Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evaluation of new chelators for clinical use is limited by the availability of models which will predict the therapeutic safety margin of chelators in iron-overloaded humans such as those with thalassaemia major. Animal models show significant differences with respect to the relative toxicity of different chelators compared with human. These differences can be ascribed to several factors: differences in iron metabolism between different species, human metabolism being significantly more conservative than in rodents or nonhuman primates; differences in drug metabolism between different species which are often difficult to predict from first principles, and difficulties in obtaining iron-overloaded models that are truly representative of transfusional iron overload clinically. These differences have been highlighted by clinical studies on hydroxypyridinone iron chelators such as 1,2-dimethyl-3-hydroxypyridin-4-one (L1, CP20, deferiprone) and 1,2-diethyl-3-hydroxypyridin-4-one (CP94). New tissue culture approaches towards understanding the mechanisms of neutropenia, cytostasis and apoptosis induced by chelators as well as the relative rates of inhibition of non-haem-iron-containing enzymes such as ribonucleotide reductase are predicted to identify chelators with a higher therapeutic safety margin.
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PMID:Evaluation of new iron chelators for clinical use. 860 83

A system based on the detection of K-shell x-ray fluorescence (XRF) has been used to investigate whether a correlation exists between the concentration of iron in the skin and the concentration of iron in the liver, as the degree of iron loading increases. The motivation behind this work is to develop a non-invasive method of determining the extent of the body's iron stores via measurements on the skin, in order to monitor the efficacy of chelation therapy administered to patients with beta-thalassaemia. Sprague-Dawley rats were iron loaded via injections of iron dextran and subsequently treated with the iron chelator CP94. The non-haem iron concentrations of the liver, heart and spleen were determined using bathophenanthroline sulphonate as the chromogen reagent. Samples of abdominal skin were taken and the iron concentrations determined using XRF. A strong correlation between the skin iron concentration and the liver iron concentration has been demonstrated (R2 = 0.86). Similar correlations exist for the heart and the spleen. These results show that this method holds great potential as a tool in the diagnosis and treatment of hereditary haemochromatosis and beta-thalassaemia.
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PMID:The use of skin Fe levels as a surrogate marker for organ Fe levels, to monitor treatment in cases of iron overload. 1084 11