The Leguminosae is an economically important family in the Dicotyledonae with many cultivated species, e. g. , beans and peas. The family also contains many well-known medicinal plants. It is composed of 17,000 or more species that constitute nearly one twelfth of the world's flowering plants (1). Traditionally the family has been divided into three subfamilies, Caesalpinioideae, Mimosoideae and Papilionoi- deae, which are sometimes recognized as separate families Caesalpinia- ceae, Mimosaceae and Papilionaceae. The International Code of Botanical Nomenclature permits alternative nomenclatures, the family names being replaced by Fabaceae, Fabales and Faboideae, and this usage will be common (2). Licorice (liquorice, kanzoh in Japanese, gancao in Chinese) is the name applied to the roots and stolons of some Glycyrrhiza species (Fabaceae) and has been used by human beings for at least 4000 years. The earliest written reference to the use of licorice is contained in the Codex Hammurabi dating from 2100 B. C. , and the subsequent history in the West has been described in the earlier reviews (3-6). In the Far East, references to the effectiveness of licorice are contained in the "Shen Nong Ben Cao Jing", the first Chinese dispensatory whose original anonymous volumes probably appeared by the end of the third century (7, 8).

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.

In order to make further progress in elucidating the mechanism of NOS catalysis it will be essential to throw light on the interaction between the enzyme and its substrate. An understanding of the catalytic site will also assist the development of therapeutically important NOS inhibitors. In particular. it will be useful to uncover any differences that exist between the substrate binding sites of the three NOS isozymes which might be exploited for the development of isoform selective NOS inhibitors. A comparison of NOS to other Arg-binding proteins has shown no significant sequence homology (159). Moreover, the lack of a 3D structure and absence of significant sequence homology between the NOS oxygenase domain and known cytochromes P450 has made it difficult to identify residues and construct a model of the distal heme pocket responsible for substrate binding. However, a number of groups are currently working towards crystallisation of the separate NOS reductase and oxygenase domains of the three isoforms for X-ray diffraction studies; the first X-ray structure is likely to be forthcoming within a matter of months. * The results of these studies are expected to resolve many of the uncertainties surrounding the structure of the NOS catalytic site. Preliminary X-ray diffraction analysis of CPR from rat liver has already been reported by MASTERS et al. (524) and the future emergence of a detailed structure for this protein should throw light on the structure and function of the NOS reductase domain.

It was in 1979 when GROVE et al. isolated from pollen of rape (Brassica nap us) a highly active plant growth promoter, named it brassinolide and elucidated its structure as (22R,23R,24S)-2

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.

The Sixth International Conference on Miniaturized Chemical and Biochemical Analysis Systems, known as IlTAS2002, will be fully dedicated to the latest scientific and technological developments in the field of miniaturized devices and systems for realizing not only chemical and biochemical analysis but also synthesis. The first IlTAS meeting was held in Enschede in 1994 with approximately 160 participants, bringing together the scientists with background in analytical and biochemistry with those with Micro Electro Mechanical Systems (MEMS) in one workshop. We are grateful to Piet Bergveld and Albert van den Berg of MESA Research Institute of the University of Twente for their great efforts to arrange this exciting first meeting. The policy of the meeting was succeeded by late Prof. Dr. Michael Widmer in the second meeting, IlTAS'96 held in Basel with 275 participants. The first two meetings were held as informal workshops. From the third workshop, IlTAS'98 (420 participants) held in Banff, the workshop had become a worldwide conference. Participants continued to increase in IlTAS2000 (about 500 participants) held in Enschede and IlTAS2001 (about 700 participants) held in Monterey. The number of submitted papers also dramatically increased in this period from 130 in 1998, 230 in 2000 to nearly 400 in 2001. From 2001, IlTAS became an annual symposium. The steering committee meeting held in Monterey, confirmed the policy of former IlTAS that quality rather than quantity would be the key-point and that the parallel-session format throughout the 3.

