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Biomedical subjects

A C Beynen

Publications and source records attributed to A C Beynen.

At least 343 records · Page 19Linked to original sources
PubMed1987

Characteristics of human hypo- and hyperresponders to dietary cholesterol.

The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

Adult↗
PubMed1987

Assessment of discomfort in gallstone-bearing mice: a practical example of the problems encountered in an attempt to recognize discomfort in laboratory animals.

In order to obtain practical experience on the recognition, assessment and evaluation of discomfort in laboratory animals, the degree of discomfort was studied in gallstone-free and gallstone-bearing mice. Out of nine parameters to which scores were assigned per individual mouse, only the response to palpation of the right hypochondrium was found to score significantly higher in gallstone-bearing mice. That is, the incidence of squeaking and the magnitude of muscular contractions were significantly higher in these animals compared with the gallstone-free mice. The stance of the gallstone-bearing mice also tended to be abnormal, although the difference between gallstone-free and gallstone-bearing animals did not reach statistical significance. Although this study does not prove unequivocally that the induction of gallstones per se causes discomfort or pain in mice, we tentatively conclude that it does. We feel that this should be taken into account in any projected work in which gallstone induction in animals may occur. There was considerable between-assessor variation in the assignment of scores to the variables used to assess discomfort, including the response to palpation. It is concluded that the selection of parameters and the experience and/or attitude of the assessor are critically important when the magnitude of discomfort, if any, is assessed in experimental animals.

Animal Welfare↗
PubMed1987

Mode of hypocholesterolemic action of probucol in animals and man.

Probucol is a widely used serum-cholesterol lowering drug. It is proposed that in humans probucol stimulates the plasma clearance of low density lipoproteins (LDL), which accounts for the drug-induced decrease in LDL cholesterol levels. In the liver the enhanced uptake of LDL cholesterol stimulates the conversion of cholesterol into bile acids, which in turn causes an increase in the output of bile acids with the feces. The increased flux through the bile acid biosynthesis pathway tends to deplete the liver pools of cholesterol. This causes stimulation of cholesterol synthesis, which is associated with a higher hepatic efflux of LDL. Thus in humans taking probucol cholesterol turnover is enhanced. In this way a new equilibrium is reached in which LDL production equals LDL catabolism, and in which cholesterol turnover is increased. The probucol-induced reduction in high density lipoprotein (HDL) cholesterol may be caused by inhibition of HDL synthesis. If we assume that the absolute rate of HDL clearance from the plasma is proportional to HDL concentration, then serum HDL will settle at a new, lower level where the clearance rate equals the rate of production. In contrast to humans, probucol may decrease the turnover of cholesterol in rats. The relatively large amounts of probucol generally fed inhibit cholesterol absorption, and this may account for the reduction in serum total cholesterol, which essentially represents HDL cholesterol. The decrease in absorption diminishes intestinal formation of HDL, which in turn leads to a diminished flux of serum cholesterol into the liver, and causes inhibition of bile acid synthesis because substrate availability is depressed. The effect of probucol on cholesterol synthesis is not clear, but the drug must lower the sum of cholesterol absorption and synthesis. In this way, serum cholesterol settles at a new, lower level, where cholesterol input equals its output.

Animals↗
PubMed1987

The composition of plasma lipoproteins and erythrocyte membranes in cholesterol-fed pigs with partial ileal bypass.

The composition of plasma lipoproteins and erythrocyte membranes was studied in cholesterol-fed pigs with a partial ileal bypass. Cholesterol feeding caused marked increases in the plasma concentrations of cholesterol and phospholipids. In spite of continuation of cholesterol feeding, PIB reduced plasma concentrations of cholesterol and phospholipids towards basal values. PIB completely counteracted the dietary cholesterol induced alterations in the lipid composition of the apoprotein B containing plasma lipoproteins, but not in the HDL2 fraction. It is suggested that PIB specifically influences the metabolism of the atherogenic, apoprotein B containing lipoproteins. Dietary cholesterol caused significant increases in the ratios of cholesterol:phospholipids and phosphatidylcholine: sphingomyelin in erythrocytes. The high-cholesterol diet also increased the content of linoleic acid in erythrocyte phosphatidylcholine. PIB completely nullified the cholesterol-induced increase in the cholesterol:phospholipid ratio, but not the increase in the phosphatidylcholine:sphingomyelin ratio. The percentage of linoleic acid in erythrocyte phosphatidylcholine was unaffected by PIB. Neither cholesterol feeding nor PIB had an effect on the lipid fluidity of erythrocyte membranes, as measured by fluorescence polarization, using the probe diphenylhexatriene. Possible compensatory mechanisms operating to control homeostasis of lipid fluidity of erythrocyte membranes are discussed.

