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Biomedical subjects

R S Tilvis

Publications and source records attributed to R S Tilvis.

At least 73 records · Page 4Linked to original sources

Fatty acids of plasma lipids, red cells and platelets in Alzheimer's disease and vascular dementia.

Fatty acids of plasma lipids, red cells and platelets were analyzed from 38 demented patients (age 53-88 years), comprising 11 patients with Alzheimer's disease (AD), 19 with multi-infarct dementia (MID) and 8 with probable vascular dementia (PVD). The mean age, body mass index, duration of dementia and content of triglycerides, total cholesterol and HDL-cholesterol in plasma were similar in AD and MID. The patients with PVD were older. As compared to AD, in MID and PVD the linoleic acid (LA) and other n-6 and n-3 polyunsaturated fatty acids (PUFA) were significantly lower in red cells and tended to be lower also in serum triglycerides, cholesterol esters (CHE) and phospholipids (PL), and platelets. The LA content of red cells was significantly correlated with that of serum CHE and PL, and n-6 PUFA (including arachidonic acid) of red cells. The low LA content of red cells was associated with old age, coronary heart disease and heart failure, but not with the severity of dementia.

Aged↗

Plasma fatty acid composition in patients with ileal dysfunction.

Chemical signs of essential fatty acid deficiency (EFD) were studied in 31 patients who has undergone an ileal resection on an average 7 years earlier by determining fatty acid composition in serum lipids. The subjects were divided into two groups in accordance with the presence (greater than 7 g/day) or absence (less than 7 g/day) of fat malabsorption. The two groups were matched for age, nutritional status, and essential fatty acid intake, but the patients with steatorrhea had higher levels of fecal bile acids and serum triglycerides and lower levels of serum cholesterol than those without steatorrhea. The contents of linoleic acid (LA; 18:2,n-6), the sum of n-6 polyunsaturated fatty acids, and eicosapentaenoic acid levels were lower, whereas those of the C 14-18 saturated and monoenoic fatty acids and eicosatrienoic fatty acid (ETA; 20:3,n-9), a characteristic fatty acid of EFD, were higher in the serum lipids of the patients with fat malabsorption. The LA of cholesterol esters, the ETA of phospholipids, and the ETA to arachidonic acid ratio of phospholipids were closely correlated with the amount of fecal fat, less significantly with the composition of dietary fat or the length of excluded intestine, and not at all with relative body weight or the amount of fecal bile acids. Changes in fatty acid patterns, considered characteristic of EFD, were found for almost a third of the patients with fat malabsorption; yet no clinical evidence of EFD was documented. Thus, the results demonstrate that chemical signs of EFD are common in patients with fat malabsorption after gut resections despite the good nutritional status. The findings suggest that, for preventive purposes, patients with gut resections should increase their dietary intake of polyunsaturated fatty acids in proportion to the amount of fecal fat.

Adult↗

Changed profile of peptic ulcer disease in hospital patients during 1969-1984 in Finland.

The annual number of hospital discharges for peptic ulcer decreased in Finland from 1969 to 1974, mainly because of a smaller number of men with uncomplicated peptic ulcer disease. After the mid-1970s the number of hospital admissions remained stable, whereas the number of elderly patients increased. From 1979 to 1984 the number of hospitalizations for perforated ulcers remained stable, whereas those for ulcer haemorrhages increased, the increase being most marked in the older age groups. The age-specific mortality from peptic ulcer remained stable from 1969 to 1984 and rose thereafter among old patients. The risk of death from peptic ulcer was about 10-fold higher in patients over 75 years old than in younger age groups, and about half of the deaths caused by peptic ulcer occurred in patients over 75 years old. The men to women ratio among hospitalized patients decreased from 3.5 in the late 1960s to 2.1 in the 1980s, and the gastric ulcer to duodenal ulcer ratio was about 1.1 throughout the observation period.

Adolescent↗

Improvement of diabetic control by continuous subcutaneous insulin infusion therapy changes fatty acid composition of serum lipids and erythrocytes in type 1 (insulin-dependent) diabetes.

The influence of improved diabetic control on the fatty composition of serum lipids, erythrocytes and platelets was investigated in 24 patients with Type 1 (insulin-dependent) diabetes treated for 6 months with either continuous subcutaneous insulin infusion (n = 14) or conventional insulin therapy (n = 10). The groups were matched for age, sex, body mass index, serum lipids, duration of diabetes, glycosylated haemoglobin and insulin dose. Glycaemic control improved, and the contents of dihomogammalinolenic acid and arachidonic acid but not linoleic acid rose significantly (p less than 0.05), in serum lipids of patients treated with continuous infusion. No changes were observed in the group treated with insulin injections. Both in serum and erythrocytes the n-6 polyunsaturated fatty acid ratios rose consistently in the patients, with improvement of control regardless of the mode of treatment. Furthermore, the change of HbA1 was negatively correlated with that of arachidonic acid in erythrocytes. No changes were found in the platelet fatty acid compositions. The findings suggest that improved diabetic control enhances the conversion of linoleic acid to arachidonic acid, probably by activating enzymes needed for chain elongation and desaturation.

