Wir prtiften die Wirkung von Verapamil (V) auf die Reizleitungszeit innerhalb des akut ischamischen Myokards bei 10 Hunden (5 Kontrollgruppe, 5 behandelt mit V) nach Unterbindung des RIVA. Verapamil wurde in einer Dosis von 0,15 mg/kg in- travenos als Bolus, unmittelbar nach KoronarverschluB bei 5 Hunden verabreicht; anschlieBend wurde eine Dosis von 7,5 J. 1g/kg/Min infundiert. Die Unterbindung des RIV A erfolgte in zwei Stufen: in einer ersten Phase distal vom 2. R. diagonalis und in einer zweiten Stufe 30 Min spater distal vom 1. R. diagonalis. Endokardiale bipolare Elektrokardiogramme wurden mittels mehrerer Nadelelektroden vor sowie 5, 15 und 30 Min nach jeder Unterbindung aufgezeichnet. Die Untersuchung wurde bei konstanter Vorhofstimulation (200/Min) und vorzeitigen Stimuli mit einem Kopplungsintervall von 50070 durchgefiihrt. Die Reizleitungszeit (definiert als der Zeitintervall zwischen der vorzeitigen Schrittmacherstimulation und der ersten hochfrequenten Schwingung im endokardialen EKG) wurde im ischamischen sowie normalen Muskelareal beider Untersuchungsgruppen gemessen. Ergebnis: (1) Vor KoronarverschluB war die Reizleitungszeit innerhalb des normalen Myokardiums bei beiden Untersuchungsgruppen gleich. (2) Nach VerschluB des RIVA verzogerte sich die Reizleitungszeit signifikant innerhalb des ischamischen Areals bei der Kon- trollgruppe. (3) In der mit Verapamil behandelten Gruppe unterschied sich die Reiz- leitungszeit innerhalb des ischamischen Myokards nicht signifikant von Werten vor dem KoronarverschluB. Dies war signifikant unterschiedlich von Werten in der Ver- gleichsgruppe. Folgerung: Nach KoronarverschluB verhindert die intravenose Gabe von Verapa- mil die Verzogerung der Impulsfortleitung im ischamischen Areal.

Volume 27 of "Progress in Drug Research" contains 5 articles, a subject index for this volume, an alphabetic subject 4ldex for volumes 1-27, and an author and subject index for altthe volumes which have so far been published. The contributions of volume 27 are particularly concerned with fungal disease, with benzimidazole anthelmintics and with the chemistry and pharmacology of quinuclidines, azoles, and nitroimida- zoles. The authors have tried, not only to summarize the current status of particular fields of drug research, but also to provide leads for future research activity. The articles of this volume will be of special value to those actively engaged in drug research, and to those who wish to keep abrest of the latest developments influencing modem therapy. In addi- tion, it is believed that the 27 volumes of "Progress in Drug Research" now available represent a useful reference work of encyclopedic charac- ter. The editor would like to take the occasion of the publication of this volume to express his gratitude both to the authors and to the readers. The authors have willingly1undertaken'the great labor of writing signifi- cant topical contributions, hnd many readers have helped the editor with criticism and advise. With these thanks, the editor would like also to express his gratitude to the publisher, Birkhauser Verlag Basel, particu- larly to Messrs. Th. Birkhauser and C. Einsele, and their associates for the excellent cooperation.

Calorimetry is one of the oldest areas of physical chemistry. The date on which calorimetry came into being may be taken as 13 June 1783, the day on which Lavoisier and Laplace presented a contribution entitled, Memoire de la Chaleur" at a session of the Academie Francaise. Throughout the existence of calorimetry, many new methods have been developed and the measuring techniques have been improved. At p- sent, numerous laboratories worldwide continue to focus attention on the development and applications of calorimetry, and a number of com- nies specialize in the production of calorimeters. The calorimeter is an instrument that allows heat effects in it to be determined by directly measurement of temperature. Accordingly, to determine a heat effect, it is necessary to establish the relationship - tween the heat effect generated and the quantity measured in the ca- rimeter. It is this relationship that unambiguously determines the mathematical model of the calorimeter. Depending on the type of ca- rimeter applied, the accuracy required, and the conditions of heat and mass transfer that prevail in the device, the relationship between the measured and generated quantities can assume different mathematical forms."

This book provides a unique and up-to-date insight into the biopharmaceutical industry. Largely written by industrial authors, its scope is multidisciplinary, rendering it an ideal reference source for students undertaking advanced undergraduate or postgraduate courses in biotechnology, pharmaceutical science, biochemistry, or medicine.

