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Biomedical subjects

C M van Gent

Publications and source records attributed to C M van Gent.

At least 19 recordsLinked to original sources

Modification of the pulmonary connective tissue developmental response in the neonatal rat by ciclosporin.

Neonatal rat pups were treated either with ciclosporin at 10 mg/kg/day dissolved in olive oil (experimental) or with pure olive oil (control). Lung protein biosynthesis was evaluated in a protocol which involved the measurement of total accumulated protein, collagen and elastin. Four time points were studied in the first 21 days of life, 12 animals contributing to each point (6 control and 6 ciclosporin). Ciclosporin levels in the treated group ranged widely (2,000-4,000 ng/ml). There were significant differences in total body weight and lung weight in treated vs. controls during and after the first week. DNA contents per unit wet weight varied significantly during the second week of life, indicating increased cellularity of the ciclosporin-treated animals. Associated with this was an increase in the lung protein/DNA ratio as well as the elastin/DNA ratio in the control animals, but not in the treated ones. The lung collagen/DNA ratio was not as dramatically affected by the ciclosporin treatment. However, the collagen content per unit wet weight of lung tissue was increased in the ciclosporin-treated animals at 15 days of life. We conclude that ciclosporin has a marked effect on lung connective tissue metabolism in early life, the long-term effects of which are unappreciated and undocumented but may well be of vital importance in the lungs of long-surviving organ transplant patients.

Animals↗

Association of cholesterol concentrations in low-density lipoprotein, high-density lipoprotein, and high-density lipoprotein subfractions, and of apolipoproteins AI and AII, with coronary stenosis and left ventricular function.

We examined the association of cholesterol levels in serum lipoprotein fractions, as well as of serum apolipoprotein-AI (apo-AI) and apo-AII levels, with coronary artery stenosis (CAS) and left ventricle function in a group of 43 patients with angina pectoris (33 men and 10 women) subjected to angiography. Cholesterol level in VLDL, LDL, HDL2, and HDL3 fractions was determined after separation of these fractions by density gradient ultracentrifugation. HDL-cholesterol is the sum of cholesterol in HDL2 and HDL3. Cineangiography yielded scores for CAS and for left ventricle ejection fraction (LVEF). On univariate regression CAS was correlated weakly with LDL-cholesterol (positive) and with HDL3-cholesterol and HDL-cholesterol (negative), and more strongly with LDL-cholesterol/HDL-cholesterol (positive), but not with HDL2-cholesterol. LVEF was correlated positively with HDL3-cholesterol, HDL-cholesterol, apo-AI, and apo-AII. Of other "risk factors," none was correlated with CAS, and a history of previous myocardial infarction (PMI) was the only one significantly correlated with LVEF. CAS itself was also correlated negatively with LVEF. In multiple regression analysis with two or three independent variables, the relation of HDL(3)-cholesterol with CAS remained significant when other risk factors were taken into account. LVEF remained related positively with HDL(3)-cholesterol, apo-AI, or apo-AII, when either of them was tested in combination with other risk factors; of these only PMI made a significant independent contribution. Conclusions for this patient group (with low HDL-cholesterol): HDL3-cholesterol, and not HDL2-cholesterol, is informative for CAS; HDL(3)-cholesterol, apo-AI, or apo-AII, as well as CAS and PMI, are associated with LVEF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

Diet, lipoproteins, and the progression of coronary atherosclerosis. The Leiden Intervention Trial.

We studied the relation between diet, serum lipoproteins, and the progression of coronary lesions in 39 patients with stable angina pectoris in whom coronary arteriography had shown at least one vessel with 50 per cent obstruction before intervention. Intervention consisted of a two-year vegetarian diet that had a ratio of polyunsaturated to saturated fatty acids of at least 2 and that contained less than 100 mg of cholesterol per day. Dietary changes were associated with a significant increase in linoleic acid content of cholesteryl esters and a significant lowering of body weight, systolic blood pressure, serum total cholesterol, and the ratio of total to high-density lipoprotein (total/HDL) cholesterol. Angiographic examination was performed after 24 months; angiograms were assessed visually (with blinding) and by computer-assisted image analysis. Both types of assessment indicated progression of disease in 21 of 39 patients but no lesion growth in 18. Coronary lesion growth correlated with total/HDL cholesterol (r = 0.50, P = 0.001) but not with blood pressure, smoking status, alcohol intake, weight, or drug treatment. Disease progression was significant in patients who had values for total/HDL cholesterol that were higher than the median (greater than 6.9) throughout the trial period. No coronary-lesion growth was observed in patients who had lower values for total/HDL cholesterol (less than 6.9) throughout the trial or who initially had higher values (greater than 6.9) that were significantly lowered by dietary intervention.

