Conditioned taste aversion (CTA) is a robust defence device protecting animals against repeated consumption of toxic food. It is characterised by the ability of many animals to learn to avoid certain substances by their sight, smell, or taste after experiencing an unpleasant or harmful reaction to them. CTA is encountered at all levels of evolution, with similar forms of food aversion learning found in vertebrate and invertebrate species whose ancestral lines diverged more than 500 million years ago. CTA has a number of unusual properties contrasting sharply with the basic assumptions of traditional learning theories, which has brought it increasingly to the attention of neurobiologists interested in neural plasticity. In CTA, the usual time parameters between stimulus and aversion are relaxed considerably, frequently with delays of hours rather than seconds. Moreover, the critical stage of CTA acquisition may proceed under deep anaesthesia incompatible with other forms of learning. In the past decade several pivotal discoveries have considerably avanced our understanding of the neural processes underlying CTA, and opened new possibilities for their analysis at the molecular and cellular levels. This book, written by three of the world's leading researchers in the subject, comprehensively reviews the current state of research into conditioned taste aversion. The first book of its kind to provide an up-to-date summary of research into the neuroanatomy, pharmacology, electrophysiology, and functional morphology of CTA, it will be welcomed by all researchers and graduate students in the field.

This book introduces some emerging functional foods that are natural resources with tremendous promise as nutraceuticals and pharmaceuticals. The author considers biodiversity and bioprospecting as a response to food security issues, drug-resistance, nutrition-poor diets and other problems, exploring the prospects of several under-utilized nutrients and bioactive repositories. Readers will discover biochemical makeups, validated health benefits, explanations of underlying mechanisms, hurdles in the path of popularity and promotion strategies. Chapters explore particular plants, seeds and fruits including the strawberry guava, opuntia fruits, the Carissa genus, grape seeds, quinoa and the milk thistle (Silybum), amongst others. They are considered as food sources where possible and from the perspective of the roles they can play in complementary and alternative medicine, such as in wound healing, antimicrobial activity, gastroprotective activity in treatment of cancers and as natural antioxidant sources. This rich compilation holds plausible solutions to a range of current issues and it endorses the much-needed goal of sustainability in terms of diet and drugs. It paves the path for further research and development on hitherto obscure natural resources. Scientists working in the area of food development, phytochemical and antioxidant analysis, bioprospecting of low-profile foods and in complementary and alternative medicine will find this work particularly valuable. It will also be of interest to the general reader with an interest in food science, food security, phytochemicals and functional food studies.

This is the first book devoted to the study of the social and economic consequences of headache. Reducing the Burden of Headache analyses the financial cost of headache diseases, the disability and suffering they cause and the impact they have on the quality of life of the sufferers and their families.

These are issues of major importance; migraine appears in the top 20 list of diseases ranked according to years lived with disability. Headache, in general, is thought to account for approximately 20% of all days lost from work. Of even greater importance is the impact on everyday life, studies have shown that migraine has a greater impact on the quality of life of sufferers than many other diseases generally considered to be more serious.

This book describes and analyses the epidemiological data accumulated in the field and suggests guidelines and interventions aimed at improving healthcare for headache. Adoption of these suggestions combined with judicious use of existing resources and modern treatment options can lead to great improvements in the lives of headache sufferers world-wide.

This book will be of interest to neurologists, general practitioners, epidemiologists, public health specialists, health service managers and all those interested in improving services and outcomes for sufferers of headache.

This monograph contains a description of the discovery and development of a antisecretory therapy in the treatment of acid-related diseases: omeprazole, the first proton pump inhibitor. Overviews compare this and other proton pump inhibitors and discuss their pharmacology, including the mechanism of action, the effect on Helicobacter pylori infection, and the consequences of profound inhibition of gastric acid secretion. The pharmaceutic delivery system is described since it constitutes a special problem with this class of drugs. The clinical experience with proton pump inhibitors in acid-related diseases is reviewed with focus on gastro-esophageal reflux disease and peptic ulcer diseases including Helicobacter pylori and NSAID-induced ulcerations and Zollinger-Ellison syndrome. Finally, an overview is presented on the socio-economic impact of proton pump inhibitors in acid-related diseases emphasizing the important aspect of quality of life. The monograph is aimed at a broad readership with an interest in the development problems of this, at present, most commercially successful drug; the pharmacology of a "tailor-made" drug for a specific target; the therapeutic strategies in acid-related diseases; and the dramatic changes in the long-term outcome results of the treatment of peptic ulcer diseases where most patients now can be cured from the disease after only one week of drug therapy.

