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Biomedical subjects

K D Croft

Publications and source records attributed to K D Croft.

At least 55 records · Page 3Linked to original sources
PubMed1997

Determinants of the kinetics of very low-density lipoprotein apolipoprotein B-100 in non-obese men.

1. Apolipoprotein B-100 (ApoB) is the principal structural and functional protein of the pro-atherogenic lipoproteins. Elevated plasma apoB is an independent risk factor for coronary artery disease. In the present study we aimed to assess the factors that determine the kinetics of apoB in the very low-density lipoprotein (VLDL) in healthy men. 2. We studied 17 non-obese men who were consuming an ad libitum diet and had the following characteristics: mean (+/-SD) age 45.5 +/- 9.7 years, body mass index (BMI) 25.1 +/- 1.4 kg/m2, waist:hip ratio 0.91 +/- 0.04, serum cholesterol 5.2 +/- 0.6 mmol/L, triglycerides 1.08 +/- 0.53 mmol/L and high-density lipoprotein-cholesterol 1.24 +/- 0.31 mmol/L. Daily dietary intake was as follows: total fat 76 +/- 26 g, carbohydrate 238 +/- 67 g, protein 103 +/- 33 g and alcohol 20 +/- 16 g. 3. The kinetics of VLDL ApoB were studied using a primed, constant infusion (1 mg/kg per h) of 1-[13C]-leucine over 8 h with measurement of isotopic enrichment of ApoB using gas chromatography/mass spectrometry. The fractional turnover rate of VLDL ApoB was estimated using a monoexponential function. The mean (+/-SD) absolute hepatic secretion rate (ASR) of ApoB was 8.5 +/- 4.6 mg/kg per day and the fractional catabolic rate (FCR) was 7.9 +/- 5.6 pools/day. The ASR was significantly correlated with the waist:hip ratio (r = 0.60; P = 0.04), but not with age, BMI, weight or nutrient intake. The FCR was significantly and inversely correlated with plasma triglycerides (r = -0.53; P = 0.03) and alcohol intake (r = -0.48; P = 0.05). 4. In conclusion, the hepatic secretion of VLDL ApoB in nonobese, healthy men is primarily determined by the waist:hip ratio, a measure of visceral fat. This is consistent with the hypothesis that the rate of lipid substrate supply in the liver regulates the output of ApoB. The fractional catabolism of VLDL ApoB may, however, be inversely related to alcohol intake and appears to determine the plasma concentration of triglycerides.

Adult↗
PubMed1997

Inhibition of cholesterogenesis decreases hepatic secretion of apoB-100 in normolipidemic subjects.

We examined the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the kinetics of very low-density lipoprotein apolipoprotein B-100 (VLDL apoB) in 13 normolipidemic men in a placebo-controlled crossover study. Simvastatin significantly decreased the plasma concentrations of low-density lipoprotein (LDL) cholesterol by 36%, triglycerides by 26%, mevalonic acid by 34%, and lathosterol by 32%. Hepatic secretion of VLDL apoB was measured using a primed constant intravenous infusion of [1-13C]leucine with monitoring of isotopic enrichment of apoB by gas chromatography-mass spectrometry; fractional turnover rate was derived using a monoexponential function. Simvastatin decreased VLDL apoB pool size by 53% and the hepatic secretion rate of VLDL apoB by 46% but did not significantly alter its fractional catabolism. The change in hepatic VLDL apoB secretion was significantly and independently correlated with changes in plasma mevalonic acid and lathosterol concentrations and the lathosterol-to-cholesterol ratio. The data support the hypothesis that the rate of de novo cholesterol synthesis directly regulates the hepatic secretion of VLDL apoB in normal subjects.

Adult↗
PubMed1996

Phenolic content of various beverages determines the extent of inhibition of human serum and low-density lipoprotein oxidation in vitro: identification and mechanism of action of some cinnamic acid derivatives from red wine.

