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Biomedical subjects

T Nikkari

Publications and source records attributed to T Nikkari.

At least 73 records · Page 4Linked to original sources

Evening primrose oil in rheumatoid arthritis: changes in serum lipids and fatty acids.

The serum concentration of lipids and composition of fatty acids after overnight fasting were studied in 18 patients with rheumatoid arthritis treated for 12 weeks with either 20 ml of evening primrose oil containing 9% of gamma-linolenic acid or olive oil. The serum concentrations of oleic acid, eicosapentaenoic acid, and apolipoprotein B decreased and those of linoleic acid, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid increased during treatment with evening primrose oil. During olive oil treatment the serum concentration of eicosapentaenoic acid decreased and those of high density lipoprotein-cholesterol and apolipoprotein A-I increased slightly. The decrease in serum eicosapentaenoic acid and the increase in arachidonic acid concentrations induced by evening primrose oil may not be favourable effects in patients with rheumatoid arthritis in the light of the roles of these fatty acids as precursors of eicosanoids.

Anti-Inflammatory Agents, Non-Steroidal↗

Cultured bovine aortic endothelial cells secrete factor(s) chemotactic for aortic smooth muscle cells.

Interactions of vascular endothelial cells (ECs) and smooth muscle cells (SMCs) were studied by testing the ability of cultured bovine aortic ECs to secrete factors influencing the migration of cultured aortic SMCs from the same species. Migration of SMCs was examined in blind-well chambers using gelatin-coated polycarbonate filters. Conditioned culture medium obtained by incubating confluent monolayers of ECs in serum-free RPMI-1640 medium for 48 hours caused a 2.4-fold increase in the migration of SMCs as compared with nonconditioned medium (p less than 0.001). The effect was dependent on the length of conditioning with the ECs and was chemotactic in nature as judged on the basis of checkerboard analysis. Preliminary characterization of the migration stimulating activity indicates that it is sensitive to trypsin, nondialyzable, and stable at 56 degrees C for 30 min. The activity was abolished by heating to 100 degrees C for 20 min but was not significantly inhibited by protamine sulphate, which suggests that most of the activity was not due to platelet-derived growth factor (PDGF)-like proteins. Our results thus show that ECs secrete polypeptide(s) chemotactic for vascular SMCs. Such interactions between ECs and SMCs in vivo might contribute to the migration of medial SMCs into the intima during atherogenesis.

Animals↗

Lipoprotein uptake in primary cell cultures of rabbit atherosclerotic lesions. A fluorescence microscopic and flow cytometric study.

To characterize the lipoprotein metabolism of lipid-filled cells of atherosclerotic lesions, uptake of 3,3'-dioctadecylindocarbocyanine (DiI)-labelled low density lipoprotein (LDL), acetylated LDL (Ac-LDL) and beta-very low density lipoprotein (beta-VLDL) was studied by fluorescence microscopy and flow cytometry in primary cultures of enzymatically dispersed aortic cells from cholesterol-fed rabbits. Most of the foam cells were identified as macrophages on the basis of Fc-receptors and high activities of nonspecific esterase and acid lipase, although cholesteryl ester (CE) inclusions were found by filipin staining also in smooth muscle cells (SMCs). During the culture only SMCs proliferated and were confluent in about 1 week. After incubation with DiI-Ac-LDL most macrophage foam cells were brightly fluorescent, but also many SMCs accumulated fluorescence. In SMCs, an excess of LDL inhibited the uptake of DiI-beta-VLDL and DiI-LDL, indicating that these lipoproteins were taken up by the apoB,E receptor; the activity of this receptor was low 2 days after cell isolation but increased considerably during SMC proliferation. DiI-beta-VLDL was not taken up by the macrophage foam cells until after 7 days' culture, when their CE content had decreased, reflecting a feed-back regulation of these receptors as well. Our results indicate that, in primary cultures of enzyme-dispersed cells from rabbit atherosclerotic lesions, most of the foam cells have lipoprotein receptors resembling those described in macrophages and that also many SMCs accumulate Ac-LDL.

Animals↗

Plasma apolipoprotein B in middle-aged Finnish men. Evidence for a regional gradient of apo B and lack of negative correlation between apo B and dietary linoleate in hyperapobetalipoproteinemia.

