Contents: B. Alcaide P. Almendros: Novel Aspects on the Preparation of Spirocyclic and Fused Unsual -Lactams.- S.S. Bari A. Bhalla: Spirocyclic -Lactams: Synthesis and Biological Evaluation of Novel Heterocycles.- L. Troisi C. Granito E. Pindinelli: Novel and Recent Synthesis and Applications of -Lactams.- C. Palomo M. Oiarbide: -Lactams Ring Opening: A Useful Entry to Amino Acids and Relevant Nitrogen-Containing Compounds.- B. Mandal P. Ghosh B. Basu: Recent Approaches Towards Solid Phase Synthesis of -Lactams.- A.Arrieta B. Lecea F.P. Cossio: Computational Studies on the Synthesis of -Lactams Via [ 2+2] Thermal Cycloadditions.- B. K. Banik I. Banik F. F. Becker: Novel Anticancer -Lactams

-Encapsulation by Miniemulsion Polymerization By K. Landfester and C. K. Weiss -Enzyme-Encapsulated Layer-by-Layer Assemblies: Current Status and Challenges Toward Ultimate Nanodevices By K. Ariga, Q. Ji, and J. P. Hill -Non-LBL Assembly and Encapsulation Uses 1 of Nanoparticle-Shelled Hollow Spheres 2 By G.C. Kini, S. L. Biswal, and M. S. Wong -Polymersomes: A Synthetic Biological Approach to Encapsulation and Delivery By M. Massignani, H. Lomas, and G. Battaglia -Reaction Vessels Assembled by the Sequential Adsorption of Polymers By A.D. Price, A.P.R. Johnston, G.K. Such, and F. Caruso

Like the previous nine volumes published between 1988 and 1996, "Medicinal" "and" "Aromatic" "Plants X" is unique in its approach. It comprises 22 chapters dealing with the distribution, importance, conventional propagation, micropropagation, tissue culture studies, and the in vitro production of important medicinal and pharmaceutical compounds in various species of "Actinidia," "Alkanna," "Arnebia," "Campanula," "Catharanthus," "Centella," "Chenopodium," "Cornus," "Cynara," "Ephedra," "Euglena," "Haplophyllum," "Morus," "Oenothera," "Otacanthus," "Oxalis," "Polypodium," "Rosmarinus," "Sesamum," "Solanum," "Taxus," and "Tephrosia." This book is tailored to the needs of advanced students, teachers, and research scientists in the field of pharmacy, plant tissue culture, phytochemistry, biochemical engineering and plant biotechnology.

Penicillins and cephalosporins have a long history in combating bacterial infections. Despite new infectious diseases and occurring resistance, beta-lactam antibiotics will for many years to come continue to play a prominent role in our therapeutic arsenal. This book covers the industrial development of the chemical and biochemical processes used to manufacture these products, as well as looking ahead to possible future processes. The interplay between synthetic organic chemistry with the understanding and application of enzymes, modeling of fermentation processes and integration through (bio-) chemical process engineering is illustrated. In-depth scientific approaches to biocatalysis and biocatalyst development including enzyme kinetics, enzyme crystal studies and semi-rational enzyme mutations are also presented. Metabolic pathway analysis and modeling of fermentation process are treated as well as molecular precision in synthetic approaches to beta-lactams, their precursors and derivatives. Process technology studies including new reactor concepts, possible short-cut routes and improved down-stream-processing methods complete a broad view on the scope and limitations of the presently developed industrial processes including an intriguing insight into future process possibilities. This book represents an excellent case study on the transformation of traditional, stoichiometric, organic synthesis and classical fermentations into modern (bio-) catalysis and biosynthesis based on insights in metabolic pathways and enzyme actions.

The search for new producers of biologically active substances (BAS) against human and animal diseases continues to be an important task in biology and medicine. Experimental work must be carried out well in advance of need because it takes an average of ten years to develop a new medication, as well as additional time to put it on the market. Study of the Protozoa forms a special branch of biology - protozoology. The traditional fields of protozoology are taxonomy, phylogeny, morphology, cytology, evolution, ecology and host parasite-interactions. The Protozoa is the only taxon among the microscopic organisms, which has not been persistently studied as a source of BAS. This book then is the result of the research on the project: "Biologically active substances of the Mastigophora (Flagellates)." The research was carried out at the Laboratory of Antibiotics, Department of Microbiology, Biological Faculty of Moscow State University. Articles of other authors on the matter have been considered as the important part of this reference book. The goal of the reference book is to elucidate scientific approaches, which lead to obtaining biologically active substances from cultures of protozoa; the book reviews the historical background in connection with contemporary development of the field. N.N. Sukhareva ACKNOWLEDGMENTS The research was performed in fruitful cooperation with my research associates (V. Urinyuk, T. Titiova, L. Udalova, R. Zeleneva, V. Brusovanik, M. Zaretskaya), postgraduate students (N. Kalenik, M. Chuenkova, V. Vasilevskaya, V. Khorokhorina), my colleagues at Moscow State University (Yu. Kozlov and I.