"The greater our knowledge increases, the more our ignorance unfolds. " U. S. President John F. Kennedy, speech, Rice University, September 12, 1962 My primary purpose for writing this book was much more than to provide another information source on Chemistry, Manufacturing & Controls (CMC) that would rapidly become out of date. My primary purpose was to provide insight and practical suggestions into a common sense business approach to manage the CMC regulatory compliance requirements for biopharmaceuticals. Such a common sense business approach would need (1) to be applicable for all types of biopharmaceutical products both present and future, (2) to address the needs of a biopharmaceutical manufacturer from the beginning to the end of the clinical development stages and including post market approval, and (3) to be adaptable to the constantly changing CMC regulatory compliance requirements and guidance. Trying to accomplish this task was a humbling experience for this author In Chapter 1, the CMC regulatory process is explained, the breadth of products included under the umbrella ofbiopharmaceuticals are identified, and the track record for the pharmaceutical and biopharmaceutical industry in meeting CMC regulatory compliance is discussed. In Chapter 2, while there are many CMC commonalities between biopharmaceuticals and chemically-synthesized pharmaceuticals, the significant differences in the way the regulatory agencies handle them are examined and the reasons for why such differences are necessary is discussed. Also, the importance of CMC FDA is stressed."

During the past decade there have been many changes in the perfumery industry which are not so much due to the discovery and application of new raw materials, but rather to the astronomic increase in the cost of labour required to produce them. This is reflected more particularly in the flower industry, where the cost of collecting the blossoms delivered to the factories has gone up year after year, so much so that most flowers with the possible exception of Mimosa, have reached a cost price which has compelled the perfumer to either reduce his purchases of absolutes and concretes, or alternatively to substitute them from a cheaper source, or even to discontinue their use. This development raises an important and almost insoluble problem for the perfumer, who is faced with the necessity of trying to keep unchanged the bouquet of his fragrances, and moreover, to ensure no loss of strength and diffusiveness. Of course, this problem applies more especially to the adjustment of formulae for established perfumes, because in every new creation the present high cost of raw materials receives imperative con sideration before the formula is approved."

Much of chemistry, molecular biology, and drug design, are centered around the relationships between chemical structure and measured properties of compounds and polymers, such as viscosity, acidity, solubility, toxicity, enzyme binding, and membrane penetration. For any set of compounds, these relationships are by necessity complicated, particularly when the properties are of biological nature. To investigate and utilize such complicated relationships, henceforth abbreviated SAR for structure-activity relationships, and QSAR for quantitative SAR, we need a description of the variation in chemical structure of relevant compounds and biological targets, good measures of the biological properties, and, of course, an ability to synthesize compounds of interest. In addition, we need reasonable ways to construct and express the relationships, i. e. , mathematical or other models, as well as ways to select the compounds to be investigated so that the resulting QSAR indeed is informative and useful for the stated purposes. In the present context, these purposes typically are the conceptual understanding of the SAR, and the ability to propose new compounds with improved property profiles. Here we discuss the two latter parts of the SARlQSAR problem, i. e. , reasonable ways to model the relationships, and how to select compounds to make the models as "good" as possible. The second is often called the problem of statistical experimental design, which in the present context we call statistical molecular design, SMD. 1.

In this volume we have included some contributions among the plenary lectures, oral presentations and posters that have been presented at the 1st Joint Greek-Italian Meeting on "The Chemistry of Biological systems and Molecular Chemical Engineering" organized at Loutraki, Club Poseidon, Greece 1990. We hope similar meetings will follow every two years alternating between the two countries in order to strengthen the scientific ties among the scientists working in this field. The inter- disciplary aspect of the meeting has been evident by the wide presence of scientists in bioinorganic, bio-organic, biological fields and molecular engineers who will get together and exchange ideas and experiences. We take this opportunity to thank the Greek Chemical Society, the Italian Chemical Society, the "Gruppo Interdivisionale di Chimica dei Sistemi e dei Processi Biologici", Consiglio Nazionale delle Ricerche, Nuclear Research Center "Demokritos" and the Greek Ministry for Research and Technology. ENRICO RIZZARELLI THEOPHILE THEOPHANIDES CONTRIBUTORS Numbers in parentheses indicate the pages on which the author's contributions begin Mojgan Aghazode Tabrizi, Department of Pharmaceutical Science, via Scandiana 21, University of Ferrara, 44100 Ferrara, ITALY (119) Maria Albano, Department of Chemistry, University of Calabria, Arcavacata di Rende, 87030 Cosenza ITALY (23) Rossano Amadelli, Photochemical Center of C. N. R. , Department of Chemistry, University of Ferrara, via L. Borsari 46, 44100 Ferrara, ITALY (103) Amalia Anagnostopoulou-Konsta, Department of Physics, National Technical University, 57 73 Athens, GREECE (45) Jane D.

