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Biomedical subjects

G Hornstra

Publications and source records attributed to G Hornstra.

At least 127 records · Page 7Linked to original sources
PubMed1991

Dietary fat modifies thromboxane A2-induced stimulation of rat platelets.

Diets containing high levels of monounsaturated, n-6 polyunsaturated and n-3 polyunsaturated fatty acids were fed to Wistar rats. This resulted in decreases in the arachidonate content in platelet phospholipids to 91%, 79% and 51% respectively of the level found after feeding a diet rich in saturated fatty acids. In the presence of CaCl2, collagen- and thrombin-induced aggregation of washed platelets from the saturated-fat dietary group (with highest level of arachidonate) was low compared with that of platelets from the other dietary groups, despite a relatively high production of thromboxane B2. On the other hand, n-3 polyunsaturated fatty acids in the diet resulted in platelets aggregating actively, but producing low levels of levels of thromboxane B2. When indomethacin-treated rat platelets were activated with the thromboxane A2 analogue U46619, the presence of a second agonist such as collagen. ADP or thrombin was necessary for aggregate formation. U46619-induced aggregation in combination with either co-activator was relatively low in arachidonate-rich platelets, and was higher in platelets with a low arachidonate content. Similarly, phospholipase C-catalysed formation of L-myo-inositol phosphates was higher in platelets with a low arachidonate content. We conclude that the ability of platelets to react with thromboxane A2 is modified by diet in such a way that a decreased substrate-limited generation of thromboxane A2 is compensated for by an increased response to thromboxane, and vice versa. No significant differences were detected in the binding of U46619 or SQ29548 to platelets from the various dietary groups. Therefore the changed response seems not to be caused by modified properties of the thromboxane A2/prostaglandin H2 receptors, but by altered transduction of the thromboxane signal.

Animals↗
PubMed1991

Blood pressure during pregnancy in Canadian Inuit: community differences related to diet.

OBJECTIVE: To assess a possible relation between the incidence of hypertension during pregnancy and the consumption of fatty acids found in fish and sea mammals. DESIGN: Retrospective survey of pregnancy-induced hypertension; prospective diet survey. SETTING: Inuit women from seven communities in the Keewatin region of the Northwest Territories. PATIENTS: All women from Arviat (formerly Eskimo Point), Baker Lake, Chesterfield Inlet, Coral Harbour, Repulse Bay, Sanikiluaq and Whale Cove who gave birth between Sept. 1, 1984, and Aug. 31, 1987. MAIN OUTCOME MEASURES: All blood pressure measurements recorded during the pregnancy, incidence of pregnancy-induced hypertension in the seven communities, harvest of country food (food obtained from the land or sea rather than bought in a store) for six of the communities, self-reported consumption of fish, sea mammals and terrestrial mammals by a subgroup of the subjects and levels of phospholipid fatty acids in cord serum samples from a subgroup of the infants. MAIN RESULTS: Significantly lower mean diastolic blood pressure values during the last 6 hours of pregnancy were noted for the women from the three communities with a higher consumption of fish and sea mammals (78.2 [95% confidence limits (CL) 76.6 and 79.9] mm Hg) than for those from the four communities with a lower consumption of such food (81.5 [95% CL 80.1 and 82.9] mm Hg) (p less than 0.005). The relation between community diet type and blood pressure was independent of other factors. Correspondingly, the women from communities with a lower consumption of marine food were 2.6 times more likely to be hypertensive during the pregnancy than those from communities with a higher consumption of marine food (p less than 0.007). Parity (p less than 0.05) and prepregnancy weight (p less than 0.005) were also significantly associated with pregnancy-induced hypertension; however, the relation between hypertension and community diet type remained significant in logistic regression analysis (odds ratio 2.56, p = 0.03). The differences between the community groups were substantiated by the results of the diet survey, the levels of eicosapentaenoic acid (EPA) in the cord serum phospholipids and the harvest data. CONCLUSIONS: Increased consumption of fish may be beneficial for women at risk for hypertension during pregnancy. A prospective randomized trial of fish or EPA supplementation during pregnancy is warranted.

