Gene/Protein Disease Symptom Drug Enzyme Compound
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We measured fasting total plasma homocysteine (Hcy) in 10 chronic hemodialysis (HD) and 10 chronic peritoneal dialysis (PD) patients. Mean (+/- SEM) Hcy was 55.7 +/- 10.1 and 50.5 +/- 14.3 mumol/l, respectively (normal range 6-19 mumol/l). Hemodialysis treatment lowered Hcy by about 30%. Daytime Hcy concentrations were stable in the PD patients. Six weeks of treatment with folic acid (FA) significantly lowered Hcy in HD and PD patients to 24.0 +/- 1.8 and 21.0 +/- 3.6 mumol/l, respectively. After withdrawal, Hcy rose slowly, in parallel with the gradually decreasing plasma FA concentrations, which were greatly elevated during treatment. Chronic treatment with FA of another group of patients showed a similar effect on Hcy. Preliminary results of oral methionine loading in chronic dialysis patients were compatible with delayed homocysteine metabolism via the transsulfuration pathway. Further studies on the optimal treatment of hyperhomocysteinemia in chronic dialysis patients are needed.
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PMID:Folic acid treatment of hyperhomocysteinemia in dialysis patients. 867 99

The mild fasting hyperhomocysteinemia commonly observed in chronic (ie, >/=6 months posttransplantation) renal transplant recipients (RTRs) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid. There are no controlled data evaluating the comparative efficacy of supraphysiological versus standard multivitamin dose folic acid supplementation in reducing fasting total homocysteine (tHcy) levels among RTRs. We block-randomized 60 chronic, stable RTRs on the basis of their screening fasting tHcy level to 3 groups of 20 subjects treated for 12 weeks with folic acid at either 2.4 (group 1), 0.4 (ie, standard multivitamin dose) (group 2), or 0.0 (group 3) mg/d. All 60 study participants also received 50 mg/d vitamin B(6) and 0.4 mg/d vitamin B(12). The mean percent reductions (+/-SEM) in fasting tHcy were as follows: group 1, 32.3+/-2.4%; group 2, 23.4+/-2.3%; and group 3, 19.1+/-2.3%. ANCOVA accounting for the pretreatment matching and adjusted for pretreatment levels of fasting tHcy, folate, and albumin; change in creatinine during the study; and cyclosporine A use revealed significant overall group differences (P=0.005) and significant differences between groups 1 and 2 (P=0. 038) and groups 1 and 3 (P=0.001), but not between groups 2 and 3 (P=0.153). Moreover, a chi(2) analysis of participants with pretreatment tHcy levels >/=15 micromol/L (n=29) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels <12 micromol/L: group 1, 5 of 10 (50%); group 2, 1 of 11 (9%); and group 3, 0 of 8 (0%) (P=0.016; test of trend P=0. 007). We conclude that a supraphysiological dose of folic acid is superior to standard multivitamin dosing for the reduction of fasting tHcy levels in chronic RTRs.
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PMID:Enhanced reduction of fasting total homocysteine levels with supraphysiological versus standard multivitamin dose folic acid supplementation in renal transplant recipients. 1059 69

Hyperhomocysteinemia is associated with several cardiovascular disease risk factors including endothelial dysfunction and abnormalities of clotting functions, which are also common features of insulin resistance syndrome observed in hypertensive patients. Recent study has shown that acute hyperinsulinemia can lower plasma homocysteine concentrations in nondiabetic but not in type 2 diabetic individuals, indicating that insulin may regulate homocysteine metabolism. To investigate the relationships between plasma homocysteine concentration and insulin sensitivity, we studied 90 Chinese hypertensive patients and a group of control subjects (n = 86) matched for age, gender, and body mass index. Fasting plasma homocysteine levels, plasma lipoprotein concentrations, plasma glucose, and insulin responses to oral glucose tolerance tests (OGTT) were determined. The results showed that fasting plasma homocysteine concentrations were significantly higher in subjects with hypertension than in those with normotension (mean +/- SEM, 8.1 +/- 0.6 v 6.8 +/- 0.2 micromol/L; P < .05). Fasting plasma homocysteine levels correlated significantly with insulin secretion in response to OGTT even after adjustment for body mass index (P < .05) in hypertensive patients but not in normotensive individuals. However, fasting plasma homocysteine concentrations showed no correlations with steady-state plasma glucose concentration, a measurement of insulin sensitivity, during an insulin suppression test in groups of hypertensive (n = 42) and normotensive (n = 37) subjects. When the steady-state plasma glucose concentrations were divided into three tertiles, fasting plasma homocysteine concentrations showed no difference across these three groups in either hypertensive patients (8.6 +/- 0.5 v 7.2 +/- 0.5 v 8.4 +/- 0.6 micromol/L; P = .148) or normotensive subjects (6.3 +/- 0.4 v 8.0 +/- 0.8 v 7.0 +/- 0.8 micromol/L; P = .199). In conclusion, hypertensive Chinese subjects had higher fasting plasma homocysteine concentrations and a higher degree of insulin resistance when compared to a group of age-, gender-, and body mass index-matched normotensive individuals. Fasting plasma homocysteine levels were associated with insulin response to OGTT in hypertensives but not in normotensives. No correlation was observed between the degree of insulin resistance and plasma homocysteine levels in either the hypertensive or the normotensive group. The role of insulin in homocysteine metabolism deserves further investigation.
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PMID:Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects. 1067 66