INHALT: The Concept of the BBB: an Historical Perspective Anatomy of the BBB Pathophysiology of BBB * Brain oedema Breakdown of the BBB BBB Dysfunction after SAH * Clinical Monitoring Neuroradiological Evaluations of BBB Dysfunction after SAH * Computerised Tomography and Magnetic Resonance * SPECT and PET Experimental Data * Literature Review of BBB Dysfunction after Experimental SAH * Qualitative Assessments * Quantitative Assessments * Time Course of BBB Dysfunction after SAH * Additional Pathophysiological Changes after SAH - Cerebral Vasospasm - CSF Eicosanoids - Cerebral Metabolism - Behavioural and Neurological Deficits - Intracranial Pressure - Blood Pressure, Blood Gases, Plasma pH, Plasma Glucose, Body Temperature Strategies for Pharmacological Interventions * Hydroxyl Radical Scavenger AVS * Glutamate Antagonist Felbamate * Calpain Inhibitor II Challenges and Future Directions * Advances in Cerebrovascular Pathophysiology Elucidation * Gene Therapy

HMG-CoA reductase inhibitors (statins) are established drugs for the treatment of hypercholesterolemia. Furthermore, they induce regression of vascular atherosclerosis as well as reduction of cardiovascular-related morbidity and death in patients with and without coronary artery disease. This book deals with statins which have substantially altered the approach to therapy of atherosclerosis and its sequelae. Emphasis is placed on the scientific background to the discoveries and the development of the therapy, including an overview of the current state of knowledge of the drugs. Clinical data are reviewed extensively. This book not only provides the reader with valuable information but also stimulates further research into the pathogenesis of atherosclerosis and the mechanisms behind the action of effective statins. It sets the stage for creative thinking among scientists of many disciplines for the accomplishment of our ultimate goals in treating atherosclerosis and its sequelae. This topical volume...

Scientists from many disciplines require making observations which are dependent upon the behavior of compounds in solution. This ranges from areas in geography, such as oceanography, to areas in chemistry, such as chromatography, to areas in biology, such as pharmacology. Historically, information would be obtained by observing a response for a given set of conditions and then the conditions would be changed and a new response obtained. In this approach there would be little effort made to actually understand how a compound was behaving in solution but rather just the response was noted. Understanding the behavior of compounds in solution is critical to understanding their behavior in biological systems. This has become increasingly important during the last twenty years as an understanding of the biochemistry related to human illness has become better understood. The development of the pharmaceutical industry and the need to rapidly screen large numbers of compounds has made scientists in the area of drug development aware that the pharmacological activity of compounds can be predicted by knowing their solution physical chemical properties. This is not to say that a specific drug-active site interaction can be predicted but rather a prediction can be made whether or not a compound will be absorbed, transported, or distributed within a physiological system in such a way that an interaction can occur.

One of the surprising things about the natural world is that animals are dying around us all the time and yet we rarely see any evidence of it. This is a testimony to the efficiency of the large variety of organisms which decompose animal corpses. Whilst bacteria and fungi are the main groups involved in decomposition processes, the larger insects additionally provide an important physical disruption of body tissues, which aids the penetration of micro organisms and speeds the collapse of the body structure. A human corpse is treated no differently and the same groups of organisms are involved. From a forensic science viewpoint the universality of the decay process provides two major advantages. Information based on the decomposition of animals is of considerable value when considering human cases and the successional pattern of decay is broadly equivalent wherever the process is being studied. Historically, the usefulness of insects in solving crime can be traced back in the literature to the 13th century. McKnight 1, 2] translated a Chinese text of this period which contains an account of how a law officer dealt with a case of murder in the rice fields. Death had been caused by a sickle and the official ordered all the field workers to line up and lay their sickles on the ground in front of them. Flies began to be attracted to one of the sickles whereupon its owner confessed to the crime."

