematical models in climatology, meteorology or oceanography to methods used in morphology, decision-making in ecology and physical modeling in oceanography. In this broad overview regarding modeling, the book is unique.