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Biomedical subjects

G Hornstra

Publications and source records attributed to G Hornstra.

At least 91 records · Page 5Linked to original sources

Comparison between the essential fatty acid status of preterm and full-term infants, measured in umbilical vessel walls.

The essential fatty acid (EFA) composition of umbilical vessel walls is increasingly being studied as a longer-term reflection of the fetal EFA status. We evaluated the EFA content of umbilical artery and vein vessel walls in 43 preterm infants and compared it with that of 43 full-term cord vessels. In addition, relations among cord vessel wall fatty acid composition, gestational age (GA) at birth, and anthropometric parameters at birth (weight, head circumference, and length) were explored in the preterm infants. Generally, n-6 and n-3 EFA levels were lower, while levels of EFA deficiency markers were higher in preterm than in term cords, both in the walls of the draining arteries and the supplying vein. In preterm cords, significant correlations were observed between GA at birth and levels of n-6 and n-3 EFAs (positive) and EFA deficiency markers (negative). Birth weight showed significant (P < or = 0.01), positive correlations with n-6 and n-3 EFA levels in the cord artery walls of preterm infants, all after correction for GA at birth. In conclusion, substantial differences between the EFA profiles of preterm and full-term cord vessel walls indicate a lower biochemical EFA status of the preterm than of the term fetus. This lower preterm EFA status might be a reflection of a physiologically lower EFA demand for growth and development of the preterm fetus than of the term fetus.

Fatty Acids, Essential↗

Effects of dietary fatty acids on signal transduction and membrane cholesterol content in rat platelets.

Previously, we have reported that dietary fatty acids can modify the thromboxane A2-dependent activation of rat platelets. Here, we present evidence that this dietary effect is part of a more general effect on platelet signal transduction, putatively involving structural changes in the platelet membranes. Four experiments were performed, where Wistar rats were fed with a high-fat diet enriched in either saturated, n-6 polyunsaturated or n-3 polyunsaturated fatty acids, or with a low-fat diet enriched in n-6 polyunsaturated fatty acids. The type of diet hardly influenced mean number of double bonds in the major platelet phospholipids. Platelet membranes from the rats fed with the saturated-fat diet had phospholipids with relatively high levels of arachidonate, but were low in cholesterol/phospholipid ratio. When compared to this diet group, platelets from other groups had an arachidonate content that was 21 to 47% lower and a cholesterol/phospholipid ratio 3 to 5% higher. The saturated-fat diet resulted in platelets that, in general, were less responsive to agonists than the platelets from other groups: with thrombin, collagen and thromboxane A2 analogue U46619, both early (shape change and phospholipase C-dependent rise in [Ca2+]i) and late (exocytosis and aggregation) responses were relatively low. However, platelet activation evoked by ADP was not influenced by diet type. When the cholesterol content of rat platelets was modified in vitro, it appeared that the early and late responses to thrombin and U46619 increased with the cholesterol/phospholipid ratio. Taken together, these results suggest that in rat platelets (i) the membrane cholesterol/phospholipid ratio can be modulated by a diet rich in saturated fatty acids, explaining, at least in part, the dietary effect on phospholipase C-mediated platelet activation, and (ii) relatively small changes in cholesterol content can have a more profound effect on platelet activation than substantial changes in arachidonate level.

Animals↗

Differential release of histamine and prostaglandin D2 in rat peritoneal mast cells: roles of cytosolic calcium and protein tyrosine kinases.

