Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium cyanate has been proposed as a therapy for sickle cell anemia. Histologic studies have suggested abnormal accumulation of glycogen in livers of rats. Quantitative liver glycogen determinations reported here showed a significant increase (P smaller than 0.05), which, however, was mobilized normally during fasting and after glucagon injections.
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PMID:Liver glycogen accumulation after cyanate treatment. 113 24

Studies have been made on the bioavailability in blood of sodium cyantate administered orally in gelatin capsules, in gelatin capsules plus antacid, in enteric-coated capsules and in cocoa butter suppositories administered rectally to patients with sickle cell disease. Maximal blood concentrations of cyanate did not exceed 0.4 mM. Sodium cyanate taken orally in gelatin capsules yielded the highest blood concentrations of the drug, but the peak concentrations and curve areas were not necessarily dose-related. The duration of the drug in the circulation was about 210 minutes. Administration of sodium cyanate in the gelatin capsules, taken with an antacid, improved the dose-response relationship within a given patient. Enteric-coated capsules and suppositories were found to show variable and low bioavailability profiles, respectively. Variability in bioavailability between patients with a given dosage form requires further study. Since the concentration of cyanate attainable in vivo does not inhibit synthesis of either the alpha- or beta-chain of hemoglobin in vitro, previous reports on the inhibitory effects of 10 to 100 mM cyanate on globin synthesis in vitro do not appear to be relevant.
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PMID:Bioavailability of sodium cyanate in patients with sickle cell disease and the lack of inhibition in vitro of globin synthesis at in vivo concentrations of cyanate. 118 2

Two carbamylating agents, carbamyl phosphate and sodium cyanate, are currently being evaluated as therapeutic drugs for the treatment of sickle cell anemia. Since the clinical usefulness of these drugs might be limited by toxicity, a comparative in vitro study of the relative inhibition of human sickle cell and rabbit reticulocyte protein synthesis was performed. Sodium cyanate was found to inhibit human sickle cell protein synthesis at concentrations one-eighth that of carbamyl phosphate. Carbamyl phosphate lowered reduced glutathione levels to a similar degree as sodium cyanate and was slightly more effective as an in vitro antisickling agent, which is evidence that carbamyl phosphate enters these cells. When rabbit reticulocyte protein synthesis was investigated, carbamyl phosphate was found to be noninhibitory at concentrations as high as 128 mol/mol of hemoglobin in the incubation medium, while cyanate was inhibitory at much lower concentrations. The effect of carbamyl phosphate on glutathione concentrations, however, was virtually identical to that of cyanate. These results show that the effect on protein synthesis does not result from the lowered glutathione levels. It is concluded that both the therapeutic and toxic effects of sodium cre, there might be differences in toxicity between animals and humans.
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PMID:Comparison of the effects of carbamyl phosphate and sodium cyanate on protein synthesis and glutathione concentration in human sickle cell and rabbit reticulocytes. 118 3