This book is aimed at those in the biomedical community that are interested in the therapeutic applications, pharmacology, biochemistry, toxicology and pharmacokinetics of the title compounds. Recent findings regarding the ability of diethyldithiocarbamate (ditiocarb, Imuthiol®) to delay the progression of HN infections and AIDS, the discovery of its potential as a rescue agent in cancer chemotherapy, and the identification of disulfiram (Antabuse®) regimens that allow alcoholics to achieve abstinence of many months' duration have made writing this book an exciting experience. At the same time the fact that the two drugs differ substantially in their pharmacological effects in spite of their easy interconvertibility has rendered the writing intellec tually challenging. Diethyldithiocarbamate, an agent seemingly less toxic than aspirin, rivals it in the multiplicity and diversity of its pharmacological proper ties. Notable among these are the manyfold potent immunostimulant effects, and though most of these involve effects on T -cells, the mechanism of diethyldithiocarbamate's action remains far from clear. The drug is also a potent chelator of heavy metals and this has led to a number of clinical applications. As might be expected, it inhibits several important enzymes. Further, it is one of the most effective radioprotective agents; it also protects organisms against a variety of toxic agents.

This book focuses on the value of supervised Disulfiram therapy, highlighting the many potential and unique benefits of Disulfiram. One of the oldest drugs available for the long-term management of alcohol dependence, Disulfiram remains a viable treatment option for alcohol dependence and has been shown in recent studies to be more successful in treating patients with alcohol dependence than Naltrexone, Topiramate and Acamprosate. It is also useful in dual diagnosis patients and those with co-morbid cocaine and alcohol dependence. Although Disulfiram’s mechanism of action in alcohol dependence was long thought to be its effects as a psychological deterrent, more recent studies point to potential anti-craving effects as well. In dedicated chapters, the book reviews major clinical trials of Disulfiram spanning nearly 60 years, its historical aspects and discovery, side effects, treatment protocols and uses in the context of alcohol dependence. The book also discusses the use of Disulfiram across diverse populations along with monitoring for compliance and various adverse effects that may manifest. Further topics include Disulfiram implant therapy and the role of Disulfiram in the modern long-term pharmacotherapy of alcohol dependence, as well as the role of cognitive behavior therapy in enhancing the effects of Disulfiram and the emerging role of Disulfiram in treating cocaine dependence and pathological gambling. As such, the book offers a “one-stop” comprehensive guide to all aspects of Disulfiram therapy.

Volume 19, entitled Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic of the series Metal Ions in Life Sciences centers on the role of metal ions in clinical medicine. Metal ions are tightly regulated in human health: while essential to life, they can be toxic as well. Following an introductory chapter briefly discussing several important metal-related drugs and diseases and a chapter about drug development, the focus is fi rst on iron: its essentiality for pathogens and humans as well as its toxicity. Chelation therapy is addressed in the context of thalassemia, its relationship to neurodegenerative diseases and also the risks connected with iron administration are pointed out. A subject of intense debate is the essentiality of chromium and vanadium. For example, chromium(III) compounds are taken as a nutritional supplement by athletes and bodybuilders; in contrast, chromate, Cr(VI), is toxic and a carcinogen for humans. The benefi cial and toxic effects of manganese, cobalt, and copper on humans are discussed. The need for antiparasitic agents is emphasized as well as the clinical aspects of metal-containing antidotes for cyanide poisoning. In addition to the essential and possibly essential ones, also other metal ions play important roles in human health, causing harm (like the metalloid arsenic, lead or cadmium) or being used in diagnosis or treatment of human diseases, like gadolinium, gallium, lithium, gold, silver or platinum. The impact of this vibrant research area on metals in the clinic is provided in 14 stimulating chapters, written by internationally recognized experts from the Americas, Europe and China, and is manifested by approximately 2000 references, and about 90 illustrations and tables. Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic is an essential resource for scientists working in the wide range from pharmacology, enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine ... not forgetting that it also provides excellent information for teaching.

Chelation Therapy in the Treatment of Metal Intoxication presents a practical guide to the use of chelation therapy, from its basic chemistry, to available chelating antidotes, and the application of chelating agents. Several metals have long been known to be toxic to humans, and continue to pose great difficulty to treat. These challenges pose particular problems in industrial settings, with lead smelting known to be associated with hemopoietic alterations and paralyses, and the inhalation of mercury vapor in mercury mining being extremely detrimental to the central nervous system. Clinical experience has demonstrated that acute and chronic human intoxications with a range of metals can be treated efficiently by administration of chelating agents. Chelation Therapy in the Treatment of Metal Intoxication describes the chemical and biological principles of chelation in the treatment of these toxic metal compounds, including new chelators such as meso-2,3-dimercaptosuccinic acid (DMSA) and D,L-2,3-dimercapto-1-propanesulfonic acid (DMPS). - Presents all the current findings on the potential for chelation as a therapy for metal intoxication - Presents practical guidelines for selecting the most appropriate chelating agent - Includes coverage on radionuclide exposure and metal storage diseases - Describes the chemical and biological principles of chelation in the treatment of toxic metal compounds

