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Biomedical subjects

G Alfthan

Publications and source records attributed to G Alfthan.

At least 37 records · Page 2Linked to original sources

Validated method for the quantitation of quercetin from human plasma using high-performance liquid chromatography with electrochemical detection.

A validated method for the quantitation of trace levels of quercetin from human plasma to be used in pharmacokinetic and biomarker studies is presented. Quercetin conjugates were hydrolysed enzymatically, plasma proteins were removed using a Bond Elut C18 extraction column and additional interferences were removed by extracting them into a toluene-dichloromethane mixture. The HPLC system consisted of an Inertsil ODS-3 column (250 x 4.0 mm) and a mobile phase with 59% methanol in phosphate buffer (pH 2.4). High selectivity and a low quantitation limit (0.63 microg/l) were achieved by using electrochemical detection at a low potential. The method has excellent reproducibility: R.S.D. values of peak-heights were 2% and 7.9%, respectively, for within-day and between-day precision. The method was applied to a small scale study of quercetin pharmacokinetics and quercetin was shown to be absorbed from a 20 mg dose. No free quercetin was detected in plasma and no evidence of significant amounts of quercetin glycosides in plasma was found.

Chromatography, High Pressure Liquid↗

Enhanced in vivo lipid peroxidation at elevated plasma total homocysteine levels.

An elevated plasma total homocysteine level (tHcy) is considered an independent risk factor for atherosclerosis. The mechanisms by which hyperhomocysteinemia induces atherosclerosis are only partially understood, but promotion of LDL oxidation and endothelial injury have been suggested. The purpose of this study was to test the hypothesis that a high plasma tHcy is associated in men with increased in vivo lipid peroxidation, as measured by plasma F2-isoprostane concentrations. We investigated this association in a subset of the participants in the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study. Of 256 male participants, a subsample of 100 consecutive men was selected for F2-isoprostane assays. The mean tHcy was 11.0 micromol/L, and the mean F2-isoprostanes was 29.6 ng/L. The simple correlation coefficient for association between tHcy and F2-isoprostane was 0.40 (P<0.001). In a linear regression model, the variables with the strongest associations with F2-isoprostane were tHcy (standardized coefficient 0.33, P<0.001), serum triglycerides (0.21, P=0.042), carbohydrate-deficient transferrin (0.15, P=0.132), and plasma lipid-standardized alpha-tocopherol (-0.11, P=0.252) (R2=0.24, P<0. 001 for model). Plasma F2-isoprostane levels increased linearly across quintiles of tHcy (P<0.001). The unadjusted mean (95% confidence interval) F2-isoprostanes was 47.5% greater in the highest tHcy quintile (37.4, 31.1 to 43.6 ng/L) than in the lowest quintile (25.3, 21.3 to 29.3 ng/L). Adjustment for the strongest other determinants of F2-isoprostane reduced this difference to 28. 2% (P=0.010). Our present data suggest that elevated fasting plasma tHcy is associated with enhanced in vivo lipid peroxidation in men.

Arteriosclerosis↗

Enterovirus infections as a possible risk factor for myocardial infarction.

BACKGROUND: An increasing body of evidence suggests that, in addition to the well-known classic risk factors, some microbial infections may be associated with the development of atherosclerosis and myocardial infarction (MI). The aim of our study was to evaluate the possible role of enteroviral infections in the pathogenesis of MI. METHODS AND RESULTS: Stored sera, collected in Eastern Finland in 1977, from a set of 12 155 randomly selected men and women aged 25 to 64 years were used in prospective, nested case-control study. The study sample comprised 183 men and 81 women with MI and matched controls. The sera were tested for IgG antibodies to a newly identified enterovirus-common (EVC) antigen, to heat-denatured coxsackievirus B5 (CBV-5), and to adenovirus hexon protein. Raw data from enzyme immunoassays were converted to relative units before analysis. In univariate analysis, EVC antibodies were significantly associated with the risk of MI in men (P=0.009) but not in women. Men with MI had a significantly higher mean level of EVC antibodies than matched controls (P=0.014). High antibody levels to EVC were associated with an increased risk of MI in men aged 25 to 49 years (relative risk [RR] 4.34, P<0.001) but not in older men (>50 years of age). Women with MI also showed a trend toward higher antibody levels than control women, but the difference was not statistically significant. Antibody levels to whole CBV-5 or adenovirus hexon protein appeared to be no different among case patients versus control subjects. CONCLUSIONS: If we assume that a high level of EVC antibodies reflects a history of relatively frequent enterovirus infections, the present observation might suggest that enterovirus infections increase the risk of MI at least in middle-aged men. Further studies are needed to understand possible clinical significance of this observation.

