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Biomedical subjects

C M Van Gent

Publications and source records attributed to C M Van Gent.

18 recordsLinked to original sources

Oxysterol incorporation into rat aorta resulting in elastin compositional changes.

The incorporation of dietary cholestan-3 beta,5 alpha,6 beta-triol (triol) into rat thoracic aortic tissue and changes in amino acid composition of the elastin were investigated to identify the cytotoxic properties of the triol. Weanling male Sprague-Dawley rats were fed the following diets for three months: (i) normal chow, (ii) normal chow with 1% (w/w) cholesterol added, or (iii) normal chow with 0.9% (w/w) cholesterol and 0.1% (w/w) triol added. Triol levels in the blood and in the thoracic aortic tissue were measured. Compositional changes of elastin were also determined. After three months on the triol-containing diet, triol was found in the thoracic aorta but was not detected in the blood. Amino acid analyses of the aortic tissue elastin revealed that the proline levels in the triol-fed animals were significantly greater than in the other two diet groups, while the elastin levels of leucine, aspartate, arginine, and phenylalanine decreased significantly. The mechanism for these observed changes induced by triol may reflect alternate splicing of elastin messenger ribonucleic acid (mRNA) resulting in structual changes in the elastin molecule. Dietary triol does contribute to tissue triol content and is associated with aortic elastin compositional changes. How these changes may contribute to the development of cardiovascular disease is not known.

Amino Acid Sequence↗

Haloperidol administration to rats during pregnancy induces permanent alterations in serum lipoprotein patterns of progeny.

The rat is notoriously resistant to vascular disease, but administration of haloperidol prenatally to the pregnant dam results in hyperlipidemic changes in F1 and F2 progeny. Total serum cholesterol concentrations in the F1 males reach levels three or more times greater than controls by one year of age. The phenomenon indicates a link between dopaminergic elements of the autonomic nervous system and cholesterol metabolism, a phenomenon heretofore unrecognized. Transfer of the hypercholesterolemia into the second generation further suggests that haloperidol induces a permanent change in the genetic control of lipoprotein metabolism. Although the observations are preliminary, they warrant consideration when administering the drug to pregnant women.

Animals↗

Diurnal changes in serum triglycerides as related to changes in lipolytic enzymes, lipoproteins and hormones in patients with primary endogenous hypertriglyceridaemia on a carbohydrate-rich diet.

Parameters of diurnal triglyceride (TG) metabolism were investigated in 5 subjects with primary endogenous hypertriglyceridaemia and compared with those of normal subjects studied previously. The patients were in a steady state on a carbohydrate-rich diet (meals at 9.00, 13.00 and 17.00 h). Serum TG showed a wavelike pattern with a maximum at around 17.00 h. Post-heparin lipoprotein lipase (LPL) activity in the fasting state was not different from that in normals, but failed to show the normal increase in the fed state (16.30 h). This was due to the inability of patients to increase their adipose tissue (AT)-LPL activity in the course of the day. AT-LPL activity was throughout the day lower than in normal subjects. Skeletal muscle LPL activity was low and showed no diurnal change, equalling our findings in normal subjects. Low density lipoprotein cholesterol and high density lipoprotein (HDL) cholesterol concentrations showed no diurnal change. However, HDL phospholipids increased significantly in the course of the day.

Adipose Tissue↗

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↗

Diurnal changes in serum triglycerides as related to changes in lipolytic enzymes, (apo) lipoproteins and hormones in normal subjects on a carbohydrate-rich diet.