Literally thousands of papers have been published on nitric oxide over the past ten years. But there is no single monograph available that has previously attempted to summarize the important features of the roles of nitric oxide in inflammation. The voluminous literature regarding the incredible range of chemical and biological effects of nitric oxide and reactive nitrogen oxide species, RNOS, may present a tangle of confusing information to the researcher. This volume brings together experts from nitric oxide and inflammation research and presents a concise up-to-date overview as well as future aspects of this rapidly growing field.

Sequence-specific DNA binding ligands, amongst which triple helix forming oligonucleotides are the most efficient as yet, represent promising tools in a number of fields. One of their most promising applications is as antiviral tools: they can specifically target a viral gene, even if it is integrated into the host genome, and be used to specifically inactivate the viral gene or even destroy the cells harboring this gene. However, from science fiction to science there remains a gap; and we are at the moment on the threshold of this fascinating field. Triple Helix Forming Oligonucleotides considers the different aspects of the design and improvement, current or future, of these molecules and their structural analysis, as well as their applications, with special emphasis on the attempts to obtain biological effects of these potentially important tools. What emerges is that the current state of the research is encouraging, and that these molecules are already useful in some biotechnology applications.

Interest in chemical entities capable of blocking or modifying cell metabolism ultimately goes back to the discovery of the structure of DNA in the 1950s. Understanding of the biochemical processes involved in cell metabolism rapidly led to the idea that compounds could be designed which might interfere with these processes, and thus could be used in the treatment of the diseases caused by viral infection. Since then, several classes of drugs have been discovered which depend for their effect on modification of the proper functioning of nucleic acids and, with the introduction of acyclovir for the treatment of Herpes infections, nucleoside analogues have become the cornerstone of antiviral chemotherapy. The success of the early nucleoside agents, the toxicity and metabolic instability of many nucleoside analogues, and the effects of viral pathogens on public health are driving the design, synthesis and evaluation of new nucleoside analogues, with much attention turning to nucleosides containing non natural' sugar analogues. This book focuses on the development of these agents, and draws together all the available material in an easily consulted form, which at the same time guides the reader into the research literature on the subject. Written primarily for the medicinal chemist, coverage includes both synthetic strategies and outline guidance on the main trends in biological activity. Particular attention is drawn to the comparison of synthetic routes to compounds with their natural analogues. Finally, the important antiviral activities of the compounds are treated, including anti-retrovirus, anti-hepadnavirus and anti-herpes virus properties. Written mainly for medicinal chemists in the pharmaceutical industry and synthetic organic chemists in academe, this book will also be attractive to researchers in institutions focusing on cellular metabolism. Advanced students of organic chemistry will find the clear discussion of the synthetic strategies adopted in the development of these compounds a useful introduction to this exciting and challenging area.

Recombinant protein drugs are intimately associated with the impressive success story of the Biotech Industry during the past thirty years, some of them belonging to the most successful pharmaceutical products. More than thirty different proteins are available for a variety of clinical applications, over 300 proteins are presently being evaluated in clinical trials. In this new volume of the MDT series, historical, technical and clinical aspects of recombinant protein drug discovery and development are presented, covering past, present and future highlights. Leading scientists and co-founders of early Biotech companies describe technical breakthroughs and the fascinating story of pioneering discoveries, as well as the long way of translating them into products and business. Therefore, this book represents an exciting documentation of the beginning of a new era in the pharmaceutical industry. In addition, scientists from basic research, clinic and industry actively involved in new developments discuss...