We studied how the release of histamine and prostaglandin D2 (PGD2) were connected in stimulated rat peritoneal mast cells, and to what extent these processes were controlled by the cytosolic Ca2+ concentration, [Ca2+]i, and protein tyrosine kinases. In the presence of 1 mM CaCl2, the G-protein activating compound 48/80 (10 micrograms/ml) evoked a transient rise in [Ca2+]i and a relatively high secretion of histamine, but only a low release of PGD2. In contrast, 5 microM thapsigargin (an inhibitor of endomembrane Ca(2+)-ATPases) and 5 microM ionomycin evoked high and prolonged rises in [Ca2+]i, and stimulated the cells to release relatively small amounts of histamine and high amounts of PGD2. Stimulation of the cells with CaCl2 and 10 microM ATP4- gave only minor quantities of histamine and PGD2, despite of the micromolar level of [Ca2+]i reached. When CaCl2 was replaced by EGTA, rises in [Ca2+]i as well as release of histamine and PGD2 were reduced with each agonist, but the preference of agonists to release more histamine or PGD2 remained unchanged. In mast cells with depleted Ca2+ stores, the addition of CaCl2 stimulated the store-regulated Ca2+ entry resulting in a prolonged rise in [Ca2+]i. However, simultaneous addition of compound 48/80 and CaCl2 was required for release of histamine and PGD2. In cells with full stores, PGD2 release evoked by compound 48/80 was greatly reduced by genistein and methyl-2,5-dihydroxycinnamate, two structurally unrelated inhibitors of protein tyrosine kinases, whereas histamine secretion was not influenced by these inhibitors. Similarly, with thapsigargin or ionomycin as agonist, PGD2 release was more sensitive to the tyrosine kinase inhibitors than histamine secretion. We conclude that in activated rat peritoneal mast cells: (i) the influx of extracellular Ca2+ potentiates agonist-evoked rises in [Ca2+]i as well as histamine secretion and PGD2 release; (ii) the amplitude of the [Ca2+]i rise does not determine the preferential effect of agonists to release more histamine or more PGD2; (iii) the relatively high PGD2 release evoked by thapsigargin and ionomycin is probably due to their potency to evoke a prolonged rise in [Ca2+]i and to activate protein tyrosine kinases.

Animals↗

The essential fatty acid status of mother and child in pregnancy-induced hypertension: a prospective longitudinal study.

OBJECTIVE: Our purpose was to investigate, in a prospective way, whether the altered essential fatty acid status observed in pregnancy-induced hypertension is a consequence of the disease or may contribute to its cause. STUDY DESIGN: Pregnant women healthy at the start of the study were asked to give a blood sample before 16 weeks, at 22 weeks, and at 32 weeks of gestation. After delivery a blood sample from the umbilical vein, a piece of the umbilical cord, and a maternal blood sample were collected. Fatty acid compositions were determined of the phospholipids isolated from plasma and umbilical arterial and venous vessel walls. The nutrient intake of the pregnant women was assessed by use of the dietary history method and food frequency questionnaires. The results of each woman with pregnancy-induced hypertension were compared with the results of three matched healthy controls. RESULTS: During pregnancy (16 to 32 weeks) no significant differences were observed in nutrient intake and maternal plasma fatty acid composition between the group with pregnancy-induced hypertension (n = 52) and the control group (n = 156). After delivery the relative amounts of 18:2(n-6) and 18:3(n-3) in maternal plasma were significantly lower in pregnancy-induced hypertension than in normal pregnancy. This was associated with significantly higher levels of (n-6) long-chain polyenes and cervonic acid (22:6[n-3]). In comparison with the situation at 32 weeks, the postpartum cervonic acid status increased in pregnancy-induced hypertension, whereas it decreased in normal pregnancy. The cervonic acid levels in umbilical plasma phospholipids were significantly higher after pregnancy-induced hypertension than after normal pregnancy. No significant differences were observed for the fatty acid content in umbilical vessel walls. CONCLUSION: The results indicate that the altered essential fatty acid status in pregnancy-induced hypertension is a late phenomenon and is therefore unlikely to have contributed to the pathogenesis of pregnancy-induced hypertension. Moreover, the neonatal essential fatty acid status is not negatively affected by pregnancy-induced hypertension.

Adult↗

Essential fatty acids in pregnancy and early human development.