Phytochemicals are components acting individually, additively or synergistically, usually as a component of whole food, that have the characteristics of providing protective, preventative and possibly curative roles in the pathogenesis of cancer and other chronic disease progressions. Nutraceutical is a term used to describe beneficial phytochemicals. The mechanisms of action of nutraceuticals may be one of several. Free radical scavenger and antioxidant nutraceuticals can nullify damage by any number of biochemical mechanisms, but some also exert benefit by enhancing immune function.

A conservative economic analysis was done in 1993 of solely hospital care costs and the roles that three nutrient antioxidants could exert on cardiovascular disease, breast cancer and cataracts. The study considered the potential impact of only three antioxidants, vitamins C and E, and beta-carotene, and the possible annual savings in hospital care costs alone, which could exceed 8 billion dollars. Expert public health physicians believe that as much as 700f disease is preventable.

The chapters in this book were organized to reveal existing and emerging knowledge of nutraceuticals found in garlic, soy and licorice. Lead chapters discuss the epidemiological evidence, and following chapters discuss chemical or biochemical evidence at the cellular level, as well as the presentation of some clinical data.

A major conclusion of the overall effort is that the science of nutraceuticals is very incomplete, but that findings to date have great promise.

Histamine is an important mediator of allergic diseases such as hay fever and bronchial asthma, food allergies, urticaria, and drug hypersensitivity. Knowledge of histamine as a cause of numerous non-allergic symptoms and signs is, however, limited. In fact, histamine intolerance can be responsible for conditions as diverse as seasickness, headaches and migraine, tachycardia, gastric disorders, diarrhea, intolerance to contrast media, parodontosis, period pains, nausea and vomiting in pregnancy, atopic dermatitis, and osteoporosis. This book offers wide-ranging coverage of histamine intolerance. There is extensive background discussion of the origin of histamine, its content in food and alcoholic beverages, and intolerance to red wine. Diagnosis of histamine intolerance is explained, and the various symptoms of histamine intolerance are clearly described. Subsequent chapters cover the conditions mentioned above and also consider the relation of histamine to vitamin B6 and the specific immunotherapy of allergies. This book will prove of value in clinical practice by facilitating differential diagnosis, which is by no means straightforward given the multiplicity of symptoms of histamine intolerance, and by assisting in the selection of therapeutic measures.

The world's population is growing at an unsustainable rate. From a baseline ?gure of one billion in 1800, global population is predicted to exceed nine billion by 2050 and 87. 8% of this growth will be localized in less developed countries. Such uneven population growth will yield a harvest of poverty, malnutrition, disease and en- ronmental degradation that will affect us all. Amongst the complex mixture of political, social, cultural and technological changes needed to address this issue, the development of improved methods of fertility regulation will be critical. The inadequacy of current contraceptive technologies is indicated by recent data s- gesting that the contraceptive needs of over 120 million couples go unmet every year. As a direct consequence of this de?cit 38% of pregnancies are unplanned and more than 50% end in an abortion, generating a total of 46 million abortions per annum particularly among teenagers. If safe, effective contraceptives were ava- able to every couple experiencing an unmet family planning need, 1. 5 million lives would be saved each year (UNFPA 2003). Progress in contraceptive technology should not only generate more effective methods of regulating fertility, but should also provide a range of methods to meet the changing needs of the world's population. Contraceptive practice was revo- tionized in 1960 in the US and 1961 in Europe by the introduction of the oral contraceptive pill by Gregory Pincus, MC Chang and colleagues, based on fun- mental hormone research conducted in Germany.