Adult↗

An explanation of the low lecithin/sphingomyelin ratio of amniotic fluid in early pregnancy.

We have attempted to determine why the lecithin/sphingomyelin (L/S) ratio of amniotic fluid is lower than 2 during an early stage of pregnancy. We found that, at 16 wk of gestation, long before the fetal lung secretes lecithin into the amniotic fluid, the L/S ratio was about 1. High-density lipoprotein isolated from the amniotic fluid also had such a low L/S ratio. The L/S ratios of the high-density lipoprotein from umbilical cord blood and maternal blood, however, were much higher, viz. 3.7 (+/- 0.25) and 6.4 (+/- 0.33), respectively. The increase coincided with a decrease in their fluorescence polarization. We suggest that the low L/S ratio of 16 wk amniotic fluid is caused by lipolysis of its lecithin, which is derived from fetal or maternal high-density lipoproteins.

Amniotic Fluid↗

The effect of dietary linoleic acid and pectin on lipoprotein and apolipoprotein A1 concentrations in rhesus monkeys.

Medium term effects (3 months) on serum lipoprotein levels of a diet with a high P/S ratio (2.2) and a low P/S ratio (0.3) were investigated in 13 normolipoproteinemic rhesus monkeys. Both diets were studied with and without added gel-forming fibre, as pectin. Addition of pectin did not have major influences on serum lipid levels. Changing from a low to a high P/S diet resulted in a significant decrease of total cholesterol (23%) and LDL cholesterol (18%) levels, but also HDL cholesterol (23%) and apolipoprotein A1 (Apo A1; 13%) concentrations fell significantly. However, after 12 weeks on the high P/S diet, HDL cholesterol concentrations rose by 24%, not significantly different from the levels during the low P/S diet. We conclude that the medium-term effects of a high P/S diet are a decrease in LDL cholesterol with only a transient effect on HDL cholesterol.

Animals↗

The lipid composition and localization of free and esterified cholesterol in different types of xanthomas.

The lipid composition of 17 xanthomatous lesions from 16 patients with different types of hyperlipoproteinaemia was analyzed. The relative amounts of free cholesterol, cholesterolesters, and phospholipids in xanthomas obtained from patients who subsequently showed regression of their remaining type of xanthomas were different in comparison with xanthomas which did not show regression. One tendinous xanthoma contained more than 50% free cholesterol and resembled in lipid composition the gruel plaques found in atherosclerotic lesions. The relative amounts of free cholesterol, cholesterolesters, and phospholipids in regressing xanthomas were similar to those of fatty streaks found in arteries of children between the ages of 5-10 yr. Histochemical studies using an enzymatic method demonstrated that free and esterified cholesterol were located in focal areas of xanthomatous tissue. It is concluded that the physical state of lipids in xanthomatous lesions can vary remarkably and plays an important role with regard to the possibility of regression.

Cholesterol↗

High density lipoprotein cholesterol and apolipoprotein A-I levels in 32-33-year-old women on steroid contraceptives-differences between two frequently used low-estrogen pills.

High density lipoprotein cholesterol and apolipoprotein A-I levels were measured in about one thousand 32-33-year-old women taking part in a cardiovascular screening programme. After corrections for differences in smoking habits and use of alcoholic drinks women on various types of steroid contraceptives had widely different levels of high density lipoprotein cholesterol and apolipoprotein A-I. Lowest levels were found in users of lynestrenol-containing minipills (progestagen-only pills) and highest levels in lynestrenol-containing minipills. Of the two commonly used low-estrogen pills ("sub-50 pills") one type (containing levonorgestrel) was associated with elevated and the other (containing lynestrenol) with depressed levels of high density lipoprotein cholesterol and apolipoprotein A-I as compared with the reference group of non-users of oral contraceptives.

Adult↗

The effect of various intakes of omega 3 fatty acids on the blood lipid composition in healthy human subjects.