Adult↗

Serum plant sterols and their relation to cholesterol absorption.

beta-Sitosterol and campesterol were measured in serum lipoproteins of 17 subjects from two families. The serum levels of the two phytosterols were closely correlated with each other (r = 0.974), less consistently with serum cholesterol (r = 0.489), and not at all with serum triglycerides. As compared to cholesterol, serum free and esterified phytosterols tended to be accumulated in HDL where the phytosterol/cholesterol ratios were almost 40% higher than in VLDL and LDL. The serum phytosterol concentrations, the phytosterol/cholesterol ratios, especially in VLDL and LDL, and the fractional absorption of cholesterol were higher in women than in men. The levels of the phytosterols in whole serum and in each lipoprotein were significantly correlated with the percentage absorption of dietary cholesterol but were independent of the amount of dietary cholesterol and plant sterols. Our findings suggest that, in general, serum levels of noncholesterol sterols are effectively determined by the absorption which in turn is proportionate to the fractional absorption of cholesterol.

Adult↗

Fatty acid compositions of serum lipids, erythrocytes, and platelets in insulin-dependent diabetic women.

The fatty acid composition of serum lipids, erythrocytes, platelets, and diet was studied in women with insulin-dependent diabetes (IDDM) and in normal subjects matched for age, sex, body weight, and serum lipid levels. The dietary intake of linoleic acid was higher in IDDM patients than in the normal subjects. The linoleic acid content of serum triglycerides, cholesterol esters, and phospholipids and of red cells and platelets were elevated in patients with IDDM proportionately to their dietary linoleate intake. The linoleic acid content of serum lipids, but not of diet, was significantly correlated with glycosylated hemoglobin A1c in IDDM patients. However, the serum lipid content of arachidonic acid and other n-6 polyunsaturated fatty acids, which are metabolites of linoleic acid, was decreased in IDDM patients, but these metabolites were normal or increased in their cell membranes. The contents of n-3 polyunsaturated fatty acids were decreased in serum and platelet lipids and tended to be increased in erythrocyte membranes of diabetic patients. The results suggest that elongation and desaturation of essential fatty acids, linoleic acid in particular, are decreased in women with IDDM.

Adult↗

Diurnal variation of plasma methyl sterols and cholesterol in the rat: relation to hepatic cholesterol synthesis.

Free cholesterol of plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) of the rat was high and that of plasma very low density lipoproteins (VLDL) was low during the dark period of the diurnal cycle. Variations in the esterified plasma sterols were inconsistent. Free methyl sterols were high in all lipoproteins during the dark phase. Simultaneously, the incorporation of 14C-acetate into nonsaponifiable sterols and the concentrations of free methyl sterols and cholesterol in the liver were elevated.

Animals↗

Absorption and metabolic fate of dietary 3H-squalene in the rat.

The absorption and metabolic fate of dietary squalene was investigated on the rat by administering a single oral dose of 3H-squalene and 14C-cholesterol. Experiments on rats with cannulated thoracic duct revealed that 3H-squalene was, like 14C-cholesterol, absorbed through the lymphatic vessels and that ca. 20% of absorbed 3H-squalene was cyclized to sterols during the transit through the intestinal wall. Feces contained 3H-sterols, indicating that newly synthesized mucosal sterols had been secreted into the gut lumen. In intact animals, 3H-squalene appeared in the circulation more rapidly than 14C-cholesterol and did not persist to any significant extent in the squalene-rich adipose and muscle tissues. The increase in dietary squalene load (8-48 mg) decreased the absorption percentage of 3H-squalene (45-26%) but did not affect the absorption of 14C-cholesterol (47%). Determination of fecal steroids revealed that during the first days absorbed 3H-squalene was eliminated to a significantly higher extent than 14C-cholesterol as fecal bile acids (34% vs 11%). The experiments indicate that the rat intestine has a marked capacity for absorbing dietary squalene and that the absorbed squalene is preferentially converted to bile acids in the liver.

Animals↗

Dietary squalene increases tissue sterols and fecal bile acids in the rat.

