Biomedical subjects
Publications and source records attributed to G Hornstra.
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Earlier studies have shown that not all saturated fatty acids are equally hypercholesterolaemic: stearic acid (C18:0) and saturated fatty acids with less than 12 carbon atoms are thought not to raise serum cholesterol levels. This suggests that the cholesterol-raising effects of saturated fatty acids can be attributed to lauric acid (C12:0), myristic acid (C14:0) and palmitic acid (C16:0). These three saturated fatty acids also have different effects on serum total cholesterol levels. Results from recent controlled dietary experiments suggest that lauric acid raises serum total and low-density lipoprotein (LDL) cholesterol levels slightly less, and myristic acid more, as compared with palmitic acid. Myristic acid, however, also causes higher levels of high-density lipoprotein (HDL) cholesterol. Stearic acid has only a slight effect on serum LDL and HDL cholesterol levels as compared with oleic acid. Trans monounsaturated fatty acids, however, increase LDL and decrease HDL cholesterol levels. Precise effects on lipoproteins of short and medium chain triglycerides (C4:0-C10:0) have never been examined.
Eleven men received a fish oil (2.4 g n-3 fatty acids), fish oil plus vitamin E (300 IU) or no supplement for 3 weeks. Dietary fish oil increased the maximum amount of conjugated dienes formed during copper-catalysed oxidation of LDL in vitro by 18-20%. Fish oil also tended to decrease the lagtime before onset of oxidation, but this effect was counteracted by vitamin E. We conclude that fish oil supplementation increases the oxidizability of LDL in vitro, and vitamin E increases its oxidation resistance.
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A highly sensitive and rapid high-performance liquid chromatographic assay for the determination of histamine and 3-methylhistamine in biological samples using 1-methylhistamine as the internal standard is described. Samples were purified and concentrated on cation-exchange columns and derivatized with fluorescamine. The lower detection limit was 20 pg on-column. Linearity was demonstrated up to 20 ng on-column. The samples could be derivatized simultaneously before injection and were stable for 7 days. The method was used for the determination of histamine and related compounds in coronary perfusates, extracts of homogenized rat hearts, and supernatants of stimulated peritoneal mast cells.
To study the influence of membrane fatty acid composition on the formation of prostanoids and hydroxy fatty acids by rat peritoneal mast cells (MC), animals were fed three different types of fatty acids: mackerel oil (MO), abundant in n-3 fatty acids; sunflower seed oil (SO), rich in linoleic acid; and hydrogenated coconut oil (HCO), mainly containing saturated fatty acids. The presence of n-3 fatty acids in the diet resulted in the incorporation of 20:5(n-3), 22:5(n-3) and 22:6(n-3) in MC phospholipids. A decrease of arachidonic acid, 20:4(n-6), was observed in MC-phospholipids of the MO-fed animals. Furthermore, increasing the relative amounts of 18:2(n-6) in the diet (SO group) led to an increased incorporation of linoleic acid, 18:2(n-6) in MC phospholipids when compared to both other dietary groups. The changes in MC phospholipid fatty acid composition were (partly) reflected in the formation of prostanoids and hydroxy fatty acids upon stimulation with the calcium ionophore A23187. The decrease in arachidonic acid content in MC phospholipids of MO-fed rats resulted in a decreased formation of PGD2 when compared to both other groups. Also, the increased amounts of 18:2(n-6) in MC phospholipids of SO-fed rats resulted in an increased formation of 9- and 13-HODE upon stimulation. The results show that modifications in the fatty acid composition of the diet influences MC membrane fatty acid composition which ultimately results in changes in prostanoid and hydroxy fatty acid synthesis by MC upon stimulation with the calcium ionophore A23187.
A method is described for the direct and continuous monitoring of lipid peroxidation in an aqueous suspension of sonicated liposomes. By means of ultraviolet difference spectroscopy using tandem cuvettes, the formation of conjugated dienes during liposome peroxidation can be followed. Using this technique, the effect of the fatty acid composition of liposomes on lipid peroxidation can be studied. The results show that both the extent and the time scale of lipid peroxidation are influenced by the fatty acid composition of the phospholipid liposomes. This was confirmed also by other methods, such as measurement of the formation of lipid hydroperoxides and measurement of the decrease in polyunsaturated fatty acids. The advantage of the method described is the direct and continuous monitoring of phospholipid peroxidation in an aqueous environment, without subsampling and extraction of peroxidation products into organic solvents. Using this experimental approach based on difference spectra the contributions from changes in liposome, CuSO4 and H2O2 concentrations are canceled, thus improving sensitivity. The method can be employed for measuring the susceptibility to peroxidation of membrane phospholipids from fatty acid modified endothelial cells.