Adult↗

Randomized clinical trial of enteral yeast-selenium supplementation in preterm infants.

There are no data in the literature on effects of supplementing infants with yeast-selenium. We therefore studied the impact of selenium-enriched yeast on the serum selenium concentration of preterm infants living in a selenium-low area (Hungary). Twenty-eight preterm infants with a mean +/- SD birthweight of 962 +/- 129 g and a gestational age of 27 +/- 1 weeks were randomized into two groups at birth with respect to selenium supplementation. In the supplemental group (n = 14) infants received 4.8 mg yeast containing 5 microgram selenium daily with naso-gastric drip during the first 14 postnatal days. The nonsupplemented infants were used as a reference group. In the supplemented group the serum selenium concentration increased from 32.1 +/- 8.5 microgram/l to 41.5 +/- 6.5 microgram/l and in the nonsupplemented group it decreased from 25.9 +/ 6.8 microgram/l to 18.2 +/- 6.4 microgram/l within two weeks. The serum glutathione peroxidase activity increased from 2.97 +/- 0.73 U/20 microliter to 6.42 +/- 3.11 U/20 microliter in the supplemented group, and it did not change significantly (from 3.53 +/- 0.94 U/20 microliter to 3.85 +/- 0.95 U/20 microliter) in the nonsupplemented group. We did not observe any complications or side effects in connection with enteral yeast-selenium supplementation. It is concluded that selenium-enriched yeast is a safe and an effective form of short term enteral selenium supplementation for preterm infants.

Food, Fortified↗

Bioavailability of enteral yeast-selenium in preterm infants.

There is no data or literature on the effects of supplementing infants with yeast selenium, although its intestinal absorption and bioavailability are higher in adults compared with other selenium compounds. The aim of the present investigation was to study the impact of selenium enriched yeast on the serum selenium concentration of preterm infants living in a low selenium area (Hungary). Twenty-eight preterm infants with mean+/-SD birth weight of 962+/-129 g and gestational age 27+/-1 wk were randomized into two groups at birth with respect to selenium supplementation. In the supplemented group (n=14) infants received 4.8 mg yeast selenium containing 5 microg selenium daily via nasogastric drip during the first 14 postnatal days. The nonsupplemented infants were used as a reference group. In the supplemented group, the serum selenium concentration increased from 32.1+/-8.5 microg/L to 41.5+/-6.5 microg/L and in the nonsupplemented group it decreased from 25.9+/-6.8 microg/L to 18.2+/-6.4 microg/L from birth in two weeks time. Compared with previous studies, our results suggest that the bioavailability of selenium in the form of yeast selenium is higher than that of other selenium compounds used for preterm infants. We did not observe any complications or side-effects owing to enteral yeast selenium supplementation. We conclude that selenium enriched yeast is a safe and an effective form of short-term enteral selenium supplementation for infants.

Biological Availability↗

Plasma selenoprotein P levels of healthy males in different selenium status after oral supplementation with different forms of selenium.

OBJECTIVE: To assess changes in selenoprotein P levels in plasma from subjects who had received oral supplements of different selenium forms. DESIGN: The same study group participated in two similar selenium supplementation trials, Trial I in 1981 (Levander et al, 1983) and Trial II in 1987 (Alfthan et al, 1991). During Trial II the mean baseline intake of selenium in Finland was higher compared to that during Trial I (100 and 40 microg/d, respectively), due to a nationwide supplementation of fertilisers which started in 1985. SUBJECTS: Fifty healthy Finnish men, 36-60 y old. INTERVENTION: The study group received daily placebo or oral supplements consisting of 200 microg selenium as selenium-enriched yeast, sodium selenate or selenium-enriched wheat (Trial I) or selenium-enriched yeast, sodium selenate or sodium selenite (Trial II). The duration of supplementation periods was 11 (Trial I) and 16 (Trial II) weeks. RESULTS: In Trial I the mean plasma selenoprotein P values in all the supplemented groups increased significantly, approaching a plateau at 2 weeks and reaching maxima at 4 weeks (mean increase 34%, P < 0.05). In Trial II the mean selenoprotein P levels of the supplemented groups were not significantly different from each other or from the placebo group at the start or at any time point of the supplementation period. CONCLUSIONS: At a low selenium status the selenoprotein P levels increased in a similar fashion after supplementation with different forms of selenium, but at a high selenium status no significant effects of supplementation with the same amount of selenium were observed. No differences in selenoprotein P levels were observed for inorganic and organic selenium supplements.

