PubMed Health⌕ Search

Biomedical subjects

J B Ubbink

Publications and source records attributed to J B Ubbink.

At least 37 records · Page 2Linked to original sources
PubMed1997

The effect of Simvastatin on the plasma antioxidant concentrations in patients with hypercholesterolaemia.

The aim of this study was to monitor the antioxidant status of patients with hypercholesterolaemia during treatment with Simvastatin. Forty-seven patients, of whom 25 had confirmed familial hypercholesterolaemia (FH), were treated with 10 or 20 mg of Simvastatin per day for 14 weeks. As expected, total cholesterol and LDL cholesterol concentrations decreased considerably, while HDL cholesterol concentrations increased during drug treatment. In neither FH nor non-FH patients were any significant changes observed for retinol status, while plasma vitamin C concentrations were also not adversely affected by the drug therapy. In both patient groups Simvastatin therapy led to a significant decrease in plasma alpha-tocopherol (P < 0.05) concentrations, however, the alpha-tocopherol/total cholesterol ratio increased by 9.1 (P < 0.01) and 12.1% (P < 0.01) in FH and non-FH patients, respectively, during the 14-week treatment period. The coenzyme Q10/total cholesterol ratio did not change significantly in non-FH patients, but was significantly lower (P < 0.05) than the baseline ratio after 4 and 14 weeks of Simvastatin treatment in FH patients. The alpha-tocopherol/total cholesterol ratio of FH patients remained consistently and significantly lower (P < 0.01) compared with non-FH patients, indicating that LDL from the former group may be more vulnerable to free radical-mediated damage and lipid peroxidation. Our results suggest that the significant decline in circulating alpha-tocopherol and coenzyme Q10 concentrations was mainly a function of the decrease in serum total cholesterol concentrations.

Adult↗
PubMed1997

Spontaneous oxidation of methionine: effect on the quantification of plasma methionine levels.

Plasma methionine (Met), methionine sulfoxide (MSO), and total Met concentrations were determined by reversed-phase chromatography and fluorescence detection after automated precolumn derivatization with an o-phthalic aldehyde mercaptoethanol reagent. Addition of pure, MSO-free L-Met to plasma samples resulted in the anticipated linear increase in plasma Met concentrations, but simultaneously effected a dose-dependent, linear increase in MSO levels. In contrast, the addition of pure L-MSO to plasma samples rendered linear calibration curves for MSO, while the Met concentration remained constant. A strong buffering effect against the spontaneous or hydrogen peroxide induced oxidation of Met to MSO was observed in plasma samples. This protective effect could be neutralized by preincubating the plasma samples with sodium azide. The addition of relatively low concentrations of red cell lysates to plasma samples, prior to hydrogen peroxide oxidation, strongly inhibited the conversion of Met to MSO. Plasma samples from 127 healthy female volunteers were analyzed: MSO concentrations (mean, 3.6 +/- 2.1 microM) exhibited a weak positive correlation (r = 0.352) with Met levels (mean, 21.3 +/- 6.1 microM) but, after the exclusion of two probable outliers from the data set, no correlation was observed. Our results suggest that plasma Met concentrations should be corrected for oxidative losses incurred during storage, sample processing and because of the action of a variety of in situ oxidants, present in plasma, in order to obtain a reliable estimate of the methionine status of an individual.

Calibration↗
PubMed1997

The role of vitamins in the pathogenesis and treatment of hyperhomocyst(e)inaemia.