Animals↗
PubMed1987

Lowering of serum cholesterol by Temoe Lawak Singer, a Curcuma mixture.

Temoe Lawak Singer (RVG 08637) consists of a mixture of an extract of the roots of Curcuma aromatica rhizoma and whole roots of Curcuma amara rhizoma and Rhamni purshianae cortex; it has cholerectic and chologougic activity. The addition of Temoe Lawak Singer to a high-cholesterol diet, but not a cholesterol-free diet, was found to lower both serum and liver cholesterol in rats. When the rats were fed Temoe Lawak Singer as 0.1, 0.5 or 1.0% (w/w) of the high-cholesterol diet for 22 days, serum cholesterol concentrations were lowered by 4, 10 and 19%, respectively. The lowest dose induced a 20-% decrease in liver cholesterol, and higher doses did not cause further reduction. The fecal excretion of bile acids was decreased by 1.0% of Temoe Lawak Singer in the diet. It is suggested that Temoe Lawak Singer taken at normal doses may lower serum cholesterol in man.

Animals↗
PubMed1987

Dietary cholesterol-fat type combinations and carbohydrate and lipid metabolism in rats and mice.

In rats fed semipurified cholesterol-free diets, dietary corn oil induced higher levels of liver cholesterol, but lower concentrations of plasma cholesterol, plasma triglycerides and blood D-3-hydroxybutyric acid, than did coconut fat. Addition of cholesterol to the diets (1%, w/w) greatly increased liver cholesterol levels but did not affect the corn oil effect upon liver and plasma cholesterol. In contrast, dietary cholesterol prevented the corn oil effects upon plasma triglycerides and blood D-3-hydroxybutyric acid. Liver glycogen levels in rats increased significantly after cholesterol feeding, the effect being independent of dietary fat type. In mice, dietary corn oil, compared to coconut fat, elevated liver cholesterol only when the diet contained cholesterol. Corn oil caused an increase of liver glycogen in mice in the presence, but not in the absence of dietary cholesterol. This study shows that dietary cholesterol-fat type combinations influence various aspects of lipid and carbohydrate metabolism in rats and mice.

Animals↗
PubMed1986

Dutch legislation.

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Animal Experimentation↗
PubMed1986

Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol.

In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and bile acids minus cholesterol intake. In addition, we determined serum concentrations of lanosterol, a precursor of cholesterol and a possible indicator of cholesterol biosynthetic activity. The study was carried out with 2 hyper- and 4 hypo-responders; these subjects had shown a consistently high or low response of serum cholesterol to a decrease in dietary cholesterol in two previous experiments. The subjects received controlled high- (on average 697 mg of cholesterol per day) and low-cholesterol (109 mg/day) diets for periods of 4 weeks in succession; cholesterol was the only dietary variable. The two hyper-responders again showed a significant decrease in serum cholesterol. There was essentially no decrease in serum cholesterol in three of the four hypo-responders. The decrease in cholesterol intake caused an increase in cholesterol synthesis in five out of the six subjects. There was no association between the individual change in serum cholesterol and the change in cholesterol synthesis. Transfer from the high- to low-cholesterol diet caused an increase in serum lanosterol in all subjects. The increase was 3- to 4-fold higher in three out of the four hypo-responders than in the two hyper-responders. We tentatively suggest that this study provides some evidence that the flexibility of cholesterol synthesis is involved in the responsiveness to dietary cholesterol.

Journal Article↗
PubMed1986

The lipid composition of serum lipoproteins in the harbour seal, Phoca vitulina.

