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Biomedical subjects

T Nikkari

Publications and source records attributed to T Nikkari.

At least 109 records · Page 6Linked to original sources

Serum fatty acids in Finnish men.

The fatty acid compositions of 4 serum lipid fractions were analysed from 244 randomly selected 30-59-year-old Finnish men from 4 areas involved in a population survey ('Mini-Finland') in 1979-80. Men in eastern Finland had significantly lower mean percentages of linoleate (18:2) in CE, TG, FFA and PL (45.1, 10.3, 9.3 and 18.8%, respectively) than men in the western part of the country (48.4, 12.5, 10.6 and 20.2%, respectively). Very low values of 18:2 were encountered in the North Karelian community of Ilomantsi, especially in men aged 50-59 (40.9, 8.0, 7.5 and 16.8%, respectively). The percentage of alpha-linolenate tended also to be lower and those of saturated and monounsaturated fatty acids higher in the east, but there were no or only inconsistent differences in the contents of the prostaglandin precursors dihomo-gamma-linolenate, arachidonate and eicosapentaenoate. Eighteen men were studied in November and the following April. Only minor changes in the mean composition of serum fatty acids took place during this period and the correlation coefficients between the percentages of 18:2 recorded at the two time points ranged from 0.70 to 0.81. The low concentrations of 18:2 in serum lipids in Finnish men obviously reflect a low dietary P/S ratio and may contribute to the high prevalence of IHD in Finland and to its regional differences.

Adult↗

Serum fatty acids in 8-year-old Finnish boys: correlations with qualitative dietary data and other serum lipids.

To survey risk factors in coronary heart disease in Finnish children, fasting serum specimens from 244 healthy 8-yr-old boys were analyzed for the fatty acid composition of cholesterol esters (CE), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL). A qualitative dietary survey was made by asking parents to answer a questionnaire including, among others, a question on the kind of fat usually used on bread by the child. The mean percentages of linoleate (18:2) in serum cholesterol esters, triglycerides, free fatty acids, and phospholipids were 53.1, 13.5, 11.5, and 22.7%, respectively, which represent an international average. The quality of dietary fat had a clear influence on serum fatty acids, eg, the content of 18:2 in CE was 56.8 +/- 3.6% in boys using soft vegetable margarine and 50.5 +/- 3.6% in those using butter. The former had also a marginally lower serum total cholesterol (4.87 +/- 0.86 mmol/l) than the latter (5.08 +/- 0.80 mmol/l). Serum total cholesterol showed significant negative correlations with the percentage of 18:2 in all four lipid fractions, the highest r values being with PL-18:2 (-0.41) and CE-18:2 (-0.24). Accordingly, serum cholesterol was lower in the highest CE-18:2 quartile (4.67 +/- 0.76 mmol/l) compared with the lowest (5.30 +/- 0.70 mmol/l; p less than 0.001). The results indicate that when serum fatty acids are used as indicators of the quality of dietary fat, a negative association between polyunsaturated fat and serum cholesterol may be demonstrable even within a free-living population.

Child↗

Role of the arterial smooth muscle cell in the pathogenesis of atherosclerosis.

The development of an atherosclerotic lesion is characterised by a proliferation of arterial smooth muscle cells and an accumulation of cholesterol, cholesteryl esters and connective tissue. The main connective tissue components of an atherosclerotic lesion, i.e. acidic glycosaminoglycans and collagen, are synthesized by the smooth muscle cells. Cholesterol is chiefly derived from plasma lipoproteins, but there is an enhanced intracellular esterification of cholesterol in the cells of the lesions. The important role of the arterial smooth muscle cell in the development of atherosclerotic lesions has resulted in cultures of these cells being used as experimental models to study the pathogenesis of atherosclerosis. Such studies have revealed many blood-derived and other substances affecting proliferation, as well as lipid and connective tissue metabolism of arterial smooth muscle cells. In this way certain risk factors for cardiovascular disease have turned out to be associated with the metabolic disturbances of atherogenesis at the cellular level. Studies with cultured arterial smooth muscle cells have also demonstrated other factors for example one derived from aggregating platelets that may significantly contribute to the development of atherosclerotic lesions. On the other hand, certain inherent features of the smooth muscle cells of the lesions, such as enhanced proliferation and synthesis of glycosaminoglycans, may also contribute to the pathological changes.

