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Biomedical subjects

A van 't Laar

Publications and source records attributed to A van 't Laar.

At least 19 recordsLinked to original sources
PubMed1991

Alterations in the metabolism of very-low- and low-density lipoproteins after partial ileal-bypass surgery in the Watanabe heritable hyperlipidaemic rabbit.

The influence of interruption of bile-acid enterohepatic circulation by partial ileal bypass (PIB) surgery on serum lipids, lipoproteins and the turnover of very-low- (VLDL) and low-density (LDL) lipoproteins was investigated in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Compared with controls, total serum cholesterol was 48% lower after PIB (16.88 +/- 1.57 versus 8.79 +/- 1.66 mmol/l; P less than 0.01), owing to lower levels of cholesterol in VLDL (-23%), intermediate-density lipoprotein (IDL; -39%) and LDL (-72%); serum triacylglycerols were 32% higher (3.86 +/- 1.35 versus 5.11 +/- 0.82 mmol/l). The ratio of the percentages of mass of cholesteryl esters to triacylglycerols was 71% lower in VLDL and LDL and 67% lower in IDL (P less than 0.01). Compared with controls, the secretion rate of LDL was 33% lower (31.1 +/- 7.2 versus 20.7 +/- 6.9 mg/day per kg; P less than 0.05) and the fractional catabolic rate (FCR) of LDL was 33% higher (0.46 +/- 0.06 versus 0.61 +/- 0.12 pool/day; P less than 0.02). The VLDL turnover showed that after PIB there was a higher secretion rate of VLDL apolipoprotein B (63.9 versus 167.4 mg/day per kg), a higher FCR (3.84 versus 8.61 pools/day), a higher direct uptake (38.8 versus 146.4 mg/day per kg) and a higher conversion of VLDL into LDL (4.8 versus 9.0 mg/day per kg). Some 82% of LDL originated from direct synthesis in controls, and after PIB this was 59%. In both controls and treated rabbits there was a direct LDL synthesis, which was 52% lower after PIB (26.3 versus 12.6 mg/day per kg). It is concluded that LDL-cholesterol lowering by PIB is due to an increased uptake of LDL, a decreased synthesis of LDL, and cholesterol depletion of the LDL particles; the decreased LDL synthesis is due to a decreased direct production of LDL, which exceeds the increased conversion of VLDL into LDL.

Animals↗
PubMed1991

Apolipoprotein E phenotypes, serum lipoproteins and apolipoproteins in angiographically assessed coronary heart disease.

To determine the influence of the apolipoprotein E polymorphism on the occurrence of coronary artery disease (CAD) and on serum lipids, lipoproteins and apolipoproteins we studied 145 patients with angiographically defined CAD and compared them with 153 control subjects without history or complaints of vascular disease and with 35 subjects without significant stenosis on coronary arteriography. Subjects with hypertension, diabetes mellitus and endocrine or metabolic disorders were excluded. Covariance analysis and logistic regression analysis were performed with adjustment for age, sex, smoking habits and relative body weight. There were no significant differences for the apoE phenotypes on risk of cardiovascular disease. The CAD group had significantly higher mean values of serum cholesterol and triglycerides, very-low-density lipoprotein (VLDL)-cholesterol and VLDL-triglycerides, low-density lipoprotein (LDL)-cholesterol and apoprotein B; they had lower high-density lipoprotein (HDL)-cholesterol and apo A-I. The combination of LDL-cholesterol, apoA-I and VLDL-cholesterol was the best model in predicting cardiovascular disease. ApoE phenotype group E3/E2 had significantly lower values for serum cholesterol, LDL-cholesterol, and apoB and higher levels of apoE in comparison with the phenotype groups E3/E3 and E4/E3. The combination of LDL-cholesterol, cholesterol, apoE and VLDL-triglycerides was the best model in predicting the apoE phenotype. Thus, taking other risk factors into account, the apoE phenotype is not an independent risk factor for CAD; the apoE polymorphism influences lipoprotein levels and possibly, in that way, indirectly also the risk for CAD.