Normal subjects in steady state on a carbohydrate-rich diet (three equivalent meals a day at 9.00, 13.00 and 17.00 h), show a wave-like serum triglyceride (TG) pattern with a peak at 14.00 h. Post-heparin lipoprotein lipase (LPL) activity increased from a mean value of 49 mU/ml +/- 13 (SD) in the fasting state to 127 mU/ml +/- 18 in the fed state (P less than 0.005). This was due to an increase in adipose tissue LPL activity which, at 16.30 and 21.30 h, was significantly higher than basal levels (128.3 +/- 81.5 and 87.7 +/- 23.2 v. 43.3 +/- 9.3 mU/g, P less than 0.05 and P less than 0.01, respectively). Skeletal muscle LPL activity was low (5.8 mU/g +/- 2.3, mean +/- SD) and showed no diurnal change. The observed changes in TG-hydrolysing capacity in the course of the day might explain the TG-pattern. High density lipoprotein (HDL) subfractions HDL2 and HDL3 were separated by density gradient ultracentrifugation and had mean hydrated densities of 1.088 and 1.135 g/ml, respectively. While HDL2 showed no diurnal change, HDL3-cholesterol and-phospholipid significantly increased during the day (P less than 0.005 and P less than 0.001 respectively), reaching their highest levels in the evening. Since te rise in HDL3-lipids follows the fall in serum TG, this provides further indication that the metabolism of these fractions in mutually related.

Adipose Tissue↗

The influence of low calorie (240 kcal/day) protein-carbohydrate diet on serum lipid levels in obese subjects.

Thirteen adult obese subjects (12 women, one man) were placed on a low-calorie diet (240 kcal = 1.02 MJ daily; mixed protein/carbohydrate) for two weeks. Mean weight loss +/- s.d. was 7.9 +/- 1.8 kg. Total serum cholesterol and HDL-cholesterol were significantly decreased after two weeks. Their ratio was unchanged. The direction of the changes in triglyceride levels was related to the pretreatment levels, subjects with a level below 120 mg/dl showed no change or a slight increase, subjects with a level over 120 mg/dl showed a significant decrease. On a normal diet, as well as after two weeks of caloric restriction, a negative correlation existed between serum Tg and the Tg fractional removal rate (K2IVFTT). The mean K2 value increased during weight loss. On a caloric restriction the relative content of linoleic acid decreased and of arachidonic acid increased in serum cholesterol esters and phospholipids. The relative content of palmitic acid increased in CE. The fatty acid composition of Tg was unchanged.

Adolescent↗

High-density lipoprotein cholesterol, monthly variation and association with cardiovascular risk factors in 1000 forty-year-old Dutch citizens.

High density lipoprotein cholesterol (HDL chol) levels were measured in about 1000 forty-year-old residents of the town of Leiden, The Netherlands. Mean levels (+/- S.D.) in women were 48.0 +/- 11.0 mg/dl; in men 42.5 +/- 10.7 mg/dl. In March mean levels in women were about 5 mg/dl lower than in June (P less than 0.001); in men there was a similar difference between mean levels in April and June (P less than 0.002). HDL chol levels were negatively related to smoking habits, relative body weight, and in women to use of oral contraceptives. Weak positive and negative correlations between HDL chol and serum cholesterol, respectively, were found in subgroups with high and low HDL chol levels, respectively.

Adult↗

The effect of digitonin-containing fixatives on the retention of free cholesterol and cholesterol esters.

The influence of several fixation and dehydration procedures on the retention of free cholesterol and cholesterol esters was studied in filter paper preparations. The retention of free cholesterol by the filter paper proved to be decreased by the addition of digitonin to the aldehyde fixative (aqueous phase) and was only slightly enhanced by partial dehydration (alcoholic phase, up to 70% ethanol). Furthermore, digitonin or the presumably formed cholesterol-digitonide complex bound hardly any osmium oxides in glass-fibre paper. Up to 26% of the cholesterol esters was mobilized during the aqueous phase when digitonin was added to the aldehyde fixative. When the glass-fibre papers containing the digitonin cholesterol-ester-osmate complexes were stored in distilled water after fixation, the fluid became turbid. Particulate material isolated from this turbid solution showed ultrastructurally a close resemblance to the 'whorls' observed by several authors in tissue fixed by a digitonin-containing aldehyde fixative. Digitonin also changed the ultrastructural appearance of liposomes, containing lecithin: cholesterol: phosphatidic acid; in a molar ratio 7:2:1. Our observations lead to the conclusion that the use of digitonin-containing fixatives should be abandoned, because they give results which cannot be interpreted. By the use of K4 [Fe(CN)6] containing OSO4 in the post-fixation step were able to demonstrate an increase in the visualization of membranous structures (liposomes).

