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Biomedical subjects

A C Beynen

Publications and source records attributed to A C Beynen.

At least 361 records · Page 20Linked to original sources
PubMed1986

Could chloroquine be of value in the treatment of hypercholesterolemia?

Chloroquine is an effective inhibitor of cholesterol synthesis in freshly isolated rat hepatocytes, cultured mouse L cells and 20,000 X g supernatants of mouse liver homogenates. Half-maximal inhibition is found at concentrations ranging from 10 to 30 microM. The drug specifically inhibits 2,3 oxidosqualene cyclase, the enzyme catalysing the conversion of squalene 2,3 oxide into lanosterol. Chloroquine also inhibits the lysosomal hydrolysis of cholesteryl esters, but probably this effect only occurs at somewhat higher concentrations of the drug. It is suggested that chloroquine at proper doses, in combination with a bile acid-binding resin, might have potential value in the treatment of hypercholesterolemia.

Animals↗
PubMed1986

Plasma and liver cholesterol concentrations in mice fed semipurified diets differing in the amount of cholesterol and type of fat.

Male and female mice of two inbred strains were fed semipurified diets with or without added cholesterol (1%, w/w) containing 18% by weight of either coconut fat or corn oil. After 28 days coconut fat had produced higher concentrations of plasma cholesterol than corn oil in almost all groups, irrespective of whether the diets contained cholesterol or were cholesterol-free. On the cholesterol-free diets, the type of fat did not influence the concentration of liver cholesterol. Dietary cholesterol caused a marked increase in liver cholesterol, the magnitude of the effect being dependent on the strain of mice and being greater in females than males. In all groups fed cholesterol corn oil caused significantly higher concentrations of liver cholesterol than coconut fat.

Animals↗
PubMed1985

Treatment of young rats with cholestyramine or a hypercholesterolemic diet does not influence the response of serum cholesterol to dietary cholesterol in later life.

Groups of 10 female Wistar rats (aged 4 weeks) were fed for 29 days either a low-cholesterol commercial diet, a commercial diet containing 2% (w/w) cholesterol, 0.5% cholate and 5% olive oil or a diet containing 2% cholestyramine. The rats were then fed the low-cholesterol commercial diet for the next 91 days and the high-cholesterol diet for another 29 days. There was no significant difference between the groups in the increase of cholesterol in serum and liver during the last period of cholesterol feeding. A fourth group of 10 animals was fed the diet containing cholesterol and cholate during the entire experimental period of 149 days. By the end of the experiment serum cholesterol in these animals was lower and liver cholesterol was higher than in the 3 groups fed the high-cholesterol diet during days 120-149 of the experiment. This study does not present evidence for imprinting effects of early diet manipulation on the later cholesterolemic response to a high cholesterol diet.

Age Factors↗
PubMed1985

Reproducibility of the variations between humans in the response of serum cholesterol to cessation of egg consumption.

To find out whether the variable response of serum cholesterol levels to changes in cholesterol intake in man is due to constitutional differences in responsiveness, we have reinvestigated in 1982 34 healthy men and women, who habitually consumed at least 1 egg/day and had participated in a trial in 1976. Serum cholesterol was measured on the habitual diet (about 800 mg cholesterol/day), and after 3 weeks during which no eggs or egg-containing products were consumed (about 300 mg cholesterol/day). Serum cholesterol decreased by 0.16 +/- 0.42 mmol/1 (6 +/- 16 mg/dl) in 1976 and by 0.31 +/- 0.35 mmol/l (12 +/- 14 mg/dl) in 1982 (mean +/- SD). Individual responses varied from -1.0 to +0.5 mmol/l (-39 to +19 mg/dl). The correlation between the responses in 1976 and 1982 was r = 0.32 (P less than 0.05). The decrease in serum cholesterol was most pronounced for subjects with a low body mass index and a high level of HDL-cholesterol. In men, the increase in serum cholesterol with age was correlated with the mean decrease in the trials (r = 0.42, n = 16, P = 0.11). In a controlled trial, 4 hypo- and 2 hyperresponders were given 11 mg cholesterol/MJ (11 mg/240 kcal; 116 mg/day) for 4 weeks followed by 72 mg/MJ for another 4 weeks; all other nutrients were kept constant. Almost all food was supplied and intakes were rigidly controlled. The 2 hyperresponders and 3 of the 4 hyporesponders were also hyper- and hyporesponsive under the controlled conditions. We conclude that part of the cholesterolemic response to dietary cholesterol in man is individually determined and stable for at least 6 years.