Pharmacogenomics supports personalized medicine by translating genome-based knowledge into clinical practice, offering enhanced benefit for patients and health-care systems at large. Current routine practice for diagnosing and treating patients is conducted by correlating parameters such as age, gender and weight with risks and expected treatment outcomes. In the new era of personalized medicine the healthcare provider is equipped with improved ability to prevent, diagnose, treat and predict outcomes on the basis of complex information sources, including genetic and genomic data. Targeted therapy and reliable prediction of expected outcomes offer patients access to better healthcare management, by way of identifying the therapies effective for the relevant patient group, avoiding prescription of unnecessary treatment and reducing the likelihood of developing adverse drug reactions.

Because progress in the field of transporters has been extraordinary, this volume will focus on recent advances in our understanding of the structure, function, physiology, and molecular biology of membrane transporters. There will be an emphasis on transporters as molecular targets for drug delivery and disposition in the body.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

Recent years have seen unprecedented outbreaks of avian influenza A viruses. In particular, highly pathogenic H5N1 viruses have not only resulted in widespread outbreaks in domestic poultry, but have been transmitted to humans, resulting in numerous fatalities. The rapid expansion in their geographic distribution and the possibility that these viruses could acquire the ability to spread from person to person raises the risk that such a virus could cause a global pandemic with high morbidity and mortality. An effective influenza vaccine represents the best approach to prevent and control such an emerging pandemic. However, current influenza vaccines are directed at existing seasonal influenza viruses, which have little or no antigenic relationship to the highly pathogenic H5N1 strains. Concerns about pandemic preparedness have greatly stimulated research activities to develop eff- tive vaccines for pandemic influenza viruses, and to overcome the limitations inh- ent in current approaches to vaccine production and distribution. These limitations include the use of embryonated chicken eggs as the substrate for vaccine prod- tion, which is time-consuming and could involve potential biohazards in growth of new virus strains. Other limitations include the requirement that the current inac- vated influenza vaccines be administered using needles and syringes, requiring trained personnel, which could be a bottleneck when attempting to vaccinate large populations in mass campaigns. In addition, the current inactivated vaccines that are delivered by injection elicit limited protective immunity in the upper respiratory tract where the infection process is initiated.

Integrative medicine strives to incorporate the best of complementary and conventional modalities. This book details integrative oncology, a nascent field building a rigorous evidenced-based clinical medicine, research, and educational foundation. It examines five prestigious, comprehensive cancer centers based in the US, covering how these centers started their programs, what they are currently doing, and recommendations for starting integrative medicine clinics. The book also discusses the potential harm of alternative and complementary medicine, legal issues, and how to communicate with patients.

Heparins remain amongst the most commonly used drugs in clinical practice. Almost 100 years have passed since the initial discovery of this complex substance and, during this time, understanding of the nature and uses of heparin and related molecules has grown dramatically. The aim of this volume is to summarise the developments that have led to the current status of both heparins as drugs and the field of heparin research, with a focus on the particularly rapid progress that has been made over the past three decades. Individual sections are dedicated to the nature of heparin as a biological molecule, the current approaches and techniques that are used to ensure the safety and reliability of heparin as a medicine, the clinical pharmacology of heparin as an anticoagulant drug, effects and potential applications of heparin aside of those involving haemostasis and, finally, the nature and potential uses of heparin-like materials from both natural and synthetic sources."

The reader will be introduced to various aspects of the fundamentals of nanotechnology based drug delivery systems and the application of these systems for the delivery of small molecules, proteins, peptides, oligonucleotides and genes. How these systems overcome challenges offered by biological barriers to drug absorption and drug targeting will also be described.