TheNATO AdvancedStudiesInstituteseries"TargetingofDrugs"wasoriginatedin 1981. It is nowamajorinternationalforum,heldeverytwo yearsin CapeSounion,Greece,in whichthepresentandthefutureofthisimportantareaofresearch in drugdeliveryisdiscussed in greatdepth. PreviousASIsoftheseriesdealtwith drugcarriersofnaturalandsynthetic origin,theirinteractionswith thebiologicalmilieu, waysby whichthefunctionofdrugcarriers iscircumvented and,morerecently,with avarietyofapproaches to carrierdesignor modificationthatcontributeto optimalcarrierfunction. Thepresentbookcontainsthe proceedings ofthe8thNATO ASI, "TargetingofDrugs:Strategies for Oligonucleotideand GeneDelivery in Therapy", held in CapeSounionduring24June-5 July 1995. Asthetitle implies,thebookdealswith avarietyofsystemsin termsoftheirability to transportnucleic acidsto targetareasin vitro andin vivo in waysthateffectivelymodify,supplement, correct, orcurtailthefunctionofgenesin therapy. Weexpressourappreciation to Mrs. ConchaPerringfor herassistance with the organizationoftheASI. TheASI washeldunderthesponsorship ofNATO ScientificAffairs Division andco-sponsored andgenerouslyfinancedby SmithKlineBeechamPharmaceuticals (KingofPrussia). Financialassistance wasalsoprovidedby SandozPharma(Baseland Athens),GeneMedicine (Houston,USA), ChironCorporation(Emeryville,USA), BYK GuldenLombergChemische (Konstanz,Gernlany),HelpSA(Athens,Greece),Avanti Polar Lipids Inc (Birmingham,USA), OxfordMolecular(Oxford,UK), Pfizer(Kent,UK), andAlza Corporation(PaloAlto, USA). GregoryGregoriadis BrendaMcCormack v CONTENTS Gene Therapy for Inherited Genetic Disease: Possibilities and Problems c. *Coutelle Gene Delivery and Therapy: The Case for Cystic Fibrosis 15 E. W. F. W. Alton Immune Responses with Direct Gene Transfer: DNA Vaccines and 21 Implications for Gene Therapy H. L. Davis Oligonucleotides: Molecular Versions for Optimal Use in Vivo 31 E. Saison-Behmoaras, A. Van Aerschot, I. Duroux, C. Hendrix, C. Helene, and P. Herdewijn Retrovirus Vectors in Gene Therapy: Targeting to Specific Cells 45 AJ. Kingsman, Y. Bae, J. c. Griffiths, N. Kim, E. E. Ramsdale, G. Romano, Y. Soneoka, P. M. Cannon, and S. M. Kingsman Adenovirus as Vectors for Gene Therapy 53 M. G. Lee Receptor-Mediated Gene Delivery with Synthetic Virus-like Particles 67 E. Wagner, M. Cotten, and K. Zatloukal Controllable Gene Therapy: Recent Advances in Non-Viral Gene Delivery 79 A.

Due to the worldwide epidemic of acquired immunodeficiency syndrome (AIDS), the past ten years have witnessed a flurry of activity in the chemotherapy of viral diseases. Unprecedented scientific efforts have been made by scientists and clinicians to combat infections of human immunodeficiency virus (HIY), the causative agent. Looking back over the past ten years, we have made remarkable progress toward the treatment of the viral disease: isolation of HIV only two years after the identification of the disease, plus major strides in the areas of the molecular biology and virology of the retrovirus, etc. More remarkably, the discovery of the chemotherapeutic agent AZT (Retrovir) was made within two years after the isolation and identification of the virus, followed by unprecedented drug development efforts to culminate in the FDA approval of AZT in twenty-three months, which was a record-breaking time for approval of any drug for a major disease. The last six to seven years have particularly been an exciting and productive period for nucleoside chemists. Since the activity of AZI' was established in 1985, nucleoside chemists have had golden opportunities to discover additional anti-HIV nucleosipes, which are hoped to be less toxic and more effective than AZT, and the opportunity continues. As we all are aware, AZT possesses extremely potent anti-HIY activity, and no other nucleoside or non nucleoside has surpassed the potency of AZT in vitro."

