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Biomedical subjects

P N Demacker

Publications and source records attributed to P N Demacker.

At least 127 records · Page 7Linked to original sources
PubMed1990

Effect of decaffeinated versus regular coffee on serum lipoproteins. A 12-week double-blind trial.

Reports on the association between caffeine intake and serum cholesterol are inconsistent. In 1988, the authors examined the effect of decaffeinated versus regular coffee on serum lipids in 45 healthy volunteers from the general population living in or near Nijmegen, The Netherlands. Twenty-three women and 22 men aged 25-45 years with a habitual intake of 4-6 cups of regular coffee per day participated in a randomized double-blind crossover trial. They received five cups of regular coffee each day for a period of 6 weeks and five cups of decaffeinated coffee for the next 6 weeks, or vice versa. The background diet was kept constant and was low in caffeine. Differences between the effects of decaffeinated and regular coffee on blood lipids were essentially zero; the effect on serum total cholesterol (+/- standard deviation) was 0.01 (+/- 0.36) mmol/liter (0 +/- 14 mg/dl), that on high density lipoprotein cholesterol was 0.01 (+/- 0.11) mmol/liter (0 +/- 4 mg/dl), and that on triglycerides was 0.03 (+/- 0.29) mmol/liter (3 +/- 26 mg/dl). It was concluded that, in healthy adults, replacement of regular coffee by decaffeinated coffee has no effect on serum cholesterol and lipoproteins.

Adult↗
PubMed1990

The effects of simvastatin on serum lipoproteins in severe hypercholesterolaemia.

The effects of simvastatin, an inhibitor of cholesterol synthesis, on serum lipids, lipoprotein composition and apolipoproteins were evaluated in a total of 50 patients with hypercholesterolaemia. In the first study, 24 patients (mean serum cholesterol 10.74 +/- 1.59 mmol/l) were treated with simvastatin 40 mg daily for 24 wk. Serum cholesterol and low density lipoprotein (LDL) cholesterol decreased to average values 29-36% and 35-42% below the basal value, respectively. Serum triglycerides decreased by 16-28%, and high density lipoprotein (HDL) cholesterol increased by 6-11%. Apolipoprotein A-I concentration increased 6-8% and that of apolipoprotein B decreased 29-33%. The composition of LDL remained unchanged whereas the very low density lipoproteins became enriched in triglycerides. Lipoprotein Lp(a) was not affected. In the second study 26 patients (mean serum cholesterol 12.35 +/- 2.05 mmol/l) were treated with simvastatin 40 mg daily as monotherapy or combined with a bile acid binding resin for 2 yr. Serum cholesterol levels decreased to values which remained stable throughout the entire study period; after 2 yr this decrease amounted to 43%. Compared to monotherapy, combination therapy yielded a further 12% decrease of cholesterol. In the entire group, triglycerides decreased by 16% and HDL cholesterol increased by 9%. Side effects were limited to slight increases in alanine aminotransferase and creatine phosphokinase in some patients. Simvastatin appears to be an important asset in the treatment of hypercholesterolaemia.

Adult↗
PubMed1990

Simvastatin in the effective reduction of plasma lipoprotein levels in familial dysbetalipoproteinemia (type III hyperlipoproteinemia).

PURPOSE: Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is characterized by an increase of serum lipids caused by an accumulation of remnant particles of triglyceride-rich lipoproteins. We studied the efficacy of simvastatin, an inhibitor of the biosynthesis of cholesterol, in this disorder. PATIENTS AND METHODS: Twelve patients participated in an open-label study. After a three-week placebo period, they were treated with increasing doses (10 mg twice a day, 20 mg twice a day, and 40 mg twice a day) of simvastatin in six-week periods. RESULTS: With the 80-mg dose, the mean serum cholesterol level decreased from 12.30 +/- 4.96 to 5.29 +/- 1.24 mmol/L (mean reduction, 54%) and the mean serum triglyceride level decreased from 8.77 +/- 7.16 to 3.61 +/- 1.33 mmol/L (-48%); this was due to a decrease in very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) lipids. There was a decrease in the ratio of VLDL cholesterol to serum triglycerides and in the apolipoproteins B and E, suggesting a reduction in the amount of circulating atherogenic remnant particles. Except for a slight increase in serum alanine aminotransferase levels in three patients, no side effects were observed. CONCLUSION: These data show that levels of serum lipids can be effectively reduced by simvastatin in familial dysbetalipoproteinemia.

Adult↗
PubMed1989

Low-density lipoprotein catabolism in WHHL rabbits after partial ileal bypass surgery.