Aging↗

Multicenter study of atherosclerosis precursors in Finnish children--pilot study of 8-year-old boys.

A multicentre study was launched to analyze the prevalence of risk factors for coronary heart disease and their determinants in Finnish infants, children and adolescents and to provide facts for the planning of intervention. The present report gives the results of the pilot study conducted among 264 8-year-old boys in 5 cities and corresponding rural areas in various parts of Finland. Data on eating habits were obtained from the parents by means of a questionnaire. Fasting serum specimens were analyzed in 249 subjects for cholesterol, HDL-cholesterol, triglycerides, and immunoreactive insulin (IRI). The fatty acid composition of serum lipids was determined in 244 subjects by gas chromatography. Soft vegetable margarine was used on bread by 29% of the boys in the rural and 46% in the urban areas. Low fat or skim milk, vegetables and fruit were used more often in the western than in the eastern part of the country. The mean values for serum lipids were as follows: cholesterol 5.0, HDL-cholesterol 1.4, and triglycerides 0.7 mmol/1. The proportion of linoleic acid in the fatty acid cholesterol ester fraction was higher than expected, 53%. The IRI values ranged from 2 to 55 (mean, antilog, 9.4) mU/l. The results served as background material for the main study of blood pressure, anthropometric, biochemical and socioeconomic variables.

Arteriosclerosis↗

Acidic glycosaminoglycans inhibit the uptake of tritiated thymidine by rabbit aortic smooth muscle cells in culture.

The effect of exogenous glycosaminoglycans on the growth rate of rabbit aortic smooth muscle cells in culture was studied by determinations of cell number, cell protein and the uptake of [3H]thymidine as well as its incorporation into DNA. Glycosaminoglycans did not affect the growth rate of the cells. Expect for heparin, however, all the glycosaminoglycans studied chondroitin 4-sulphate, chondroitin 6-sulphate, dermatan sulphate and hyaluronic acid interfered with the uptake of [3H]thymidine into the cells. So errors may arise if [3H]thymidine-methods alone are used when studying the growth rate of cultured cells in the presence of glycosaminoglycans.

Animals↗

Effect of cell density on the incorporation of [3H] proline into collagen by rabbit aortic smooth muscle cells in culture.

When stationary phase cultures of rabbit aortic smooth muscle cells (SMCs) with different cell densities were incubated with [3H] proline in order to study the rates of collagen and total protein syntheses, the incorporation of [3H] proline into collagen and total protein decreased with increasing cell density. This association was mainly due to a negative correlation between cell density and the specific activity of [3H] proline within the free intracellular proline pool. After correction for the specific radioactivity of free intracellular proline, the synthesis rate of collagen was not significantly correlated with cell density, but the negative association between cell density and the incorporation of [3H] proline into total protein was not completely abolished.

Animals↗

Characterisation of cells cultured from advanced atherosclerotic lesions of the rabbit.

The present study focused on cells cultured from late atherosclerotic lesions produced in rabbits by 6 months' cholesterol feeding followed by another 6 months' feeding with a normal rabbit chow. The growth rates of cells from both atherosclerotic and normal aortas were equal. The incorporation of [3H]proline into total protein and collagen as well as into collagen types I and III was also similar in cells from both origins. The cells from atherosclerotic rabbit aortas incorporated less [3H]glucosamine into sulphated glycosaminoglycans, but more into hyaluronic acid than cells from normal aortas. Cells from both origins were typical arterial smooth muscle cells as judged by electron microscopic examination. The results show that the enhanced metabolism of cells cultured from proliferative atherosclerotic lesions of the rabbit is no longer present in cells cultured from more advanced lesions.

Animals↗

Xanthomas of the Achilles tendon.

The patients with xanthomas bilaterally in the Achilles tendons associated with type-II hyperbetalipoproteinaemia are reported. Both patients had elevated serum cholesterol, normal or slightly elevated serum triglycerides and an electrophoretic pattern of elevated beta and pre-beta lipoproteins. Subtotal resection of the tumours was found to be satisfactory in both patients with less risk of complications when compared with the earlier methods reported with total excision and reconstruction of the defect with fascial grafts. The early recognition and evaluation of the patients with hyperbetalipoproteinaemia is important because it is associated with an increased incidence of atheromatous coronary disease, often manifestated at an early age. That is why surgical interventions of tendon xanthomas must be connected with adequate medical treatment of the basic disorder in lipid metabolism

Achilles Tendon↗

Enhanced synthesis of collagen and total protein by smooth muscle cells from atherosclerotic rabbit aortas in culture.