The relation between vitamin nutritional status and circulating plasma homocyst(e)ine concentrations is reviewed. Several studies have shown that plasma concentrations of folate, vitamin B12 and pyridoxal 5'-phosphate are inversely associated with plasma total homocyst(e)ine concentrations. Of the three vitamins mentioned above, folate is the most powerful homocyst(e)ine lowering agent and a daily supplement of 0.65 mg/day is sufficient to normalize moderate hyperhomocyst(e)inaemia in most individuals with normal renal function. In patients with severe renal failure, high doses of folate are required to treat hyperhomocyst(e)inaemia. Folic acid is ineffective in reducing plasma total homocyst(e)ine concentrations in patients with a vitamin B12 deficiency. Vitamin B6 supplementation has no effect on fasting plasma total homocyst(e)ine concentrations, but attenuates the post-methionine load plasma homocyst(e)ine peak. At least one report has shown that some individuals appear to be unable to maintain plasma total homocyst(e)ine concentrations in the normal reference range by a dietary intake of folic acid only. Long-term vitamin supplementation may be indicated in these individuals. However, the clinical benefit of vitamin supplementation has not yet been demonstrated and controlled trials are urgently required.

Homocysteine↗
PubMed1997

Hyperhomocysteinaemia in black patients with cerebral thrombosis.

Hyperhomocysteinemia is regarded as a risk factor for stroke but its pathogenetic role has not yet been established in Black patients. We studied 24 Black patients admitted with cerebral thrombosis, and compared them with age- and sex-matched apparently healthy controls from the same community. Total homocysteine (tHcy) (free homocysteine, protein-bound homocysteine, the disulfide homocystine and the mixed disulfide homocysteine-cysteine) concentration was 10.91 (4.95-23.05) mumol/l in the stroke patients and 8.73 (3.95-15.10) mumol/l in controls (p = 0.031). This difference could not be explained by differences in vitamin B12, vitamin B6 or folate status. A subgroup of nine stroke patients with hypercreatininaemia (> 90 mumol/l, 75% of control concentrations) had significantly higher plasma tHcy concentrations [median (range) 9.10 (5.40-15.10) mumol/l] compared with controls [8.65 (3.96-13.89) mumol/l] (p = 0.002). Plasma tHcy concentrations of stroke patients with normal serum creatinine concentrations were not significantly different to those of controls. Hyperhomocysteinemia in Black patients with stroke may be partially caused by renal insufficiency. Therefore, while hyperhomocysteinemia may increase the risk of stroke, it is unlikely to be a primary initiating factor.

Black People↗
PubMed1997

Ubiquinol/ubiquinone ratio as marker of oxidative stress in coronary artery disease.

The purpose of the study was to investigate changes in serum ubiquinol/ubiquinone ratio with copper ion induced oxidative stress, and to assess the ubiquinol/ubiquinone ratio as marker of in vivo oxidative stress in patients with coronary artery disease (CAD). Plasma ubiquinol, ubiquinone, vitamin E (alpha-tocopherol) and total cholesterol (TC) concentrations were measured in 40 patients with angiographically confirmed coronary artery disease and 100 apparently healthy controls. The mean (SD) ubiquinol/ubiquinone ratio of 26.5 (7.5) of the CAD patients was significantly lower than the mean ratio of 30.2 (8.8) of the controls (p = 0.02). Our results indicate that the ubiquinol/ubiquinone ratio is a sensitive marker of oxidative stress and that an altered ubiquinol/ubiquinone ratio is the first sign of lipoprotein exposure to oxidative stress. The altered ratio in CAD patients cannot be explained by differences in plasma vitamin E levels. The vitamin E concentrations were in fact significantly higher in CAD patients, and did not appear to protect the ubiquinol from increased oxidation due to free radical reactions. These results may indicate that circulating lipoproteins of CAD patients are more exposed to, or are more susceptible to, free radical reactions compared with apparently healthy controls.

Adult↗
PubMed1997

Zinc status in vitamin B6 deficiency.