The effect of partial ileal bypass surgery (PIB) on lipoprotein concentrations and compositions and on the catabolism of low-density lipoproteins (LDL) was studied in Watanabe heritable hyperlipidemic (WHHL) rabbits. After PIB, total serum cholesterol was 65% lower (6.22 +/- 1.58 vs. 17.24 +/- 3.22 mmol/l) and LDL cholesterol 81% lower (2.02 +/- 0.95 vs. 10.90 +/- 3.60 mmol/l) than in control WHHL rabbits; cholesteryl esters, expressed as percentage of mass, were 55% lower in the very-low and intermediate-density lipoprotein (VLDL + IDL) fractions, and 45% lower in LDL, whereas triacylglycerols were 89% higher in VLDL + IDL and 121% higher in LDL. The fractional catabolic rate (FCR) of LDL protein (apoLDL) from operated animals was 10% higher than that from controls in all animals (0.55 +/- 0.10 vs. 0.50 +/- 0.10 pools/day; P less than 0.01). The FCR of autologous apoLDL in PIB rabbits was 50% higher than that of autologous apoLDL in control rabbits (0.63 +/- 0.05 vs. 0.42 +/- 0.06 pools/day); this was not caused by induction of receptor-mediated clearance of LDL. The production rate of apoLDL after PIB in PIB rabbits was 50% lower compared to control apoLDL in controls (26.0 +/- 6.7 vs. 51.7 +/- 16.4 mg/kg per day). We conclude that PIB lowers LDL cholesterol in WHHL rabbits by a decreased production of LDL, by an increased non-specific clearance of LDL and by compositional changes, which lead to LDL particles containing less cholesterol.

Animals↗
PubMed1989

The relevance of a protein-enriched low density lipoprotein as a risk for coronary heart disease in relation to other known risk factors.

The significance of a decreased low density lipoprotein cholesterol/apolipoprotein B ratio (LDL-chol/LDL apo B), or protein-enriched LDL, to predict atherosclerosis was studied in 121 males with angiographically defined coronary artery disease (CAD) and compared to 98 male controls, without history or complaints of vascular disease. Controls were selected for similar age, smoking habits and relative body weight characteristics compared to the CAD group. Covariance analysis with adjustment for hyperlipoproteinemia, apoprotein E phenotype, smoking, age and relative body weight revealed that high density lipoprotein (HDL)-cholesterol was the only parameter that differed significantly between both groups. By logistic regression analysis HDL-cholesterol had the highest predictive power for the development of CAD. The LDL-chol/LDL apo B ratio appeared significantly different between controls and CAD patients (3.1 +/- 0.7 vs. 2.9 +/- 0.6 mmol/g, P less than 0.05), indicating a predominance of subjects with protein-enriched LDL in the CAD group. However, within the group of CAD patients with normal LDL-cholesterol levels no clear distinction could be found between patients with normal and increased LDL apo B levels. Furthermore, it appeared that the LDL-chol/LDL apo B ratio correlated significantly with age (p = -0.24), serum triglycerides (p = -0.24), and HDL-cholesterol (p = 0.24). Thus, the LDL-chol/LDL apo B ratio cannot be considered an independent risk factor for CAD. When adjusted for age, smoking habits and relative body weight the significance of protein-enriched LDL as a risk factor for coronary heart disease diminishes, and HDL-cholesterol appears to be the best indicator for CAD.

Adult↗
PubMed1989

Effects of monounsaturated fatty acids v complex carbohydrates on serum lipoproteins and apoproteins in healthy men and women.

The effects of a high-carbohydrate, high-fiber diet and an olive-oil-rich diet on the distribution of cholesterol over the various lipoproteins, on serum apolipoproteins, and on the composition of HDL2 and HDL3 were studied under strict dietary control. Forty-eight healthy subjects first consumed a high-saturated-fat diet [proportion of energy, en%] (saturated fat 20 en%, total fat 38 en%) for 17 days. For the next 36 days, 24 subjects consumed a diet high in complex carbohydrates (monounsaturated fat 9 en%, total fat 22 en%) and the other 24 consumed a high-fat, olive-oil-rich diet (monounsaturated fat 24 en%, total fat 41 en%). The amounts of protein (12% to 14 en%), polyunsaturated fat (4 to 5 en%), and cholesterol (31 to 35 mg/MJ) were similar in all three diets. Serum cholesterol levels fell by 0.44 mmol/L in subjects consuming the carbohydrate diet and by 0.52 mmol/L for those receiving the olive-oil-rich diet. VLDL-cholesterol levels rose by 0.08 mmol/L in the carbohydrate group and fell by 0.08 mmol/L in the olive oil group (P less than .05 for difference between test diets). HDL2 and LDL cholesterol levels fell to the same extent on both diets. HDL3 cholesterol fell by 0.09 mmol/L on the high-carbohydrate diet and increased by 0.01 mmol/L on the olive oil diet (P less than .05). There was no change in the composition of HDL3, suggesting that the fall was due to a decrease in the total number of circulating particles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Apo E polymorphism and the removal of remnants of triglyceride-rich lipoproteins in normolipidemic subjects during a carbohydrate-rich diet.

