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Biomedical subjects

G Hornstra

Publications and source records attributed to G Hornstra.

At least 145 records · Page 8Linked to original sources

Habitual fish consumption, fatty acids of serum phospholipids and platelet function.

To clarify whether the inverse relation between habitual fish consumption and cardiovascular mortality in the Dutch town of Zutphen could be explained by changes in platelet function or fibrinolysis, 40 healthy elderly men were selected from the Zutphen study population on the basis of their fish consumption over the last 26 years. In the high-fish group (n = 25) fish consumption was on average 33 g per person per day; in the low-fish group (n = 15) it was on average 2 g per person per day. This difference was reflected by significant differences in the concentrations of timnodonic acid (20:5n - 3) and cervonic acid (22:6n - 3) in the serum phospholipids of the participants. Between both groups no significant differences were observed in cutaneous bleeding time, platelet number, and collagen-induced platelet aggregation and ATP-release in whole blood. The same holds for the actual as well as the potential thromboxane B2 formation of activated platelets and for the activity of the plasminogen activator inhibitor. For most of the platelet-related variables a trend was found for a lower activity in the high-fish group. Therefore changes in platelet function might not explain, but may have slightly contributed to the inverse relationship between coronary heart disease and fish consumption, as observed in Zutphen.

Adenosine Triphosphate↗

Altered platelet function during mental stress and adrenaline infusion in humans: evidence for an increased aggregability in vivo as measured by filtragometry.

1. The effects of mental stress induced by a colour word conflict test (CWT; n = 9) or 3 h infusions of placebo or adrenaline (0.4 nmol min-1 kg-1; n = 9) on platelet function in vivo were studied in 16 healthy male volunteers. 2. Platelet function was assessed by a filtragometry technique, which reflects aggregability in vivo, and by measurements of the plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4). 3. Adrenaline and CWT induced marked cardiovascular responses as expected. Venous plasma adrenaline increased from 0.1-0.2 nmol/l at rest to 4.87 +/- 0.42 nmol/l during adrenaline infusion and to 0.46 +/- 0.10 nmol/l during CWT. 4. Filtragometry measurements were reproducible within individuals with coefficients of variation of 7.9% during placebo infusion and 5.4% for resting measurements between days. 5. Platelet aggregability, as measured by filtragometry, was similarly increased during both adrenaline infusion (P less than 0.05) and CWT (P less than 0.01). 6. The coefficients of variation for beta-TG and PF4 levels were 17.3% for log beta-TG and 27.9% for log PF4 between days, but could not be calculated for within-day variability. Both beta-TG (P less than 0.05) and PF4 (P less than 0.01) levels decreased time-dependently during placebo infusion, indicating that long resting periods (hours) are needed to attain basal levels. Artefactual results could not be identified by evaluating beta TG/PF4 ratios. 7. beta-TG and PF4 levels did not decrease time-dependently during adrenaline infusion. There were no significant changes of beta-TG or PF4 during CWT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of dietary fish oil on arterial thrombosis and atherosclerosis in animal models and in man.

In animal models of arterial thrombosis, fish-oil-enriched diets have been shown to have an antithrombotic effect. There is strong evidence, however, that this only holds if the fish-oil consumption is associated with a reduction of the saturated fat intake. In animal models of atherosclerosis the effect of a marine diet is not consistent. Although in some studies with cod-liver oil (which is relatively low in saturated fatty acids) a beneficial effect is observed, studies with other, more saturated fish oils do not confirm this. The influence of fish-oil consumption on some thrombotic complications of human atherosclerosis is not well documented. So far, the few results reported are not very promising, but it should remembered that this mainly concerns short-term studies. Studies with respect to human fibrinolysis are equivocal. Evidence has been obtained that fish consumption may even have an adverse effect on certain aspects of the fibrinolytic process. The studies performed so far do not provide conclusive evidence as to the importance of fish- and fish-oil-enriched food for prevention and therapy of ischaemic cardiovascular disease. Further research is needed, especially with long-term, high-quality animal models. Moreover, long-term, well-controlled, prospective human intervention studies are required to investigate the effect of feasible fish(oil)-enriched diets on morbidity and mortality of ischaemic cardiac and vascular diseases.