This advanced text-cum-reference book presents a comprehensive account of the syntheses, reactions, properties and applications of all the most significant classes of heterocyclic compounds. This second volume in the series is an essential tool not only for advanced undergraduates and graduates, but also for academic and industrial researchers in organic, medicinal, pharmaceutical, dye and agricultural chemistry.

Nearly three thousand papers and patents are dedicated to the actual or potential uses of cyclodextrins in pharmacy and pharmaceutical formulations. This is the first book written for pharmacists and pharmaceutical technologists which not only critically summarizes the enormous amount of literature available, but which can be used as a handbook when looking for solutions to practical problems. The fundamentals -- chemistry of cyclodextrins and their derivatives -- their physical and chemical properties are condensed to the most relevant items in Chapters 1 and 2. Chapter 3 deals with the adsorption, metabolism and toxicological properties of cyclodextrins. Chapter 4 explains the formulation, structure, composition and advantageous effects of the cyclodextrin inclusion complexes. Chapter 5 describes the methods for preparation and characterization of drug/cyclodextrin complexes. Chapters 6 and 7 are dedicated to the pharmacokinetics, biopharmaceutical and technological aspects of drug/CD complexes. Chapter 8 treats the application and effects of cyclodextrins in various drug formulations. The Appendix comprises a collection of recipes for any type of drug formulation. This book is aimed at those who use cyclodextrins in drug formulations, to improve the properties of existing drug formulations, or who want to prepare quite new formulations.

A collection of readily reproducible bioinformatic methods to advance the drug discovery process from gene identification to protein modeling to the identification of specific drug candidates. The authors demonstrate these techniques, including microarray analysis, the analysis of genes as potential drug targets, virtual screening and in silico protein design, and cheminformatics, in a variety of practical situations. Because these technologies are still emergent, each chapter contains an extended introduction that explains the theory and application of the technology and techniques described.

The present book entitled "Novel Frontiers in the Production of Compounds for Biomedical Uses" can perhaps be placed in its best perspective by the Shakespearean character in The Tempest who exclaimed" What's past is prologue". Indeed, this compilation of some of the outstanding presentations in the field of biomedicine made at th the 9 European Congress on Biotechnology (Brussels, Belgium, July 11-15, 1999) not only reflects the achievements of the recent past, but provides a privileged glimpse of the biotechnology that is emerging in the first decade of the new Millennium. It is becoming increasingly apparent that biotechnology is offering biomedicine novel approaches and solutions to develop a sorely needed new generation of biopharmaceuticals. This is all the more necessary because in recent years, new diseases have emerged with extraordinary lethality in all corners of the globe, while age-related chronic illnesses have filled the gap wherever biomedicine has made successful inroads. The rise of antibiotic resistance also poses major threats to public health. Thus, as disease patterns evolve, the rational development of new drugs is becoming urgent, not only for the clinical outcome of patients, but also in optimising the allocation of scarce health care resources through the use of cost-effective productions methods. It is in response to all these challenges that biotechnology offers new strategies that go beyond the more traditional approaches. By the mid-1990's, the number of recombinant products approved annually for therapeutic use reached double digits. With the advent of the genomics revolution.

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

Application of polymers from renewable resources - also identified as biopolymers - has a large potential market due to the current emphasis on sustainable technology. For optimal R&D achievements and hence benefits from these market opportunities, it is essential to combine the expertise available in the vast range ofdifferent disciplines in biopolymer science and technology. The International Centre of Biopolymer Technology - ICBT - has been created with support from the European Commission to facilitate co operation and the exchange of scientific knowledge between industries, universities and other research groups. One of the activities to reach these objectives, is the organisation ofa conference on Biopolymer Technology. In September 1999, the first international conference on Biopolymer Technology was held in Coimbra, Portugal. Because of its success - both scientifically and socially - and because ofthe many contacts that resulted in exchange missions or other ICBT activities, it was concluded that a second conference on Biopolymer Technology was justified. This second conference was held in Ischia, Italy in October 2000. And again, the scientific programme contained a broad spectrum ofpresentations in a range of fields such as biopolymer synthesis, modification, technology, applications, material testing and analytical methods."