Aged↗
PubMed1989

The absorption of subcutaneously injected insulin.

Insulin has been used for the treatment of diabetes mellitus for 65 years. Still, little is known about the processes governing its absorption after subcutaneous injection. Since normoglycaemia is the general aim nowadays, knowledge about the absorption process is important. In this review, the physiology and the pharmacological and clinical factors influencing the absorption rate are dealt with, resulting in recommendations for the injection procedure of insulin.

Absorption↗
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

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

Nifedipine in primary Raynaud's phenomenon and in scleroderma: oral versus sublingual hemodynamic effects.

In 16 patients with Raynaud's phenomenon a placebo-controlled single-dose study was performed on the hemodynamic effects of 10 mg nifedipine, sublingually administered, followed by an open eight-week study on the therapeutic efficacy of chronic oral nifedipine, 10 mg qid. After the acute sublingual nifedipine administration, a pronounced objective improvement of finger skin (P = .013) and forearm muscle blood flow (P = .04) during a standard finger-cooling test was found. During the chronic oral study the improvement in objective efficacy parameters disappeared, except for laser Doppler estimated shunt flow (P = .07). The acute hemodynamic effects did not predict the long-term results in individual patients. Patients with systemic sclerosis reacted as well as patients with primary Raynaud's phenomenon. This study shows that orally administered nifedipine does not convey long-term objective benefit to patients with Raynaud's phenomenon. The apparent increase in vasodilation during acute administration suggests that sublingual nifedipine prophylactically or during a vasospastic attack may be more useful.

Administration, Oral↗
PubMed1987

Evidence for an antagonism between caffeine and adenosine in the human cardiovascular system.

A randomized, double-blind and placebo-controlled study was performed in 10 normotensive male subjects to analyze a possible antagonism between caffeine and adenosine with respect to their effects on the cardiovascular system in humans. Caffeine alone, 250 mg intravenously (i.v.), increased blood pressure by 9/12 mm Hg, and resulted in a fall of heart rate (HR) of 3 beats/min. Plasma epinephrine (E) rose by 114% after caffeine. Adenosine alone, in an increasing dose of 0.04-0.16 mg/kg/min, induced an increase in systolic blood pressure (SBP) (17 mm Hg), and HR (33 beats/min), a moderate fall in diastolic blood pressure (DBP) (-4 mm Hg), and no change of mean arterial pressure (MAP). At the highest adenosine infusion rate, forearm blood flow, skin temperature (ST), and transcutaneous oxygen tension were lowered, whereas plasma (nor)epinephrine was increased 227.2 and 215.9%, respectively. Adenosine infusion after caffeine induced comparable effects, but the fractional adenosine-induced changes of SBP, HR, plasma catecholamines, plasma renin activity (PRA), and aldosterone all were significantly reduced by previous administration of caffeine. Our results indicate an antagonism between caffeine and adenosine in humans, which may support the suggestion that some circulatory effects of caffeine are caused by an interaction with endogenous adenosine.

Adenosine↗
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↗
PubMed1986

Influence of slow calcium-channel blockade on the cardiovascular effects of coffee.

An increase in blood pressure after coffee and caffeine has recently been reported. A possible pharmacological mechanism for this pressor response is a rise in the intracellular calcium concentration, caused by an increase in calcium influx due to a direct effect of caffeine. Accordingly, the cardiovascular effects of drinking coffee after placebo and verapamil 3 X 80 mg in 1 day in 10 normotensive volunteers have been examined in a single-blind study. After placebo, coffee led to an increase in blood pressure (7/14 mm Hg), and a fall in heart rate (-7 beats/min); forearm blood flow did not change. Plasma epinephrine rose (257%), plasma norepinephrine did not change and the plasma renin activity fell significantly. The haemodynamic and humoral changes after coffee were not altered by pretreatment with verapamil. It is concluded that increased transmembrane calcium influx after caffeine does not appear to be an important pharmacological mechanism for the circulatory effects of coffee.

Adult↗
PubMed1986

Double-blind, placebo-controlled study of prazosin in Raynaud's phenomenon.