Angina Pectoris↗

Effect of dietary lipids on platelet function and thrombosis.

In rats, diets rich in polyunsaturated fatty acids of the (n-6) and (n-3) families (P) reduce the tendency to arterial thrombosis, whereas diets containing long-chain saturated fatty acids (S) are prothrombotic. Monounsaturated fatty acids seem to have a neutral influence on arterial thrombus formation. Consequently, the P/S ratio is an important determinant of the thrombogenicity of a dietary fat, the effect of which is probably mediated by an influence on platelet aggregability. In man, the type of dietary fat also affects platelet aggregation. Methodological problems, however, have resulted in equivocal results from studies, especially with respect to diets enriched with fish oil. Therefore, more research is required with methods than can quantify thrombotic risk in a reliable way. Nevertheless, the available evidence already justifies an active policy to increase people's consumption of (poly)unsaturated fatty acids at the expense of long chain saturated fatty acids.

Animals↗

A moderate fish intake increases plasminogen activator inhibitor type-1 in human volunteers.

For a period of 6 weeks, 76 healthy male volunteers consumed during their daily main meal the contents of one tin (approximately 135 g) of either fish (mackerel) paste or meat paste. Fibrinolytic parameters were determined in plasma samples obtained at the beginning and at the end of the experimental period. No changes were found in plasminogen, alpha 2-antiplasmin, tissue-type plasminogen activator (t-PA) antigen, and euglobulin t-PA activity. In the control group (n = 39), plasminogen activator inhibitor activity did not change. In the fish group (n = 37), however, total plasma PA inhibitor (PAI) activity increased by 45%, due to a 71% increase in PA inhibitor type-1. This increase could not be ascribed to a diet-induced acute phase-type reaction and could not be explained by changes in serum triglycerides or insulin.

Acute-Phase Proteins↗

Effect of dietary fish oils on the nature of urinary prostaglandin metabolites in rats.

Four different fish oils were compared with sunflower seed oil (SO) and hydrogenated coconut oil (HCO) for their effect on the prostaglandin turnover in vivo in rats, reflected by the mono- and dicarboxylic tetranor prostaglandin metabolites in the urine, measured as tetranor prostane monoic (TPM) and dioic acid (TPD), respectively. Prostaglandin turnover was highest for the animals fed SO and lowest after feeding HCO. Most animals fed fish oil were positioned between the other two oils. The ratio between TPM and TPD, reflecting the ratio between beta and (beta + omega) oxidation, was highest for the animals fed fish oil, intermediate after HCO feeding, and lowest for SO administration. The results clearly indicate that various dietary lipids have different effects on the metabolic pathway of prostanoids. This implies that the level of one single urinary prostanoid metabolite cannot be taken as a measure for the turnover of its parent prostanoid in vivo, unless it has been proven that the treatment under investigation does not affect the metabolic pathway of the prostanoid of interest.

Animals↗

Comparison between habitual intake of polyunsaturated fatty acids and their concentrations in serum lipid fractions.

To evaluate the validity of the cross-check dietary history method for the assessment of the habitual intake of polyunsaturated fatty acids, the relationship was investigated between the estimated intake of these fatty acids and their relative amounts in the various serum lipid fractions. Food intake data were obtained from a group of volunteers participating in a long-term epidemiological study in the Dutch town of Zutphen. The fatty acid composition of total lipids, phospholipids, triglycerides and cholesterol esters was determined in fasting serum samples from these volunteers. Although correlations between the calculated dietary intake of timnodonic acid (20:5(n-3), TA) and cervonic acid (22:6(n-3), CA), on the one hand, and the relative amounts of these fatty acids in the various serum lipid fractions, on the other, appeared to be statistically significant, no more than about 20 per cent of the variance in the serum values could be explained on the basis of dietary intake. For linoleic acid (18:2(n-6), LA) this was 55 per cent. It is concluded that the cross-check dietary history method is an acceptable technique for estimating the habitual intake of linoleic acid of a given individual. For the fish-related fatty acids, however, this method is less reliable. This discrepancy most probably results from the large differences in TA and CA contents in the same foods. In addition, a negative association with the calculated LA intake on the proportional amount of TA for most of the serum lipid fractions was demonstrated. This indicates an interference of dietary LA on the metabolism of TA.