The density profile of serum lipoproteins and their lipid composition was studied in 12 adult, female harbour seals. The animals were sampled after an approximate 20 hr fast. The density profile of lipoproteins showed that the harbour seals displayed a distinct VLDL (density less than 1.006 g/ml) and HDL band (density about 1.125 g/ml), but no clear LDL band. There was a rather diffuse population of lipoproteins in the density range of 1.019-1.100 g/ml. Mean serum total cholesterol concentration was 5.7 mmol/l; about 60% of this cholesterol was located in the HDL fraction (density greater than 1.063 g/ml). The fasted seals were found to carry 4% of serum total lipids in chylomicrons. These lipoproteins consisted of 51% of triaclyglycerols (on the basis of total chylomicron lipids). The LDL (defined as heparin-manganese precipitable lipoproteins in VLDL and chylomicron-deficient serum) contained 49% of cholesterol and 43% of phospholipids (on the basis of total LDL lipids). The HDL (defined as heparin-manganese soluble lipoproteins in VLDL and chylomicron-deficient serum) contained 36% of cholesterol and 58% of phospholipids (on the basis of total HDL lipids).

Animals↗
PubMed1986

Fecal steroid excretion in relation to the development of casein-induced hypercholesterolemia in rabbits.

Two groups of nine rabbits fed a purified diet containing soy protein were injected intravenously with [4-14C]cholesterol. One group was fed the same diet for 78 d while the other group was fed a diet containing casein. The feces of the rabbits were collected and analyzed for radioactivity present in the neutral steroid and bile acid fractions. The excretion of neutral steroids and bile acids was lowered within 3 d after soy protein was replaced by casein and before the serum cholesterol concentration was increased. However, in the casein-fed rabbits the specific radioactivity of the bile acids was greater, whereas the amount of excreted bile acids was lower than in the soy protein-fed rabbits. After the serum cholesterol level in the casein-fed animals became constant (d 35), a further injection of [4-14C]cholesterol was given to all animals. Kinetic parameters of cholesterol metabolism according to a two-pool model were estimated from the die-away curve of [4-14C]cholesterol in serum. The size of the rapidly exchangeable pool (pool A) was greater in the casein-fed rabbits than in the soy protein-fed rabbits, whereas the size of pool B was similar in the two groups. The partial turnover rate of pool A was lower, as was the partial turnover of the slowly exchangeable pool (pool B), and the production rate of cholesterol was significantly lower on the casein-fed rabbits than in the soy protein-fed rabbits. This study suggests that the reduced excretion of steroids in casein-fed rabbits could be the cause of the hypercholesterolemia and is not the result of it.

Animals↗
PubMed1986

Existence of consistent hypo- and hyperresponders to dietary cholesterol in man.

Hyper- and hyporesponsiveness of serum cholesterol to dietary cholesterol is an established concept in animals but not in man. The authors studied the stability of the individual response of serum cholesterol to dietary cholesterol in three controlled experiments in 1982. The subjects were volunteers from the general population living in or near Wageningen, the Netherlands. Each experiment had a low-cholesterol baseline period (121, 106, and 129 mg/day in experiments 1, 2, and 3, respectively) and a high-cholesterol test period (625, 673, and 989 mg/day). Duplicate portion analysis showed that dietary cholesterol was the only variable. The 94 healthy men and women who completed experiment 1 showed an increase (mean +/- standard deviation (SD] in serum cholesterol of 0.50 +/- 0.39 mmol/liter (19 +/- 15 mg/dl). Seventeen putative hyperresponders, defined by their response in experiment 1, were retested in experiments 2 and 3; they showed responses of 0.28 +/- 0.38 mmol/liter (11 +/- 15 mg/dl) and 0.82 +/- 0.35 mmol/liter (32 +/- 14 mg/dl), respectively. Fifteen hyporesponders, selected in experiment 1, showed responses in experiments 2 and 3 of 0.06 +/- 0.35 mmol/liter (2 +/- 14 mg/dl) and 0.47 +/- 0.26 mmol/liter (18 +/- 10 mg/dl), significantly lower than the corresponding values for hyperresponders. The standardized regression coefficient for individual responses in experiment 2 on those in experiment 1 was beta = 0.34 (p = 0.03, n = 32); the corresponding regression coefficient for experiment 3 and experiment 1 was 0.53 (p less than 0.01). After correction for intraindividual fluctuations the true responsiveness distribution was found to have a between-subject standard deviation of about 0.29 mmol/liter (11 mg/dl). This implies that if the mean response to a certain dietary cholesterol load amounts to e.g., 0.58 mmol/liter (22 mg/dl), then the 16% of subjects least susceptible to diet will experience a rise of only 0.29 mmol/liter (11 mg/dl) or less, while in the 16% of subjects most susceptible to diet, serum cholesterol will rise by 0.87 mmol/liter (34 mg/dl) or more. The authors conclude that modest differences in responsiveness of serum cholesterol to dietary cholesterol do exist in man, and that the wide scatter of responses observed in single experiments is largely due to chance fluctuations.