Protein synthesis in smooth muscle cells from normal and atherosclerotic rabbit aortas was studied. Cultures of cells from the third passage were incubated with [3H]proline and the synthesis rates of collagen and total protein measured from the radioactivities incorporated into protein-bound hydroxyproline and proline, respectively. The synthesis ratio of collagen types I and III was studied by separating the radioactive procollagens of the culture media by DEAE column chromatography. The synthesis rates of both collagen and total protein were higher in cells cultured from atherosclerotic rabbit aortas. There was no difference in the synthesis ratios of types I and III collagen between cells from the two origins. In addition to procollagens, a third protein eluted before procollagen I in the DEAE chromatography of medium proteins. Compared with control cells, cells from atherosclerotic aortas incorporated relatively less radioactivity into this protein. No differences were detected in the amino acid compositions of cellular proteins between cells from both origins. It was concluded that cells grown from atherosclerotic rabbit aortas synthesize more collagen and total protein than those from normal aortas, the synthesis of collagens I and III being equally enhanced. The results also suggest that there are proteins which are not involved in the general enhancement of protein synthesis.

Animals↗

Metabolism of glycosaminoglycans and lipids in smooth muscle cells from atherosclerotic rabbit aortas in culture.

Glycosaminoglycan (GAG) and lipid synthesis in smooth muscle cells cultured from normal and atherosclerotic rabbit aortas were studied. The incorporation of [14C]glucosamine into acidic GAGs taken to represent their synthesis rate, was enhanced in cells from atherosclerotic aortas as compared with controls. The synthesis of sulphated glycosaminoglycans was affected most and the percentage of radioactivity incorporated into sulphated GAGs was 48 +/- 3% in cells from atherosclerotic and 38 +/- 4% in cells from healthy aortas. Non-radioactive GAGs secreted into incubation media were fractionated by electrophoresis. There was an elevated ratio of sulphated GAGs to hyaluronic acid in the cultures of cells from atherosclerotic aortas and the fraction corresponding to dermatan sulphate was increased most. The incorporation of [3H]oleate into phospholipids was enhanced in cells from atherosclerotic aortas indicating more rapid synthesis of this lipid fraction in these cells. Concentrations of free and esterified cell cholesterol were similar. The results indicate that the enhanced synthesis of sulphated GAGs typical of proliferative atherosclerosis in vivo is maintained in the third passage cultures of cells from atherosclerotic rabbit aortas. In addition there was an enhancement in the synthesis of phospholipids in these cells.

Animals↗

Enhanced growth of smooth muscle cells from atherosclerotic rabbit aortas in culture.

It has been suggested that cells in atherosclerotic lesions differ from normal arterial smooth muscle cells. The present study was aimed at elucidating this possibility. The morphology and growth characteristics of cells cultured from atherosclerotic rabbit aortas were compared with those obtained from control rabbits of the same age. Primary cultures were started from aortic intima-medial explants and they were subcultured after trypsinising the outgrowths. There were no differences in morphology between cells cultured from atherosclerotic and control animals as judged with phase contrast and electron microscopy. However, both the primary and subsequent growth rates of the cells cultured from atherosclerotic aortas were higher than those of control cells. Also the uptake of [3H]thymidine by cells derived from the atherosclerotic aortas was enhanced both in the exponential and stationary phases of cell growth. The results suggest that although the cells from atherosclerotic aortas are morphologically similar to normal arterial smooth muscle cells, atherogenesis is associated with the development of metabolic changes in the arterial cells that are carried over to daughter cells and persist even in culture.

Aging↗

Prostaglandins enhance the synthesis of glycosaminoglycans and inhibit the growth of rabbit aortic smooth muscle cells in culture.