Animals↗
PubMed1991

Rat platelets are deficient in internal Ca2+ release and require influx of extracellular Ca2+ for activation.

Calcium fluxes were studied in fura-2-labeled rat platelets. Thrombin, ADP and ionomycin induced rapid mobilization of internally stored Ca2+, which resulted in only a moderate increase of cytosolic [Ca2+]i. Thrombin and ADP stimulated influx of extracellular Ca2+, which was monitored as uptake of 45Ca2+ and of Mn2+. With either agonist, the influx of Ca2+ magnified the initial increase of [Ca2+]i. Since responses of rat platelets were dependent on external [Ca2+], we conclude that Ca2+ influx complements the mobilization of internal stores to reach sufficiently high [Ca2+]i for full activation. A regulatory effect of protein kinase C modulators was observed on both agonist-induced elevation of [Ca2+]i and receptor-mediated Ca2+ entry.

Adenosine Diphosphate↗
PubMed1991

Membrane fatty acid composition and endothelial cell functional properties.

In order to study the influence of endothelial cell fatty acid composition on various membrane related parameters, several in vitro methods were developed for manipulating the fatty acid content of human endothelial cell membranes. Changes in membrane fatty acid profile were induced by using fatty acid modified lipoproteins or free fatty acids. The largest changes in endothelial fatty acid composition were obtained by culturing the cells in media supplemented with specific free fatty acids. An increase in arachidonic acid content of endothelial phospholipids was induced by supplementation with saturated fatty acids or with arachidonic acid itself. A decrease in arachidonic acid content was obtained by supplementation with other unsaturated fatty acids. Under the experimental conditions used endothelial cells showed a low desaturase activity and a high elongase activity. Considerable alterations in membrane fatty acid composition did not greatly influence certain membrane related parameters such as polymorphonuclear leukocyte adherence and endothelial cell procoagulant activity. In general, for fatty acid modified endothelial cells an association between endogenous arachidonic acid content and total production of eicosanoids was found. This study demonstrates that considerable changes in membrane fatty acid profile affect endothelial cell arachidonic acid metabolism, but it also illustrates homeostasis at the level of endothelial cell functional activity.

Blood Coagulation Factors↗
PubMed1991

Fatty acid composition of serum lipids of mothers and their babies after normal and hypertensive pregnancies.

The biochemical essential fatty acid (EFA) status of neonates born after normal and hypertensive pregnancies (PIH) and that of their mothers was assessed by measuring the fatty acid composition of phospholipids (PL), triglycerides (TG) and cholesterol esters (CE) of umbilical cord serum and maternal serum, respectively. Relative contents of linoleic acid of serum PL and CE were significantly lower in mothers with PIH compared to normal pregnancies. Most other (n-6) polyenes in PL tended to be higher under hypertensive conditions. Total maternal (n-3) polyenes of serum PL were significantly higher in PIH, mainly due to clupanodonic acid, 22:5 (n-3), and cervonic acid, 22:6 (n-3). Total maternal (n-7) and (n-9) fatty acids were also significantly higher in PIH (PL and CE). The results indicate that PIH is associated with a relative increased unsaturation of maternal serum PL, which might facilitate the placental transfer of long-chain, polyunsaturated fatty acids. As a result, the neonatal EFA status after PIH only slightly differs from normal.

Cholesterol Esters↗
PubMed1991

Dietary omega 3 fatty acids and gestational hypertension in the Inuit.

Blood pressure at the end of pregnancy and the incidence of pregnancy-induced hypertension were monitored in Inuit communities in the Keewatin region of the Northwest Territories. Communities with more fish and sea mammals in their diet had a lower blood pressure at the end of pregnancy and a lower incidence of gestational hypertension. The lower incidence of gestational hypertension was independent of other variables, including pregravida weight and parity. Cord blood phospholipid fatty acid analysis confirmed higher levels of eicosapentanoic acid, a fatty acid enriched in fish and sea mammals, in infants born to mothers from communities with higher fish in their diets.

