Myocardial ischemia and subsequent reperfusion of the ischemic myocardium represent complex phenomena encompassing numerous physiological processes. This book aims at enhancing our understanding of these processes and stresses recent important developments in this very active area of research. The concise, state-of-the-art reviews cover recent advances in many fields important to the area of myocardial ischemia and reperfusion including physiology, pathology, pharmacology, biochemistry and molecular biology with reference to clinical relevance and applicability of these findings. Major areas which are highlighted include vascular mechanisms resulting in myocardial ischemia, cellular events in the ischemic, postinfarcted and reperfused myocardium as well as new exciting developments in cardiac protection that involve both novel pharmacological approaches as well as endogenous cardioprotective mechanisms such as preconditioning. Aimed at both the basic and clinical cardiovascular investigator, the book comprehensively reviews the rapid progress made in recent years in understanding the etiology of myocardial ischemia and reperfusion. It will further serve as an authoritative reference for all those interested in learning about the important developments in the treatment of myocardial ischemic and reperfusion disorders.

Bioassay Methods in Natural Product Research and Drug Development contains the proceedings from the Phytochemical Society of Europe's very successful symposium on this topic, held August 24-27, 1997 in Uppsala, Sweden. In this volume, leading academic and industrial scientists discuss novel methods for assaying natural products to find new structure-activity relationships. Of key importance in this process is the availability and reliability of specific bioassay methods, but chapters also discuss chemical and biological diversity and how to dereplicate natural product extracts to increase efficiency in lead discovery. Anti-tumor, HIV-inhibitory, antiprotozoal, anti-infective and immunomodulatory natural products are discussed. Various industrial projects are presented for the first time. This volume bridges the gap between academic and industrial research and scientists, and should be required reading in drug companies and faculties of pharmacy, as well as serving scientists in pharmacognosy, pharmacology, phytochemistry, natural products and drug discovery.

This volume contains the proceedings of the Ninth International Symposium on Cyclodextrins, held in Santiago de Compostela, Spain, May 31 - June 3, 1998. The papers collected represent a summary of the last two years' achievements in the application of cyclodextrins in such diverse fields as pharmaceuticals, biotechnology, textiles, chromatography and environmental sciences. Highlights: Chiral selection of chemicals, nuclear waste management, cyclodextrins in nasal drug delivery, cyclodextrins in pulmonary drug delivery, cyclodextrins as pharmaceutical excipients, pharmacokinetics, stabilization of drugs by cyclodextrins, structural characterization of cyclodextrin complexes by nuclear magnetic resonance and molecular modeling, artificial receptors, large cyclodextrins, cyclodextrins as enzyme models, new cyclodextrin derivatives and potentials. Audience: This book will be of interest to researchers whose work involves biotechnology, pharmaceuticals, food and chemicals and chromatographic methods, as well as fundamental cyclodextrin research.

Hydroxybenzophenones are most useful synthetic intermediates in the chemical industry, for example in pharmaceuticals, dyes, fragrances, agrochemicals, explosives and plastics. In this handbook, the diverse methods of obtaining over 1900 hydroxybenzophenones are described, and their physico-chemical properties and spectroscopic data references are indicated. Hence, ketones are classified methodically. They are thus easily accessible from three tables; the molecular formula index, the chemical abstracts registry numbers, and the usual names index. This work will prove to be a valuable tool for laboratory work and research and development departments. It is set to become the reference on hydroxybenzophenones. This handbook is particularly intended for engineers in chemical synthesis and academic as well as industrial researchers from various branches of chemistry.

This volume contains the proceedings of the Eighth International Symposium on Cyclodextrins, held in Budapest, Hungary, March 31-April 2, 1996. The 147 papers collected here are milestones in the exponentially increasing cyclodextrin literature, and represent a summary of the last two years' achievement in this field, with applications in such diverse disciplines as pharmaceuticals, food, cosmetics, textiles, plastics, and chromatography. Some highlights: lipophilicity profiles of cyclodextrins by computer molecular graphics; recent toxicological studies on cyclodextrins; Buckminsterfullerene/cyclodextrin complexes; hydroxypropyl-beta-cyclodextrin; pharmacokinetics and toxicology; peracylated cyclodextrins as drug carriers; cyclodextrins in nasal drug delivery; textile fibre surface modification by a reactive cyclodextrin; cyclodextrin-containing fabric care products; drug targeting by cyclodextrin-dimers for photodynamic cancer therapy; cyclodextrins in ophthalmologic drugs; new cyclodextrin derivatives and their potentials. Audience: This book will be of interest to researchers whose work involves pharmaceuticals, food chemicals and flavours, food additives, chromatographic methods, and biotechnology, as well as fundamental cyclodextrin research.