The role of the apo E polymorphism in the removal of remnants of very low density lipoproteins and chylomicrons was studied after a carbohydrate-rich diet in 10 healthy normolipidemic volunteers with different apo E phenotypes during 7 days. The cholesterol concentration in the heparin-sepharose bound part of the VLDL + IDL fraction (d < 1.019 g/ml) was taken as an estimate of the remnant concentration. Before and after carbohydrate-rich diet retinyl palmitate, mixed with cream, was consumed by each subject the evening before the fasting venepuncture to quantify the removal of chylomicron remnants. After the diet there was a comparable mean rise in the three groups in serum and in very low density lipoprotein triglycerides of about 30% and 50%, respectively. The concentration of remnants of very low density lipoproteins increased slightly in all subjects. The concentration of retinyl palmitate in the d < 1.019 g/ml fraction was 20% lower than before this diet in the E-2 homozygous subjects. In the other two groups, however, 25 to 80% higher retinyl palmitate levels were found. It is concluded, that after a carbohydrate-rich diet there is only a slight increase of very low density lipoprotein remnants, independent of the apo E polymorphism. The removal of chylomicron remnants, however, seems to be facilitated in E-2 homozygous subjects, in contrast to a slower removal in the groups with other apo E phenotypes.

Journal Article↗
PubMed1989

Effects of inhibition of cholesterol synthesis by simvastatin on the production of adrenocortical steroid hormones and ACTH.

Simvastatin, a derivative of lovastatin, is a potent inhibitor of cholesterol biosynthesis and may interfere with steroid hormone production, for which cholesterol is required. In a single-blind, placebo-controlled study, 24 patients with severe primary hypercholesterolaemia (mean serum cholesterol +/- SD = 10.74 +/- 1.59 mmol/l) were treated with simvastatin 40 mg per day for 8 weeks. Before and after treatment, the following parameters were evaluated: basal levels of ACTH, cortisol, androstenedione, dehydroepiandrosterone and 17-hydroxyprogesterone; urinary excretion of free cortisol; the cortisol response after short-term infusion of ACTH; the ACTH and cortisol response during insulin-induced hypoglycaemia. Total serum cholesterol decreased by 35.0 +/- 8.1% (P less than 0.001) and low-density lipoprotein (LDL) cholesterol by 39.8 +/- 9.8% (P less than 0.001); high-density lipoprotein (HDL) increased by 9.2 +/- 11.1% (P less than 0.001). Basal levels of ACTH were higher after simvastatin (2.9 +/- 1.9 pmol/l vs 4.1 +/- 2.9 pmol/l; P less than 0.05) whereas basal levels of steroid hormones were not significantly changed. The excretion of free cortisol was unaltered. The peak cortisol after ACTH infusion was lower after treatment (0.87 +/- 0.23 mumol/l vs 0.78 +/- 0.10 mumol/l; P less than 0.05), but was unaltered during insulin-induced hypoglycaemia. We conclude that simvastatin lowers serum cholesterol without clinically relevant effects on the adrenocortical steroid hormone secretion and the hypothalamic-pituitary-adrenal axis.

Adrenal Cortex Hormones↗
PubMed1988

Some metabolic characteristics of low-density lipoprotein subfractions, LDL-1 and LDL-2: in vitro and in vivo studies.

Two low-density lipoprotein subfractions, LDL-1 and LDL-2, with density ranges of respectively 1.023-1.034 and 1.036-1.041 g/ml, were isolated by aspiration after density gradient ultracentrifugation of human pooled serum. In vitro interactions of both LDL subfractions with the LDL receptor of human cultured fibroblasts, human hepatoma cell line Hep G2 and human hepatocytes were compared. No difference in association (binding and internalization) nor in degradation between LDL-1 and LDL-2 by these cells was found. However, kinetic studies in guinea pigs showed that LDL-2 disappeared faster from the circulation and accumulated to a greater extent in the liver, compared to LDL-1. Thus, we were unable to show a difference in the LDL receptor-mediated uptake of both LDL subfractions by various cells in vitro. The results obtained in vivo suggest that LDL-1 is more atherogenic than LDL-2, because its longer half-life renders the particle more susceptible to uptake by the scavenger LDL receptor on macrophages.