We performed a randomized, double-blind, placebo-controlled, crossover study of the therapeutic efficacy of prazosin (1 mg t.i.d.) in 24 patients with Raynaud's phenomenon. Comparison of prazosin vs. placebo showed a moderate subjective improvement with a reduction of the daily number (P = 0.003) and duration (P = 0.02) of attacks. Patients showed a marked preference (P = 0.0002) for prazosin. Finger skin temperature and laser Doppler estimated finger skin blood flow, assessed during a standard finger cooling test, revealed a beneficial effect of prazosin (P = 0.0001 and P = 0.003, respectively). No differences in reaction to therapy could be found between patients with Raynaud's disease and secondary Raynaud's phenomenon. We conclude that prazosin is useful in the treatment of digital vasospastic disease, with an overall good response in two thirds of patients.

Adolescent↗
PubMed1985

Alpha and beta-blockade and beta-stimulation in Raynaud's syndrome: a double-blind, placebo controlled, single dose study.

We examined in a double blind fashion and placebo controlled the effects of some alpha and beta adrenergic receptor agonists and antagonists on the recovery of finger skin temperature 12 min after finger cooling (5 min waterbath for both hands) in twelve patients with Raynaud's syndrome. A favourable effect was established on phenoxybenzamine 20 mg as compared to placebo. A significant but rather small effect on orciprenaline 10 mg. The beta-agonists prenalterol (10 mg) and terbutaline (5 mg) did not influence the recovery of finger skin temperature. The beneficial effect of phenoxybenzamine 20 mg was not influenced by the addition of beta-agonists (prenalterol 10 mg or terbutaline 5 mg) or a beta-blocker (propranolol 40 mg). The beta-agonists terbutaline and orciprenaline caused a fall in diastolic pressure and an increase in heart rate. These effects presumably were connected with one collapse and three near-collapses. On alpha- and beta-blocker (phenoxybenzamine and propranolol) a decrease in systolic pressure appeared, whereas diastolic pressure did not significantly differ from the placebo value. While physical exercise is considered to exacerbate the hypotensive effect of alpha-blockers, a fall in blood pressure during physical exercise could not be established in our experiments after the addition of propranolol to the alpha-blocker phenoxybenzamine. Our results suggest that an alpha-blocker is a good choice in Raynaud's syndrome, whereas the addition of a beta-blocker may have some advantages.

Adrenergic Agonists↗
PubMed1984

Partial ileal bypass reduces the production rate of low density lipoproteins in Watanabe heritable hyperlipidemic rabbits.

Partial ileal bypass surgery in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits resulted in a decrease of low density lipoproteins (LDL)-cholesterol from 14.2 +/- 2.4 to 7.0 +/- 1.2 mmol/l. To investigate the effect of partial ileal bypass on receptor-mediated and receptor-independent LDL catabolism, turnover studies were performed of radiolabeled native LDL and chemically modified LDL (methyl-LDL) in WHHL rabbits after partial ileal bypass, in WHHL control rabbits, and in New Zealand White ("normal") rabbits. The plasma LDL pool in WHHL control rabbits was increased 10-fold. The receptor-mediated LDL clearance was essentially zero in WHHL rabbits, both in controls and after ileal bypass surgery; the fractional catabolic rates for total LDL were equal in both WHHL groups and were also similar to that for methyl-LDL in the normal rabbits. Seventy percent of the total LDL clearance in the normal rabbits occurred via the LDL receptor pathway. In the animals with a partial ileal bypass, the plasma LDL-protein pool was appreciably lower than in WHHL controls (41.6 +/- 5.7 vs 73.4 +/- 9.9 mg/kg, P less than 0.02). The absolute catabolic rate was almost 50% lower in the PIB group (21.4 +/- 2.0 vs 40.0 +/- 7.5 mg X kg-1 X day-1, P less than 0.02). These results indicate that the decrease of LDL after partial ileal bypass surgery in WHHL rabbits is the result of a reduced production rate of LDL.

Animals↗