Essential fatty acids (EFA) are vitally important structural elements of cell membranes and, therefore, instrumental in the formation of new tissues. The primary EFA cannot be synthesized by man and, consequently, humans depend on dietary sources for an adequate EFA supply. Fetal development is associated with a high EFA requirement, and for its EFA supply, the developing fetus depends on the availability of maternal EFA. At delivery, a strong correlation is observed between the relative amounts of the various EFA in maternal and umbilical plasma phospholipids (PL), which underlines this fetal dependence. In a longitudinal study, we observed that, in women, the EFA status progressively decreases during pregnancy. This particularly holds for cervonic acid (CA, 22:6n-3, also named Docosahexaenoic acid, DHA), the major structural and functional EFA in the CNS. In addition, evidence was obtained for CA mobilization from maternal stores during pregnancy. Furthermore, the maternal CA status appeared significantly higher in primigravida than in multigravida. This was associated with a tendency for the first child of a given woman to have a higher CA status than her following children. This suggests that maternal CA mobilization during pregnancy occurs from a pool that is not easily replenished after pregnancy. The fetal CA status of premature infants is positively related to head circumference, birth weight and birth length. This may imply that increasing the fetal CA status could promote fetal growth and, thereby, improve the general prognosis of prematures. In conclusion, our data suggest that increasing the maternal EFA intake during pregnancy may be beneficial to both mother and child.(ABSTRACT TRUNCATED AT 250 WORDS)

Docosahexaenoic Acids↗

Differential effects of endothelial cell fatty acid modification on the sensitivity of their membrane phospholipids to peroxidation.

In order to study the relationship between the fatty acid (FA) composition of human umbilical vein endothelial cells (HUVEC) and their susceptibility to oxidative stress, we modified their FA composition by long-term culturing in media supplemented with a saturated, monounsaturated, or polyunsaturated FA. Sensitivity of the cellular phospholipids to peroxidation was monitored by measuring conjugated diene formation and decrease of polyunsaturated FAs induced by CuSO4 and H2O2 in liposomes prepared from the respective phospholipid extracts. The extent of phospholipid peroxidation was found to increase with increasing content of polyunsaturated FAs. In addition, the sensitivity of individual polyunsaturated FAs to peroxidation was directly proportional to the number of double bonds present. However, no unequivocal relationship was observed between conjugated diene formation and the phospholipid unsaturation index (an indicator for the combined effect of number of double bonds and polyunsaturated FA contents of the membrane phospholipids). The results suggest that long-term FA modification of endothelial cells differentially alters the sensitivity of their membrane phospholipids to peroxidation: long-term modification with oleic acid may protect against lipid peroxidation, whereas linoleic acid may increase sensitivity to peroxidation. In contrast to what might be expected, long-term modification of endothelial cells with eicosapentaenoic or docosahexaenoic acid does not increase the sensitivity of phospholipids to peroxidation.

Cells, Cultured↗

Long-chain polyunsaturated fatty acids in preterm infants: status at birth and its influence on postnatal levels.

To determine the influence of the prenatal long-chain polyunsaturated fatty acid (LCP) supply on prenatal growth and on postnatal LCP levels, we studied 52 preterm infants and assessed the relations between the LCP status at birth (reflecting the prenatal LCP supply), gestational age and prenatal growth, and the relation between the LCP status at birth and at 37 to 42 weeks of gestational age. After a correction for gestational age at birth, significant relations (p < or = 0.05) were observed between anthropometric measurements at birth (weight, head circumference, and length) and LCP levels in the umbilical artery wall, the LCP content of which reflects the long-term fetal LCP status. Independent of the neonatal diet (human milk or formula), LCP levels in erythrocyte phospholipids at term were positively related to levels in the umbilical artery wall (docosahexaenoic acid (22:6n-3): p < or = 0.0003; arachidonic acid (20:4n-6): p = 0.02). Postnatal diet significantly influenced LCP levels in plasma phospholipids at term (docosahexaenoic acid: p < or = 0.004; arachidonic acid: p = 0.02); formula-fed infants had lower values. We conclude that the LCP status of preterm infants at birth is related to prenatal growth. Moreover, next to the postnatal enteral diet, the LCP status at birth significantly affects LCP levels at term postconceptional age. This finding may warrant further studies of the effects of essential fatty acid-enriched maternal diets during pregnancy on the neonatal LCP status at birth.