Plasma apolipoprotein B (apo B) concentrations were determined in 178 randomly selected 40-49-year-old men from Eastern and Southwestern Finland and compared with the concentrations of plasma lipids and the fatty acid composition of plasma and adipose tissue determined previously from the same populations. The plasma apo B concentrations ranged from 50 to 209 mg/dl. Although men from the two regions had similar mean concentrations of plasma triglyceride, total cholesterol and high density lipoprotein (HDL)-cholesterol, men from Eastern Finland had significantly higher mean apo B levels (139 +/- 25 mg/dl) and a lower ratio of total cholesterol to apo B (1.85 +/- 0.25) than the Southwestern men (125 +/- 33 mg/dl and 2.05 +/- 0.40, respectively). In the whole population, apo B and total cholesterol had significant negative correlations with the percentages of linoleate in the fatty acids of plasma and adipose tissue, which are known to reflect the quality of dietary fat. As the percentages of linoleate have previously been shown to be lower in the Eastern population, part of the regional difference in apo B is obviously explained by differences in the quality of dietary fat. On the other hand, men (n = 59) who had high plasma apo B (greater than 130 mg/dl) but low density lipoprotein (LDL)-cholesterol within the reference values (less than 5.17 mmol/l) showed no correlation between linoleate and apo B. This suggests that other factors than dietary fat determine the concentration of apo B in this group of men.

Adipose Tissue↗

Effect of repeated endotoxin treatment and hypercholesterolemia on preatherosclerotic lesions in weaned pigs. Part II. Lipid and glycosaminoglycan analysis of intima and inner media.

We compared the effects of mild hypercholesterolemia and repeated endotoxin infusions on the biochemical composition of aortic intima and inner media of 24 piglets divided into 4 groups 5 days after weaning: controls on normal diet (group I); normal diet and endotoxin (group II); fat-supplemented diet (group III); and fat-supplemented diet and endotoxin (group IV). It was found that mild hypercholesterolemia increased the concentration of arterial esterified cholesterol and the relative amount of the fraction containing chondroitin sulphates A and C in total glycosaminoglycans. Endotoxin infusions partly prevented the increase of serum cholesterol caused by the fat-supplemented diet but had no independent effect on the arterial biochemical composition; nor did they affect the biochemical changes caused by hypercholesterolemia. When the results of all groups were combined, chondroitin sulphates A and C showed a significant positive correlation with the concentration of arterial esterified cholesterol and the percentage of linoleic acid in arterial cholesteryl esters. Serum total cholesterol did not correlate with arterial cholesterol fractions, but the ratio of high density lipoprotein-cholesterol to total serum cholesterol showed a negative association with arterial esterified cholesterol. The present findings indicate that (1) mild hypercholesterolemia is atherogenic in young piglets, and (2) changes in arterial glycosaminoglycan composition might be one of the earliest biochemical alterations in atherogenesis.

Animals↗

Characterization of the phenotype of smooth muscle cells in human fetal aorta on the basis of ultrastructure, immunofluorescence, and the composition of cytoskeletal and cytocontractile proteins.

The phenotype of smooth muscle cells (SMCs) in the aortic media of 7 human fetuses (14-20 weeks of gestation) was examined with transmission electron microscopy, immunofluorescence microscopy, and gel electrophoresis of the cytoskeletal and cytocontractile proteins. Ultrastructurally, virtually all medial cells were identified as SMCs having a poorly differentiated phenotype with a cytoplasm rich in rough endoplasmic reticulum and organelles, and with only a few myofilaments. All medial cells stained intensely with antibodies to vimentin, but only in a 20-week-old fetus could we find a few SMCs staining with antibodies to desmin. Nor was desmin detectable with SDS gel electrophoresis followed by immunoblotting, while clear bands corresponding to vimentin, myosin, and actin were present. In isoelectric focusing and two-dimensional gel electrophoresis beta-actin was the most prominent of the 3 actin isoforms in all cases. The present results show that SMCs in the media of fetal human aorta have a poorly differentiated phenotype, which morphologically and biochemically resembles that previously described in the aorta of fetal and newborn rat, in the arterial intima after endothelial injury, in atherosclerotic lesions, and after spontaneous modulation of medial SMCs in culture.

Actins↗

HPLC method for the simultaneous determination of beta-carotene, retinol and alpha-tocopherol in serum.

A method is described for the simultaneous analysis of alpha-tocopherol, beta-carotene, and retinol in n-hexane extracts of serum. The technique uses normal-phase HPLC in a silica gel column with n-hexane-2-propanol (97:3, v/v) as the mobile phase. The compounds are eluted from the column in the order alpha-tocopherol, beta-carotene, tocol (internal standard) and retinol. The compounds are quantified by use of the following detectors connected in series: retinol and tocol by a spectrophotometer, beta-carotene by a filter photometer, and alpha-tocopherol and tocol by a spectrophotofluorimeter. The time taken for separation is less than 6 min but a further 14 min is allowed for elution of the more polar compounds before the next run. With an automatic injector, the method is suitable for the analysis of a large number of samples because of the relatively short time for analysis and the small volume (0.2 ml) of serum required. The method has been used in a study of the relationships between serum levels of the fat-soluble vitamins and subsequent cancer in 2332 subjects.