Three groups of young male Wistar rats were maintained on diets consisting of 7 mg pyridoxine hydrochloride/kg diet (control and pair-fed groups) and 0 mg pyridoxine hydrochloride/ kg diet (deficient group) for six weeks. The zinc status of all rats was assessed by measuring their erythrocyte zinc-metallothionein-1 (Zn-Mt-1) and plasma zinc levels. A significant difference (p < 0.001) in plasma zinc levels was observed between the deficient group and the control and pair-fed groups (1.35 micrograms/ml +/- 0.08, 1.99 micrograms/ml +/- 0.06 and 2.03 micrograms/ml +/- 0.07 respectively). Erythrocyte Zn-Mt-1 levels were significantly lower in vitamin B6 deficient rats when compared to control animals. No significant difference in Zn-Mt-1 levels existed between vitamin B6 deficient and pair-fed groups suggesting that the reduced Zn-Mt-1 levels in vitamin B6 deficient rats may be due entirely to their decreased food intake (8.9 g/day compared to 15 g/day of control rats).

Animals↗
PubMed1997

Zinc, copper and iron levels in tissues of the vitamin B6 deficient rat.

Tissue zinc (Zn), copper (Cu) and iron (Fe) were determined in three groups of young male Wistar rats that received a daily pyridoxine hydrochloride (PN.HCl) intake of 45, 23 and 0 micrograms respectively in their diets over 8 weeks. No significant differences were found in the Zn and Cu levels in the liver, kidney, skeletal and cardiac tissue of all 3 groups. The Fe levels were significantly higher in the heart and liver and significantly lower in the skeletal muscle of the group receiving no PN.HCl in the diet (P < 0.05). This study indicates that the increased fecal excretion of Zn and Cu observed during a previous balance study on the above vitamin B6 deficient group of animals may be due to a decreased absorption of these elements from the diet rather than their excretion from tissue stores. The changes in Fe levels in the heart, liver and skeletal muscle points towards some alteration in tissue stores of this element during a vitamin B6 deficiency.

Animals↗
PubMed1996

The effect of a subnormal vitamin B-6 status on homocysteine metabolism.

Homocysteine, an atherogenic amino acid, is either remethylated to methionine or metabolized to cysteine by the transsulfuration pathway. The biochemical conversion of homocysteine to cysteine is dependent upon two consecutive, vitamin B-6-dependent reactions. To study the effect of a selective vitamin B-6 deficiency on transsulfuration, we performed oral methionine load tests on 22 vitamin B-6-deficient asthma patients treated with theophylline (a vitamin B-6 antagonist) and 24 age- and sex-matched controls with a normal vitamin B-6 status. Both groups had normal circulating vitamin B-12 and folate concentrations. Methionine loading resulted in significantly higher increases in circulating total homocyst(e)ine (P < 0.01) and cystathionine (P < 0.05) concentrations in vitamin B-6-deficient patients compared with controls. 6 wk of vitamin B-6 supplementation (20 mg/d) significantly (P < 0.05) reduced post-methionine load increases in circulating total homocyst(e)ine concentrations in deficient subjects, but had no significant effect on the increase in total homocyst(e)ine concentrations in controls. The increases in post-methionine load circulating cystathionine concentrations were significantly (P < 0.01) reduced in both groups after vitamin supplementation. It is concluded that a vitamin B-6 deficiency may contribute to impaired transsulfuration and an abnormal methionine load test, which is associated with premature vascular disease.

Administration, Oral↗
PubMed1996

Plasma homocysteine concentrations in a population with a low coronary heart disease prevalence.

To evaluate hyperhomocysteinemia as a possible coronary heart disease risk factor, the South African black population as example of a population with a low coronary heart disease prevalence was investigated and compared with a population prone to coronary heart disease (South African Whites). In traditionally living adult black men, plasma homocysteine concentrations were significantly lower compared with Whites. The plasma homocysteine frequency distribution in Whites was positively skewed; individuals with high plasma homocysteine concentrations probably acquire these during or after young adulthood, because the plasma homocysteine frequency distribution in children was normal. Compared with Blacks, young adult Whites showed methionine intolerance expressed as high plasma homocysteine concentrations after an oral methionine load test. The results indicate that Blacks generally have lower circulating plasma homocysteine concentrations and more effective homocysteine metabolism after oral methionine loading, which may partially explain their relative resistance against coronary heart disease.