Animals↗
PubMed1991

Dietary fish and prostanoid formation in man.

Dietary mackerel causes the increase of timnodonic acid (eicosapentaenoic acid) in all platelet phospholipid classes, at the expense of arachidonic acid. Because of these fatty acid changes, the potency of platelets to produce cyclo oxygenase products from the 2-series is greatly reduced. However, upon mild platelet triggering, changes in TxB2 formation are hardly significant, strongly depend on dietary compliance and require a high fish intake. The reduced formation of 2-series prostanoids is only partly compensated for by the increased formation of timnodonic acid-derived products. Urinary PGI metabolites suggest that dietary fish is associated with the enhanced turnover of PGI3 without a concomitant reduction in PGI2 formation. Since the site of PGI formation is not known, and an effect of dietary fish on the prostanoid metabolic routes cannot be excluded, the physiological relevance of these results is uncertain.

Arachidonic Acid↗
PubMed1990

Membrane fluidity of non-activated and activated human blood platelets.

The steady-state fluorescence anisotropy of membranes labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH) or its 4'-trimethylammonio derivative, TMA-DPH, is generally considered a measure for the lipid order and, hence, inversely related to membrane fluidity. We now report that anisotropy values of DPH- and TMA-DPH-labeled human platelets are considerably influenced by experimental conditions like the platelet concentration, which do not affect membrane fluidity. Activation of platelets with thrombin increases, but activation with ionomycin decreases anisotropy values with both labels. Such anisotropy changes are not detected in platelet membranes or platelet lipids, when isolated after activation of the intact platelets. We present evidence that the anisotropy changes of intact platelets are not a consequence of modified lipid composition (e.g., as would be induced by phospholipase A2 activity) but are, at least partially, caused by changed optical properties of the cell suspension. Measurement of membrane fluidity of platelets by fluorescence polarization is severely hindered by a high turbidity of the platelet suspension and also by changes in the turbidity and platelet morphology during the activation process.

Blood Platelets↗
PubMed1990

Biochemical EFA status of mothers and their neonates after normal pregnancy.

The essential fatty acid (EFA) status of neonates was compared with that of their mothers by determining the fatty acid compositions of phospholipids (PL), isolated from umbilical arterial and venous tissue, blood cells (BC) and plasma, from maternal venous plasma and BC, and from non-infarcted placental tissue. The PL of umbilical arterial tissue (efferent fetal vessels) contained fewer fatty acids of the (n-6) family and more of the (n-9) family than umbilical venous tissue (afferent fetal vessel). The relative amounts of (n-6) and (n-3) fatty acids were less in arterial than in venous plasma. Mead acid, 20:3(n-9), the presence of which indicates a poor EFA status, was 5 times higher in the efferent than in afferent cord vessels. In neonatal plasma and BC it was twice as high as compared with maternal levels. In general, the fatty acid composition of the placenta PL showed a comparable pattern as neonatal venous plasma PL. These findings demonstrate that the biochemical EFA status of neonates after a normal pregnancy is not optimal. The significant correlations between neonatal and maternal EFAs indicate that the neonatal EFA status depends on the EFA content of the maternal diet.

8,11,14-Eicosatrienoic Acid↗
PubMed1990

Dietary-fish effects on serum lipids and apolipoproteins, a controlled study.

In Maastricht and Zeist, The Netherlands, and Tromsø, Norway, a well-controlled study was performed on the effect of a fish-enriched diet on serum lipids, apolipoproteins A-1 and B, and fatty acid compositions of serum triglycerides and cholesterol esters. For 6 wk healthy male volunteers were given a daily dietary supplement consisting of 135 g mackerel paste (experimental group, n = 42) or meat paste (control group, n = 42). Dietary adherence was calculated on the basis of urinary excretion of a standard amount of lithium added to the supplements. Average compliance was 80%. Low-density-lipoprotein (LDL) and total serum cholesterol concentrations were unaffected. High-density-lipoprotein (HDL) cholesterol increased to a comparable degree in both groups. Triglyceride content of serum decreased in the fish group. Apolipoproteins A-1 and B (both in Maastricht subjects only) were only slightly affected. In the mackerel group the n-3 fatty acids increased significantly in serum cholesterol esters and triglycerides; the n-6 fatty acids decreased in cholesterol esters only.