Anthropometry↗

Long-chain polyene status of preterm infants with regard to the fatty acid composition of their diet: comparison between absolute and relative fatty acid levels in plasma and erythrocyte phospholipids.

The long-chain polyene (LCP) status of thirty-nine premature infants (birth weight < 1800 g) was evaluated. Twenty-seven infants were fed on an artificial formula, twelve received their own mother's breast milk. Fatty acid compositions of both plasma and erythrocyte (RBC) phospholipids (PL) were determined in umbilical venous blood and in weekly postnatal blood samples until the 28th day of life. Individual fatty acid levels were expressed as absolute quantities (mg fatty acid/l plasma or RBC suspension) and as relative (mg/100 mg total fatty acids) values. The changes with time in the absolute values for 22:6n-3 and 20:4n-6 in plasma were strikingly different from those of the relative values for these fatty acids. In plasma PL the inter-group differences in the absolute postnatal values for 22:6n-3 (P < 0.0005) and 20:4n-6 (P < 0.05) and the relative values for 22:6n-3 (P < 0.02) were significant, with lower fatty acid values in the formula-fed infants. In RBC PL, no significant inter-group differences in the postnatal 22:6n-3 and 20:4n-6 values were found. Based on the assumption that it is desirable for formula-fed infants to achieve postnatal plasma LCP values at least comparable with those found in infants fed on human milk, the findings of the present study indicate that both n-3 and n-6 LCP should be added to preterm infant formulas. Moreover, the additional importance of absolute fatty acid levels was demonstrated, although analytical procedures need to be standardized to enable effective comparison of results from different research groups.

Dietary Fats↗

The proportion of trans monounsaturated fatty acids in serum triacylglycerols or platelet phospholipids as an objective indicator of their short-term intake in healthy men.

Unfavourable effects of trans monounsaturated fatty acid (trans-C18:1) isomers on health variables have been reported. Reports on their actual intake, however, are scarce, because of the absence in many nutrient databases of values for trans-C18:1, and the wide variation in the level of trans fatty acids between different brands of the same product. We therefore examined whether the intake of trans-C18:1 is reflected by trans-C18:1 concentrations in serum triacylglycerols or platelet phospholipids. Thirty-eight men received two diets in random order. During the first experimental period twenty men consumed a Western-type control diet for six weeks, and eighteen men consumed a modified diet in which 70% of the fat was replaced by palm oil. After a wash-out period of 3 weeks, regimens were crossed over (second experimental period). The proportion of total fatty acids from trans-C18:1 in the diet decreased from 4.7 (SEM 0.27) during the control to 2.1 (SEM 0.16) on the modified diet (P < 0.001). Trans-C18:1 in serum triacylglycerols decreased from 3.5 (SEM 0.13) to 2.8 (SEM 0.11)% (P < 0.001), and in platelet phospholipids from 1.0 (SEM 0.06) to 0.7 (SEM 0.04)% (P < 0.001). After the first experimental period trans-C18:1 in the diet correlated with trans-C18:1 in serum triacylglycerols (r 0.41; P = 0.014), and platelet phospholipids (r 0.52; P = 0.001). Also, differences in the intake between the two periods correlated with changes in the proportion of trans-C18:1 in serum triacylglycerols (r 0.56; P = 0.001) and platelet phospholipids (r 0.58; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status.