Recombinant proteins and polypeptides continue to be the most important class of biotechnology-derived agents in today's pharmaceutical industry. Over the past few years, our fundamental understanding of how proteins degrade and how stabilizing agents work has made it possible to approach formulation of protein pharmaceuticals from a much more rational point of view. This book describes the current level of understanding of protein instability and the strategies for stabilizing proteins under a variety of stressful conditions.

Piper is an economically and ecologically important genus of plant that includes a fascinating array of species for studying natural history, natural products chemistry, community ecology, and evolutionary biology. The diversification of this taxon is unique and of great importance in understanding the evolution of plants. The diversity and ecological relevance of this genus makes it an obvious candidate for ecological and evolutionary studies, but surprisingly, most research on Piper spp. to-date has focused on the more economically important plants P. nigrum (black pepper), P. methysticum (kava), and P. betle (betel leaf). While this book does address the applied techniques of studying Piper, its focus is more on Piper in its natural setting. Piper: A Model Genus for Studies of Phytochemistry, Ecology, and Evolution synthesizes existing data and provides an outline for future investigations of the chemistry, ecology, and evolution of this taxon, while examining its key themes of Piper as a model genus for ecological and evolutionary studies, the important ecological roles of Piper species in lowland wet forests, and the evolution of distinctive Piper attributes. This volume has a place in the libraries of those studying or working in the fields of ecology, evolutionary biology, natural products chemistry, invasive species biology, pharmaceutics, and ethnobotany.

Comprising 26 chapters, this volume deals with the genetic transformation of medicinal plants. It describes methods to obtain plants resistant to insects, diseases, herbicides, and plants with an increased production of compounds of medicinal and pharmaceutical importance. The plant species included are "Ajuga reptans," "Anthemis nobilis," "Astragalus" spp., "Atropa" "belladonna," "Catharanthus roseus," "Datura" spp., "Duboisia" species, "Fagopyrum" spp., "Glycyrrhiza" "uralensis," "Lobelia" spp., "Papaver" "somniferum," "Panax" "ginseng," "Peganum" "harmala," "Perezia" spp., "Pimpinella" "anisum," "Phyllanthus" "niruri," "Salvia" "miltiorrhiza," "Scoparia dulcis," "Scutellaria" "baicalesis," "Serratula" "tinctoria," "Solanum aculeatissimum," "Solanum " "commersonii," "Swainsona galegifolia," tobacco, and "Vinca minor."
This book is of special interest to advanced students, teachers, and researchers in the field of pharmacy, plant tissue culture, phytochemistry, molecular biology, biomedical engineering, and plant biotechnology in general.

While advances in modem medicine largely parallel our understanding of morphology, discoveries in morphology are propelled by developments of new tools and means to visualize and measure tissue elements. The invention of dissecting, light, fluorescence and electron microscopes together with advances in labeling and staining techniques are among the stepping stones of morphological progress. Today, we are in an exciting new era when classical morphology is being combined with developments from other disciplines. The combination of morphology and immunology resulted in immunocytochemistry; morphology and molecular biology led to in situ hybridization and in situ PCR. Adding computer science to morphology gave birth to image analysis. Combining laser technology and the microsope evolved into confocal microscope. For more than a decade, modem morphology has continued to develop by merging with other disciplines at a rate that is still gathering momentum, providing exciting and dynamic new frontiers for other biological fields. "Modem Methods in Analytical Morphology," based largely on the "First International Workshop on Modem Methods in Analytical Histochemistry, "is an updated review of the current trends in the field. It covers an extensive array of new technical developments in major disciplines of modem morphology. The authors are not only leaders in their fields but also have extensive "hands on" experience with "bench work. " Their chapters are written in a comprehensive manner including discussion of both theoretical considerations and practical applications to give the readers a broad view of the topics covered.