Adult↗

Beta-carotene concentration in buccal mucosal cells with and without dysplastic oral leukoplakia after long-term beta-carotene supplementation in male smokers.

OBJECTIVE: To measure the beta-carotene concentration in buccal mucosal cells in smoking men who had received long-term beta-carotene (BC) supplementation in a controlled trial. To assess the association of cellular BC on the prevalence of dysplasia in oral leukoplakia. DESIGN: An end-of-trial examination of a part of subjects in the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study. SUBJECTS AND METHODS: 343 men who for 5-7 years had received BC (20 mg/d) or alpha-tocopherol (AT) (50 mg/d), or both of these or placebo. BC concentration of buccal mucosal cells was compared in the subjects with BC supplementation (n = 173) to that of those without it (n = 170). Oral mucosae were examined clinically and lesions showing leukoplakia histopathologically. RESULTS: Mean (s.d.) BC concentration in buccal mucosal cells was 7.7 (10.3)mg/kg protein in the subjects who received BC compared to 1.1 (1.7) mg/kg protein in those who did not. The BC concentration in the cells of supplemented subjects correlated with their serum BC levels (P < 0.001). AT supplementation had no effect on BC concentration nor was daily amount of smoking statistically significantly associated with the BC concentration in buccal cells. Altogether 17 subjects showed oral leukoplakia, 7 had dysplasia. In these 7 subjects, the BC concentration in buccal mucosal cells did not differ statistically significantly compared to subjects with only hyperkeratosis (n = 10) (F-test, P = 0.74). CONCLUSIONS: After long-term BC supplementation, BC concentration in oral mucosal cells was 7-fold greater than without supplementation. There was no evidence to support an association between cellular BC concentration and precancerous lesions among the few subjects having them in their oral mucosae.

Aged↗

Enteral yeast-selenium supplementation in preterm infants.

AIM: To study the bioavailability of selenium enriched yeast in preterm infants living in a low selenium area (Hungary). METHODS: Thirty six preterm infants were randomly assigned to two groups at birth with respect to selenium supplementation. In the supplemented group (n = 18) infants received 4.8 mg of selenium enriched yeast containing 5 micrograms selenium daily. RESULTS: In the supplemented group the serum selenium concentration increased from 36.1 (+/- 12.8) micrograms/l to 43.5 (7.9) micrograms/l and in the non-supplemented group it decreased from 34.4 (20.4) micrograms/l to 26.1 (16.6) micrograms/l from birth in two weeks. No complications or side effects as a result of supplementation were observed. CONCLUSIONS: Selenium enriched yeast is a safe and an effective form of short term enteral selenium supplementation for preterm infants.

Biological Availability↗

Association between elevated plasma total homocysteine and increased common carotid artery wall thickness.

Homocysteine is increasingly recognized as a risk factor for atherothrombotic arterial diseases. We investigated the relation between plasma concentrations of total homocysteine (tHcy) and common carotid artery intima-media wall thickness, measured by B-mode ultrasonography, in 513 asymptomatic men and women from eastern Finland aged 45-69 years. The subjects were examined in 1994-95 at the baseline of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study, a randomized double-blind placebo-controlled two by two factorial trial on the effect of vitamin E and C supplementation in the prevention of atherosclerotic progression. The subjects were assigned into two categories according to the plasma tHcy concentration; concentration over 11.5 micromol/L (highest quartile) or concentration below 11.5 micromol/L. In this study population the mean plasma tHcy concentration was 10.0 micromol/L, and the prevalence of plasma tHcy concentration exceeding 11.5 micromol/L was 33% in men and 18% in women. The adjusted mean intima-media thickness of the right and left common carotid arteries was 1.12 mm in men with elevated plasma tHcy concentration and 1.02 mm in men with a plasma tHcy concentration below 11.5 micromol/L (P = 0.029). In women there was no significant difference. We conclude that elevated plasma tHcy concentrations are associated with early atherosclerosis, as manifested by increased common carotid artery intima-media wall thickness, in middle-aged eastern Finnish men.

Adult↗

Selenium and arsenic in the environment in Finland.

