Background-Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver using a gerbil iron-overload model. Methods and Results-Twelve gerbils underwent iron dextran loading (200 mg · kg Ϫ1 · wk

Brain cells and glioma cells in culture release a protein which induces neurite outgrowth in neuroblastoma cells. This neurite‐promoting factor (NPF), which has been purified from serum‐free glioma conditioned medium, has an apparent mol. wt. of 43 000. NPF inhibits urokinase as well as plasminogen activator‐dependent caseinolysis or fibrinolysis. NPF and urokinase form an SDS‐resistant complex. The fact that this glia‐derived NPF is a potent protease inhibitor indicates that glial cells modulate the proteolytic activity associated with neuronal cells and suggests that this phenomenon is one of the biochemical events involved in the regulation of neurite growth.

Labile iron in hemosiderotic plasma and tissue are sources of iron toxicity. We compared the iron chelators deferoxamine, deferiprone, and deferasirox as scavengers of labile iron in plasma and cardiomyocytes at therapeutic concentrations. This comprised chelation of labile plasma iron (LPI) in samples from thalassemia patients; extraction of total cellular iron; accessing labile iron accumulated in organelles and preventing formation of reactive-oxidant species; and restoring impaired cardiac contractility. Neonatal rat cardiomyocytes were used for monitoring chelator extraction of LCI (labile cell iron) as 59 Fe; assessing in situ cell iron chelation by epifluorescence microscope imaging using novel fluorescent sensors for iron and reactive oxygen species (ROS) selectively targeted to organelles, and monitoring contractility by timelapse microscopy. At plasma concentrations attained therapeutically, all 3 chelators eliminated LPI but the orally active chelators rapidly gained access to the LCI pools of cardiomyocytes, bound labile iron, attenuated ROS formation, extracted accumulated iron, and restored contractility impaired by iron overload. The effect of deferoxamine at therapeutically relevant concentrations was primarily by elimination of LPI. The rapid accessibility of the oral chelators deferasirox and deferiprone to intracellular labile iron compartments renders them potentially efficacious for protection from and possibly reversal of cardiac damage induced by iron overload. (Blood. 2006;108: 3195-3203)