Journal Article↗

Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up.

The association between serum alpha-tocopherol levels and the subsequent incidence of cancer was investigated in a longitudinal study of 21,172 men initially aged 15-99 years in six geographic areas in Finland. The baseline examination was conducted in 1968-1972, and during the follow-up of 6-10 years, 453 cancers were diagnosed. The serum alpha-tocopherol levels were measured from stored serum samples from these men and from 841 male controls, matched for municipality and age, who did not develop cancer during the follow-up. The mean levels of serum alpha-tocopherol among the cancer cases and controls were 8.02 and 8.28 mg/liter, respectively. A high serum alpha-tocopherol level was associated with a reduced risk of cancer. The relative risk of cancer in persons in the two highest (threshold 8.70 mg/liter) quintiles of serum alpha-tocopherol was 0.64 (95 per cent confidence interval = 0.49-0.85) in comparison with those in the three lowest quintiles. The association was strongest for the combined group of cancers unrelated to smoking and varied between subgroups of the study population as well as between different cancers. The association persisted when adjusted for serum cholesterol, serum vitamin A, serum selenium, and various confounding factors. It also persisted when subjects with possible signs of cancer at the time when the blood samples were drawn or with cancers diagnosed during the first two years of follow-up were excluded. These findings agree with the hypothesis that high vitamin E intake protects against cancer.

Adolescent↗

Characterization of two lipoproteins containing apolipoproteins B and E from lesion-free human aortic intima.

Lesion-free areas of aortic intimas from seven men, 30 to 49 years old, were extracted with aqueous buffer within a few hours after an accidental or sudden death. Two lipoprotein fractions could be isolated by density gradient ultracentrifugation from all cases. The mean composition of fraction I (d less than 1.012 g/ml) resembled that reported for the cholesteryl ester-rich, beta-migrating very low density lipoprotein (beta-VLDL); the composition of fraction II (d 1.021-1.046 g/ml) resembled that of plasma low density lipoprotein (LDL). Mean diameter of the particles was 35 +/- 8 nm in fraction I and 25 +/- 5 nm in fraction II (22 +/- 2 nm in plasma LDL). Both fractions contained apolipoproteins B (apoB) and E (apoE), and had increased electrophoretic mobilities and reduced contents of linoleic acid. The immunoreactivity of apoB to a polyclonal and two monoclonal antibodies in both fractions was not different from that of plasma lipoproteins. The apoE isoform patterns in both fractions were similar to those obtained from the respective postmortem plasmas. When incubated with mouse peritoneal macrophages, fractions I and II enhanced the incorporation of radioactive oleate into cholesteryl esters by 10- to 20-fold and 3- to 4-fold, respectively, in comparison to plasma LDL. In conclusion, our results indicate that lesion-free human aortic intima contains two types of apoB- and apoE-containing lipoprotein particles, both of which might be potentially atherogenic.

Adult↗

Stability of plasma total cholesterol, triglycerides, and apolipoproteins B and A-I during the early postmortem period.

The stability of plasma lipids and apolipoproteins during the early postmortem period was studied by taking four duplicate blood samples from eight cadavers 2, 6, 12, and 24 h after death. The bodies were kept at +4 degrees C. The plasma samples were analyzed for total cholesterol (TC), triglycerides (TG), apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I). In TC, values rose by 6 and 11% in two cases, and in six cases diminished 3 to 15% during the first 6 h compared to values obtained 2 h postmortem. The greatest changes were a continuing rise in one case by 33% and a fall by 21% in another case during 24 h. In TG values marked changes took place including one case with a rise of 67% within 24 h. The concentrations of apo B rose by 9 to 11% in three cases and fell by 3 and 4% in two cases during 6 h, but during the whole study period a rise up to 78% occurred. In the concentrations of apo A-I, cases fell by as much as 42% in 6 h, and in one case rose by 20% during 6 h. The results indicate that unpredictable fluctuations occur in plasma lipid and apolipoprotein values within 24 h after death, and they should be interpreted cautiously if the samples have been taken after a prolonged postmortem period.

Adult↗

Effect of omega-3 fatty acid supplementation on platelet aggregability and platelet produced thromboxane.