Although essential fatty acids (EFA) and their longer chain, more unsaturated derivatives play a major role during pregnancy, hardly any information is available with respect to the course of the maternal EFA status during an uncomplicated pregnancy and its relationship to the neonatal EFA status. Therefore, a longitudinal study was started in which 110 pregnant women gave repeated blood samples from the 10th week of gestation until delivery. After birth a blood sample from the umbilical vein and a maternal venous blood sample were collected as well, and 6 months after delivery a final blood sample from the mother was taken. The absolute (mg/l) and relative (% total fatty acids) amounts of the fatty acids in plasma phospholipids were determined. The total amounts of fatty acids increased significantly during pregnancy. This pattern was similar for the individual fatty acids and fatty acid families. The relative amount of linoleic acid (18:2n-6) did not change during pregnancy, whereas the relative amount of arachidonic acid (20:4n-6) decreased. Despite maternal mobilization of docosahexaenoic acid (22:6n-3, DHA), suggested by a temporary increase in the DHA status until 18 weeks gestation, the DHA status steadily declined thereafter. This pattern was associated with a progressive increase in the DHA deficiency index in maternal blood throughout pregnancy and resulted in a sub-optimal neonatal DHA status. The overall maternal EFA status also declined steadily during pregnancy. Therefore, the question arises whether the mother, under the prevailing dietary conditions, is able to meet the high fetal requirement for EFA.

Adult↗

Essential fatty acid status in neonates after fish-oil supplementation during late pregnancy.

Healthy pregnant women (n 23) were supplemented with fish-oil capsules (2.7 g n-3 polyunsaturated fatty acids/d) from the 30th week of gestation until delivery. Subjects in a control group were either supplemented with olive-oil capsules (4 g/d, n 6) or received no supplementation (n 10). Fatty acid compositions of the phospholipids isolated from umbilical plasma and umbilical arterial and venous vessel walls were determined. Fatty acid compositions of maternal venous plasma phospholipids were determined as well. Maternal plasma phospholipids of the fish-oil-supplemented group contained more n-3 fatty acids and less n-6 fatty acids. Moreover, the amounts of the essential fatty acid deficiency markers Mead acid (20:3n-9) and Osbond acid (22:5n-6) were significantly lower. The extra amount of n-3 fatty acids consumed by the mothers resulted in higher contents of n-3 fatty acids, and of docosahexaenoic acid (22:6n-3) in particular, in the phospholipids of umbilical plasma and vessel walls. It is, indeed, possible to interfere with the docosahexaenoic acid status at birth: children born to mothers supplemented with fish oil in the last trimester of pregnancy start with a better docosahexaenoic acid status at birth, which may be beneficial to neonatal neurodevelopment.

Adult↗

Some aspects of neonatal essential fatty acid status are altered by linoleic acid supplementation of women during pregnancy.

To study the effect of maternal linoleic acid [18:2(n-6), LA] supplementation during pregnancy on neonatal essential fatty acid status, pregnant women with relatively low plasma linoleic acid concentrations before 16 wk of gestation (n = 21) were supplied with foods rich in linoleic acid, resulting in an additional intake of 10 g/d of linoleic acid from the 20th week of gestation until delivery. One of the two control groups consisted of pregnant women with comparably low plasma linoleic acid concentrations at the start of the study (LL-control group, n = 22); the other consisted of women with habitually high plasma linoleic acid concentrations (HL-control group, n = 21). The neonatal essential fatty acid status was assessed by determining the fatty acid composition of phospholipids (PL) isolated from umbilical plasma and umbilical vessel walls. The maternal linoleic acid status in the LA-supplemented group increased to a level comparable to that of the HL-control group, but the neonatal linoleic acid status did not differ from that of either control group. Linoleic acid supplementation did result in slightly, but significantly, higher total amounts of (n-6) long-chain polyenes in umbilical plasma and vein vessel wall phospholipids compared with the LL-control group. This increase was associated with significantly lower total amounts of (n-3) long-chain polyenes. In the HL-control group, the concentration of (n-3) long-chain polyenes in umbilical plasma and vessel walls was significantly lower than in the LA-supplemented and the LL-control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