Since 1994, the Phytochemical Society of North America has devoted its annual symposia to topics with biological perspectives. Our last four volumes have dealt with medicinal plants (1994), plant/insect interactions (1995), food phytochemicals (1996), and plant/microbe interactions (1997), respectively. The Symposium held in Pullman, Washington, July 26-31, 1998 brought many aspects of these previous symposia once again to the forefront. This time, however, there was greater emphasis on the potential applications of phytochemistry to the diverse topics of human health and nutrition and plant defense. As we learned about innovative uses of molecular biology as it is being applied to these topics, we were reminded once again of the biochemical th foundation on which these advances rest. On the occasion of the 75 birthday of G.H. Neal Towers, which we were privileged to celebrate, a perspective of where we began and how far we have advanced was made patently real for those in attendance. The papers assembled in this volume were presented during the Sympo- sium. Roughly grouped under three broad topics, they include: I. Drug Discov- ery and Pathway Engineering toward New MedicinallNutriceutical Targets (papers by Cragg, Croteau, Thompson, Costa, McLaughlin, Dixon, and Matern), 2. Roles for Polyphenols-Biosynthesis and Applications (Gross, Hillis, Haslam, and Ferreira), 3. New Chemical Prospects and Plant Defense (Asakawa, Selmar, Houghton, and Mizutani).

In this era of biotechnology there have been many books covering the fundamentals of recombinant DNA technology and protein chemistry. However, not many sources are available for the pharmaceutical develop ment scientist and other personnel responsible for the commercialization of the finished dosage forms of these new biopharmaceuticals and other products from biotechnology. This text will help to fill this gap. Once active biopharmaceutical molecules are candidates for clinical trial investigation and subsequent commercialization, a number of other activities must take place while research and development on these molecules continues. The active ingredient itself must be formulated into a finished dosage form that can be conveniently used by health care professionals and patients. Properties of the biopharmaceutical molecule must be clearly understood so that the appropriate finished product formulation can be developed. Finished product formulation development includes not only the chemical formulation, but also the packaging system, the manufacturing process, and appropriate control strategies to assure such good manufacturing practice attributes as safety, identity, strength, purity, and quality.

In recent years cell-based technologies have gained significant scientific attention, and have become a matter of intense public debate as well. Namely, (i) tissue engineering, the construction of tissues and whole organs using molecularly-designed resorbable biomaterials to create new tissue de novo with or without transplanting cells; (ii) the potential use of human embryonic stem cells for transplantation and regenerative medicine (with similar potential for adult-derived stem cells); (iii) and gene therapy, in relation with cell transplantation, have taken their places as the most discussed biomedical issues of the day. New findings in biomimetic materials, cell signalling pathways, extracellular matrix receptors and ligands, growth factors, and the human genome project are motivating the developments in these challenging research areas. This book includes manuscripts on tissue engineering, stem cells and gene therapies authored by world-renowned scientists of the field. The first section of the volume consists of four chapters giving perspectives for the current status and potential future of tissue engineering and stem cell technologies. The second section of the volume includes five chapters based on experimental and clinical data. In this section, the role of stem cells in liver tissue engineering, cell-based therapies in diabetes mellitus, and chronic degenerative diseases of the central nervous system, and adult-derived stem cell therapies are discussed. The two chapters of the third section focus on the biomarkers for tissue-engineered products, namely for tissue-engineered skin. The eight chapters of the fourth section discuss novel biomaterials developed for neural-, vascular-, aortic-, bone-, cartilage- and endocrine pancreas-tissue engineering applications. The last section of the book includes chapters on practical gene targeting applications, controlled release in gene therapy and tissue engineering, antibodies in cancer, acute-phase genes and phage-displayed peptide libraries. Proceedings of BIOMED 2002 The 9th International Symposium on Biomedical Science and Technology, held September 19-22, 2002, in Antalya, Turkey.

