Dysregulation of methionine metabolism in multiple sclerosis.

We report a significant reduction in plasma methionine concentrations in relapse remitting multiple sclerosis (MS) patients compared to controls. In vivo studies demonstrate that changes in peripheral methionine levels in mice can regulate histone H3 methylation and expression of DNA methyltransferase 3A (DNMT3A) centrally, in the cerebral cortex. Therefore, we propose that decreases in circulating methionine represent one of the earliest manifestations of dysregulated methionine metabolism in MS with potential impacts on both histone H3 and DNA methylation in the central nervous system.

Susceptibility to neuromediated syncope after acute myocardial infarction.

BACKGROUND: Syncope after acute myocardial infarction (AMI) is a common clinical problem. It may be hypothesised that remodelling and neurohormonal changes following AMI may predispose to neuromediated syncope. DESIGN: To address this issue we prospectively evaluated the incidence of positive results of head-up tilt-table testing in 40 patients following AMI and 40 age and sex matched controls without a history of syncope. The mechanisms of tilt-induced changes in autonomic tone were assessed using spectral analysis of heart rate variability. The patients were followed-up for one year. RESULTS: Positive results of tilt-test occurred in 4 (10%) controls and 13 (33%) AMI patients (P = 0.01). No significant differences in sympathovagal interaction (assessed by a low frequency/high frequency ratio) were detected between the groups before tilting (2. 9 +/- 1.9 vs. 3.1 +/- 2.2; NS). However, dynamic changes of this parameter differed significantly during the first 5 symptomless minutes of the active phase of tilt-test. The ratio increased in the majority of controls (87%) and decreased in the majority of patients (62%) (P < 0.0001). During one year follow-up, syncope or presyncope occurred in 10 (25%) AMI patients but did not occur in any control subject (P < 0.001). The sensitivity, specificity and predictive accuracy of an early tilt-test after AMI for the prediction of syncope or presyncope was 70%, 80% and 78%, respectively. CONCLUSION: Patients after AMI are prone to neuromediated reactions. Sympathetic withdrawal seems to be the most likely mechanism of syncope. The role of tilt testing for identification of patients susceptible to syncope or presyncope after AMI needs further investigation.

Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction.

Clinical studies suggest that neutrophil activation during acute myocardial infarction (MI) aggravates tissue injury. Activated neutrophils are an important source of oxygen free radicals (OFR), the injurious effects of which are counteracted by endogenous antioxidants. We have previously shown in healthy subjects that supplementation with antioxidant vitamins C and E suppresses OFR production by isolated neutrophils assayed by chemiluminescence (CL). The present study, performed in patients with acute MI aimed (1) to investigate the effect of vitamin C and E supplementation upon neutrophil OFR production and serum lipid peroxides, (2) to evaluate serum levels of vitamins C and E in the course of MI. Forty-five patients with acute MI were randomized to receive either conventional treatment only (control, n=22). All measurements were performed on the 1st and 14th day. Neutrophil OFR production assayed by CL decreased significantly in VIT patients (Wilcoxon test for paired data P<0.01, Chi square test P<0.01). In the control group, changes in OFR production were not significant. Serum lipid peroxides (measured as TBARS) increased in controls (P<0.05), but remained stable in VIT patients. Mean (+/-SE) serum ascorbic acid and tocopherol on the 1st day were 0.43 +/- 0.18% and 3.25 +/- 1.32 microM.M(-1) cholesterol, respectively, in all patients. On the 14th day in non-supplemented patients mean tocopherol was unchanged, whereas ascorbic acid increased significantly (0.63 +/- 0.24 mg%, P<0.01) suggesting that a low basal level was associated at least in part with the acute phase of the disease. An expected increase in serum vitamin levels occurred in VIT patients. In conclusion, supplementation with vitamins C and E suppresses neutrophil OFR production and lowers the marker of lipid peroxidation in patients with MI.

Inhibitory effect of vitamins C and E on the oxygen free radical production in human polymorphonuclear leucocytes.

Beneficial effects of dietary supplementation with antioxidant vitamins are attributed mainly to the influence upon lipid metabolism, endothelial and vascular functions. Their effect upon leucocyte oxygen free radical producing capacity has not been investigated. In 13 healthy volunteers we examined the influence of oral supplementation with vitamins C and E (aa 600 mg per day for 14 days) upon leucocyte oxygen free radical production estimated by lucigenin-amplified chemiluminescence in isolated leucocytes stimulated with arachidonic acid. After supplementation with vitamins, significant increase in serum content of ascorbic acid and tocopherol was concomitant with significant (P < 0.001) decrease of leucocyte chemiluminescent response (mean 63.2 + 23.0 SD, % of initial values) and lowering of serum lipid peroxides (P < 0.05). These findings suggest that suppression of leucocyte capacity to produce oxygen free radicals as shown in this study, may contribute to vasoprotective action of vitamins C and E.