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)

Serum half-lives for antipyrine were normal or shorter than normal in 19 subjects between 7 and 23 yr of age with beta-thalassemia major. The mean antipyrine serum half life (+/-SE) for the group as a whole was 8.5 +/- 0.6 hr. The mean antipyrine half-lives (t1/2) for the younger subjects were within the range reported for normal children, while the mean t1/2 for the older males approached the values reported for normal adult males. The mean t1/2 for the older females was shorter than has been reported for normal adult females. The mean apparent volume of distribution for antipyrine (+/-SE) in the subjects with thalassemia was 0.69 +/- 0.01 L/kg. Thus, total body water appears to be increased in thalassemia. The mean metabolic clearance rate for antipyrine (+/-SE) in the group as a whole (1.07 +/- 0.08 ml/min/kg) is substantially higher than the metabolic clearance rates for antipyrine reported in normal adults. Thus, the relatively short t1/2s of antipyrine in subjects with thalassemia are attributable to rapid rates of clearance of the drug. The data indicate that antipyrine clearance is unimpaired in patients with thalassemia despite evidence of liver damage and iron overload. Our study supports the proposition that hepatic microsomal hemoprotein synthesis is not adversely affected in homozygous beta-thalassemia.
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PMID:Antipyrin clearance in homozygous beta-thalassemia. 97 19

Iron is an essential mineral for normal cellular physiology, but an excess can result in cell injury. Iron in low-molecular-weight forms may play a catalytic role in the initiation of free radical reactions. The resulting oxyradicals have the potential to damage cellular lipids, nucleic acids, proteins, and carbohydrates; the result is wide-ranging impairment in cellular function and integrity. The rate of free radical production must overwhelm the cytoprotective defenses of cells before injury occurs. There is substantial evidence that iron overload in experimental animals can result in oxidative damage to lipids in vivo, once the concentration of iron exceeds a threshold level. In the liver, this lipid peroxidation is associated with impairment of membrane-dependent functions of mitochondria and lysosomes. Iron overload impairs hepatic mitochondrial respiration primarily through a decrease in cytochrome C oxidase activity, and hepatocellular calcium homeostasis may be compromised through damage to mitochondrial and microsomal calcium sequestration. DNA has also been reported to be a target of iron-induced damage, and this may have consequences in regard to malignant transformation. Mitochondrial respiratory enzymes and plasma membrane enzymes such as sodium-potassium-adenosine triphosphatase (Na(+) + K(+)-ATPase) may be key targets of damage by non-transferrin-bound iron in cardiac myocytes. Levels of some antioxidants are decreased during iron overload, a finding suggestive of ongoing oxidative stress. Reduced cellular levels of ATP, lysosomal fragility, impaired cellular calcium homeostasis, and damage to DNA all may contribute to cellular injury in iron overload. Evidence is accumulating that free-radical production is increased in patients with iron overload. Iron-loaded patients have elevated plasma levels of thiobarbituric acid reactants and increased hepatic levels of aldehyde-protein adducts, indicating lipid peroxidation. Hepatic DNA of iron-loaded patients shows evidence of damage, including mutations of the tumor suppressor gene p53. Although phlebotomy therapy is effective in removing excess iron in hereditary hemochromatosis, chelation therapy is required in the treatment of many patients who have combined secondary and transfusional iron overload due to disorders in erythropoiesis. In patients with beta-thalassemia who undergo regular transfusions, deferoxamine treatment has been shown to be effective in preventing iron-induced tissue injury and in prolonging life expectancy. The use of the oral chelator deferiprone remains controversial, and work is continuing on the development of new orally effective iron chelators.
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PMID:Iron toxicity and chelation therapy. 1241 32