The aim of this study was to elucidate whether prostaglandins (PGs) could be mediators of some of the early changes in atherogenesis. The effect of PGs E1, E2, F1 alpha and F2 alpha on the synthesis of glycosaminoglycans (GAGs) (incorporation of 3H-glucosamine into GAGs) and on the esterification of lipids (incorporation of 3H-oleic acid into lipids) and on cell proliferation (uptake of 3H-thymidine by the cells) was tested in cultured smooth muscle cells. All the PGs studied enhanced the incorporation of 3H-glucosamine into sulphated GAGs with a maximum stimulation at a concentration of 10(-5) mol/l. The synthesis of hyaluronic acid was less clearly increased. The PGs had no effect on cholesterol esterification and they inhibited the uptake of 3H-thymidine by the cells, PGE1 having greatest effect. It was concluded that PGs are not likely mediators of the enhance cell growth or cholesterol esterification in early atherogenesis, but they may contribute to the formation of atherosclerotic lesions by enhancing the synthesis of sulphated GAGs.

Animals↗

Plasma lipids and lipoproteins in Down's syndrome.

Since mongoloids have been reported to differ from other patients with mental retardation by being virtually free of atheromatosis, we analysed plasma lipids and lipoproteins in twenty mongoloid and in twenty age-matched non-mongoloid mentally retarded patients living in the same institution. Plasma total cholesterol in the mongoloids did not differ significantly from that of the control group, but it was low in both groups in comparison with the Finnish population in general. Plasma total triglyceride concentration was higher (P less than 0.01) in the mongoloids than in the controls. This was reflected in higher VLDL-triglyceride and-cholesterol concentrations in the mongoloids. Plasma apolipoprotein B levels were higher (P less than 0.05) and the ratio of apolipoprotein A-1 to apolipoprotein B was lower (less than 0.05) in the mongoloids. The plasma lipid concentrations were in accordance with the significantly higher relative body weights in the mongoloid group. Blood pressure was slightly but significantly lower and cigarette smoking was less common in patients with Down's syndrome. Our results did not explain the reported lower frequency of atheromatosis in Down's syndrome.

Adolescent↗

Effect of phase of growth and hyperlipidemic serum on the synthesis of collagen in rabbit aortic smooth muscle cells in culture.

The aim of this study was to elucidate wheter long-term cultivation in the presence of hyperlipidemic serum is able to induce changes in the rate of synthesis of collagen and other proteins by arterial smooth muscle cells. Rabbit aortic medial cells were grown in 10% sera and their collagen and total protein synthesis were studied by incubation of the cells with radioactive proline. When the cells were grown in fetal calf serum, their collagen synthesis was low after trypsinization but reached a constant level in one week, whereafter it remained within 4--5% of total protein synthesis for up to 30 days. Cultivation in hyperlipidemic rabbit serum for up to 14 days caused an accumulation of lipid droplets in the cells, but there were no detectable changes in the rate of collagen of total protein synthesis when compared with cells grown in normal rabbit serum.

Animals↗

Effect of calcium p-chlorphenoxyisobutyrate and calcium carbonate on plasma lipids and lipoproteins of patients with hyperlipoproteinaemia.

Since dietary calcium had been reported to reduce plasma lipids, the effects of calcium carbonate (CaCO3, 2 g/day) and the calcium salt of p-chlorphenozyisobutyrate (Ca-CPIB, 2 g/day), both singly and in combination, were studied in outpatients with primary hyperlipidaemia. Three groups of five patients were followed in a double-blind cross-over study, in which placebo and the drugs were given alternately during four-week periods. The main results were: 1) CaCO3 alone did not produce any significant changes in plasma lipids. 2) Ca-CPIB reduced LDL-cholesterol in patients with type IIa and IIb by an average of 29 and 21%, respectively. It also lowered VLDL-triglyceride by 50% in type IIb and by 48% in four out of five patients with type IV. 3) The combination of CaCO3 and Ca-CPIB reduced LDL-cholesterol by 31 and 25% in types IIa and IIb, respectively. It also lowered VLDL-triglyceride by 48-52% in types IIa and by 46% in four out of five patients with type IIb. 4) Three out of five patients with type IV had a rise of LDL-cholesterol while on Ca-CPIB alone; two of the patients had the rise while on the combination. 5) After treatment with Ca-CPIB, either singly or in combination, there was a statistically significant lowering of ESR and of plasma inorganic phosphate and alkaline phosphatase. No clinical side effects were noted.

Adult↗