In the present study the effect of replacement of dietary fat by palm oil in the normal Western diet on the in vitro release of the inflammatory cytokines tumour necrosis factor (TNF), interleukin (IL)-6 and IL-8 was examined. A maximal replacement of 700 g/kg dietary fat was achieved for thirty-eight male volunteers who consumed either a palm-oil diet or a control diet in a double-blind, cross-over study with 6-week experimental periods, and 3-week run-in and wash-out periods. At the end of both experimental periods, whole blood was stimulated in vitro with 0.02 (sub-optimal), or 10 ng lipopolysaccharide (LPS)/ml (maximal), whereafter TNF, IL-6, and IL-8 concentrations in the culture supernatant fraction were measured using specific enzyme-linked immunosorbent assays (ELISA). Mean cytokine production with sub-optimal, or maximal LPS stimulation of peripheral whole blood was similar for both the palm oil, and the control group. The relative TNF response, however, was reduced by replacement of dietary fat with palm oil. Separate analysis of the data from the first and second experimental periods strongly suggested that the residual effect of the palm-oil diet on the relative TNF response was longer than 9 weeks. Cytokine homeostasis determines the course of the inflammatory response and the progression of atherosclerosis. The effect of palm-oil consumption on the proneness of the peripheral blood cells to produce TNF may, therefore, alter the prevalence of these common diseases.
Human umbilical vein endothelial cells were cultured in various fatty acid-modified media until equilibrium conditions were reached (7-8 days). The effects on the fatty acid composition of phospholipid classes and on the metabolism of arachidonic acid (20:4(n-6)) were studied. The results showed that in every phospholipid class large changes in fatty acid composition, including 20:4(n-6) content, were induced by long-term modification with unsaturated as well as saturated fatty acids. However, the mean levels of saturated and unsaturated fatty acids per phospholipid class remained relatively constant, except for cells modified with oleic acid, which showed an increase in monounsaturated fatty acids at the expense of both saturated and polyunsaturated fatty acids. The rate of incorporation of radiolabeled 20:4(n-6) in endothelial lipids was not influenced by long-term fatty acid modification. Cells modified with 20:4(n-6) (having a high 20:4(n-6) content) tended to "store" excess 20:4(n-6) as the elongated product 22:4(n-6) mainly in phosphatidylserine and ethanolamine phospholipids. On the other hand, endothelial cells modified with 20:5(n-3) (having a low 20:4(n-6) content) differed typically from other fatty acid-modified cells by a relatively high level and high incorporation rate of 20:4(n-6) in phosphatidylinositol, with a low extent of elongation. These results indicate extensive homeostatic control of membrane unsaturation in each phospholipid class and economical control of 20:4(n-6) content in all modified endothelial cells, irrespective of a considerable variation of 20:4(n-6) levels in cellular lipids. Moreover, the observed maintenance of a critical level of 20:4(n-6) in phosphatidylinositol, when 20:4(n-6) supply was strongly decreased, may be important for maintaining proper signal transduction upon endothelial cell stimulation.
This paper describes a controlled study of the effects of a fish supplement on haemostasis. This was evaluated by measuring bleeding times from skin incisions, the volume of the emerging blood, the number of platelets taking part in the formation of the haemostatic plug (platelet retention), and the release of thromboxane B2 and beta-thromboglobulin in volunteers, before and after consuming a daily supplement of 100 g of fish (n = 20) or meat (n = 20) paste for 6 weeks. The fish supplement decreased the amount of thromboxane B2 released per platelet incorporated into the plug. Despite this, the skin bleeding times were hardly changed. There was also no difference in platelet retention, which was consistent with there being no difference in the release of beta-thromboglobulin. These results suggest that in the effect of marine diets on haemostasis, a reduced vascular reactivity plays a more important role than decreased plug formation.
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Preliminary studies indicated that the EFA status of normal neonates is marginal, if not insufficient. Since a better knowledge of the physiology of maternal-fetal essential fatty acid transfer is relevant for nutritional recommendations during pregnancy, we investigated the course of the fetal EFA status during fetal development by analysing the absolute (micrograms/g dry fetal tissue) and relative (% of total fatty acids) fatty acid composition of phospholipids in human fetal tissue, (n = 40, gestational age 5-15.2 weeks). The total content of fatty acids (mg/g dry fetal tissue) increased with gestational age. The absolute amount of virtually all fatty acids increased with maturation. Linoleic acid (18:2n-6, LA), however, was an exception. A highly significant, negative correlation between gestational age and the relative amount of LA in fetal tissue was observed during this first trimester of pregnancy. Our results show that the fetal-maternal difference in linoleic acid content observed at birth, initiates early in pregnancy. Since the fetus completely depends on the mother for its EFA supply, the maternal EFA status was measured simultaneously by analysing the fatty acid composition of phospholipids, isolated from plasma and red blood cells. Significant positive correlations between maternal rbc and fetal tissue were found for the relative amounts of LA. Similar relationships were observed between maternal plasma and fetal tissue for the relative amounts of cervonic acid (22:6n-3), the most abundant essential fatty acid in brain and retina. The relation between maternal and fetal EFA in phospholipids is significantly more pronounced after 10 weeks of gestation than before. This might be connected with the increased importance of the placenta with respect to maternal-fetal fatty acid transfer after 10 weeks of gestation.
