The success that has been made in the care of patients with thalassemia has led to the emergence of unrecognized complications including several renal abnormalities. Chronic anemia and iron overload as well as the use of iron chelator are believed to lie behind these abnormalities. Many investigators document the presence of tubular dysfunction and abnormalities in glomerular filtration rate in...

The traditional role of iron chelation therapy has been to reduce body iron burden via chelation of excess metal from organs and fluids and its excretion via biliary-fecal and/or urinary routes. In their present use for hemosiderosis, chelation regimens might not be suitable for treating disorders of iron maldistribution, as those are characterized by toxic islands of siderosis appearing in a b...

The growth rate of Staphylococcus epidermidis was controlled for populations growing as a biofilm and perfused with supplemented, simple-salts medium. Production of iron chelators, extracellular protease and exopolysaccharide (EPS) by these populations was assessed as a function of specific growth rate and compared to that by planktonic populations grown in the same medium within a chemostat. P...

To address the problem of iron-deficiency anemia, one of the most prevalent human micronutrient deficiencies globally, iron-biofortified rice was produced using three transgenic approaches: by enhancing iron storage in grains via expression of the iron storage protein ferritin using endosperm-specific promoters, enhancing iron translocation through overproduction of the natural metal chelator n...

Iron-responsive elements (IREs) are the RNA stem loops that control cellular iron homeostasis by regulating ferritin translation and transferrin receptor mRNA stability. We mapped a novel iron-responsive element (IRE-Type II) within the 5'-untranslated region (5'-UTR) of the Alzheimer's amyloid precursor protein (APP) transcript (+51 to +94 from the 5'-cap site). The APP mRNA IRE is located imm...

The present study introduces a method for determining the labile iron pool (LIP) in human lymphocytes. It is measured using the probe CP655, the fluorescence of which is stoichiometrically quenched by the addition of iron. The intracellular CP655 fluorescence in lymphocytes was quenched by increasing intracellular iron concentrations using the highly lipophilic 8-hydroxyquinoline iron complex. ...

Iron is both essential and toxic for cells and impaired iron homeostasis has been shown to cause or potentiate various forms of liver injury. Research in our laboratory suggests that iron also plays a pivotal role in intracellular signaling for NF-kappa B activation in hepatic macrophages (HM). Our results showed: 1) HM from alcohol-fed rats had a increase in the nonheme iron content accompanie...

Iron chelators of the hydroxamate class arrest in vitro proliferation of malaria parasites end of mammalian cells. The factors determining the biological activity of the chelators have classically been attributed to the chelators' capacity for binding iron and to their ability to traverse membranes as free chelators and as chelator-iron complexes. We show in this work that the nature of the che...

The emergence of new chelators is likely to have a major impact on the treatment of thalassemia major, sickle cell disease and other hematologic disorders for which regular red cell transfusions are required either to correct severe anemia or to prevent major complications of the underlying disease. In comparison with deferoxamine, which requires prolonged parenteral infusion to achieve negativ...

We have continued the preclinical evaluation of the efficacy and safety of the hexadentate phenolic aminocarboxylate iron chelator N, N'-bis(2-hydroxybenzyl) ethylenediamine-N, N'-diacetic acid monosodium salt (NaHBED) for the treatment of both chronic transfusional iron overload and acute iron poisoning. We examined the effect of route of administration by giving equimolar amounts of NaHBED an...