Advancing with Biomedical Engineering Today, in most developed countries, modem hospitals have become centers of sophis ticated health care delivery using advanced technological methods. These have come from the emergence of a new interdisciplinary field and profession, commonly referred to as "Bio medical Engineering." Although what is included in the field of biomedical engineering is quite clear, there are some disagreements about its definition. In its most comprehensive meaning, biomedical engineering is the application of the principles and methods of engi neering and basic sciences to the understanding of the structure-function relationships in normal and pathological mammalian tissues, as well as the design and manufacture of prod ucts to maintain, restore, or improve tissue functions, thus assisting in the diagnosis and treat ment of patients. In this very broad definition, the field of biomedical engineering now includes: * System analysis (modeling, simulation, and control of the biological system) * Biomedical instrumentation (detection, measurement, and monitoring of physio logic signals) * Medical imaging (display of anatomic details or physiologic functions for diag nosis) * Biomaterials (development of materials used in prostheses or in medical devices) * Artificial organs (design and manufacture of devices for replacement or augmen tation of tissues or organs) * Rehabilitation (development oftherapeutic and rehabilitation procedures and de vices) * Diagnostics (development of expert systems for diagnosis of diseases) * Controlled drug delivery (development of systems for administration of drugs and other active agents in a controlled manner, preferably to the target area)

Nitric oxide is an endogenously produced gas with a wide range of biological effects and has been implicated in many physiological and pathophysiological processes. It is released by many cell types in various organs but is particularly important in the maintenance of normal lung function. Nitric oxide in exhaled breath has been identified as a marker for lung disease in some patients. Thus, it is appropriate to consider the lung separately for the role and functioning of nitric oxide. The authors identify key areas in the history, biochemistry, physiology, pathophysiology, immunology and clinical applications of nitric oxide in the lung. The contents of this book will be of particular importance to scientists and clinicians with an interest in lung disease. Moreover, the authors encompass state of the art opinions of and rational for the therapeutic potential of nitric oxide and its inhibitors.

State-of-the-Art Chirality Stereochemistry in general and chirality in particular have long been recog- nized as major structural factors influencing pharmacological activity and pharmacokinetic behavior. For more than a century, relevant information in these fields has been accumulating at an accelerating pace, leading to rationalizations, concepts and theories of increasing breadth and depth. Frequently, fundamental advances in stereochemical aspects of molecular pharmacology, drug disposition and pharmacochemistry have been translated into corresponding progress in clinical pharmacology and pharmacotherapy. There have been exceptions, however, since some extrapolations from the biochemical and in vitro situations to the in vivo human situation have proven premature. This notion resulted in the now appeased, but far from closed, debate regarding racemic versus enantiopure drugs, which saw some pro- ponents state that "in many cases, only one isomer contributes to the thera- peutic action while the other, the 'isomeric ballast', only contributes to the side effects and toxicity" (ARIENS 1986,1989,1992). Other authors, in contrast, have cautioned against hasty generalizations and advocated a more pragmatic, case- by-case and evidence-based view (CALDWELL 1995; DE CAMP 1989; SZELENYI et al. 1998; TESTA 1991; TESTA and TRAGER 1990; TESTA et al. 1993).

For centuries preparations containing resin from the root of Thapsia garganica L. (Fig. 1) have been used in Arabian and European medicine for treatment of pulmonary diseases, catarrh and as counterirritants for relief of rheumatic pains (1). The properties of the resin were described already by Theophrastos (372-287 B. C. ), Dioscorides (approximately A. D. 50), and Plinius (A. D. 24-79) (2). Radix Thapsiae and Resina Thapsiae have been included in several pharmacopoeias, the latest in the French pharmacopoeia from 1937. The two major active principles were about Fig. I. Thapsia garganica References, pp. 163-167 Sesquiterpenoids from Thapsia Species 131 Thapsigargin (1), Rl: Oct, R2= But Thapsigargicin (2), Rl= Hex, R2 = But Thapsitranstagin (3), Rl: iVai, R2= 2-MeBut Thapsivillosin A (4), Rl= Ang, R2= Sen Thapsivillosin B ( 5), Rl: Ang, R2= 2-MeBut Thapsivillosin C ( 6), Rl= Oct, R2= 2-MeBut Thapsivillosin D ( 7), Rl: 6-MeOct, R2= Sen Thapsivillosin E ( 8), Rl: 6-MeOct, R2= 2-MeBut Thapsivillosin G ( 9), Rl= 6-MeHcp, R2= 2-MeBut Thapsivillosin H ( 10), Rl or R2= Ang or Sen Thapsivillosin I ( 11), Rl= Ang, R2= But Thapsivillosin J ( 12), Rl: iVai, R2= But Thapsivillosin K ( 13), Rl: Sen, R2= 2-MeBut Chart 1. Hexaoxygenated thapsigargins found in Thapsia two decades ago found to be the sesquiterpene lactones thapsigargin (1) and thapsigargicin (2) (3).