Adult↗
PubMed1996

Will an increased dietary folate intake reduce the incidence of cardiovascular disease?

Based on a meta-analysis of published studies, it has been estimated that approximately 10% of coronary artery disease cases are attributable to hyperhomocyst(e)inemia. It has also been calculated that food fortification with folate might reduce the number of cases of coronary artery disease in the United States by 50,000 per year. However, the use of statistical concepts to estimate the expected benefits of this intervention strategy may be misleading.

Cardiovascular Diseases↗
PubMed1996

Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress.

It has been postulated that lipid peroxidation plays a crucial role in the pathogenesis of atherosclerosis. As CoQ10H2 (reduced form of coenzyme Q10) is easily oxidized to CoQ10 (oxidized form of coenzyme Q10), it has been proposed that the CoQ10H2/CoQ10 ratio may be used as a possible marker of in vivo oxidative stress. However, sample preparation has an important effect on the redox status of coenzyme Q10 due to the extreme sensitivity of CoQ10H2 towards oxidation. We now report a rapid, simple isocratic HPLC procedure for the determination of CoQ10H2 and CoQ10 in plasma isopropanol extracts, and we used this method to investigate conditions by which the CoQ10H2/CoQ10 ratio can be reliably measured. Our results indicate that CoQ10H2 is unstable in whole blood, plasma, and isopropanol extracts; subsequently the CoQ10H2/CoQ10 ratio changes considerably soon after a blood sample has been obtained. The time period since blood sampling and HPLC analysis, as well as the sample pretreatment procedure, are two factors that have a profound effect on the pre-analytical variation in the determination of the CoQ10H2/CoQ10 ratio. If these two factors are properly controlled, the CoQ10H2/CoQ10 ratio may be a sensitive and practical way to measure in vivo oxidative stress. Furthermore, this indicator is independent from plasma total cholesterol concentrations, implying that groups who differ with respect to cholesterol levels may be compared directly.

Adolescent↗
PubMed1995

Effective homocysteine metabolism may protect South African blacks against coronary heart disease.

L-Methionine (0.1 g/kg body wt) was administered to young white [n = 18; mean (+/- SD) age 20.0 +/- 1.0 y] and black [n = 12; mean (+/- SD) age 22.0 +/- 1.3 y] volunteers who had a similar lifestyle and who did not differ significantly from each other with respect to plasma folate or vitamin B-12 concentrations. Blacks, however, had significantly lower plasma pyridoxal-5'-phosphate concentrations compared with whites (P < 0.001). Fasting plasma homocysteine concentrations in blacks and whites were not significantly different. The mean (+/- SD) maximum increase in plasma homocysteine concentration measured after methionine loading was significantly lower (P < 0.01) in blacks (11.0 +/- 3.6 mumol/L) than in whites (18.0 +/- 6.2 mumol/L). Six weeks of vitamin supplementation (1.0 mg folic acid, 400 micrograms vitamin B-12, and 10 mg pyridoxine/d) reduced the mean (+/- SD) fasting plasma homocysteine concentration from 9.6 +/- 3.5 to 7.2 +/- 1.6 mumol/L in whites (P < 0.05) and from 8.4 +/- 2.4 to 5.6 +/- 1.4 mumol/L in blacks (P < 0.01). The mean (+/- SD) maximum increase in plasma homocysteine concentration after methionine loading declined from 18.0 +/- 6.2 to 11.1 +/- 2.3 mumol/L (P < 0.01) in whites, but vitamin supplementation did not have a significant effect on the methionine-load test in black volunteers. A significant race-by-time interaction shows that blacks metabolized homocysteine more effectively than did whites, which may partly explain their relative resistance against coronary heart disease despite a high prevalence of obesity, hypertension, and smoking.

Adult↗
PubMed1995

The determination of allantoin, a possible indicator of oxidant status, in human plasma.