Feeding 1% squalene increased markedly the concentrations of squalene and methyl sterols in each serum lipoprotein class, intestinal mucosa, liver and also in adipose tissue. It also increased cholesterol concentration of the liver and serum VLDL, and esterified cholesterol in serum LDL as well as fecal bile acids. The results suggest that absorbed dietary squalene contributes to some extent to the squalene content of adipose tissue, effectively increases the overall cholesterol synthesis and enhances cholesterol elimination preferentially as fecal bile acids.

Adipose Tissue↗

Clofibrate decreases jejunal cholesterol synthesis and activity of postheparin plasma lipoprotein lipase in the rat.

Clofibrate treatment decreased drastically the activity of serum postheparin lipoprotein lipase of rats fed with fat-free test diet but had no effect on hepatic lipase. 3 weeks' treatment was followed by a significant fall in serum cholesterol caused by a marked decrease in HDL-cholesterol. Clofibrate decreased in vitro synthesis of cholesterol and fatty acids in jejunal villous cells but not in the crypt cells.

Animals↗

Regulation of cholesterol synthesis in jejunal absorptive cells of the rat.

Cholesterol metabolism was studied in jejunal mucosa of the rat with special emphasis on cholesterol synthesis of villous cells, the site of intestinal lipid absorption. The type of diet and nutritional state clearly affected the cholesterologenesis of villous cells. Consequently, the incorporation of 14C-acetate into nonsaponifiable lipids (NSL; includes squalene and sterols) decreased in the following order of magnitude: 1) fat-free diet supplemented with safflower oil (FFD-SO), 2) FFD alone, 3) standard rat chow, 4) 1% cholesterol in FFD-S(, 5) total fast. Both the cholesterol feeding and the fast increased the total cholesterol concentrations in the villous cells, but the concentrations were unaffected by the other diets. In rats fed FFD-SO diet the cholesterol synthesis was significantly higher in the villous than in the crypt cells, although the cellular cholesterol concentrations were similar. The hepatic cholesterol synthesis from 14C-acetate was low in rats fed FFD-SO as compared with chow diet, whereas the incorporation of 14C-acetate into hepatic fatty acids and the incorporation of 3H-mevalonate into NSL were not affected by the diet. 5% cholestyramine had no significant effect on the cholesterol synthesis or cholesterol concentrations of the villous cells during high (FFD-SO diet) or low cholesterol synthesis (chow or cholesterol feeding). FFD-SO increased serum total cholesterol compared with chow diet and total fast, whereas cholestyramine and cholesterol feeding had no effect. Intraperitoneal administration of the hypocholesterolemic agent, 4-aminopyrazolopyrimidine, to fasting rats decreased markedly crypt cell cholesterol and increased cholesterol synthesis in the crypt cells and in the villous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fate of intravenously administered squalene in the rat.

To investigate the metabolism of serum squalene rats were given intravenously serum or isolated lipoprotein containing [3H]squalene and [14C]cholesterol. Labeled squalene disappeared multiexponentially from serum and the rate of disappearance was consistently faster than for [14C]cholesterol. [3H]Squalene given by injection did not accumulate in tissues, but was rapidly cyclized to sterols, resulting in the labeling of serum methyl sterols and cholesterol as well as biliary and fecal sterols and bile acids. Independent of the form of administration, the fractional conversion of squalene to serum cholesterol was less than one. This was caused by the fact that [3H]squalene was eliminated initially more rapidly than serum [14C]cholesterol in the feces and was converted to a greater extent than serum cholesterol to bile acids, whereas both labels were eliminated in parallel as neutral sterols. The results support the role of newly synthesized hepatic cholesterol as the preferred substrate of bile acid synthesis.

Animals↗

In vitro synthesis of triglycerides and cholesterol in human gallbladder mucosa.

Triglyceride and sterol synthesis was investigated in vitro in the gallbladder mucosa from control subjects and patients with acalculous cholesterolosis. The incorporation rate of 14C-acetate was 1.6 +/- 0.2 nmol/g/h into cholesterol (sum of squalene, methyl sterols, and cholesterol) and 5.7 +/- 0.8 nmol/g/h into triglycerides. The rates were significantly correlated with each other (r = 0.667). The conversion of 3H-mevalonate into cholesterol (49 +/- 10 nmol/g/h) and triglycerides (4.7 +/- 1.2 nmol/g/h) indicated a high activity in the postmevalonate cholesterol synthesis and an active shunt pathway of mevalonate metabolism. The synthesis rates of cholesterol, triglycerides, and sterol esters were closely interrelated, were unaltered in cholesterolosis, and were not correlated with the serum, biliary, and mucosal lipid concentrations. Thus, despite marked lipid accumulation the lipid synthesis proceeds effectively in the gallbladder mucosa with cholesterolosis.

Cholesterol↗

Lipid composition of bile and gallbladder mucosa in patients with acalculous cholesterolosis.