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 majority of cancers present at a relatively advanced stage in which invasion within the primary organ is well established and metastases to lymph and distant organs are either clinically apparent or present at the microscopic level. However, it is increasingly recognized that the natural history of cancer formation is a long and complex path taking many years to develop to a clinically apparent stage in most cases. Furthermore, for most solid tumours there is a pre-invasive or intraepithelial stage of disease. This affords the opportunity for early detection and prevention of invasive disease and hence a cure. However, with this advancing knowledge comes a whole plethora of questions which will be explored in this monograph. Firstly, we need to understand the global burden of pre-invasive disease and what the public health implications might be for wide-scale screening programmes. In the western world we already have experience of screening for cervical, breast, prostate and more recently colon cancer. As well as their potential benefits these programmes have financial and psychosocial implications which need to be carefully weighed. This is especially true since many pre-invasive lesions will not progress to cancer in a individual's lifetime. In addition, there are questions concerning whether screening reduces the cancer burden or in fact distorts the survival figures through lead-time bias. Secondly, at the level of epidemiology and molecular pathogenesis there are important questions regarding the aetiology of pre-invasive lesions; an understanding of which might lead to possible chemopreventive strategies. For example, it would be helpful to know the extent to which the likelihood of developing a pre-invasive lesion is influenced by lifestyle or genetic factors and how these factors influence the risk of progression to invasive disease. At the molecular level we need to understand the pathways and molecular mechanisms, both genetic and epigenetic, by which cells achieve the capacity to invade. Thirdly, in order make clinical progress we need biomarkers to identify and risk stratify individuals with pre-invasive lesions. These biomarkers might be applied to the serum as in Prostate Specific Antigen in prostate cancer or be applied to tissue samples, such as oestrogen receptor status in breast cancer. In order to utilize biomarkers in the context of a screening programme there are issue around the invasiveness of the test as well as its positive and negative predictive value. With advances in molecular imaging there is now the exciting possibility of incorporating a molecular tag to a non-invasive imaging modality. Fourthly, in order to justify screening early detection must be coupled to a treatment strategy. If the chemopreventive agent is very well tolerated, then as well as targeting high risk groups, one might consider treatment at the population level. Aspirin is one such drug which has been extensively assessed in the context of colon cancer chemoprevention trials. Trials of aspirin chemoprevention are now being applied to other cancers such as oesophageal adenocarcinoma and since many individuals take aspirin for .chemoprevention of cardiovascular disease the cancer incidence can be ascertained in these populations. In order to understand the more general issues raised from the discussions above it is useful to consider disease specific examples. Our understanding of pre-invasive disease varies according to the organ site and there are lessons to be learned from these experiences. For example, there is now the prospect of a vaccine for cervical cancer with important questions about how this might be applied to the high incidence areas of the developing world. On the other hand, ductal carcinoma in situ is currently treated by mastectomy which is more radical than the treatment received by many women with invasive disease. Oesophageal adenocarcinoma, which is my own area of expertise is interesting because of the rapid rise in incidence in the western world and the clinically accessible pre-invasive lesion called Barrett's oesophagus. However, most cases of Barrett's oesophagus remain undiagnosed and it is not yet clear how to effectively diagnose, monitor and treat this condition without recourse to mass endoscopy with substantial cost implications. In conclusion, in an era in which preventive medicine is a major concern for consumers, health-policy makers and politicians pre-invasive disease is likely to become a major part of cancer medicine.

This book continues as volume 5 of a multicompendium on Edible Medicinal and Non-Medicinal Plants. It covers edible fruits/seeds used fresh, cooked or processed as vegetables, cereals, spices, stimulant, edible oils and beverages. It covers selected species from the following families: Apiaceae, Brassicaceae, Chenopodiaceae, Cunoniaceae, Lythraceae, Papaveraceae, Poaceae, Polygalaceae, Polygonaceae, Proteaceae, Ranunculaceae, Rhamnaceae, Rubiaceae, Salicaceae, Santalaceae, Xanthorrhoeaceae and Zingiberaceae. This work will be of significant interest to scientists, medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, botanists, agriculturists, conservationists, lecturers, students and the general public. Topics covered include: taxonomy; common/English and vernacular names; origin and distribution; agroecology; edible plant parts and uses; botany; nutritive/pharmacological properties, medicinal uses, nonedible uses; and selected references.