This book is an update of Interferon, published in 1969 by Dr. Jan Vilcek. The field of interferon research has since expanded from its former narrow treatment of interferon strictly as an antiviral substance, such that The Interferon System now encompasses cellular modulations ranging from immune alterations to cell proliferative restrictions to antitumor activities. The steadily increasing number of these non-antiviral functions of interferons emphasizes the need for a comprehensive - and critical - review of the entire literature of interferon studies. The text, with its supporting bibliography, provides complete coverage of interferon research. A newcomer to the area should find here all the informa tion necessary to understand why interferon, which has been studied for more than twenty years and which originally stirred excitement over its clinical pros pects, is still inspiring speculation about this potential. For those already fa miliar with the seemingly perpetual clinical promise of interferon, this volume should serve as a valuable reference source, the largest bibliography on the subject ever to appear under one cover. Clearly, this book should be considered only as an introduction to the topic and as a reference source; most questions about the interferon system are still unanswered - even unasked. Hopefully this summation and critical evalua tion of work done to date will stimulate and facilitate further progress.

Founded in 1959 by its current Editor, the series has moved from its initial focus on medicinal chemistry to a much wider scope. Today it encompasses all fields concerned with the development of new therapeutic drugs and the elucidation of their mechanisms of action, reflecting the increasingly complex nature of modern drug research. Invited authors present their biological, chemical, biochemical, physiological, immunological, pharmaceutical, toxicological, pharmacological and clinical expertise in carefully written reviews and provide the newcomer and the specialist alike with an up-to-date comprehensive list of prime references. Each volume of Progress in Drug Research contains fully cross-referencing indices which link the books together, forming a virtually encyclopaedic work. The series thus serves as an important, time-saving source of information for researchers concerned with drug research and all those who need to keep abreast of the many recent developments in the quest for new and better medicines.

Oxireductases in the Enzymatic Synthesis of Water-Soluble Conducting Polymers, by E. Ochoteco and D. Mecerreyes
*

Transferases in Polymer Chemistry, by J. van der Vlist and K. Loos
*

Hydrolases Part I: Enzyme Mechanism, Selectivity and Control in the Synthesis of Well-Defined Polymers, by M.A.J. Veld and A.R.A. Palmans
*

Hydrolases in Polymer Chemistry: Chemoenzymatic Approaches to Polymeric Materials, by A. Heise and A.R.A. Palmans
*
Hydrolases in Polymer Chemistry: Part III: Synthesis and Limited Surface Hydrolysis of Polyesters and Other Polymers, by G.M. Guebitz
*

Exploiting Biocatalysis in the Synthesis of Supramolecular Polymers, by S. Roy and R. V. Ulijn

The discovery of mammalian nitric oxide (NO-) synthesis from I-ar- ginine has led to profound increases in our understanding of basic physiological and pathophysiological processes. This understanding has been achieved by major advances in several areas. Three major ni- tric oxide synthase (NOS) isoforms have been identified at the protein and gene level and their specific tissue localization has been linked to processes subject to regulation by NO-. The molecular basis for the di- verse effects of NO- on cell function has been shown to derive from its chemical reactivity with oxygen-containing species and both heme and non-heme iron-dependent enzymes. The potential regulation of heme- dependent enzymes such as cytochromes P450, guanylate cyclase, cy- clooxygenase, and mitochondrial cytochrome oxidase continues to emerge as a key area in NO- research. In addition, it has become clear that the expression of NOS isoforms and NO- release from cells is subject to regulation by sexual steroids and that, in tum, NO- has the potential to regulate steroid biosynthesis via inhibition of cytochromes P450 involved in steroidogenesis. These recent observations on interactions between the NO-/NOS and cytochrome P450/sexual steroid pathways have important implica- tions for understanding fundamental mechanisms involved in endocri- nological processes. They are also likely to lead to novel insights and novel therapeutic approaches for the management of pathophysiologi- cal conditions associated with alterations in sexual steroid hormones.

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

Protein folding remains one of the most exclusive problems of modern biochemistry. Structure analysis has given access to the wealth of the molecular architecture of pro teins. As architecture needs static calculations, protein structure is always related to thermodynamic factors that govern folding and stability of a particular folded protein over the non-organized polypeptide chain. During the past decades a huge amount of thermodynamic data related to protein folding and stability has been accumulated. The data are certainly of importance in dechiffring the protein folding problem. At the same time, the data can guide the con struction of modified and newly synthesized proteins with properties optimized for particular application. The intention of this book is a generation of a data collection which makes the vast amount of present data accessible for multidisciplinary research where chemistry, phy sics, biology, and medicine are involved and also pharmaceutical and food research and technology. It took several years to compile all the data and the author wishes to thank everyone who provided data, ideas or even unpublished results. The author is, in particular, indebted to Prof. Wadso (Lund, Sweden) and IUPAC's Steering Committee on Bio physical Chemistry. Furthermore, support by the Deutsche Forschungsgemeinschafi (INK 16 AI-I) is acknowledged."

