The homozygous form of beta-thalassemia, the most common single gene disorder, is treated by red cell transfusion therapy. Following transfusion, the chelator, deferoximine, is administered to patients to remove excess iron. However, when this drug is given to young children, metaphyseal dysplasia and abnormalities of linear growth are frequently observed. To explore the notion that deferoximine interferes with endochondral growth by chelating zinc, we examined the effect of the drug on chondrocytes maintained in long-term culture. We found that deferoximine caused a dose-dependent inhibition of a wide range of functions including cell proliferation, protein synthesis (and possibly under-hydroxylation of type X collagen), and mineral deposition. Directly relevant to the mineralization process was the observation that the drug dramatically lowered the activity of alkaline phosphatase, a zinc-requiring enzyme. To test the hypothesis that enzyme inhibition was due to chelation of zinc by deferoximine, the cell culture medium was supplemented with excess zinc. However, this treatment did not overcome the deferoximine-dependent change in enzyme activity. We next examined the possibility that deferoximine, in the presence of ascorbate, could form a free radical system that would serve to inactivate the enzyme. Using alkaline phosphatase extracted from chick cartilage, we noted that the activity of the phosphatase was markedly reduced in the presence of deferoximine and ascorbate. These effects were consistant with the notion that deferoximine and ascorbate can act as a prooxidant couple. This conclusion was confirmed when we measured the oxidative activities of the system using nitrobule tetrazolium and cytochrome c. Indeed, we noted that deferoximine markedly activates the autocatalytic oxidation of ascorbate.(ABSTRACT TRUNCATED AT 250 WORDS)
In this retrospective electronic chart review, we evaluated the metabolic changes that occurred in Native American patients with type 2 diabetes who were treated with rosiglitazone and then converted to pioglitazone with no other changes in medication regimens for diabetes or dyslipidemia. Thirty-four patients were included in the analysis. After the conversion from rosiglitazone to pioglitazone, significant decreases in the levels of total cholesterol (10.1%), low-density lipoprotein cholesterol (11.7%), and triglycerides (15.3%) were seen. No significant changes occurred in weight, body mass index, fasting glucose, hemoglobin A(1c), high-densitylipoprotein cholesterol, blood pressure, or liver function tests. Significantly more patients achieved low-density lipoprotein cholesterol and triglyceride target goals when taking pioglitazone than when taking rosiglitazone. No drug discontinuations or adverse effects were reported among the evaluable population. These results are consistent with results of other studies evaluating these two drug therapies.
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