Yair Galili, MD and Arie Bass, MD
Seth J. Corey, MD and Quan-Sheng Zhu, MD
Tomas Ganz, PhD, MD
Systemic infection or inflammation causes a decrease in intestinal iron absorption and impairs the release of recycled iron from macrophages. Decreased availability of iron may deny this essential element to invading pathogens and may inhibit their multiplication and other metabolic processes but also results in anemia of chronic disease. This article reviews recent discoveries that shed light on the regulation of iron metabolism during infection and iron overload, and point to the central role of a newly discovered peptide, hepcidin. Evidence to date indicates that hepcidin is a negative regulator of intestinal iron absorption, placental iron transport, and the release of iron from macrophages that recycle iron from senescent red cells. It may also be the central mediator of iron sequestration during infections and inflammatory states and the mediator of anemia of chronic disease. Rapid progress in this area is a good example of the beneficial effects of improvements in peptide analysis and chemistry, advances in genomics, and the increasing use of transgenic mice to determine the function of newly discovered genes and proteins.
Avinoam Shuper, MD, Batia Stark, MD, Liora Kornreich, MD, Ian J. Cohen, MBChB, Gali Avrahami, MD and Isaac Yaniv, MD
The addition of methotrexate to treatment protocols in children with acute lymphoblastic leukemia has been found beneficial in preventing central nervous system relapse. However, MTX itself may be associated with neurologic morbidities, the most significant of which is leukoencephalopathy. The present study describes the clinical spectrum of leukoencephalopathy, which ranges from a subclinical disease manifested only radiologically to a progressive, devastating encephalopathy. The interaction of MTX with other components of the treatment protocol is discussed, as is the effect of leucovorin. A summary is presented of the metabolic pathways that may be involved in the development of MTX toxicity. Researchers are still seeking a biochemical marker to aid in the determination of the amount of MTX that may be safely administered.
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Joseph D. Rosenblatt, MD, Seung-Uon Shin, PhD, Hovav Nechustan, MD, PhD, Kyung Hee Yi, BSc and Khaled Tolba, MD
Pesach. J. Shteper, MSc and Dina Ben-Yehuda, MD
Jacob Cohen, MSc, Lia Supino-Rosin, MSc, Eran Barzilay, BSc, Ronit Eisen-Lev, DMD, Moshe Mittelman, MD and Drorit Neumann, PhD
Yair Herishanu, MD and Shlomo Berliner, MD, PhD
Eitan M. Gross, MD, Phillip D. Levin, MB, Chir and Ezekiel H. Landau, MD
Ami Neuberger, MD, Sigal Fishman, MD and Ahuva Golik, MD
Martin H. Ellis, MD and Rivka Zissin, MD
Gabriel S. Breuer, MD, David Raveh, MD, Bernard Rudensky, PhD, Raina Rosenberg, MD, Rose Ruchlemer, MD and Jonathan Halevy, MD