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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).
List of contents
Pathopysiology of Iron Overload.- 1.Animal Models of Hereditary Iron Transport Disorders.- 2.Mechanism of Iron Toxicity.- 3.Role of Non-Transferrin-Bound Iron in the Pathogenesis of Iron Overload and Toxicity.- 4.Intacellular and Extracellular Labile Iron Pools.- 5.Cardioprotective Effect of Iron Chelators.- Chelation Therapy in Transfulional Siderosis.- 6.Results of Long Term Iron Chelation Treatment with Deferoxamine.- 7.Long Term Deferiprone Chelation Therapy.- Development of New Iron Chelators.- 8.Iron Chelator Chemistry.- 9.Structure-Activity Relationships Among Desazadesferrithiocin Analogues.- 10.ICL670A: Preclinical Profile.- 11.Pyridoxal Isonicotinoyl Hydrazone and Its Analogues.- Novel Strategies in Iron Chelation Treatment.- 12.Therapeutic Potential of Iron Chelators in Cancer Therapy.- 13.Antimalarial Effect of Iron Chelators.
Summary
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).