A characteristic feature of glaciated Precambrian environments is their low selenium content, as a chalcophile element, Se, replaces sulfur in many of the sulfide minerals, for example, pyrite, chalcopyrite, pyrrhotite, and pentlandite. The average Se concentration in rocks and related till deposits in Finland is in the range of 0.01 to 0.2 mg/kg. Due to geological conditions, Se concentrations in surface and ground water are low in Finland compared with other countries. In a nationwide study dealing with the hydrogeochemistry of headwater streams, the median Se concentration in streams during August to September 1990 was 30 to 180 microg/L. For comparison, Se concentrations in shallow well waters are generally in the range of 50 to 1000 microg/L. The Se concentrations in stream sediments varied from 0.03 to 3.94 mg/kg. There was a highly significant correlation between the Se concentrations in stream water and in stream sediment. The streams with Se concentrations exceeding the general level in both water and sediment were most common in southern Finland. A speciation study on Finnish stream waters revealed that there were equal proportions of Se complexed with humic substances (36%) and Se as a selenate species (36%), whereas selenite accounted for less than 10% of total Se. About 8% of the Se in stream water occurred in particulate form. In an effort to enhance the Se intake of Finns through diet, Se-supplemented fertilizers have been used nationwide since 1985. While greatly improving Se levels in the population, the measure has raised concerns about undesirable environmental effects. Therefore, the amount of Se added to fertilizers has been reduced since 1991. Differing in behavior from Se, arsenic is considered one of the most toxic metals derived from the natural environment. Alarm has been triggered in Finland by the recent lowering from 50 microg/L to 10 microg/L of the upper level of As permissible in potable water, the recent information of high As concentrations in water from drilled bedrock wells, and the findings of international medical studies suggesting that As is a carcinogen. The most important source of As is arsenopyrite (FeAsS). Hence, high As concentrations most frequently occur in areas of sulfide mineralization, often in connection with occurrences of mafic rocks such as gabbros, amphibolites, and peridotites. The As concentrations in till fines, the most common glaciogenic soil type in Finland, reflect those in bedrock. The concentrations in groundwater are controlled by the chemical composition of the bedrock and the soil and prevailing hydrogeochemical conditions, for example, pH and Eh levels. Arsenic concentrations are lowest in surface water and swiftly flowing shallow ground water discharged by springs and are somewhat higher in shallow wells dug into overburden. By far, the highest As concentrations are to be found in wells drilled into bedrock (maximum 1 to 2 mg/L), although the concentrations vary by several orders of magnitude from well to well. The highest probability of encountering deleteriously arsenious well water is in areas with characteristic As anomalies in the till and bedrock. Hence, it is important to understand local geological conditions, particularly in the case of wells drilled into bedrock. The risk of deleteriously high As concentrations occurring in captured springs and shallow wells is slight.

Animals↗

Reference values for serum selenium in various areas-evaluated according to the TRACY protocol.

Published reports on selenium concentrations in serum and plasma were critically reviewed according to the criteria set up by the expert group of the international project TRACY. The aim was to examine both pre-analytical (sampling conditions and characteristics of the group) and analytical factors described in papers to establish reference values for evaluation of persons with deficiency or excessive exposure to the element. Out of 291 papers published during the period 1983 to 1993, which we reviewed, 36 were considered suitable for the TRACY project. In order to eliminate sources of variation due to age and health status, only data concerning healthy adults were retained. Of the sampling and other pre-analytical factors, geographical area and time of sampling were found to be of high importance. Gender, occupation, diet data and use of supplements or medications were also considered important determinants, but ethnic origin, smoking and fasting, contamination control and storage of sample were held to be of relatively low importance. Concerning analytical factors, accuracy criteria were generally satisfied although not extensively documented. Reference materials for serum selenium, which contribute to better analytical reliability have been available for over 10 years. Due to the geographical variation of selenium intake, one universal reference serum selenium value for the world's population was not feasible but the data selected allowed documentation of the serum selenium concentration levels among populations of different areas, mostly in Europe. Critical use of the published TRACY criteria in future papers will certainly extend their reliability and scientific significance.

Adult↗

Affinity-purified cardiolipin-binding antibodies show heterogeneity in their binding to oxidized low-density lipoprotein.