Adult↗
PubMed1985

Effect of egg yolk feeding on the concentration and composition of serum lipoproteins in man.

The effect of egg yolk consumption on the composition of LDL and on the concentration of HDL subclasses was studied in healthy subjects. Six volunteers consumed a diet low in cholesterol for 10 days and then daily added 6 egg yolks to their diet for another 10 days; the experiment was repeated 1 year later with the same subjects. Egg yolk consumption caused the cholesterol intake to increase by 1600 mg/day, and the fat intake by 7 energy % at the expense of carbohydrates; this increase was due almost exclusively to monounsaturated fatty acids. Upon egg yolk feeding the mean level of serum total cholesterol rose by 13%; the bulk of this rise was due to LDL cholesterol, which increased by 21%. VLDL and IDL cholesterol decreased by 19 and 11%, and serum total triglycerides by 17%. Marked relative increases of 35 and 36% were seen in the cholesterol level of the HDL subfractions with densities of 1.055-1.075 g/ml (HDL1) and 1.075-1.100 g/ml (HDL2), respectively. The HDL2/LDL cholesterol ratio increased by 16%. No change in cholesterol in HDL3 (d greater than 1.100 g/ml) was observed. The increase in cholesterol in HDL isolated by density gradient ultracentrifugation significantly exceeded the increase in cholesterol in heparin-Mn2+ soluble HDL. This suggests the formation of apo E-containing HDL, i.e. HDLc, which has HDL density but is not soluble in heparin-Mn2+. The composition of the LDL particles was significantly altered; the core became enriched in esterified cholesterol at the expense of triglycerides, and the ratio of core components to surface components increased by 7%.

Adult↗
PubMed1985

[Corneal opacity].

A case with bilateral corneal opacification in the form of a half-ring is described. Routine laboratory tests revealed no abnormalities, and serum lipoprotein composition was normal. The authors suspect that this was a case of primary lipoidal keratopathy.

Adult↗
PubMed1985

Rapid sampling and long-term storage of subcutaneous adipose-tissue biopsies for determination of fatty acid composition.

The fatty acid composition of fat tissue is a valid indicator of the fatty acid composition of the diet over the preceding 1 to 3 yr. Here we describe a rapid method for sampling of buttock fat without anesthesia. On average, 35 mg can be obtained using a common blood-sampling system. Sampling of 40 subjects takes about 3 h. The procedure caused no more anxiety or discomfort than a routine venipuncture. Application in about 500 subjects has as yet yielded no infectious or other complications. With regard to the fatty acid composition of the biopsy, sampling site (left versus right buttock) was not found to be a source of error. The biopsies could be stored for periods up to 1.5 yr without changes in the fatty acid profile. With this method one can obtain biopsies from a large number of subjects and determine objectively the long-term fatty acid composition of their diet.

Adipose Tissue↗
PubMed1985

Why do polyunsaturated fatty acids lower serum cholesterol?

Replacement of saturated by polyunsaturated fatty acids in the diet may lower serum very low-density and low-density lipoprotein concentrations because the liver preferentially converts polyunsaturated fatty acids into ketone bodies instead of into very low-density lipoprotein triglycerides. Thus unlike saturated fatty acids, polyunsaturated fatty acids are transported to the tissues for oxidation without leaving a trail of lipoprotein remnants in the form of low-density lipoproteins.

Cholesterol↗
PubMed1985

Serum lipoproteins in cholesterol-fed pigs after partial ileal bypass.