Aged↗

No acute effect of cigarette smoking on bleeding time of habitual smokers.

To study the influence of cigarette smoking on blood platelet function, bleeding time was measured in two groups of 14 habitual smokers before and after a 20-minute period during which the subjects either smoked two cigarettes (experimental group) or rested (control group). The second bleeding time appeared to be slightly shortened upon cigarette-smoking (-0.1 min) and was found to be prolonged in the control group (+0.4 min). These changes did not differ significantly from each other (P = 0.38). Consequently, bleeding time of habitual smokers is not affected by smoking two cigarettes.

Adolescent↗

Effect of a moderate fish intake on platelet aggregation in human platelet-rich plasma.

This paper describes the results of an international study to investigate the effect of a reasonable amount of dietary fish on platelet aggregation in platelet-rich plasma (PRP) induced by collagen and thrombin. In Maastricht, Tromsø, and Zeist two groups of healthy male volunteers were given a daily dietary supplement consisting of 135 g of canned mackerel paste (experimental group, n = 40) or meat paste (control group, n = 42) for a 6-week period. Compliance, calculated on the basis of the urinary excretion of lithium, added to the supplements, was about 80%. Platelet number in PRP decreased significantly in the fish group. Collagen-induced platelet aggregation in PRP differed widely between the three centres despite the attempt to use exactly the same conditions. Nonetheless, aggregation decreased significantly in the fish group. The mackerel effect on thrombin-induced aggregation was inconsistent.

Adolescent↗

Purification and characterization of a novel protein from bovine aorta that inhibits coagulation. Inhibition of the phospholipid-dependent factor-Xa-catalyzed prothrombin activation, through a high-affinity binding of the anticoagulant to the phospholipids.

A novel inhibitor of blood coagulation has been isolated from the intima of bovine aorta. The inhibitor, vascular anticoagulant (VAC), has been purified to an active fraction that contains two Coomassie-blue-staining bands (Mr = 34,000 and Mr = 32,000, as judged by sodium dodecyl sulfate/polyacrylamide electrophoresis). Both bands are single-chain proteins, having no glycoprotein features. Furthermore, they do not contain any detectable 4-carboxyglutamic acid residues. Both proteins have an identical isoelectric pH of approximately 4.5. VAC binds in the presence of calcium ions to a bilayer consisting of 20% dioleoylglycerophosphoserine and 80% dioleoylglycerophosphocholine with a Kd = 6 nM. The binding is dependent on the calcium concentration: half-saturation of binding occurs at a calcium concentration of 0.8 mM. The binding is completely reversible with EDTA. Furthermore the phospholipid/VAC ratio at saturation was n = 112 and n = 32 mol/mol for 0.5 mM Ca2+ and 2 mM Ca2+, respectively. Binding does not occur between VAC and pure dioleoylglycerophosphocholine. In a system with purified coagulation factors VAC inhibits the activation of prothrombin by factor Xa and calcium only in the presence of negatively charged phospholipids. VAC decreases the Vmax and increases the Km of the factor-Xa-catalyzed prothrombin activation. Based on these results, we conclude that we have purified from bovine aortic intima an anticoagulant protein, which exerts its activity through a calcium-dependent binding to negatively charged phospholipids, and thus interferes with the assembly of prothrombinase on the phospholipid surface.

Animals↗

Effects of dietary palm oil on arterial thrombosis, platelet responses and platelet membrane fluidity in rats.