To investigate pathogenetic factors of cholesterolosis of the gallbladder, the lipid composition of both the hepatic and gallbladder bile and gallbladder mucosa were compared with each other in 6 patients with and 5 patients without acalculous cholesterolosis. The molar percentage of biliary cholesterol and total bile acid pattern were similar in the two groups. Of the biliary cholesterol precursors, methyl sterols, but not squalene, correlated closely with cholesterol both in the hepatic (r = 0.901) and gallbladder bile (r = 0.747). Methyl sterols, expressed either per cholesterol or bile acids, were higher and squalene was lower in the gallbladder bile than in the hepatic bile. In addition, methyl sterols were increased in the hepatic and gallbladder bile of the patients with cholesterolosis, as if the hepatic production of these precursors had been enhanced--probably as a consequence of altered hepatic cholesterol synthesis. In cholesterolosis the gallbladder mucosa was characterized by a marked increase in triglycerides and significant elevations of the esterified sterols and free methyl sterols. The esterification degrees of sterols, which were consistently higher for methyl sterols than for cholesterol, were closely correlated with the respective mucosal sterol concentrations. The methyl sterols/cholesterol ratio in the bile correlated significantly with mucosal free and esterified methyl sterols, esterified cholesterol, and the methyl sterols/cholesterol ratio. The data suggest that free sterols can be transferred from the bile to the gallbladder mucosa, and that altered hepatic cholesterol synthesis is associated with the development of the cholesterolosis of human gallbladder.

Adult↗

Squalene and sterol synthesis in isolated small-intestinal cells of the rat.

To compare the synthesis rate of cholesterol in different cells of the small intestine, isolated villous and crypt cells were incubated with a mixture of 14C-acetate and 3H-mevalonate in the presence of unlabeled carriers. The synthesis rate of squalene (includes the portion converted to sterols) from acetate was tenfold higher in the crypt than villous cells. The synthesis rate of squalene from mevalonate and the cyclization rate of squalene (the portion found in sterols) were about twofold higher in crypt than in villous cells. The conversion of acetate to squalene was correlated with that to fatty acids in the crypt cells only (r = 0.823), and the ratio of the two synthesis rates (squalene/fatty acids) was threefold higher in crypt than in villous cells. Despite the significant differences in the synthesis rates of squalene and sterols the concentrations of squalene and methyl sterols were similar in the two cell types. THe cholesterol content was, however, consistently higher in villous than in crypt cells, but the concentration was not correlated with the synthesis of squalene in the two cell types. The appearance of labeled squalene was clearly lower than that of labeled sterols in the lipoprotein-free incubation medium, but no differences were found between villous and crypt cells.

Acetates↗

Cholesterol synthesis and storage in adipose tissue.

A markedly-high cholesterol production characterizes human obesity. So far, the site of origin of this extra synthesis has not been defined, even though the liver may play an important role. A marked expansion of adipose tissue in obesity raises a question on the local cholesterol synthesis, particularly because this organ can store a lot of cholesterol and its precursors, methyl sterols and squalene particularly. Some aspects of cholesterol synthesis and storage in adipose tissue will be dealt with in this paper. Available data have demonstrated that human fat tissue is capable of synthesizing cholesterol at a low rate.

Adipose Tissue↗

A lack of esterification of lanosterol and other methyl sterols in human serum in vitro.

Human serum contains small amounts of free and esterified cholesterol precursors, such as lanosterol and other methyl sterols. Incubating the serum for 24 h at room temperature without and with different additions of free methyl sterols was not followed by any detectable esterification of these sterols during the subsequent 24 h incubation period, though the amount of cholesterol esters was markedly increased. [3H]dihydrolanosterol added to serum was not esterified in any lipoprotein fraction either, whereas the [14C]cholesterol added was found to be esterified during the 24 h incubation period. The lack of methyl sterol esterification in vitro suggests that these sterols are not proper substrates for serum lecithin: cholesterol acyltransferase and that esterified serum methyl sterols originate from tissues.

Cholesterol↗

Release of newly synthesized squalene, methyl sterols and cholesterol from human adipocytes in the presence of lipoproteins.

Upon incubation of free fat cells for 3 h with labelled mevalonate, more than 90% of the radioactivity of the non-saponifiable material was found in the squalene fraction and less than 10% in the methyl sterol and cholesterol fractions. About 25, 30 and 65% of the cholesterol counts were found respectively in VLDL, LDL, or HDL added to the medium while none of the newly synthesized squalene was released into the lipoproteins. The results indicate that adipose tissue squalene can originate from local synthesis. It is not released from the cells into the medium, but can contribute to local cholesterol synthesis in both rapidly and slowly exchangeable cholesterol pools of adipose tissue.

Adipose Tissue↗