Iron Chelation 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.

Within the last few years, iron research has yielded exciting new insights into the under standing of normal iron homeostasis. However, normal iron physiology offers little protec tion from the toxic effects of pathological iron accumulation, because nature did not equip us with effective mechanisms of iron excretion. Excess iron may be effectively removed by phlebotomy in hereditary hemochromatosis, but this method cannot be applied to chronic anemias associated with iron overload. In these diseases, iron chelating therapy is the only method available for preventing early death caused mainly by myocardial and hepatic iron toxicity. Iron chelating therapy has changed the quality of life and life expectancy of thalassemic patients. However, the high cost and rigorous requirements of deferoxamine therapy, and the significant toxicity of deferiprone underline the need for the continued development of new and improved orally effective iron chelators. Such development, and the evolution of improved strategies of iron chelating therapy require better understanding of the pathophysiology of iron toxicity and the mechanism of action of iron chelating drugs. The timeliness of the present volume is underlined by several significant develop ments in recent years. New insights have been gained into the molecular basis of aberrant iron handling in hereditary disorders and the pathophysiology of iron overload (Chapters 1-5).

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

Representing an integration of basic and clinical sciences, this book focuses on new concepts in the design, synthesis, and testing of iron chelators for clinical application. It provides an overview of the pathophysiology of iron metabolism as it relates to the origins of iron-mediated tissue damage, and it clearly outlines successes and shortcomings of current iron chelation therapy in preventing such damage. The book also describes a number of other exciting potential therapeutic applications of iron chelators, such as in the treatment of malaria. Other topics covered include iron coordination chemistry, recent advances in synthetic methods for accessing iron chelators, siderophore models, subcellular iron storage targets, and the possible application of biotechnology in the production of therapeutically useful iron chelators. The book also describes new animal models for evaluating chelators.

Metal chelators are emerging as versatile tool with many medical applications. Their versatility allows them to be used in chelation therapy for treating diseases caused by toxic and heavy metal poisoning, chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. In addition, metal chelators can also be applied as contrast agents in MRI scanning. Metal Chelation in Medicine provides a clear and timely perspective on the role of chelating agents in the management of metal intoxications and storage diseases. Written by leaders in the field of chelators, this publication is at the cutting-edge of the subject. It covers a broad range of topics such as the use of metal chelators in non-invasive assessment of brain iron overload, and the treatment of systemic iron overload and neurodegenerative diseases. As such it is particularly valuable to clinicians treating metal poisonings and metal storage diseases. However, it is also a useful text for researchers, industry professionals and university students with a specific interest in medicinal chemistry, chelation, metal ions, imaging and non-invasive techniques.

Written by the foremost authority in the field, this volume is a comprehensive review of the multifaceted phenomenon of hepatotoxicity. Dr. Zimmerman examines the interface between chemicals and the liver; the latest research in experimental hepatotoxicology; the hepatotoxic risks of household, industrial, and environmental chemicals; and the adverse effects of drugs on the liver. This thoroughly revised, updated Second Edition features a greatly expanded section on the wide variety of drugs that can cause liver injury. For quick reference, an appendix lists these medications and their associated hepatic injuries. Also included are in-depth discussions of drug metabolism and factors affecting susceptibility to liver injury.

Provides state-of-the-art coverage of CMR technologies and guidelines, including basic principles, imaging techniques, ischemic heart disease, right ventricular and congenital heart disease, vascular and pericardium conditions, and functional cardiovascular disease. Includes new chapters on non-cardiac pathology, pacemaker safety, economics of CMR, and guidelines as well as new coverage of myocarditis and its diagnosis and assessment of prognosis by cardiovascular magnetic resonance, and the use of PET/CMR imaging of the heart, especially in sarcoidosis. Features more than 1,100 high-quality images representing today’s CMR imaging. Covers T1, T2 and ECV mapping, as well as T2* imaging in iron overload, which has been shown to save lives in patients with thalassaemia major Discusses the cost-effectiveness of CMR.