We investigated the sustained effect of 12-week supplementation of 2.880 g/day of omega-3 fatty acids on platelet aggregability, platelet produced thromboxane B2 concentration and serum fatty acid composition in a double-blind controlled trial in 44 healthy mildly overweight eastern Finnish men recruited from a representative population sample. The supplementation was discontinued seven days before the biochemical measurements. Body weight, alcohol consumption and dietary composition remained constant during the study. Even though the percentage of eicosapentaenoic acid (20:5 omega 3) in total serum lipids increased by 37% (p less than 0.01) and that of dihomo-gamma-linolenic acid (20:3 omega 6) decreased by 18% (p less than 0.01) more in the omega-3 supplemented than placebo group during supplementation, there were no significant differences in the changes in either the ADP induced platelet aggregation or in vitro platelet produced thromboxane B2 concentration between the groups. These data suggest that omega-3 fatty acids have no detectable sustained effect either on ADP induced platelet aggregation or on thromboxane produced by the platelets in vitro.

Adult↗

Atherosclerosis and biochemical composition of coronary arteries in Finnish men. Comparison of two populations with different incidences of coronary heart disease.

Men in Eastern Finland show a substantially higher rate of coronary heart disease (CHD) than men in the Western part of the country. To study possible differences in the biochemical composition and atherosclerotic involvement of coronary arteries between these two populations, we analyzed major lipid and non-lipid components of coronary arteries from 15- to 60-year-old Finnish men after accidental death. The material consisted of 59 age-matched pairs from East and West Finland, respectively, collected at successive autopsies during 1979-1983. The coronary arteries from East Finland contained significantly more esterified cholesterol and a higher percentage of oleate in cholesteryl esters. The findings were most conspicuous under the age of 40 years, and imply a higher degree of atherosclerosis together with an increased rate of intracellular cholesterol esterification in coronary arteries in Eastern as compared with Western Finland. The vessels from East Finland also tended to contain more free cholesterol and raised lesions, but the differences were not statistically significant. No major regional differences were seen in total phospholipids, phospholipid subfractions, DNA, calcium, collagen, total protein, or glycosaminoglycans.

Adolescent↗

Three-year tracking of serum fatty acids in Finnish boys and girls.

The composition of fatty acids in serum lipids has been shown to reflect the quality of dietary fat. In order to examine the long-term stability (tracking) of the serum (and hence dietary) fatty acid composition serum cholesteryl ester fatty acids were analysed by gas chromatography in a randomly selected population sample of 1029 Finnish boys and girls aged 3, 6, 9, 12, 15 and 18 years, and again from the same individuals 3 years later. The tracking was evaluated by calculating linear correlation coefficients for the percentages of individual fatty acids between the 2 time points. For all fatty acids the correlations were highly significant, e.g. for linoleate and arachidonate they were 0.58 and 0.61, respectively. In 1980 the means of the percentages of some fatty acids showed certain differences between the various age and sex groups; in 1983 these differences had become smaller and had largely shifted towards three years older age groups, implying that the differences were due to dietary differences between the cohorts rather than to age and sex per se. The present results indicate that serum fatty acid composition has a fairly good biological reproducibility (tracking) and suggest that age and sex as such are only minor determinants of the serum fatty acid composition.

Adolescent↗

Adipose tissue fatty acids and blood pressure in middle-aged men from southern Italy.

Adipose tissue (AT) biopsies were performed in a random population sample of 74 clinically healthy middle-aged men (40-49 years) from southern Italy. The percentage of saturated fatty acids (FA) in AT was directly correlated with systolic (SBP) and diastolic (DBP) blood pressure (p less than 0.01). This relationship was independent of smoking habit and body weight. AT of men in the upper DBP quintile (range 90-102 mmHg) was significantly richer in palmitic acid (p less than 0.01) compared to that of men in the lowest DBP quintile. Dietary history demonstrated that the overall intake of saturated fat (% energy) was similar in the two extreme DBP quintiles. There was a relatively higher consumption of fish by those in the lowest DBP quintile (p less than 0.05). The amount of monounsaturated fat consumed (% energy) was also higher (p less than 0.05) in men with low blood pressure. Men in the upper quintile of DBP consumed more eggs (p less than 0.05).

Adipose Tissue↗

Linoleic acid content in adipose tissue and coronary heart disease.