Antifolates are an important class of anticancer drugs originally developed as anti leu- kemic agents, but now used, usually in combination with other drugs, for the treatment of a wide range of tumors, notably carcinomas of the head and neck, breast, germ cell tumors, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, and osteogenic sar- comas. 5-Fluorouracil and its prodrugs also target, in part, the folate-dependent enzyme, thymidylate synthase. Furthermore, folate supplementation in the form of leucovorin, modulates 5-fluororuacil activity. 5-Fluorouracil is widely used in the treatment of colorectal and gastric cancer and in combination for other solid tumors such as breast and head and neck cancers. Ongoing clinical trials with the newer antifolates suggest that the range of solid tumors where these agents will be of use may broaden further. Half a century ago, interesting scientific and clinical discoveries suggested that folie acid was a vitamin involved in vital cellular metabolic processes. The folate analogs, aminopterin and methotrexate, were synthesized by the American Cyanamid Company in an attempt to interfere with these processes and were shown to have anticancer activity by Farber and his colleagues. Hence, the principle of antimetabolite therapy for the treatment of cancer was established. Biomedical research over the following years led to a deeper understanding of the complex biochemical pharmacology of folates and antifolates. Selective antimicrobial agents were discovered, but more tumor-selective anticancer agents did not immediately emerge.

The most important development in studies of the metabolic effects of anes- thetics has been the recent demonstration that anesthetics may alter the rate of transport of metabolites across biologic membranes. The membranes affected include cell membranes as well as mitochondrial membranes. Inhalation anesthe- tics generally have little effect on glycolysis but may sigrllficantly alter oxidative phosphorylation and mitochondrial oxygen consumption. The direct effects of anesthetics on cell metabolism may be overshadowed in vitro by secondary effects anesthetics exert on endocrine balance, organ blood flow, and changes in oxygen and carbon dioxide tensions. References ALBERS, C., BRENDEL, W., USINGER, W.: Kreislaufrespiratorischer Stoffwechsel undAtmung in Athernarkose. Arch. expo Pathol. Pharmakol., Naunyn-Schmiedeberg's 226, 278 (1955). ALEXANDER, S. C., COHEN, P. J., WOLLMAN, H., SMITH, T. C., REIVICH, ~L, MOLEN, R. A. U.: Cerebral carbohydrate metabolism during hypocarbia in man. Studies during nitrous oxide anesthesia. Anesthesiology 26, 624 (1965). ANDERSEN, N. B.: Effect of general anesthetics on sodium transport in the isolated toad bladder. Anesthesiology 27, 304 (1966). - Synergistic effect of cyclopropane and epinephrine on sodium transport in toad bladder. Anesthesiology 28, 438 (1967). ANNAMUNTHODO, H., KEATING, V., PATRICK, S. J.: Liver glycogen alteration in anaesthesia and surgery. Anaesthesia 13, 429 (1958). APRAHAMIAN, H. A., VANDERVEEN, J. L., BUNKER, J. P., MURPHY, A. J., CRAWFORD, J. D.: The influence of general anesthetics on water and solute excretion in man. Ann. Surg. 100, 122 (1959).

This is truly an exciting time to be in the ?eld of polymer science. Advances in polymerization methods are providing polymer scientists with the ability to specify and control polymer composition, structure, architecture, and molecular weight to a degree that was not possible just a decade ago. This, in turn, is resulting in many novel application possibilities of polymers ranging from drug delivery systems and nanolithographyto stimuli-responsivematerials and many others. In addition,many of the application areas of polymers - such as coatings, adhesives, thermoplastics, composites, and personal care - are also taking advantage of the ability to design polymersduringtheir developmentefforts. Not to forget,manyof these applications of polymers involve mixing polymers with solvents, catalysts, colorants, and many other ingredients to prepare a formulated product. However, the tuning of polymer composition and structure as well as polymer formulations to optimize the ?nal performance properties can be challenging, - pecially since in many cases several interacting variables need to be optimized simultaneously. This is where the methodologies and techniques of combinatorial and high-throughput experimentation to synthesize and characterize polymer - braries can be an invaluable approach. Simply put, a polymer library is a collection of multiple polymer samples having a systematic variation in one or more variables related to composition, structure, or process. Various methods and strategies have been explored to ef?ciently prepare a large number of polymer samples and also to screen these samples for key properties of interest.