In a study with 52 healthy volunteers, the effect of different amounts of omega 3 fatty acids on the blood lipid composition was investigated. Doses of 1.4, 2.3, 4.1, and 8.2 g of omega 3 fatty acids were administered to these subjects daily over a period of 4 wk. Total cholesterol, high-density lipoprotein cholesterol, total triglycerides, and glucose were determined in blood serum and hemoglobin in whole blood in all individuals before, during, and after the intake of omega 3 fatty acids. In pooled serum samples, the lipoprotein composition and the fatty acid composition of blood lipids were determined. All dosages caused a shift in the fatty acid composition of blood serum lipids in a favor of omega 3 fatty acids and at the expense of omega 6 and/or omega 9 acids. In the sterol esters, only the percentage of C20:5 omega 3 increased. Maximum shifts depended on the amount of omega 3 acids ingested and were evident within 1 to 2 wk. Two wk after the last ingestion of omega 3 acids, the fatty acid composition of blood serum lipids had returned to the original state. In the groups receiving 8.2 of omega 3 fatty acids, there was a significant decrease in serum triglyceride and very low-density lipoprotein levels, which is in accord with earlier observations. In the other parameters, including cholesterol and high-density lipoprotein cholesterol, no decrease or increase was observed.

Adolescent↗

Diurnal levels of lipids, glucose and insulin in type IV hyperlipidemic patients on high carbohydrate and high fat diet: comparison with normals.

Diurnal levels of serum triglyceride (TG), cholesterol, free fatty acids (FFA), glucose and insulin were measured in three type IV hyperlipidemic patients on a fixed solid 65% carbohydrate and a 65% fat diet when in steady state conditions in a metabolic unit. The carbohydrate-rich food was divided into either three or eight equivalent portions, differently spaced over the day and night. The fat-rich food was given in three equivalent portions only. The diurnal TG profiles on these diets showed the same characteristics as those found in normals, but increments and mean levels were considerably higher. On the carbohydrate-rich diet, mean TG levels decreased during the study. This was not seen either on the fat-rich diet or in normals. In contrast to our findings in normals, chylomicrons formed the major contribution to the serum TG pattern. FFA levels were markedly higher on the high-fat than on the carbohydrate-rich diet, but not different from those in normals. Postprandial glucose responses did not differ significantly between the diets. Insulin responses were markedly higher on the carbohydrate-rich than on the fat-rich food. Glucose levels did not differ from those in normals. Insulin levels were significantly higher in the patients. Cholesterol showed minimal fluctuations, parallel to the TG pattern, which could be attributed to chylomicron cholesterol.

Adult↗

The lipoprotein composition of amniotic fluid.

The lipoprotein composition of amniotic fluid (AF) has been studied and it was found that it consists of high density lipoprotein (HDL) only. At about the 26th week of pregnancy the HDL content reaches a maximum and decreases thereafter. On crossed immunoelectrophoresis the HDL of AF was separated into two components if the agar layer contained an antiserum against apolipoprotein A-I. The component with the higher electrophoretic mobility (but not the slower moving component) could also be visualized with an antiserum against HDL. When maternal or umbilical cord serum (UCS) was analysed by crossed immunoelectrophoresis using the anti-apoA-I antiserum, we found that they only contained the faster moving lipoprotein component. If UCS was treated with phospholipase A2 and then subjected to crossed immunoelectrophoresis, the slower moving component appeared at the expense of the faster one. Likewise when UCS was incubated with AF from the 15th week of pregnancy or later, the lipoprotein component of UCS with the high mobility was partially converted to the component with the slower mobility. It is concluded that AF probably contains a phospholipase, an enzyme which may promote the onset of labour.

Amniotic Fluid↗

The determination of lipids and proteins in suction blister fluid.

The concentration of 5 different proteins in suction blister fluid and serum was determined by immunotechniques. These proteins, varying in size and molecular weight (6,600-2,300,000) were insulin, albumin, high density lipoprotein determined as apoprotein A-I, alpha 2-macroglobulin and low density lipoprotein measured as apoprotein B. The difference in the blister fluid/serum concentration ratio of the proteins was dependent on the molecular weight and followed mainly the law of diffusion. Moreover, the amounts of insulin, albumin and apoproteins A-I and B in suction blister fluid were the same as those reported in peripheral lymph. The results indicate that the sieve function of the capillary basement membrane remains intact during the formation of the suction blisters. Suction blister fluid might therefore be regarded as representative of interstitial fluid. The concentrations of 4 different lipids (cholesterol, cholesterolesters, triglycerides and phospholipids) were also determined and their blister fluid/serum concentration ratio proved to have a fairly constant value of 0.25.

Blister↗