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)

Coronary artery disease is the leading cause of death in the United States. Serum cholesterol is a widely used screening test to detect persons at high risk for coronary artery disease, including those with familial hypercholesterolemia. However, universal screening of currently healthy persons is not without risk. Previous experience in screening for sickle cell anemia and hypertension has shown that these risks include misunderstanding of test results, misdiagnosis, labeling, stigmatization, and decreased psychological well-being. Results of screening programs may be misused by industry or insurance companies to exclude individuals from positions or benefits. Consideration of these harms suggests that screening should not be implemented until certain safeguards are in place. Physicians and the public should be educated about the potential risks and benefits of screening. Screening tests should be accurate, reliable, valid, and of demonstrated sensitivity. Informed consent for screening should be obtained. Follow-up surveillance and recommended treatments, including dietary counseling and drug therapy, should be available to all individuals identified as being at high risk regardless of their socioeconomic status. Finally, procedures to protect the right to privacy of individuals and their families should be implemented well in advance of the actual screening.
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PMID:Psychological and ethical considerations in screening for disease. 821

Previously we showed L-4F, a novel apolipoprotein A-I (apoA-I) mimetic, improved vasodilation in 2 dissimilar models of vascular disease: hypercholesterolemic LDL receptor-null (Ldlr(-/-)) mice and transgenic sickle cell disease mice. Here we determine the mechanisms by which D-4F improves vasodilation and arterial wall thickness in hypercholesterolemic Ldlr(-/-) mice and Ldlr(-/-)/apoA-I null (apoA-I(-/-)), double-knockout mice. Ldlr(-/-) and Ldlr(-/-)/apoA-I(-/-) mice were fed Western diet (WD) with and without D-4F. Oral D-4F restored endothelium- and endothelial NO synthase (eNOS)-dependent vasodilation in direct relationship to duration of treatments and reduced wall thickness in as little as 2 weeks in vessels with preexisting disease in Ldlr(-/-) mice. D-4F had no effect on total or HDL cholesterol concentrations but reduced proinflammatory HDL levels. D-4F had no effect on plasma myeloperoxidase concentrations but reduced myeloperoxidase association with apoA-I as well as 3-nitrotyrosine in apoA-I. D-4F increased endothelium- and eNOS-dependent vasodilation in Ldlr(-/-)/apoA-I(-/-) mice but did not reduce wall thickness as it had in Ldlr(-/-) mice. Vascular endothelial cells were treated with 22(R)-hydroxycholesterol with and without L-4F. 22(R)-Hydroxycholesterol decreased NO (*NO) and increased superoxide anion (O2*-) production and increased ATP-binding cassette transporter-1 and collagen expression. L-4F restored *NO and O2*- balance, had little effect on ATP-binding cassette transporter-1 expression, but reduced collagen expression. These data demonstrate that although D-4F restores vascular endothelial cell and eNOS function to increase vasodilation, HDL containing apoA-I, or at least some critical concentration of the antiatherogenic lipoprotein, is required for D-4F to decrease vessel wall thickness.
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PMID:Effects of D-4F on vasodilation and vessel wall thickness in hypercholesterolemic LDL receptor-null and LDL receptor/apolipoprotein A-I double-knockout mice on Western diet. 1630 51