Glycosmis is a clearly defined genus within the tribe Clauseneae of the Aurantioideae subfamily of the family Rutaceae comprising about 40 species (1). Its range of distribution is centered in south and southeast Asia (India, Sri Lanka, Myanmar, Thailand, Malaysia, Indonesia) and extends to south China and Taiwan as well as to New Guinea and north Australia. Exceptions are only cultivated species like the Chinese G. parvijiora (Sims) Little, formerly called G. citrifolia (Willd. ) Lindley, which became naturalized in tropical America and Africa (Angola) (1). The shrubs or small trees are unarmed and possess pinnate or simple leaves with translucent punctate glands emitting an aromatic odor when crushed. The axillary inflorescences are usually dispersed closed panicles with small white flowers. The fruits are mostly pink, reddish or white berries of about I cm in diameter with only one or two seeds. The genus name Glycosmis originates from the sweet smell of the flowers and the sweet taste of the fleshy pericarp of the fruits. A good field and herbarium character of the genus is that the buds of new leaves are usually covered with short rusty-red hairs. In spite of the good delimitation of Glycosmis from the other closely related Clauseneae genera Clausena, Micromelum, Murraya, and Merrillia and the already existing subrevisionary treatment by Stone (1), there are still many unresolved taxonomic problems at the species level.

Galenical pharmacy or galenics is the science dealing with the pro duction of drug substances from raw materials, the purity of such substances, their formulation into pharmaceutical preparations with the desired effects and safety in use, and the quality control, stability and storage of the preparations. The field has taken its name from the Greek physician Galen (131-201 A.D.), who had a profound influence on medicine for many centuries because he collected and systematized the medicinal knowledge of his time. The discovery of insulin is attributed to Banting and Best who, in 1921, prepared an extract of the pancreas of the fetal calf and showed that the extract was capable of reducing the blood sugar level of a diabetic dog. This outstanding discovery gave rise to the rapid develop ment of the manufacture of insulin of bovine and porcine origin. By 1925, two Danish manufacturers of insulin preparations were established; both have since been in the forefront ofthe development of insulin preparations, the latest achievement being the marketing of human insulin by Novo in 1982. The development of highly purified human insulin produced semisynthetically from porcine insulin or by DNA recombinant methods are significant contributions to safe and efficient insulin therapy. Insulin is a protein which is destroyed in the gastrointestinal tract."

Leading scientists summarize the latest findings on signal transduction and cell cycle regulation and describe the effort to design and synthesize inhibiting molecules, as well as to evaluate their biochemical and biological activities. They review the relevant cell surface receptors, their ligands, and their downstream pathways. Also examined are the latest findings on the components of novel signaling networks controlling the activity of nuclear transcription factors and cell cycle regulatory molecules. Cutting-edge and highly suggestive, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases presents a wealth of information on the emerging principles of the field, as well as an invaluable guide for all experimental and clinical investigators of cell regulation and its rapidly emerging pharmacological opportunities today.

Originally published in 1995, The History of Pharmacy is a critical bibliography of selected information on the history of pharmacy. The book is designed to guide students and academics through the history of science and technology. Topics range from medicine, chemical technology and the economics and business of pharmacy to pharmacy's influence in the arts. The bibliography includes an exhaustive selection of primary and secondary sources and is arranged chronologically. This book will be of interest to those researching in the area of the history of science and technology and will appeal to students and academic researchers alike.

The idea for publishing these books on the mechanism of action and on the biosynthesis of antibiotics was born of frustration in our attempts to keep abreast of the literature. Gone were the years when we were able to keep a biblio graphy on antibiotics and feel confident that we could find everything that was being published on this subject. These fields of investigation were moving for ward so rapidly and were encompassing so wide a range of specialized areas in microbiology and chemistry that it was almost impossible to keep abreast of developments. In our naivete and enthusiasm, however, we were unaware that we were toying with an idea that might enmesh us, that we were creating an entity with a life of its own, that we were letting loose a Golom who instead of being our servant would be our master. That we set up ideals for these books is obvious; they would be current guides to developments and information in the areas of mechanism of action and bio synthesis of antibiotics. For almost every subject, we wished to enlist the aid of an investigator who himself had played a part in determining the nature of the phenomena that were being discussed. One concept for the books was that they include only antibiotics for which a definitive, well-documented mechanism of action or biosynthetic pathway was known.