Fatty acid compositions were determined of phospholipids isolated from venous cord plasma and from the walls of umbilical arteries and veins, collected from healthy, a terme, Inuit and Caucasian (Dutch) neonates. The Inuit fatty acid profiles were characterized by a lower essential fatty acid (EFA) status, with higher levels of monounsaturated fatty acids, of Mead acid [20:3(n-9)] and its direct elongation product, and with lower amounts of the longer chain (greater than or equal to 20 carbon atoms), highly unsaturated (greater than or equal to 4 double bonds) fatty acids of both the (n-3) and (n-6) families. Levels of linoleic- and dihomo-gamma-linolenic acids were higher in Inuit as compared to Caucasian neonates, which suggests a low activity of the delta-5-desaturase in the Inuit. Within the Inuit group, a higher intake of marine food was associated with a better neonatal (n-3) status. Although the differences between Inuit and Caucasian neonates may be of genetic rather than of dietary origin, the results imply that dietary long-chain (n-3) or (n-6) fatty acids may be particularly important during pregnancy in Inuit mothers. Further studies are indicated with respect to the EFA content of the habitual Inuit diet and levels of delta-5-desaturase activity in the Inuit.
Thirty-eight male volunteers participated in a double-blind cross-over trial evaluating the effect of replacing the usual sources of saturated fat in the Dutch diet (animal fats and hydrogenated oils) by palm oil, which is virtually free of cholesterol and trans-fatty acids, on serum lipids, lipoproteins and apolipoproteins. Maximum (about 70%) replacement had no significant effect on serum total cholesterol or most lipoprotein fractions, but resulted in an 11% increase in serum high-density-lipoprotein (HDL)2-cholesterol relative to the control (P2 = 0.01). The palm-oil diet also caused an 8% decrease in low-density-lipoprotein (LDL):HDL2 + HDL3-cholesterol ratio (P2 = 0.02) as well as a 9% decrease in triacylglycerols in the low-density-lipoprotein fractions (P2 = 0.01). Palm oil consumption resulted in a 4% increase in serum apolipoprotein AI (P2 = 0.008) and a 4% decrease in apolipoprotein B (P2 = 0.01) relative to the control diet; the B:AI apolipoprotein ratio was decreased by 8% (P2 < 0.0001). These results were not significantly affected by the different lipoprotein E phenotypes of the volunteers. Although the observed differences were relatively modest, the present study, nonetheless, indicates that dietary palm oil, when replacing a major part of the normal fat content in a Dutch diet, may slightly reduce the lipoprotein- and apolipoprotein-associated cardiovascular risk profiles.
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The effect of dietary manipulation on eicosanoid formation in rat peritoneal macrophages was studied in relation to some of their effector functions: cellular procoagulant activity, production of reactive oxygen species (measured as chemiluminescence), and phagocytosis of antibody-coated erythrocytes. Rats were fed adequate diets for eight weeks containing mackerel oil (MO), sunflowerseed oil (SO) or hydrogenated coconut oil (HCO). The release of eicosanoids from resident macrophages stimulated by opsonized zymosan was significantly lower for the MO group as compared to the other dietary groups. Infection of the animals via intraperitoneal injection with rat cytomegalovirus resulted in a significant decrease in eicosanoid production in all groups, irrespective of dietary fat type. However, in the HCO group a partial restoration of TXB2 and HHT production could be observed at day 10 post infection. Resident macrophages obtained from the mackerel oil fed animals showed a significantly higher procoagulant activity than those from the other diet groups. Infection of the animals resulted in an increase in procoagulant activity in all groups. In contrast, no significant differences in chemiluminescence and in phagocytosis were detected between macrophages obtained from rats fed the different diet groups. It is concluded that peritoneal macrophages obtained from mackerel oil fed rats produce less eicosanoids and are more procoagulant than those from the other dietary groups, but a viral infection eradicates these differences. Therefore, a correlation between eicosanoid formation and effector functions studied could not be established.
Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a control diet high in saturated fatty acids for 17 days. For the next 36 days, 6.5% of total energy intake from saturated fatty acids was replaced by monounsaturates plus polyunsaturates (monounsaturated fatty acid diet; n = 29) or by polyunsaturates alone (polyunsaturated fatty acid diet; n = 29). Both diets caused a slight, nonsignificant, increase in median Lp[a] levels, with no difference between diets. In Expt. II, 10% of energy from the cholesterol-raising saturated fatty acids (lauric, myristic, and palmitic acid) was replaced by oleic acid or by trans-monounsaturated fatty acids. Each of the 59 participants received each diet for 3 weeks in random order. The median level of Lp[a] was 26 mg/l on the saturated fatty acid diet; it increased to 32 mg/l (P less than 0.020) on the oleic acid diet and to 45 mg/l (P less than 0.001) on the trans-fatty acid diet. The difference in Lp[a] between the trans-fatty acid and the oleic acid diets was also highly significant (P less than 0.001). Expt. III involved 56 subjects; all received 8% of energy from stearic acid, from linoleic acid, or from trans-monounsaturates, for 3 weeks each. All other nutrients were equal.(ABSTRACT TRUNCATED AT 250 WORDS)