This book puts hydrogen sulfide in context with other gaseous mediators such as nitric oxide and carbon monoxide, reviews the available mechanisms for its biosynthesis and describes its physiological and pathophysiological roles in a wide variety of disease states. Hydrogen sulfide has recently been discovered to be a naturally occurring gaseous mediator in the body. Over a relatively short period of time this evanescent gas has been revealed to play key roles in a range of physiological processes including control of blood vessel caliber and hence blood pressure and in the regulation of nerve function both in the brain and the periphery. Disorders concerning the biosynthesis or activity of hydrogen sulfide may also predispose the body to disease states such as inflammation, cardiovascular and neurological disorders. Interest in this novel gas has been high in recent years and many research groups worldwide have described its individual biological effects. Moreover, medicinal chemists are beginning to synthesize novel organic molecules that release this gas at defined rates with a view to exploiting these new compounds for therapeutic benefit.

Volume 8 is part of a multicompendium Edible Medicinal and Non-Medicinal Plants, on plants with edible flowers from Geraniaceae to Zingiberaceae (tabular) and 82 species in Geraniaceae, Iridaceae, Lamiaceae, Liliaceae, Limnocharitaceae, Magnoliaceae, Malvaceae, Meliaceae, Myrtaceae, Nyctaginaceae, Nymphaeaceae, Oleaceae, Onagraceae, Orchidaceae, Paeoniaceae, Papaveraceae, Plantaginaceae, Poaceae, Polygonaceae, Primulaceae, Proteaceae, Ranunculaceae, Rosaceae, Rubiaceae, Rutaceae, Solanaceae, Theaceae, Tropaeolaceae, Tyhpaceae, Violaceae, Xanthorrhoeaceae and Zingiberaceae in detail. This work is of significant interest to medical practitioners, pharmacologists, ethnobotanists, horticulturists, food nutritionists, botanists, agriculturists, conservationists and general public. Topics covered include: taxonomy; common/ vernacular names; origin/ distribution; agroecology; edible plant parts/uses; botany; nutritive/medicinal properties, nonedible uses and selected references.

In this volume of Reviews of Physiology, Biochemistry and Pharmacology there a contributions by M.D. Swope, E. Lolis, F.Hofmann, L. Lacinova, N. Klugbauer, M. Hermann, P. Berger, S.S. Shen, J.S. Kim, M.E. Weksler, M. Hirsch-Kauffmann and M.Schweiger.

There are only very few chemical classes of antibiotics in medical use, and these have originated over a span of more than 60 years of research. Almost half a century ago, the first member of the macrolides, erythromycin, was introduced as a treatment option for bacterial infections. Erythromycin is a very complex fermentation product obtained from the soil bacterium Saccharopolyspora ery thraea (originally named Streptomyces erythreus). The success of erythromycin, based on its efficacy and tolerability, stimulated researchers throughout the world to undertake intense efforts to understand the biology and chemistry of macrolides and to use this experience to improve the properties of this compound class. The second generation of macrolides, based on chemical modifications of erythromy cin, is currently being in broad use, especially for treatment of respiratory tract infections. We presently foresee the introduction of a new generation of macro lides, i. e. the ketolides, which have the potential to overcome rising resistance problems. This monograph is intended to give the interested reader an overview on "macrolide experience," covering important areas from basic research to clinical use. Starting from a historic overview, the essential basic parameters - efficacy, pharmacokinetics, pharmacodynamics, and pharmacology - are highlighted in order to introduce the reader to the rationale for clinical use of macrolides. The following group of chapters cover the complex chemistry of the macro lactone structures, giving historic background, basic structure-activity relation ships of various derivatization strategies, and perspectives for future discovery of new semisynthetic macrolide antibiotics."

Medicinal and Aromatic Plants XII comprises 18 chapters. It deals with the distribution, importance, conventional propagation, micropropagation, tissue culture studies, and the in vitro production of important medicinal and pharmaceutical compounds in the following plants: Artemisia annua, Coriandrum sativum, Crataegus, Dionaea muscipula, Hyoscyamus reticulatus, Hypericum canariense, Leguminosae, Malva, Ocimum, Pergularia tomentosa, Phellodendron amurense, Sempervivum, Solanum aculeatissimum, S. chrysotrichum, S. kasianum, Stephania, Trigonella, and Vaccinium. It is tailored to the needs of advanced students, teachers, and research scientists in the fields of pharmacy, plant tissue culture, phytochemistry, biomedical engineering, and plant biotechnology in general.