Cholesterol↗

Ultrastructural findings on lipoproteins in vitro and in xanthomatous tissue.

The application of OSO4 plus K3 [Fe(CN)6] as a secondary fixative following aldehyde fixation, permitted demonstration of the presence of 30-300 nm 'membrane-bound' particles in xanthomatous tissue. With the same fixation method, isolated low density lipoprotein particles in a fibrin matrix could be observed in the transmission electron microscope in a way permitting comparison with similarly fixed tissue. However, isolated particles of very low density lipoproteins treated in the same way as low density particles had an irregular appearance and a diameter varying between 30 and 80 nm.

Cholesterol↗

The influence of meal frequency on diurnal lipid, glucose and cortisol levels in normal subjects.

Diurnal levels of serum triglyceride, cholesterol, free fatty acids, glucose, and cortisol were measured in four normal persons on a fixed solid 65% carbohydrate diet under steady state conditions in a metabolic unit. Triglyceride levels in all subjects showed similar patterns, which unexpectedly did not bear a simple relation to meal frequency or distribution. With three equivalent meals per day at 09.00, 12.00 and 17.00 hours, 'fasting' triglyceride levels increased by about 0.3 g/l from a minimum value between 03.00 and 05.00 hours in the morning till before breakfast. After breakfast there was a continued rise till about 15.00 hours and then a overall fall in spite of the meal at 17.00 hours. Isocaloric change to eight equivalent meals, consumed between 09.00 and 23.00 hours, resulted in a similar although slightly more even triglyceride pattern. On eight equivalent meals, spaced evenly over the entire 24 h period, a different pattern was found with lower triglyceride values at daytime than at night. Increase in meal frequency did not result in a lowering of mean diurnal triglyceride levels. The cholesterol pattern followed the triglyceride pattern most clearly in subjects with high triglyceride levels. Glucose showed the expected postprandial increments. Cortisol rhythm did not change on varying meal frequency.

Adult↗

An enzymatic method for the histochemical localization of free and esterified cholesterol separately.

An enzymatic method for the histochemical localization of cholesterol is presented. It makes possible the localization of free cholesterol, cholesterol esters, or both and is compatible with routine histological staining procedures. The method is based on the production of H2O2 from free cholesterol by cholesterol oxidase. Sites of peroxide production are visualized by a brown reaction product formed in a peroxidase-catalysed reaction between diaminobenzidine and H2O2. Cholesterol esters can be demonstrated as cholesterol after hydrolysis by cholesterol ester hydrolase. Some examples of the application of the method are given.

Adrenal Glands↗

Primary hyperlipoproteinemia in xanthomatosis.

Blood lipid values, clinical data and effects of therapy are reported on 74 patients with hyperlipidemia and xanthomatosis. A natural subdivision into two groups was observed on the basis of low density lipoprotein lipid values: one corresponding to Frederickson's type II, characterized by elevated low density lipoproteins, tendinous xanthomata, absence of eruptive xanthomata and a high incidence of cardiovascular diseases and the other resembling Frederickson's type III, with elevated very low density lipoproteins, eruptive xanthomata, xanthomata striata palmaria, elevated cholesterol/triglyceride ratios in the very low density lipoproteins and irregular appearance of floating beta lipoproteins. The latter group consisted of 32 patients in whom cardiovascular symptoms were relatively rare, despite mean cholesterol levels of 500 mg/dl.

Adult↗