Animals↗
PubMed1988

Studies on the function of hepatic lipase in the cat after immunological blockade of the enzyme in vivo.

In order to investigate the in vivo function of hepatic lipase, cats were injected with anti-cat hepatic lipase antibodies which produced a complete and specific inhibition of heparin-releasable hepatic lipase. The cat was chosen as an animal model because it displays, like man, a relative deficiency of lipoprotein lipase compared to hepatic lipase and because the possession of two subfractions of high density lipoproteins, HDL2 and HDL3. In fasted cats no changes were observed in plasma triglycerides or phospholipids. In fed animals triglycerides increased considerably, indicating that hepatic lipase may have a function in the postprandial phase. In fat-loaded cats (6 g of fat/kg) triglycerides in the d less than 1.019 g/ml fraction increased from 4 h after the blockade due to accumulation of lipoproteins with pre-beta-mobility containing the apoproteins, apo B-100, apo E and apo A-I. Apo B-48 did not accumulate consistently. Phospholipids in the HDL2-fraction and those in the HDL3-fraction of the fat-loaded cats tended to increase and decrease from 6 and 9 h after the blockade, respectively. The absolute change in HDL2 phospholipids approximated that of HDL3-phospholipids. Overall, the density of HDL particles decreased, apparently secondary to the accumulation of apo A-I in the d less than 1.019 g/ml fraction. Our findings suggest that hepatic lipase is involved in the hydrolysis of a special class of apo A-I containing triglyceride-rich lipoproteins synthesised in the postprandial phase.

Animals↗
PubMed1988

Comparative studies on the low density lipoprotein subfractions from pig and man.

(1) By means of a single spin density gradient ultracentrifugation method, sera from six human volunteers and six pigs were studied; three or four distinct low density lipoprotein (LDL) subfractions could be seen in the pig serum (LDL-1A, LDL-1, LDL-2 and LDL-3) and three in the human serum (LDL-1A, LDL-1B and LDL-2). The subdivision of LDL into subfractions was less clear for the human subjects than for the pigs. (2) Physicochemical characteristics (chemical composition, apoprotein content, size and density) of the LDL subfractions were determined and showed many similarities. (3) In both species, in order of increasing density, relative protein content of the LDL subfractions increased, accompanied with a decrease in size. However total pig LDL was of higher density, smaller and contained more protein. (4) In conclusion, the pig appears a suitable animal model for the study of LDL heterogeneity. For these studies the density gradient ultracentrifugation method with visualization of the lipoprotein bands is the method of choice.

Adult↗
PubMed1988

Deleterious effects of anabolic steroids on serum lipoproteins, blood pressure, and liver function in amateur body builders.

The effects of self-administered anabolic steroids (AS) on lipoproteins, liver function, and blood pressure were studied in male amateur body builders. Twenty body builders were studied at the end of a course of AS (group 1) and 42 body builders were studied after discontinuation of the AS for a mean of 5 months (group 2). Sixteen body builders were studied after discontinuation of AS for at least 2 months and at the end of a 9-week course of AS (group 3). A group of 13 body builders who never used AS served as a control group. Both groups 1 and 2 showed higher levels of transaminas and a higher systolic blood pressure than the controls (P less than 0.05). Group 3 showed an increase of the transaminases an a slight but significant increase of systolic blood pressure (+3 mm Hg) and heart rate (+7 bts/min) after one course of AS (P less than 0.05). Group 1 showed a considerably lower high-density lipoprotein cholesterol (HDLC) (P less than 0.001), a higher low-density lipoprotein cholesterol (LDLC) (P less than 0.05), and a lower apoprotein A-l/B ratio (Apo A-l/ApoB) (P less than 0.001) than the controls and group 2. The ratio of LDLC/HDLC in group 1 was fourfold higher than in the controls (P less than 0.01). In group 3 HDLC decreased from 1.18 +/- 0.05 to 0.60 +/- 0.08 mmol/l (P less than 0.001) and LDLC increased from 3.97 +/- 0.39 to 5.74 +/- 0.71 mmol/l (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Interference of blood clotting factors in the determination of HDL2- and HDL3-cholesterol by the dual precipitation method.

