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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ever-increasing body of information regarding the molecular pathogenesis of sickle cell disease has raised expectations that a specific and effective therapy could be devised to inhibit polymerization of hemoglobin S. Despite an intense international research effort, this goal has not yet been realized. Supportive care continues to be the mainstay in the management of patients with sickle cell anemia. Empiric measures were used in early attempts to treat sickle cell anemia. Herrick reported gratifying improvement after "rest, nourishing food, the administration of iodide, arsenic, thymol and the application of boric ointment to leg ulcers." Many of these suggestions are similar to those of today. Several factors have significantly improved the prognosis of patients with this disease. Improved medical care, genetic counseling, and universal neonatal screening have directly resulted in improved outcome. Molecular biologic techniques have allowed us to approach this disease in a pathophysiologic way. Now we can envision antenatal diagnosis with the use of molecular probes and treatment by gene amplification. Still, however, the most important and challenging link in the chain between the biology of the disease and the clinical sequelae is an astute and interested physician who must remain objective at all times.
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PMID:Management of patients with sickle cell disease. 157 63

The blood biochemistry of 84 young homozygous sickle cell patients aged 1 to 11 years was analysed for evidence of liver disease. A comparison of the values found in their blood with those seen in normal children from an identical age group, assessed at the same time, shows no convincing evidence of liver cell damage except in 12% of cases. The normal transaminase observed in many of the patients assessed, together with the high alkaline phosphatase activity which seemed to be out of proportion to plasma bilirubin, is a picture compatible with localised obstructive lesions of the liver or bone lesions, both of which are common in sickle cell disease. This biochemical pattern suggests that the conjugated bilirubin, which dominates the picture in 40% of patients who have 'haemolytic jaundice', is due largely, not to liver cell damage, but to a combination of two factors, namely, intrahepatic cholestasis and the presence of actively functioning liver cells. Adequate albumin synthesis found in these patients, together with normal thymol reactions, provides further evidence of the absence of severe liver cell damage.
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PMID:Liver function and the diagnostic significance of biochemical changes in the blood of African children with sickle cell disease. 743 Mar 68

The ionic mechanisms and cytoprotective activities of 4-piperidinomethyl-2-isopropyl-5-methylphenol (THPI), an analogue of thymol, were investigated in HL-60 granulocytes and in human erythrocytes, respectively. THPI inhibited K+ outward current (I(K)) in a concentration-dependent manner in HL-60 leukocytes, with an IC50 value of 4 microM. Neither iberiotoxin (200 nM) nor paxilline (1 microM) suppressed the amplitude of I(K), whereas clotrimazole (5 microM) significantly inhibited it. In the inside-out configuration of single channel recordings, application of THPI (5 microM) into the bath medium did not alter the single-channel conductance of intermediate-conductance Ca2+-activated K+ (IK(Ca)) channels (i.e K(Ca)3.1 channels), but it suppressed the channel activity significantly. THPI-induced inhibition of IK(Ca) channels was reversed by a further application of 1-ethyl-2-benzimidazolinone (10 microM). THPI-induced reduction in IK(Ca)-channel activity in these cells was primarily due to a decrease in mean open time. These results provide direct evidence that THPI is capable of suppressing the activity of IK(Ca) channels in HL-60 cells. The antioxidant action of THPI also revealed a beneficial cytoprotective effect against mitomycin C-mediated haemolytic effect in human erythrocytes. The results of this study suggest that blockade of IK(Ca) channels and the membrane-protecting activity of THPI would combine to have beneficial effects in lessening the severity of haemolytic crisis and reducing anaemia in sickle cell disease.
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PMID:Inhibition of intermediate-conductance Ca2+-activated K+ channel and cytoprotective properties of 4-piperidinomethyl-2-isopropyl-5-methylphenol. 1752 33