Contents: V. Zingel, C. Leschke and W. Schunack: Developments in research on histamine (H1) receptor agonists / P.D. Hoeprich: Antifungal chemotherapy / G. de Stevens: The diversity of heterocyclic compounds and their biological activities / R.M. Schultz: Newer antifolate compounds in cancer therapy / P.K. Mehrotra, S. Batra and A.P. Bhadun: Non-steroidal agents for regulation of the menstrual cycle / A.K. Saxena and M. Saxena: Developments in anti-convulsant drugs

Bioactive Spin Labels focusses on nitroxyl radicals, their chemistry, biological activity and their application as paramagnetic contrast agents in biomedical research. New EPR techniques for in-vivo studies utilizing nitroxyl radical reagents are described. Recent results on stable nitroxyl radicals as anticancer, antishock, antiaggregant and antischemic drugs are summarized.

La composition particuliere des lipides des Bacteries justifie pleinement la redaction de la presente revue; en effet, les Bacteries elaborent des lipides dont la composition est tres differente de celle des lipides des autres organismes, que ce soient des Champignons, des Algues ou des Animaux superieurs. L'interet porte actuellement a 1'etude des lipides bacteriens est egalement justifie par 1'importance biologique de certaines fractions lipidiques. Le domaine que nous allons resumer est d' ailleurs encore peu developpe; a part des etudes nombreuses et tres detaillees sur les lipides des Myco- bacteries et sur ceux du Bacille diphterique, nous ne possMons que des renseignements sporadiques concernant ceux d'autres especes bacteriennes. R. ]. ANDERSON, a qui nous devons la plus grande partie de nos connaissances sur les lipides des Mycobacteries, a publie dans Ie volume III de la presente collection, une revue intitulee {

These proceedings contain the papers presented at the Bayer-Symposium V which was held in Grosse Ledder on October 16-21, 1973 and which was simultaneously the Second International Research Conference on Proteinase Inhibitors. The cordial atmosphere, the frank discussions and the profitable exchange of ideas during the First International Research Conference on Proteinase Inhibitors which was held on November 4--6, 1970 in Munich were a stimulant for us to consider holding a Second Conference especially as the steadily increasing research activities in this and related fields called for a new assessment of recent efforts in proteinase inhibitor research. In the three years since the First Conference was held, this field has developed particularly in the areas of molecular aspects of protein-protein interactions and in the extension to inhibitors of nonserine proteinases and peptidases. In planning this meeting the Organizing Committee was faced with the problem of selecting a limited number of participants and we decided that it was appropriate and necessary to focus in detail on the chemistry of proteinase inhibitors, their interac tions with a variety of enzymes and also to invite more general papers to survey the physiological and clinical aspects of the subject which we felt would be of importance in the future.

This report on Future Trends in Inflammation IV records another of the multidisciplinary meetings organized by the European Biological Research Association. The organizers wish to record their thanks to all the participants and delegates who made this such an enjoyable meeting. Our thanks are due to a number of members of the pharmaceutical industry who so kindly donated funds. These funds were used to provide grants for young research workers to attend this meeting. Many people have kindly given their time and help to make this congress possible. It is impossible to list them by name, but we are profoundly grateful. We were dubious at the outset as to whether to hold this meeting in a period when many other meetings are being organized on inflammation. The enthusiastic attendance proves that we were right in going ahead. The next international meeting will be held in France in 1983. For further details please contact: Professor J. P. Giroud Department of Pharmacology, Hopital Cochin 75014 Paris, France D. A. Willoughby J. P. Giroud xxxiii Section I Future Trends CHAIRMAN: L. Chedid CO-CHAIRMAN: Dame Honor Fell 1 The participation of mononucleur phagocytes in immune based inflammatory processes with special reference to their secretory responses P. DAVIES AND R. J.

The study of biogenic amines, which from the beginning of modern pharma- cology has always attracted the enthusiastic attention of research workers and has led to some of the most brilliant and illuminating experimental results in biology, has been unexpectedly extended in the last fifteen years. 'With the discovery of 5. hydroxytryptamine (enteramine, serotonin), in fact, the vast field of indole- alkylamines has been opened up for research. In a decade of intensive and dedicated work, an immense amount of experi- mental data has been collected, the significance of which, having rapidly overrun the limits of pharmacology, physiology, and biochemistry, has spread into all fields of biology and medicine, as previously occurred with choline esters, catechol- amines and imidazolealkylamines. Thus, the study of indolealkylamines, espe- cially that of their metabolism, has led not only to explanation of the mechanism of action, formerly largely obscure, of some important drugs, to clarification of the pathogenesis of some morbid syndromes and to a parallel flourishing of research on other biogenic amines, but also to surprising achievements in the field of therapeutics. The discovery of monoamineoxidase and dopadecarboxylase inhibitors, and of drugs which block the storage of biogenic amines in the body depots are among the most striking results of research on the indolealkylamines.