Previously we found that in the dual precipitation method for determination of HDL2- and HDL3-cholesterol the optimal concentration of dextran sulfate was 0.87 g/l instead of 1.3 or 1.5 g/l. In the present study, we performed the dual precipitation method both in serum and in EDTA-plasma samples in order to investigate whether the method is sensitive for plasma-serum differences. It was found, that in the analysis of EDTA-plasma samples a twice higher final concentration of dextran sulfate was needed. Addition of the dextran sulfate resulted in the appearance of fibrin structures in the HDL-fraction which may have diminished the effective dextran sulfate concentration in the precipitation reaction. Although the use of plasma is advised in the analysis of lipoproteins, the use of EDTA-plasma in precipitation methods for determination of HDL-cholesterol and its subfractions cannot be recommended.

Blood Coagulation Factors↗
PubMed1987

A study of the lipid transport system in the cat, Felix domesticus.

Feline serum lipoproteins were fractionated into four distinct classes by density gradient ultracentrifugation and characterized with respect to physical and chemical properties. The distribution of serum lipids, lipoproteins and apolipoproteins was quite unlike that in man, the cat having five times as much high density lipoproteins (HDL) as low density lipoproteins (LDL). The lipoproteins in the d less than 1.019 g/ml fraction of cats were larger and were richer in triglycerides than their human counterparts and contained a considerable amount of beta-migrating particles. The low density lipoproteins of cats and man had similar chemical composition, but cat LDL had a higher negative charge, were smaller and contained apoprotein A-I. Cat HDL consisted of two distinct subfractions HDL2 and HDL3 with similar density boundaries and particle size as in man. In cat serum and HDL fraction apoprotein A-II was a minor component. Like human serum, fasting cat serum contained only the larger species of apoprotein B, apo B-100, whereas intestinal lymph contained exclusively the smaller apo B-48. Post heparin feline and human plasma possessed both lipoprotein lipase and hepatic lipase. Chylomicrons formed after a fat load in cats were removed from the circulation as rapidly as in man. It is concluded, that the cat is another animal model of potential interest for the study of lipoprotein metabolism.

Animals↗
PubMed1987

Catabolism of chylomicron remnants in normolipidemic subjects in relation to the apoprotein E phenotype.

The role of the various apolipoprotein E isoproteins in the removal of chylomicrons and their remnants from plasma was studied in 16 normolipidemic subjects with various apoE phenotypes: 5 homozygous for apoE-2, 6 heterozygous for apoE-2 (phenotype E3/2), and 5 without apoE-2 (phenotypes E3/3, E4/4, and E4/3). The subjects were given an oral fat load as cream (50 g/m2). Retinyl palmitate was added as a marker for chylomicrons and their remnants. Blood was sampled at regular time intervals for 8 hr. Remnant particles were isolated from the d less than 1.019 g/ml fraction by heparin-Sepharose chromatography (heparin-bound fraction) after removing the large chylomicrons by flotation at 7,8 X 10(5) g-min. All groups showed a rise in triglycerides in serum and in the chylomicron fraction between 3 and 6 hr to about twice the basal value, followed by a decrease to nearly fasting values. In the homozygous E-2 subjects, fasting lipids in the remnant fraction were increased. In all three groups the fat load did not induce a significant rise in the lipids of the remnant fraction. The homozygous E-2 group showed a strong continuing rise in the retinyl palmitate concentration in the chylomicron and remnant fractions up to 8 hr, whereas in the other groups its maximum was already reached at 5 hr at a much lower level. At 8 hr similar retinyl palmitate concentrations were found in both fractions in the heterozygous E-2 subjects compared to the non-E-2 subjects. These results indicate a delayed removal of chylomicrons and chylomicron remnants in normolipidemic homozygous E-2, but not in heterozygous E-2 subjects.

Adult↗
PubMed1987

Single spin density gradient ultracentrifugation method for the detection and isolation of light and heavy low density lipoprotein subfractions.

A single spin density gradient ultracentrifugation method in a swinging bucket rotor has been applied for the detection and isolation of low density lipoprotein (LDL) subfractions. The visualization of the LDL heterogeneity was facilitated by prestaining the serum with Coomassie Brilliant Blue R prior to density gradient ultracentrifugation for 19.5 hr. A total of 13 human serum pools was analyzed. In each pool, two LDL subfractions, a lighter LDL1 subfraction, occasionally showing a subdivision into two bands, LDL1A and LDL1B, and a heavier LDL2 could be clearly distinguished by the banding pattern in the density gradient. Physicochemical characteristics of the isolated LDL subfractions were determined. The simple method for detection and isolation of these subfractions presented here may facilitate future studies on LDL heterogeneity.

Adolescent↗