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)."

1) Mechanism of Fe(II) Oxidation and Core Formation in Ferritin.- 2) Chemico-Physical and Functional Differences Between H and L Chains of Human Ferritin.- 3) Iron Oxidation in Sheep, Horse and Recombinant Human Apoferritins.- 4) The Transferrin Receptor and the Release of Iron from Transferrin.- 5) The Roles of Secondary Binding Sites for Transferrin in the Liver and on Macrophages.- 6) Optimized Separation and Quantitation of Serum and Cerebrospinal Fluid Transferrin Subfractions Defined by Differences in Iron Saturation or Glycan Composition.- 7) Mechanism of Production of the Serum Transferrin Receptor.- 8) Iron Absorption and Cellular Uptake of Iron.- 9) Ferric Iron Reduction and Iron Uptake in Eucaryotes: Studies with the Yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe.- 10) Cellular Responses to Iron and Iron Compounds.- 11) The Structure and Function of Iron Regulatory Factor.- 12) Structure and Function of IREs, the Noncoding mRNA Sequences Regulating Synthesis of Ferritin, Transferrin Receptor and (Erythroid) 5-Aminolevulinate Synthase.- 13) Translational Control by Iron-Responsive Elements.- 14) The Role of Cytokines in the Regulation of Ferritin Expression.- 15) Stimulation of IRE-BP Activity of IREF by Tetrahydrobiopterin and Cytokine Dependent Induction of Nitric Oxide Synthase.- 16) Reciprocal Modulation of Aconitase Activity and RNA-binding Activity of Iron Regulatory Factor by Nitric Oxide.- 17) A New Look at Ferritin Metabolism.- 18) Bacterioferritin: A Hemoprotein Member of the Ferritin Family.- 19) Intracellular Iron.- 20) Distinct Features of Iron Metabolism in Erythroid Cells: Implications for Heme Synthesis Regulation.- 21) Cellular Ferritin Uptake: A Highly Regulated Pathway for Iron Assimilation in Human Erythroid Precursor Cells.- 22) Differential Effects of Iron and Iron Carrier on Hematopoietic Cell Differentiation and Human ADA Gene Transfer.- 23) A Hemin-Inducible Enhancer Lies 4. 5 Kb Upstream of the Mouse Ferritin H Subunit Gene.- 24) Iron Deficiency: The Global Perspective.- 25) Iron Regulation in the Brain at the Cell and Molecular Level.- 26) Pathophysiology of Iron Toxicity.- 27) Morphologic Observations in Iron Overload: An Update.- 28) Identification of Thiolic Sarcolemmal Proteins as a Primary Target of Iron Toxicity in Cultured Heart Cells.- 29) Iron Overload and the Biliary Route.- 30) Changing Concepts of Haemochromatosis.- 31) Epidemiology, Clinical Spectrum and Prognosis of Hemochromatosis.- 32) The Morbidity of Hemochromatosis Among Clinically Unselected Homozygotes: Preliminary Report.- 33) Genetics of Haemochromatosis.- 34) Localization of Seven New Genes Around the HLA-A Locus.- 35) Searching for the Hemochromatosis Grail.- 36) Iron Chelator Design.- 37) Results from a Phase I Clinical Trial of HBED.- 38) Lessons from Preclinical and Clinical Studies with 1,2-Diethyl-3-Hydroxypyridin-4-One, CP94 and Related Compounds.- 39) Iron Chelation Therapy for Malaria.- 40) The Biochemical Basis for the Selective Antimalarial Action of Iron Chelators on Plasmodium Falciparum Parasitized Cells.

This book summarizes the most current research on the anemia of chronic disease and identifies effective diagnostic strategies for this common clinical condition-covering key topics related to the design and selection of therapeutic options including the treatment of the underlying disease, the biology of erythropoietin and the regulation of erythropoiesis, the disturbance of iron homeostasis, and the complex nature of the systemic inflammatory response.

The 4th International Conference on Hemochromatosis and the 11th International Conference on Iron and Iron Proteins took place in Jerusalem on April 27 -30 and on May 2 -7 1993, respectively. The first, a clinical meeting, and the second, a forum designed primarily for basic scientists. Both meetings are held regularly on alter nate years and represent probably the most important forum for the exchange of information in iron research. The present volume "Progress in Iron Research" is based on a selection of presentations delivered at these meetings. However, this volume represents much more than a publication of conference proceedings. It offers a comprehensive state-of-the-art review on most aspects of iron metabolism. We have tried to offer a balanced review of the most important recent developments in iron research including both basic research and clinical investigation. However, the scope of chapters was based, by definition, on the actual participants at the meetings and some important fields in iron research such as plant physiology, microbial aspects of iron metabolism, and free radical research have not been dealt with. Many of the authors of the 40 chapters have beel). pt1rsonally responsible for some of the most important developments in iron research ~~vidffig: n~~~ights into iron physiology and pathophysiology. The Editors wish to express their gratitude for the outstanding and timely cooperation of all contributors to this volume.

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)."