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Dietary alpha-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.

BackgroundPericonceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention.MethodsThis study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; II) Dietary assessment; III) Blood analysis; IV) Assessment of knowledge and use of folic acid supplements.ResultsThe annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34). The rates of NTDs fell by 78% (95% CI 65%–86%) after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%.ConclusionsBased on these findings, mandatory food fortification in Canada should continue at the current levels. Public education regarding folic acid supplement use by women of childbearing age should also continue.

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Serum digoxin and metabolites were assayed in plasma and urine by HPLC in 10 dialysis-dependent patients with end-stage renal failure (group I) and in five patients with comparatively normal renal function (group II) after ingestion of 150 muCi 3H-digoxin-12 alpha. Thirteen patients were on maintenance digoxin therapy and were at steady state. Metabolites found regularly but usually in small amounts, were 3 beta-digoxigenin and its mono- and bis-digitoxosides, and 3-keto and 3 alpha(epi)-digoxigenin. Quantitatively the most abundant metabolites were polar and averaged 26% (7 to 76) of the radioactivity in plasma 6 hr after drug, and 60% (11 to 88) for digoxin for all 15 patients. Neither values between group I and II for the polar metabolites nor digoxin differed significantly. The metabolites reacted with antibody to digoxin to varying degrees and may make up an important component of the serum digoxin concentration when determined by standard radioimmunoassay. In some patients, digoxin undergoes extensive biotransformation, mainly, we suggest by hydrolysis, oxidation, epimerization, and conjugation to polar end-metabolites.

Apolipoprotein (a) – Lp(a) – is reported to be an independent risk factor for coronary artery disease and for hemodialysis (HD) access occlusion. Homology with plasminogen may predispose to thrombosis. High concentrations usually have been reported in patients on HD and on continuous ambulatory peritoneal dialysis (CAPD), but near-normal values in many kidney transplants (TP). We used Pharmacia immunoradiometric assay in 52 patients on HD, 58 on CAPD, 94 after TP, and 56 controls. The Lp(a) mean levels for CAPD, HD, TP, and control groups were 738, 647, 348, and 368 U/l and the medians were 542, 537, 96 and 143 U/l, respectively. The means and medians for CAPD and HD were significantly greater than those for TP and controls (p < 0.003 for means and < 0.005 for medians). We found no significant difference between: (1) Lp(a) means or medians comparing HD and CAPD or TP and controls; (2) Lp(a) means for the 33 patients with insulin-dependent diabetes mellitus and the 171 without; (3) number of occlusions of HD fïstulae or grafts in patients with high Lp(a) values and without; (4) mean Lp(a) for CAPD patients on gemfibrozil and also for TP patients on 3-hydroxy-methylglutaryl coenzyme 1 reductase inhibitors, or diet alone, before and after treatment, and (5) mean Lp(a) values for HD and CAPD patients with and without myocardial infarction. Lp(a) did not correlate significantly with fractional shortening or left ventricular end systolic or diastolic diameter by echocardiogram or with ejection fraction. For TP patients, Lp(a) and serum creatinine correlated (p = 0.004), and mean Lp(a) for 71 TP on ciclosporin A exceeded that for the other 23 patients (p < 0.03). Lp(a) fell in 13 of 14 patients after TP (mean fall 77%). The dominant Apo(a) isoform in 10 of 13 patients on CAPD or HD with high Lp(a) values was the equivalent of S2 (Utermann). Lp(a) in HD or CAPD is often elevated and regulated by both genetic and renal failure factors, but falls after TP with return of renal function and mainly genetic regulation. Lp(a) was not a risk factor for coronary artery disease in HD or CAPD patients and did not fall significantly with two drugs or diet.

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In fructose-induced hypertension in Wistar-Kyoto (WKY) rats, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound N-acetyl cysteine prevents fructose-induced hypertension by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether dietary supplementation of vitamin E and vitamin C which are known to increase tissue glutathione, a storage form of cysteine, prevents this hypertension and its associated biochemical and histopathological changes. Starting at 7 weeks of age, animals were divided into four groups of six animals each and treated as follows: control group, normal diet and normal drinking water; fructose group, normal diet and 4% fructose in drinking water; fructose + vitamin E group, diet supplemented with vitamin E (34 mg/ kg feed) and 4% fructose in drinking water; fructose + vitamin C group, diet supplemented with vitamin C (1,000 mg/kg feed) and 4% fructose in drinking water. At 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugates were significantly higher in the fructose group. These animals also displayed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin E and C supplementation in fructose-treated WKY rats prevented the increase in systolic blood pressure by normalizing cytosolic [Ca2+]i and kidney and aortic aldehyde conjugates and preventing adverse renal vascular changes.