Adult↗
PubMed1986

Long-term effects of partial ileal bypass on the health status of rabbits.

Partial ileal bypass (PIB) surgery is a method for the treatment of familial hypercholesterolaemia in man. Since the rabbit is frequently used as an animal model in experimental studies on PIB, we have investigated the long-term effects of this surgical procedure on the health status of rabbits. Forty-eight weeks after surgery plasma and liver cholesterol levels were decreased by about 40%. The inner diameter of the bypassed ileum was drastically reduced, unlike its length. The bypassed segment did not show clear histological abnormalities. The microflora of the caecum was similar in control and PIB rabbits. PIB did not influence liver histology. The bile of the rabbits with PIB was less lithogenic than that of control animals. Blood haemoglobin levels, haematocrit values and plasma concentrations of alkaline phosphatase, alanine aminotransferase, gamma-glutamyl transferase and lactate dehydrogenase were not changed after PIB. Plasma levels of albumin, creatinine, calcium, phosphorus, vitamin B12 and folic acid were not significantly affected by PIB. Rabbits with PIB had significantly higher plasma levels of bilirubin and zinc than control rabbits, but plasma vitamin E concentrations were significantly lower. These results may be of importance for further studies on the effects of PIB in rabbits.

Animals↗
PubMed1986

Effect of partial ileal bypass on ileum morphology in cholesterol-fed pigs.

We have studied ileum morphology in pigs 3.5 months after partial ileal bypass (PIB) surgery. PIB caused a reduction in the length of the bypassed ileum by 60%, while the circumference was decreased by about 70%. We did not find evidence for dilatation of the functional, neo-terminal ileum. These results in pigs are contrary to those found earlier in rabbits. This may be of importance concerning the choice of animal model to study the effects of PIB.

Animals↗
PubMed1986

Partial ileal bypass surgery in the treatment of heterozygous familial hypercholesterolemia: a review.

Partial ileal bypass (PIB) surgery is a method in the treatment of heterozygous familial hypercholesterolemia (FH). Since the first report in 1964 about 150 cases of FH who underwent the surgical procedure have been described. This number is very low when compared to other types of cholesterol-lowering treatment. On average, PIB decreases the level of plasma total cholesterol by 35% in FH patients, and the surgical procedure can be considered the most effective, single cholesterol-lowering method. PIB-induced reduction of plasma cholesterol is permanent. Further decrease of plasma cholesterol may be obtained in combination with an inhibitor of cholesterol biosynthesis. PIB specifically lowers plasma LDL cholesterol; the concentration of HDL cholesterol is not systematically influenced. The mechanism underlying the hypocholesterolemic action of PIB is discussed. Until now there is no evidence that PIB reduces atherosclerotic coronary death in FH patients. After PIB more patients experience improvement of angina pectoris rather than deterioration (15 versus 2 out of 41), but the number of patients is too small to allow solid conclusions. In 50% of FH patients PIB may cause regression of xanthomata. Out of 209 hyperlipidemic patients described, 14 patients had postoperative complications, which caused death in 3 patients. Diarrhea is the most common side-effect of PIB; out of 99 operated patients serious diarrhea troubled 38 patients, whereas 40 patients had minor complaints during the first year postoperatively. Diarrhea may persist as long as 10 years after PIB. There is no evidence that PIB enhances gallstone formation and severely impairs liver function, but PIB may increase the incidence of renal stones. It is suggested that PIB can be considered in the treatment of FH. However, in each individual case the disadvantages and possible advantages should be carefully weighed out, and this consideration should form the basis to decide whether or not surgery is indicated.

Bile Acids and Salts↗