Drug Discovery Targeting Drug-Resistant Bacteria explores the status and possible future of developments in fighting drug-resistant bacteria. The book covers the majority of microbial diseases and the drugs targeting them. In addition, it discusses the potential targeting strategies and innovative approaches to address drug resistance. It brings together academic and industrial experts working on discovering and developing drugs targeting drug-resistant (DR) bacterial pathogens. New drugs active against drug-resistant pathogens are discussed, along with new strategies being used to discover molecules acting via new modes of action. In addition, alternative therapies such as peptides and phages are included. Pharmaceutical scientists, microbiologists, medical professionals, pathologists, researchers in the field of drug discovery, infectious diseases and microbial drug discovery both in academia and in industrial settings will find this book helpful.

A panel of leading academic and pharmaceutical investigators takes stock of the remarkable work that has been accomplished to date with proteasome inhibitors in cancer, and examines emerging therapeutic possibilities. The topics range from a discussion of the chemistry and cell biology of the proteasome and the rationale for proteasome inhibitors in cancer to a review of current clinical trials underway. The discussion of rationales for testing proteasome inhibitors in cancer models covers the role of the proteasome in NF-kB activation, the combining of conventional chemotherapy and radiation with proteasome inhibition, notably PS-341, new proteasome methods of inhibiting viral maturation, and the role of protesome inhibition in the treatment of AIDS. The authors also document the development of bortezomib (VelcadeTM) in Phase I clinical trials and in a multicentered Phase II clinical trials in patients with relapsed and refractory myeloma.

Early in 1985, a meeting was held to discuss the organization of a work shop in honour of Professor Reinier L. Zielhuis on the occasion of his retirement on November 30,1986. Various themes for such a workshop were considered, but it was Zielhuis himself, who ultimately selected "Health surveillance of individual workers exposed to chemical agents" as the theme of the workshop. Although this topic is of the utmost im portance for occupational health practice, it is also a very difficult one, given our currently limited knowledge on the subject. The choice of this topic is characteristic of Reinier Zielhuis, a scientist and scholar who throughout his career has been deeply concerned with the health and health risks of workers. Because he regards occupational and environmental exposure - including life style - as two aspects of the total exposure to chemical and physical factors, he emphasizes the need to assess the impact of this total exposure on workers' health. The impact of total exposure probably detennines to a large extent the in dividual variability in response. This was the main reason why he selected the above-mentioned topic for the workshop.

Despite the efficiency of current cancer treatments, cancer is still a deadly disease for too many. In 2008, 7.6 million people died of cancer; with the current development, it is estimated that the annual cancer death number will grow to 13 million by 2030. There is clearly a need for not only more research but also more innovative and out of the mainstream scientific ideas to discover and develop even better cancer treatments. This book presents the collective works published in the recent Special Issue entitled “Killing Cancer: Discovery and Selection of New Target Molecules”. These articles comprise a selection of studies, ideas, and opinions that aim to facilitate knowledge, thoughts, and discussion about which biological and molecular mechanisms in cancer we should target and how we should target them.

Radicals for Life: the Various Forms of Nitric Oxide provides an up-to-date overview of the role of nitrosocompounds and nitrosyl-iron complexes in physiology. Nitrosocompounds can be considered as stabilised forms of nitric oxide, one of the most important regulatory molecules in physiology today. Many nitrosocompounds share some of the physiological functions of nitric oxide, and may be formed inside living organisms. This is the first book to be published that is dedicated to the role of such nitrosocompounds in physiology, with particular emphasis on the nitrosocompounds that are endogenously formed in higher organisms and humans. Points of discussion include: physical and chemical properties of the compounds, the main chemical pathways in vivo, as well as the physiological effects that have been recognised to date. Each of the nineteen chapters is written by distinguished specialists in the field, well known for their original and important contributions to the subject. Also included are results from a wide range of studies in vitro, in cell cultures, animal models and human volunteers. Examples of alternative forms of nitric oxide, with special emphasis on their protective role against widespread human diseases like atherosclerosis, Alzheimer's disease, diabetes, sexual dysfunction, and renal insufficiency to stroke and ischemia are also included. - First monograph to consider and provide an overview of endogenous nitrosocompounds and nitrosyl-iron complexes - Extensive bibliographic references, written by specialists of human physiology - Providing high scientific quality with a focus on implications for human diseases