Partial ileal bypass (PIB) surgery was performed in hypercholesterolaemic mini-pigs and Yorkshire pigs fed a semipurified diet containing 1% (W/W) of cholesterol. PIB drastically reduced serum total cholesterol and phospholipid concentrations and the cholesterol: phospholipid ratio in spite of continuation of cholesterol feeding. The relative distribution of cholesterol between serum lipoproteins was affected by PIB; the surgical treatment caused an increase in the ratio of high-density lipoprotein (HDL) to low-density lipoprotein (LDL) cholesterol. Serum apo B and apo A levels were rapidly decreased by PIB. The operation induced a decrease in the cholesterol: apo B and cholesterol: apo A ratios. It is suggested that the pig is a suitable animal model to study PIB-induced changes in lipoprotein metabolism.

Animals↗
PubMed1984

Studies on the assay, activity and sedimentation behaviour of acetyl-CoA carboxylase from isolated hepatocytes incubated with insulin or glucagon.

The activity of acetyl-CoA carboxylase, measured in various ways, was studied in 15000g extracts of rat liver hepatocytes and compared with the rate of fatty acid synthesis in intact hepatocytes incubated with insulin or glucagon. Hepatocyte extracts were prepared by disruption of cells with a Dounce homogenizer or by solubilization with 1.5% (v/v) Triton X-100. Sucrose-density-gradient centrifugation demonstrated that the sedimentation coefficient of acetyl-CoA carboxylase from cell extracts was 30-35S, regardless of the conditions of incubation or disruption of hepatocytes. Solubilization of cells with 1.5% Triton X-100 yielded twice as much enzyme activity (measured by [14C]bicarbonate fixation) in the sucrose-gradient fractions as did cell disruption by the Dounce homogenizer. Analysis by high-performance liquid chromatography of acetyl-CoA carboxylase reaction mixtures showed that [14C]malonyl-CoA accounted for 10-60% of the total acid-stable radioactivity, depending on the method for disrupting hepatocytes and on the preincubation of the 15000g extract, with or without citrate, before assay. Under conditions in which incubation of cells with insulin or glucagon caused an activation or inhibition, respectively, of acetyl-CoA carboxylase, only 25% of the acid-stable radioactivity was [14C]malonyl-CoA and enzyme activity was only 13% (control), 16% (insulin), and 57% (glucagon) of the rate of fatty acid synthesis. Under conditions when up to 60% of the acid-stable radioactivity was [14C]malonyl-CoA and acetyl-CoA carboxylase activity was comparable with the rate of fatty acid synthesis, there was no effect of insulin or glucagon on enzyme activity.

Acetyl-CoA Carboxylase↗
PubMed1984

The effect of dietary saturated fat versus polyunsaturated fat on serum cholesterol and phospholipid concentrations in rabbits with partial ileal bypass.

Rabbits were fed semipurified diets containing either corn oil or coconut fat. Dietary coconut fat significantly elevated serum total cholesterol and phospholipid concentrations. Rabbits with partial ileal bypass (PIB) had significantly lower serum cholesterol and phospholipid values, irrespective of whether the diet contained corn oil or coconut fat. The effect on serum lipids of the type of fat was similar in control and PIB animals. Since PIB rabbits are known to excrete extremely high amounts of steroids with the feces, we suggest that our data point to a lack of interaction of the type of dietary fat with the fecal excretion of steroids.

Animals↗
PubMed1984

Relations between fatty acid synthesis, pyruvate concentration and cell concentration of suspensions of isolated rat hepatocytes.

The cell concentration of suspensions of isolated rat hepatocytes affects both the rate of pyruvate accumulation in the incubation medium and the rate of fatty acid synthesis. At low cell concentrations pyruvate accumulation is directly related to the cell concentration but levels off at higher concentrations even when maximum pyruvate concentrations in the medium are not yet reached. The rate of fatty acid synthesis in the 30-60-min incubation interval is proportional to the cell concentration. In contrast, the rate of fatty acid synthesis during the 0-30-min incubation period decreases with increasing cell concentrations and subsequently becomes independent of the cell concentration.

Animals↗