Saponins are complex molecules made up of sugars linked to a triterpenoid or a steroid or a steroidal alkaloid. These natural products are attracting much attention in recent years because of the host of biological activities they exhibit. The diversity of structural features, the challenges of isolation because of their occurrence as complex mixtures, the pharmacological and biological activities still to be discovered, and the prospect of commercialization - these all are driving the study of saponins. Triterpenoid saponins are dominating constituents of this class and occur widely throughout the plant kingdom including some human foods e. g. beans, spinach, tomatoes, and potatoes, and animal feed e. g. alfalfa and clover. Saponins were initially a rather neglected. area of research primarily because of great difficulties in their isolation and characterization. With the advent of more sophisticated methods of isolation and structure elucidation through the last two decades, there has been increased interest in these natural products. Besides structure determination, research activities are now moving forward to clarify structure-activity relationships. Our previous reviews on triterpenoid saponins (l, 2) covered literature from 1979 to mid-1989. The literature on triterpenoid saponins up to 1988 has also been covered by two reviews by HILLER et at. (3, 4). This review incorporates newer trends in isolation and structure determination of triterpenoid saponins, new triterpenoid saponins isolated and biological properties of these products reported during the period late 1989-mid 1996. 2."

Phytochemists are aware that their focus of interest is receiving attention from a wider segment of society and from a greater diversity of disciplines within the scientific community than ever before. Nonetheless, they were bemused to learn three years ago that "until recently scientists didn't even know phytochemi cals existed" (Newsweek, April 24, 1994). Changing public perception of the positive contributions of phytochemicals to human well-being has foundations in scientific advances. With popular reports emphasizing the important implica tions of phytochemicals in the daily lives of people, there is a pressing need for those working in this area to explain their diverse scientific activities to the public. Chemicals from plant foods are linked through epidemiological and ex perimental studies with reduced incidence of chronic degenerative diseases. Phytomedicines, standardized according to particular constituents, are making increasing contributions to health care. Naturally occurring constituents of plants are recognized as fundamental to the appeal, quality, and marketability of food products. In light of such developments, perceptions by phytochemists of their own discipline and its applications are expanding. Until recently, food phyto chemistry largely implied food toxicants. Food plants were familiar, but seldom the source of novel economically important compounds. Increasingly sophisti cated methods of analysis, however, have opened new opportunities for under standing the nature and functions offood constituents, and for manipulating them to improve the quality, acceptability, and value of food products.

Micro-TAS '98 is the third of a series of symposia initiated by MBSA (University of Twente) in 1994, on the subject of miniaturizing, and integrating within a monolithic structure, the chemical, biochemical and biological procedures commonly used for analysis and synthesis. The primary tool used to develop micro-total analysis systems (mu- TAS) has been micro-photolithographic patterning and micromachining. These powerful tools of Micro System Technology (MST or MEMS) have been applied in highly imaginative ways to develop microchip chemical arrays, fully integrated pump and fluid manifolds, and electrokinetically driven micro-channel systems to be used for genetic analysis, clinical diagnostics and environmental monitoring, and to integrate reactions as diverse as the polymerase chain reaction (PCR) and the large volume, partial oxidation of ammonia. This text illustrates the rapid expansion of the field, the extensive industrial involvement, the increasing number of participating researchers, the expanding range of concepts and applications that utilize MST and microfluidic devices, and new MST-compatible plastic micro-machining to meet the needs of the life science community. This volume contains the proceedings of the Third International Symposium on Micro-Total Analysis Systems, mu-TAS '98, held on October 13-16 in Banff, Alberta, Canada. State-of-the-art invited and contributed papers presented by the world's leading mu- TAS research groups provide a highly informative picture of the growth since 1994 and of the promising future of this exciting and rapidly growing field.

The volumes of this classic series, now referred to simply as "Zechmeister" after its founder, L. Zechmeister, have appeared under the Springer Imprint ever since the series' inauguration in 1938. The volumes contain contributions on various topics related to the origin, distribution, chemistry, synthesis, biochemistry, function or use of various classes of naturally occurring substances ranging from small molecules to biopolymers. Each contribution is written by a recognized authority in his field and provides a comprehensive and up-to-date review of the topic in question. Addressed to biologists, technologists, and chemists alike, the series can be used by the expert as a source of information and literature citations and by the non-expert as a means of orientation in a rapidly developing discipline.