The possibility of an inverse relation between essential fatty acids in adipose tissue, in particular linoleic acid, and mortality from coronary heart disease was studied by a cross sectional survey of random population samples of apparently healthy men aged 40-49 from four European regions with differing mortality from coronary heart disease. The proportion of linoleic acid in adipose tissue was lowest in men from north Karelia, Finland, where mortality from coronary heart disease is highest, and highest in men from Italy, where mortality is lowest, with intermediate proportions in men from Scotland and south west Finland. Similar gradients were observed for the desaturation and elongation products dihomo-gamma-linolenic and arachidonic acid. The proportion of saturated fatty acids in adipose tissue was highest in Finland, intermediate in Scotland, and lowest in Italy. Italian men also had the highest proportion of oleate in their adipose tissue and the lowest proportion of myristoleate and palmitoleate. Finnish men were more obese and had a higher blood pressure. Serum cholesterol concentration was higher in north Karelia and south west Finland than in Scotland or Italy. High density lipoprotein (HDL) cholesterol concentrations reflected the regional differences in serum cholesterol, being higher in Finland and lower in Italy. The ratios of HDL cholesterol to total cholesterol, however, did not differ. The regional differences in linoleic acid in adipose tissue remained highly significant when the observed differences in other known risk factors for coronary heart disease among the four areas were taken into account by multivariate analysis. The gradients in proportions of polyunsaturated fatty acids probably reflect differences in dietary intake of linoleic acid.

Adipose Tissue↗

Dietary fatty acids and platelet thromboxane production in puerperal women and their offspring.

The effects of the ratio of polyunsaturated to saturated fatty acids in the diet of puerperal women on maternal and neonatal fatty acids and thromboxane A2 synthesis were studied in 91 mother-infant pairs on the fourth to fifth day after delivery. The mothers received a diet with either a low (0.1) or a high (1.5) polyunsaturated to saturated fatty acid ratio for 4 to 5 days. The fatty acid composition in maternal and neonatal serum and in breast milk was determined in 34 mother-infant pairs from both dietary groups. The capacity of the platelets to produce thromboxane B2, a stable metabolite of thromboxane A2, was determined in another 57 mother-infant pairs. The percentage of linoleic acid was increased in maternal and neonatal sera as well as in the breast milk in the group with a high dietary polyunsaturated to saturated fatty acid ratio, whereas the content of arachidonic acid was increased only in maternal serum. This was accompanied by increased platelet thromboxane B2 production in the mothers, and maternal and neonatal thromboxane B2 synthesis correlated significantly with each other (r = 0.43, p less than 0.05). This finding may provide therapeutic possibilities in the future.

Arachidonic Acid↗

The effect of proteoglycans, collagen and lysyl oxidase on the metabolism of low density lipoprotein by macrophages.

To study the interactions of lipoproteins, connective tissue components and cells, mouse peritoneal macrophages were incubated in the presence of human low density lipoproteins (LDL) that had been complexed with pig aortic proteoglycans (PG) or incubated in the presence of soluble collagen and/or lysyl oxidase, which catalyses the formation of cross-linkages in collagen and elastin by oxidising epsilon-amino groups of lysine residues to aldehydes. Soluble and insoluble PG-LDL complexes increased the incorporation of [3H]oleate into cellular cholesteryl esters (CE) 1.6- and 2.8-fold, respectively, while LDL incubated with collagen and lysyl oxidase had no effect compared to control LDL. As judged on the basis of incubations with fucoidin, spermine and 125I-labelled lipoproteins, the mechanism of internalisation of the PG-LDL complexes is different from that of acetylated LDL or dextran sulphate-LDL complexes. The formation of PG-LDL complexes in the arterial intima may lead to an increased uptake of lipoproteins by intimal macrophages during the early phase of atherogenesis.

Amino Acid Oxidoreductases↗

Fatty acid composition of serum cholesteryl esters in relation to serum lipids and apolipoproteins in 3-18-year-old Finnish children and adolescents.

Serum cholesteryl ester (CE) fatty acids, serum lipids and apolipoproteins were analysed from 1348 Finnish children aged from 3 to 18 years. The study was part of a comprehensive survey of coronary heart disease risk factors and their determinants in Finnish children and adolescents. The percentage of CE linoleate (18:2) had significant negative correlations with the serum concentrations of total and LDL cholesterol, triglycerides as well as apo B. The associations of HDL to CE fatty acids were weak, although there was a significant positive correlation of CE-18:2 to HDL cholesterol and apo A-I. The ratio of HDL to total cholesterol and the ratio of apo A-I to apo B increased strongly in quintiles of increasing percentage of CE-18:2. In conclusion, the present results show significant associations between serum CE fatty acid composition and the different components of serum lipoproteins among free-living Finnish children and imply a relation between the quality of dietary fats and serum lipoproteins within this population.

Adolescent↗