In spite of important advances in asymmetric synthesis, chiral compounds cannot all be obtained in a pure state by asymmetric synthesis. As a result, enantiomer separation remains an important technique for obtaining optically active materials. Although asymmetric synthesis is a once-only procedure, an enantiomer separation process can be repeated until the optically pure sample is obtained. This book discusses several new enantiomer separation methods using modern techniques developed by experts in the field. These methods consist mainly of the following three types: 1) Enantiomer separation by inclusion complexation with a chiral host compound 2) Enantiomer separation using biological methods 3) Enantiomer separation by HPLC chromatography using a column containing a chiral stationary phase. Separation of a racemic compound has been called "optical resolution" or simply "resolution." Nowadays, the descriptions "enantiomer resolution" or "enantiomer separation" are also commonly used. Accordingly, "Enantiomer Separation" is used in the title of this book. The editor and all chapter contributors hope that this book is helpful for scientists and engineers working in this field.

This lab manual guides chemists through demonstrations of synergistic effects between polyelectrolytes and nanoparticles. After a short introduction into the field of polyelectrolytes and polyelectrolyte characterization, the book discusses the role of polyelectrolytes in the process of nanoparticle formation. The book also explains methods for characterization of the polyelectrolyte-modified nanoparticles.

1 T.J. Deming: Polypeptide and Polypeptide Hybrid Copolymer Synthesis via NCA Polymerization.- D.W.P.M. Loewik, L. Ayres, J.M. Smeenk, J.C.M. van Hest: Synthesis of Bio-inspired Hybrid Polymers Using Peptide Synthesis and Protein Engineering.- 3 H. Schlaad: Solution Properties of Polypeptide-Based Copolymers.- 4 H.-A. Klok, S. Lecommandoux: Solid State Structure, Organization and Properties of Peptide -Synthetic Hybrid Block Copolymers.- 5 K. Osada, K. Kataoka: Drug and Gene Delivery Based on Supramolecular Assembly of PEG-Polypeptide Hybrid Block Copolymers.-

Leading experts survey the currently available technologies designed to improve the delivery of today's cancer chemotherapeutic agents. The authors review both the theoretical and practical considerations governing conventional and nonconventional methods of drug administration, and identify promising opportunities for product development. In their outline and discussion of the use of novel formulation technologies-including synthetic polymers and biomaterials for prolonged or sustained drug release to achieve potentially greater therapeutic effect-they profile those technologies that have resulted in a number of approved and late-stage clinical products.

The herbai medicine industry is growing at an astounding rate. Trade group estimates suggest that total sales exceeded $4 billion dollars in 1999. Herbai remedies are for sale not just in health food stores, but in supermar kets, drug stores, and even discount warehouses. Along with the proliferation in sales has come a proliferation ofinformation sources. Not all ofthe sources are equally reliable, or even intelligible. Traditional herbalists c1assify thistle and mugwort as "cholagogues," substances used to make the gallbladder con tract and release bile. Medical school graduates are unlikely to have ever heard the term, or even accept the notion that most right-sided abdominal pain is a result of diminished bile flow. Heroin and cocaine may not be the only drugs to come from plants, but a practicing physician or toxicologist might be forgiven for thinking so. In 1998, 1264 papers were published about cocaine and only 17 about kava kava, an abused herb that is not without toxic side effects. Unfortunately, the majority of the papers about kava kava were published in journals not found in ordi nary hospitallibraries. In recognition ofthis fact, and ofthe obvious need for a reliable reference work on herbai toxicology, The Toxicology and Clinical Pharmacology 0/ Herbal Products was an early addition to our new series in Forensie Science and Medicine. It is very badly needed."

Drugs of Abuse: Neurological Reviews and Protocols is intended to provide insightful reviews of key current topics and, particularly, state-- the-art methods for examining drug actions in their various neuroanato- cal, neurochemical, neurophysiological, neuropharmacological, and molecular perspectives. The book should prove particularly useful to n- comers (graduate students and technicians) in this field, as well as to those established scientists (neuroscientists, biochemists, and molecular biologists) intending to pursue new careers or directions in the study of drugs. The book's protocols cover a wide variety of coherent methods for gathering inf- mation on quantitative changes in proteins and mRNAs at both tissue and cel- lar levels. Inducible gene expression in striatal neurons has been a hot topic over the last decade. Alterations in gene expression for a wide range of proteins in the striatum have been investigated in response to drug administration. Altered expression of given mRNAs and their product proteins constitutes essential molecular steps in the development of neuroplasticity related to long-term addictive properties of drugs of abuse. With the multiple labeling methods that are also described in the book, gene expression can be detected in a chemically identified cell phenotype; the expression of multiple genes of interest can be detected in a single cell simultaneously. Hundreds or thousands of gene expr- sion products can today be detected in one experimental setup using the pow- ful systematic cDNA macroarray or microarray screening technology. Moreover, protocols useful in analyzing the functional roles of genes and proteins (e. g.