Because uric acid may be oxidized to allantoin by various reactive oxygen species, it is postulated that uric acid functions as an antioxidant in human bodily fluids. The measurement of allantoin concentrations may therefore be useful for the quantitation of oxidant generation in humans. We develop a reliable assay for the quantitation of human plasma allantoin levels. The method consists of rapid and selective separation of allantoin from uric and glyoxylic acid (which interfere in the assay) using anion-exchange solid-phase extraction prior to conversion of allantoin to glyoxylic acid and derivatization with 2,4-dinitrohenylhydrazine. Determination of glyoxylate-2,4-dinitrophenylhydrazone is achieved by using reversed-phase high-performance liquid chromatography with gradient elution and ultraviolet detection at 360 nm. The analytical performance of the method is satisfactory, with a day-to-day coefficient of variation of 8.9% and a within-batch coefficient of variation of 7.2%. The method is applied to the measurement of allantoin concentrations in the plasma of 99 apparently healthy men, and a preliminary reference range is reported. Clinical studies can now be performed to evaluate allantoin as a possible indicator of free radical damage in vivo.

Allantoin↗
PubMed1995

Homocysteine--an atherogenic and a thrombogenic factor?

A recent study found that hyperhomocysteinemia is associated with an increased risk of extracranial carotid artery stenosis, while another study demonstrated that hyperhomocysteinemia is a common risk factor for recurrent venous thrombosis. It seems as if an elevated circulating homocysteine is atherogenic as well as thrombogenic, possibly indicating extensive involvement of homocysteine in the pathogenesis of coronary heart disease.

Arteriosclerosis↗
PubMed1995

Is an elevated circulating maternal homocysteine concentration a risk factor for neural tube defects?

The mechanism by which folic acid supplementation reduces neural tube defect (NTD) incidence is unknown. Recent evidence suggests that mothers with NTD neonates have higher circulating homocysteine concentrations compared with controls. This presumably indicates impaired homocysteine remethylation, resulting in a possible methionine shortage at a crucial stage of fetal development.

Biomarkers↗
PubMed1995

Results of B-vitamin supplementation study used in a prediction model to define a reference range for plasma homocysteine.

Because high plasma concentrations of homocysteine constitute an enhanced risk for premature coronary heart disease, it is necessary to establish a reference range for normal concentrations of plasma homocysteine. The frequency distribution of plasma homocysteine concentrations tails to the right, and the nonparametric approach is unsatisfactory for defining a normal plasma homocysteine reference range. By using subjects' responses to appropriate vitamin supplementation, we developed a mathematical prediction model to calculate the plasma homocysteine concentration that could be expected for each individual treated with a vitamin supplement. With this model, we can predict that plasma homocysteine concentrations will approach a normal frequency distribution with a 95% reference range (mean +/- 2 SD) of 4.9-11.7 mumol/L, provided the vitamin status of the study population is improved.

Adolescent↗
PubMed1994

Vitamin B-6 supplementation and theophylline-related effects in humans.

This study investigates whether vitamin B-6 supplementation reduces the stimulatory effects of theophylline (a pyridoxal kinase antagonist) on the nervous system. Twenty young, healthy adults entered this double-blind, randomized, crossover study but only 15 completed the experiment. The dependent measures were a battery of psychomotor tests, electrophysiological tests, and self-report questionnaires. Most tests, including spectral electroencephalography, aspects of the electromyograph, the Sternberg Test of information processing, and questionnaires of sleep quality and daytime sleepiness failed to distinguish between vitamin B-6 and placebo supplementation. However, theophylline-related tremor was markedly reduced (p < 0.01) with vitamin B-6 supplementation after a single dose of theophylline and a similar but nonsignificant trend was observed with repeated doses. There was a tendency for vitamin B-6 supplementation to reduce many side effects related to nervous system function. These findings suggest that vitamin B-6 supplementation with theophylline therapy may have some beneficial effects.

Adult↗