Adult↗
PubMed1990

Platelet aggregability in humans: contrasting in vivo and in vitro findings during sympatho-adrenal activation and relationship to serum lipids.

Platelet aggregability was studied in 18 healthy volunteers during mental stress (a colour word test; CWT) and low- and high-dose adrenaline infusions using an ex vivo technique (filtragometry) and conventional in vitro aggregometry. CWT and high-dose adrenaline (3.4 nmol l-1 in plasma) shortened filtragometry readings, suggesting increased platelet aggregability in vivo. Low-dose adrenaline had no effect despite higher adrenaline levels in plasma (0.9 nmol l-1) than during CWT (0.4 nmol l-1). Platelet sensitivity to ADP in vitro was reduced following CWT and further reduced following adrenaline infusions. In vitro, adrenaline (50 nmol l-1) had little effect on platelet aggregation per se, but enhanced aggregability evoked by ADP (at ED50). Adrenaline potentiation of ADP-induced aggregation was enhanced after CWT, but was not related to filtragometry responsiveness to stress in vivo. Serum LDL-cholesterol levels were inversely correlated to filtragometry readings at rest, suggesting an adverse influence on platelet aggregability in vivo. HDL-cholesterol levels were inversely correlated to platelet sensitivity to ADP in vitro, suggesting a positive influence. Thus, sympatho-adrenal activation enhances platelet aggregability in vivo (as assessed by ex vivo filtragometry), but adrenaline alone cannot explain the pro-aggregatory effect of mental stress. Serum lipoprotein alterations associated with increased risk for atherosclerosis seem to enhance platelet aggregability. The conventional in vitro technique may poorly reflect platelet aggregability in vivo.

Adult↗
PubMed1989

Influence of dietary fatty acids on membrane fluidity and activation of rat platelets.

The apparent steady-state fluorescence anisotropy of DPH- or TMA-DPH-labeled washed rat platelets is strongly affected by factors that also influence the turbidity by these platelet suspensions. Sonicated preparations from platelet lipids have a low turbidity and give anisotropy values which are hardly affected by the experimental conditions. We studied the effect of four high-fat diets on membrane fluidity, lipid composition and activation tendency of washed platelets. The diets contained 50 energy% of oils with different levels of saturated and (poly)unsaturated fatty acids. Only small diet-induced differences in DPH fluorescence anisotropy were found, which were comparable for intact platelets and platelet lipids. These differences were unrelated to the degree of saturation of the dietary fatty acids. Platelets from rats fed mainly saturated fatty acids differed significantly from other diet groups in a higher unsaturation degree of phospholipids and a lower cholesterol/phospholipid ratio, but this was not detected by DPH in terms of decreased anisotropy. These platelets aggregated less than other platelets in response to thrombin or collagen. The lower response to collagen persisted in indomethacin-treated platelets activated with the thromboxane A2 mimetic U46619, indicating a different sensitivity of these platelets for thromboxane A2. We conclude that in rat platelets: (a) the overall membrane fluidity and phospholipid unsaturation degree are subject to strong homeostatic control; (b) steady-state anisotropy with DPH or TMA-DPH label is inadequate to reveal subtile changes in lipid profile; (c) changes in platelet responsiveness to thrombin and thromboxane A2, rather than (plasma) membrane fluidity, determine the effect of dietary fatty acids on platelet aggregation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Effect of a moderate fish intake on haemostatic parameters in healthy males.