Wistar rats were fed a control diet containing 5 energy % (en %) sunflowerseed oil or diets containing 50 en % of either palm oil, rich in saturated fatty acids, or sunflowerseed oil, high in linoleic acid, for at least eight weeks. Arterial thrombosis tendency, measured by the aorta loop technique, tended to be lowered by the palm oil diet and was lowered significantly by the sunflowerseed oil diet, compared with the control. Aggregation of platelets in whole blood activated with collagen was not altered by palm oil feeding, but was enhanced in the sunflowerseed oil group, compared with the control. The concomitant formation of thromboxane A2 was decreased by palm oil feeding, although formation of prostacyclin did not change; the ratio of thromboxane/prostacyclin formed was decreased significantly in the palm oil group. Compared with the control diet, platelet membrane fluidity, measured by fluorescence polarization, was not altered in the palm oil group and was significantly increased only by sunflowerseed-oil feeding. Thus, although palm oil contains about 50% saturated fatty acids, it did not increase arterial thrombosis tendency and tended to decrease platelet aggregation, as compared with highly polyunsaturated sunflowerseed oil.

Animals↗

Effect of a moderate fish intake on blood pressure, bleeding time, hematology, and clinical chemistry in healthy males.

This paper describes the outline and first results of an international study to investigate the effect of a reasonable amount of dietary fish on some aspects of cardiovascular risk. In Maastricht and Zeist, The Netherlands, and Tromsø, Norway, healthy male volunteers were given a dietary supplement consisting of 100 g/d of mackerel or meat for a 6-wk period. Compliance was monitored on the basis of the urinary excretion of lithium, which was added to the supplements. Average compliance was approximately 80% and this decreased slightly in time. Systolic blood pressure decreased in both groups to a comparable degree; consequently no specific effect of the fish supplement was observed. The fish supplement significantly prolonged bleeding times. Hematology was hardly affected but platelet counts decreased significantly. No indications were obtained for adverse effects of the fish supplement.

Adult↗

Effects of dietary sunflowerseed oil and marine oil on platelet membrane fluidity, arterial thrombosis, and platelet responses in rats.

The relationships among platelet membrane fluidity, arterial thrombosis tendency, and platelet aggregation and prostanoid formation were investigated after feeding rats diets enriched in (n-6) or (n-3) polyunsaturated fatty acids. For at least 8 weeks, rats were fed a control diet containing 5 energy % (en%) sunflowerseed oil, a diet high in sunflowerseed oil (50 en%) which contains large amounts of 18:2(n-6), or a diet high in marine oil (5 en% sunflowerseed oil plus 45 en% sperm-whale oil) which contains considerable amounts of 20:5(n-3) and its desaturation and elongation products. Compared with the control diet, platelet membrane fluidity, measured by fluorescence polarization using platelets labelled with 1,6-diphenyl-1,3,5-hexatriene, was significantly increased upon feeding of the sunflowerseed-oil diet or the marine-oil diet. Both of these diets lowered arterial thrombosis tendency, measured by Hornstra's loop technique. Aggregation of platelets in whole blood activated with collagen tended to be higher upon sunflowerseed-oil feeding and lower in the marine-oil group. The concomitant formation of thromboxane A2 was not altered in the sunflowerseed-oil group, but was significantly reduced upon feeding the marine-oil diet. The results indicate that an increase in platelet membrane fluidity may be associated with a reduction in arterial thrombosis tendency. With the techniques used, no direct relationship could be observed among platelet membrane fluidity, platelet aggregation and platelet prostanoid production.

Animals↗

Aspirin and the prevention of experimental arterial thrombosis: difficulty in establishing unequivocal effectiveness.

A trial of the efficacy of aspirin in the prevention of thrombotic occlusion of an "aortic loop" in rats was made simultaneously by two experimental surgeons. A relatively large dose of aspirin (80-100 mg/kg/day) was used, starting two days before operation. It appeared that aspirin was of limited benefit, reducing thrombotic occlusions by about 17% seven days after the insertion of the loop into the abdominal aorta. Although the average occlusion time was prolonged by about 17% in aspirin-treated animals, the separate trials gave no conclusive result. When the data from both operators were pooled, a statistically significant protection by aspirin was apparent (p = 0.02), by a two-tailed Student's t test. However, on using the powerful non-parametric randomization test, the occlusion times in control and aspirin-treated groups appeared not statistically different (p = 0.07). No significant difference was also found between control and treated groups when data were analyzed by X2 test. Independently of the statistical analysis, these data are quite similar to those obtained from aspirin trials in men surviving myocardial infarction. This finding points to the usefulness of the aorta loop as an animal model for arterial thrombosis.

Animals↗