In vitro utilization of liposomes is now recognized as a powerful tool in many bioscience investigations and their associated clinical studies, e.g., liposomes in drug targeting; liposomes in gene transport across plasma and nuclear membranes; liposomes in enzyme therapy in patients with genetic disorders. However, before these areas can be effectively explored, many basic areas in liposome research require elucidation, including: (a) attachment of liposomes to cell surfaces; (b) permeation of liposomes through the plasma membranes; and (c) stability of liposomes in cell or nuclear matrices. None of these areas have been exhaustively explored and liposome researchers have ample opportunities to contribute to our knowledge. The aim of Liposome Methods and Protocols is to bring together a wide range of detailed laboratory protocols covering different aspects of liposome biology in order to assist researchers in those rapidly advancing medical fields mentioned earlier. With this goal in mind, in each protocol chapter we have detailed the materials to be used, followed by a step-by-step protocol. The Notes section of each protocol is also certain to prove particularly useful, since the authors include troubleshooting tips straight from their benchtops, valuable information that is seldom given in restricted methods sections of standard research journals. For this reason we feel that the book will prove especially useful for all researchers in the liposome field.

An authoritative and up-to-date survey of the fundamental principles, and practice of drug delivery at the cellular level. On the principles side, the authors discuss the broad spectrum of cellular delivery, ranging from coverage of cell-mediated immunity, gene delivery, and protein targeting, to cellular drug transport, cellular drug permeability, and a variety of carrier system related to targeted drug delivery. On the practice side, the authors focus on technological developments in cellular drug delivery, including novel formulations for the delivery of DNA and antisense oligonucleotides, as well as drug targeting with immunoglobulin formulations and antibody-mediated approaches.

Recent analyses of drug attrition rates reveal that a significant number of drug candidates fail in the later stage of clinical development owing to absorption, distribution, metabolism, elimination (ADME), and toxicity issues. Lead optimization in drug discovery, a process attempting to uncover and correct these defects of drug candidates, is highly beneficial in lowering the cost and time to develop therapeutic drugs by reducing drug candidate failures in development. At present, parallel synthesis combining with high-throughput screening has made it easier to generate highly potent compounds (i. e. , hits). However, to be a potential drug, a hit must have drug-like characteristics in addition to potency, which include optimal physicochemical properties, reasonable ph- macokinetic parameters, and good safety profiles. Therefore, research tools must be available in drug discovery to rapidly screen for compounds with favorable drug-like properties, and thus adequate resources can be directed to projects with high potential. Optimization in Drug Discovery: In Vitro Methods is a compilation of detailed experimental protocols necessary for setting up a variety of assays important in compound evaluation. A total of 25 chapters, contributed by many experts in their research areas, cover a wide spectrum of subjects including physicochemical properties, abso- tion, plasma binding, metabolism, drug interactions, and toxicity. A good pharmacokinetic profile has long been recognized as an imp- tant drug-like characteristic. Pharmacokinetic parameters are affected by many properties of drug molecules such as physicochemical nature, abso- tion, metabolic stability, and so on.

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

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

Computational molecular and materials modeling has emerged to deliver solid technological impacts in the chemical, pharmaceutical, and materials industries. It is not the all-predictive science fiction that discouraged early adopters in the 1980s. Rather, it is proving a valuable aid to designing and developing new products and processes. People create, not computers, and these tools give them qualitative relations and quantitative properties that they need to make creative decisions.
With detailed analysis and examples from around the world, Applying Molecular and Materials Modeling describes the science, applications, and infrastructures that have proven successful. Computational quantum chemistry, molecular simulations, informatics, desktop graphics, and high-performance computing all play important roles. At the same time, the best technology requires the right practitioners, the right organizational structures, and - most of all - a clearly understood blend of imagination and realism that propels technological advances. This book is itself a powerful tool to help scientists, engineers, and managers understand and take advantage of these advances.

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

A compendium of proven experimental approaches and strategies for studying the bioactivation, detoxification, tissue distribution, and elimination of xenobiotics in the metabolism and/or transport of various chemicals. The authors address several of the major drug metabolizing systems, including the cytochrome P450 family, flavin-containing monooxygenases, glutathione, S-transferase, glucuronidation, N-acetylation, and sulfotransferases. Additional chapters present novel approaches to the study of: signaling pathways in the regulation of drug metabolism enzymes, how the modulation of thiols and other low molecular-weight cofactors can alter drug metabolism, and how modulation of drug metabolism pathways can influence antiviral therapy.

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