This article describes the results of a dietary intervention study performed in three different centers. In the study the effect of a diet enriched with fish on the coagulation tendency of blood was investigated. Two groups of 40 volunteers were given a dietary supplement consisting of 135 g of canned mackerel or meat paste (control) for a 6 weeks period. Compliance, monitored by measuring the urinary excretion of lithium, added to the supplements, was about 80%. Before, during and at the end of the experimental period a number of hemostatic parameters, reflecting the coagulation tendency of blood and the procoagulant activity of monocytes, were measured. The fish supplement did not cause a significant effect on the prothrombin time and on the levels of factor VII, activated factor VII, antithrombin III, von Willebrand factor, fibrinogen, plasminogen and alpha 2-antiplasmin. A slight but transient prolongation in the activated partial thromboplastin time was observed as well as a significant increase in the factor X level, which became more pronounced with prolongation of the experimental period; no activated factor X was found. A tendency towards a stimulation of monocyte procoagulant activity was noticed.

Adult↗
PubMed1989

Dietary lipids, platelet function and arterial thrombosis.

In rats, diets rich in polyunsaturated fatty acids of the (n-6) and (n-3) families (P) lower arterial thrombosis tendency, whereas long-chain saturated fatty acids (S) are prothrombotic. Monounsaturated fatty acids seem to behave neutrally as to 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 dietary fat type also affects platelet aggregation. Methodological problems, however, resulted in equivocal results, especially with respect to diets enriched with fish oil. Thus, more research is required with methods that are able to quantify thrombotic risk in a reliable way. Nonetheless, the available evidence already justifies an active policy to increase the consumption of (poly)unsaturated fatty acids at the expense of long-chain saturated fatty acids.

Animals↗
PubMed1989

Normalization by dietary cod-liver oil of reduced thrombogenesis in essential fatty acid deficient rats.

Rats, deficient in essential fatty acids (EFA), were given diets containing 5 energy% sunflowerseed oil (SO, rich in linoleic acid), cod-liver oil (CLO, rich in timnodonic acid and cervonic acid), or hydrogenated coconut oil (HCO), containing no EFAs at all. SO and CLO feeding resulted in normalization of the reduced arterial thrombus formation in EFA-deficient animals. SO feeding was associated with the normalization of the arachidonic acid content of platelet phospholipids. CLO feeding did not have this effect but greatly increased the availability of timnodonic acid (EPA) and cervonic acid (DHA). Further research is required to investigate whether these changes in fatty acid composition can be hold responsible for the normalizing effect of dietary CLO on the disturbed arterial thrombosis tendency in EFA deficient rats, possibly via the formation of eicosanoids.

Animals↗
PubMed1989

Fatty acid composition of umbilical arteries and veins: possible implications for the fetal EFA-status.

Fatty acid compositions were determined of phospholipids, isolated from umbilical arteries and veins, obtained from Dutch neonates after vaginal delivery, terminating normal pregnancy. The fatty acid profiles of the cord vessels were characterized by the absence of eicosapentaenoic (timnodonic) acid, a low (2-3%) content of linoleic acid and reasonable amounts of arachidonic acid (10-15%) and docosahexaenoic (cervonic) acid (3-5%). Significant amounts of Mead acid (1-4%) and its direct elongation product (0.5-2%) were also observed. In each cord, the efferent blood vessels contained significantly more Mead acid and other fatty acids of the oleic acid (n-9) family and less fatty acids of the linoleic (n-6) and linolenic (n-3) families than the afferent blood vessel. This indicates that the essential fatty acid (EFA) status of 'downstream' neonatal tissue may be marginal. No signs of EFA-deficiency were observed in endothelial and smooth muscle cells in culture, or in blood vessels from adults. In all cords 22:5(n-6) was significantly higher in the artery compared to the vein, whereas for all other (n-6) fatty acids this difference was negative. Since the synthesis of 22:5(n-6) is known to be stimulated when the required amount of cervonic acid, 22:6(n-3), is too low, our observations also suggest that the cervonic acid status of the neonates investigated was not optimal. Further studies are in progress to relate these findings to maternal EFA status and complications of pregnancy.

Adult↗