In response to the tremendous increase in the number of protein and peptide drugs, this treatise critically reviews transport and metabolism mechanisms relating to the delivery of endogenous and recombinant proteins to mammalian organs, tissues, and cells. It will promote fruitful collaboration among academic and industrial scientists in the fields of pharmacology, cell biology, biochemistry, physiology, and immunology.

Cosmetic Science has developed greatly since the publication of the 8th edition of this textbook in 1974. Although the first part of this volume still consists of chapters about product preparations in alphabetical order, each product category has been revised and updated by a specialist. An outline of the biology, structure and function of skin, hair, teeth and nails and the reasons for the need for cosmetics are given in those dealing with the relevant preparations. Throughout, the word Cosmetics includes toiletries and thus all products which protect, cleanse, adorn, and perfume the human body, and combat body odour and perspiration. The 'f' spelling for the element 'sulfur' and its derivatives has been used following the recommendations of the International Union of Pure and Applied Chemistry (IUP AC) and the decision taken by the Royal Society of Chemistry (RSC) and the British Standards Institute (BSI) to use 'f' instead of 'ph' in all their publications. This stems from the derivation of the use of the 'f' from Latin and its use in England until the 15th century.

The "First International Conference on Traditional Chinese Medicine: Science, Regulation and Globalization" was held from August 30 to September 2, 2000 at the University of Maryland at College Park, Maryland. There were approximately 250 participants from the Peoples Republic of China, Taiwan, Hong Kong and the United States. This objective of this conference was to promote international collaboration for the modernization of Traditional Chinese herbal medicines (TCM) and their introduction into the global health care system. It was mainly sponsored by the Ministry of Science and Technology of the People's Republic of China and the NllI National Center for Complementary and Alternative Medicine (NCCAM). It was organized by Dr. William Tai, then director of the Institute of Global Chinese Affairs at the University of Maryland and Dr. Yuan Lin, president of Marco Polo Technologies, Bethesda, MD. This conference was conceived by Dr. Tai two years earlier recognizing that this was an appropriate time and also the unique location of the University of Maryland. Today, there is a growing recognition of the of alternative medicine in modem societies and the rapid loss of importance knowledge about traditional methods for the treatment of the multitude of human illnesses found throughout the world. TCM has been in common use in China for thousands of years; and many of its formulations are well defined.

It was a great honor for us to organize ChiCat, a symposium devoted to Chiral Reactions in Heterogeneous Catalysis and to be the hostsofmore than 120 scientists coming from everywhere in the industrialized world, to celebrate together one century of existence ofInstitut Meurice. This school was established in 1892when an industrial chemist, named Albert Meurice, decided to educate practical chemists according to the perceived needs ofthe industry ofthat time. This is exactly what we are still trying to do. It is the reason why, thirty years ago, we started a research activity in catalysis, and why we progressively devote this research to the applications of catalysis in the field of fine chemicals. In this respect, we are very close to another initiative of Albert Meurice, who started the first production of synthetic pharmaceuticals in Belgium during World War I. This business later on became a part ofthe Belgian corporation DCB, still very active in pharmaceuticals today. The school created by Albert Meurice merged in the fifties with another school that had been created to meet the same needs in the field of the food industries, mainly distilleries and breweries. This merger was done in the frame of the establishment of CERIA. For people in catalysis, ceria stands for cerium oxide, but for those who engineered the concept, CERIA stood for Center of Education and Research for the Food and Chemical Industries.

Table of Contents -Shape-Memory Polymers and Shape-Changing Polymers By M. Behl, J. Zotzmann, and A. Lendlein -Shape-Memory Polymer Composites By Samy A. Madbouly and Andreas Lendlein -Characterization Methods for Shape-Memory Polymers By W. Wagermaier, K. Kratz, M. Heuchel, and A. Lendlein -Shape-Memory Polymers for Biomedical Applications By Christopher M. Yakacki and Ken Gall -Controlled Drug Release from Biodegradable Shape-Memory Polymers By ChristianWischke, Axel T. Neffe, and Andreas Lendlein