Antiphospholipid antibodies in autoimmune sera have been shown to react with a complex of phospholipids (cardiolipin) and a plasma phospholipid-binding protein, beta 2-glycoprotein I (apolipoprotein H). The binding of these antibodies was inhibited by oxidized low-density lipoprotein (LDL) in sera from patients with systemic lupus erythematosus (SLE), suggesting cross-reactivity between antiphospholipid antibodies and antibodies binding to oxidized LDL. We purified antiphospholipid antibodies by cardiolipin-polyacrylamide column from seven SLE sera and studied the reactivity of eluted fractions with cardiolipin-beta 2-glycoprotein I complex and oxidized LDL (malondialdehyde-conjugated LDL) in solid-phase enzyme immunoassay. In four sera the binding of IgG antibodies to cardiolipin-beta 2-glycoprotein I complex and to oxidized LDL appeared in the same fractions, whereas in three sera reactivities against cardiolipin and oxidized LDL were observed, at least in part, in separate fractions. The binding to solid-phase cardiolipin was dependent on the presence of exogenous beta 2-glycoprotein I in all fractions. Our findings show that antiphospholipid antibodies are heterogeneous in their binding to oxidized LDL, indicating that these two antibodies may have different subspecificities. Some eluted fractions reacted only with oxidized LDL, and did not show binding to cardiolipin-beta 2-glycoprotein I complex, suggesting that the lipid part in the antigenic complex might be responsible for the cross-reactivity of these antibodies. Accordingly, the biological functions of antibodies against phospholipid-beta 2-glycoprotein I complex and antibodies against oxidized LDL may also be different.

Adult↗

Plasma ascorbic acid concentrations in the Republic of Karelia, Russia and in North Karelia, Finland.

OBJECTIVES: To determine the plasma ascorbic acid concentrations among men in North Karelia (Finland) and in Pitkäranta (Republic of Karelia) and to test how a short intervention would affect the plasma concentrations. DESIGN: The baseline survey was done as a cross-sectional population survey. A subsample was selected to the intervention study and randomised to treatment and control groups. SETTING: North Karelia province in Finland and the Pitkäranta area in the Republic of Karelia. SUBJECTS: In the cross-section population survey the stratified random sample of men between 25 and 64 years of age was 1000 in North Karelia and 500 in Pitkäranta. Participation rates were 68% and 77%, respectively. Plasma ascorbic acid measurements were made in one-third of the sample. In Pitkäranta 60 men, having very low plasma ascorbic acid concentrations, were invited to the intervention study. INTERVENTIONS: A controlled intervention study was made with blackcurrant-strawberry nectar in which vitamin C content was approximately 70 mg/100 g. The treatment group drank two times daily 200 ml nectar for 4-5 weeks. After intervention plasma ascorbic acid concentration was measured from both treatment and control groups. RESULTS: Plasma ascorbic acid concentrations were very different in the two areas. In Pitkäranta 93% of the men and in North Karelia only 2% of the men had plasma levels suggesting severe vitamin C deficiency. After intervention 46% of the men in the experimental group compared with 5% in the control group had plasma ascorbic acid concentrations exceeding 23 mumol/l (4.0 mg/l). CONCLUSIONS: In addition to a high smoking prevalence the very low ascorbic acid concentration among men in the Republic Karelia can have an effect on the high cardiovascular disease mortality.

Administration, Oral↗

Effect of extreme fish consumption on dietary and plasma antioxidant levels and fatty acid composition.

OBJECTIVE: To assess the effects of high-fish and low-fish diets on plasma concentrations of fatty acids and selected antioxidants. DESIGN AND SUBJECTS: The effects of fish consumption on dietary and plasma antioxidant levels and fatty acid composition were studied as part of a large dietary survey of Finnish adults (n = 1861). High-fish consumers were matched with low-fish consumers and 41 pairs were identified. The members of each pair were of the same sex, from the same 10 y age group, and from the same or adjacent areas. There were 21 men and 20 women in each group, with a mean age of 54.3 y. METHODS: The fish consumption of the subjects was investigated with a qualitative food questionnaire. Additionally, a 3 d food record was used to estimate the diet. Two indices were defined to describe the oxidation potential of the diets. The plasma alpha-tocopherol, gamma-tocopherol, and beta-carotene concentrations and various fatty acids were analysed. RESULTS: The mean fish intake was 103 g/d in the high-fish and 5 g/d in the low-fish group. The dietary intakes of vitamin C, protein, total n-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid, docosahexaenoic acid, mercury, selenium, and salt and the theoretical oxidative potential were higher (P < 0.05) and the saturated fatty acid intake lower (P < 0.01) in the high-fish than in the low-fish group. The dietary vitamin E intake was similar in both groups but the ratio of dietary vitamin E/PUFA was higher (P < 0.01) in the high-fish than in the low-fish group (0.85 and 0.75, respectively). The plasma n-3 PUFAs were higher (P < 0.001) and n-6 PUFAs lower (P < 0.001) in the high-fish than in the low-fish group. There were no differences in plasma antioxidant levels between the groups. CONCLUSION: This study shows that extreme fish consumption does not affect plasma antioxidant levels.

Adult↗