1. An antioxidant effect of phenolic substances in red wine to reduce oxidizability of low-density lipoprotein has been proposed as the basis for a relatively lower incidence of coronary disease in populations with high red wine intake. We have now investigated the possible antioxidant effects of various beverages, including red wines, white wines, beers and red grape juices (diluted 1:500), on metal ion-dependent (copper) and -independent (aqueous peroxyl radicals) oxidation of isolated human low-density lipoprotein. We also tested the effects of these beverages on copper-initiated oxidation of lipoproteins in serum. 2. The higher the polyphenolic content of a beverage, the greater was its antioxidative effect measured as change in lag time in the different oxidation systems. Upon stripping the polyphenolics from the drinks, the lag times returned to control levels in isolated low-density lipoprotein; however, the low concentrations of phenolics remaining after stripping had a lesser but still significant effect on oxidation of lipoproteins in serum. The inhibitory effect of these phenolics appeared to be more pronounced for metal ion (copper)-induced oxidation than for those induced by aqueous peroxyl radicals, suggesting that both copper-binding and free radical-trapping activities may be involved. A mixture of the carboxylic acids representative of those present in red wine exhibited no significant effect on lag time of metal ion-dependent and -independent low-density lipoprotein oxidations. Ethanol, at concentrations of 0.1-0.5%, had no effect on either copper-induced or aqueous peroxyl radical oxidations. 3. Extracts of acid-hydrolysed red wine were separated by thin-layer chromatography and the most active antioxidant fractions identified. GC-MS and HPLC analysis of these fractions resulted in the identification of several cinnamic acid derivatives, such as coumaric acid, caffeic acid and protocatechuic acid. Dose-response studies using the pure compounds indicated that caffeic acid was the most active antioxidant with an IC50 < 1 mumol/l for copper-initiated low-density lipoprotein oxidation. Caffeic acid (1 mumol/l) significantly inhibited lipid hydroperoxide formation while sparing alpha-tocopherol consumption. Caffeic acid at the same concentration also inhibits aqueous peroxyl radical-induced oxidation of low-density lipoprotein, sparing alpha-tocopherol. There was no evidence of caffeic acid preventing the binding of copper to low-density lipoprotein. 4. We conclude that phenolics in both alcoholic and non-alcoholic beverages can give dose-dependent protection against oxidation of low-density lipoprotein. Caffeic acid and protocatechuic acid are two compounds likely to contribute to these effects. These findings may be relevant to the putative cardiovascular-protective effects of high phenolic content alcoholic beverages such as red wine; however, the widespread occurrence of antioxidants such as caffeic acid in fruits and vegetables suggests that these protective principles are not limited to red wine.

Adult↗
PubMed1996

Plasma and urinary 8-iso-prostane as an indicator of lipid peroxidation in pre-eclampsia and normal pregnancy.

1. This study was designed to seek evidence for excessive lipid peroxidation in pre-eclamptic women using 8-iso-prostane as a novel bioactive marker of lipid peroxidation in vivo. Plasma free, total and urinary 8-iso-prostane were measured in 20 women with proteinuric pre-eclampsia, and compared with 18 age- and gestation-matched pregnant control subjects, before delivery and at 6 weeks post-partum. 2. Plasma free 8-iso-prostane was significantly elevated in the pre-eclamptic women compared with control subjects before delivery, and fell to control levels post-partum. Conversely, levels in women with normal pregnancy rose post-partum. 3. Total plasma 8-iso-prostane levels were not significantly elevated in pre-eclamptic women compared with control subjects during pregnancy, but fell significantly in the pre-eclamptic women post-partum, suggesting that they had relatively higher levels compared with their non-pregnant state. 4. Urinary 8-iso-prostane excretion was significantly lower in the pre-eclamptic women compared with control subjects during pregnancy, suggesting that renal clearance of 8-iso-prostane is impaired in pre-eclampsia. 5. Increased levels of plasma free 8-iso-prostane in pre-eclampsia could be due to an increase in lipid peroxidation, an increase in phospholipase A2 activity or a reduction in renal clearance of 8-iso-prostane, or a combination of all three. The potent direct and indirect vasoconstrictor actions of 8-iso-prostane may contribute to the pathogenesis of pre-eclampsia.

Adult↗
PubMed1996

Oxidative susceptibility of low-density lipoproteins--influence of regular alcohol use.

In population studies, a low-to-moderate intake of alcohol has been consistently linked to a lower risk of coronary artery disease. The recent suggestion that alcoholic beverages may be conferring this decrease in risk because they contain antioxidant phenolic compounds that reduce the oxidizability of low-density lipoprotein (LDL) has to be reconciled with the possible counteracting influence of a pro-oxidant effect of alcohol. In a controlled crossover study, we have now measured the oxidizability of LDL in 27 regular beer drinkers during consecutive 4-week periods, wherein they consumed a high versus low alcohol beer (4.9 vs. 0.9% alcohol v/v, respectively), with the two beers being similar in phenolic content. This resulted in a decrease in alcohol consumption by approximately 80% (408 +/- 25 ml/week vs. 75 +/- 11 ml/week). During the low alcohol period, there was no change in LDL vitamin E or its cholesterol or protein content. Analysis of LDL oxidation kinetics revealed an increase in oxidizability during the high alcohol phase. This was despite a decrease in arachidonic acid content of LDL and a corresponding increase in palmitic acid during high alcohol intake--a change in fatty acid composition that has the potential to favor a decrease in oxidizability. Our results suggest that alcohol ingestion increases LDL oxidation, despite reducing the polyunsaturated fatty acid composition. The overall effect of alcoholic beverages on LDL oxidation may be a balance between the pro-oxidant and antioxidant activity of its various constituents. The predominant pro-oxidant effect demonstrated in these beer drinkers, although not relevant to any potential decrease in coronary artery disease, may be important in the pathogenesis of alcohol-related disease in other organ systems.

Adult↗
PubMed1995

Oxidation of low-density lipoproteins: effect of antioxidant content, fatty acid composition and intrinsic phospholipase activity on susceptibility to metal ion-induced oxidation.

The oxidative modification of low-density lipoprotein (LDL) may play an important role in atherogenesis. Our understanding of the mechanism of LDL oxidation and the factors that determine its susceptibility to oxidation is still incomplete. We have isolated LDL from 45 healthy individuals and studied the relationship between LDL fatty acid, vitamin E and beta-carotene composition, intrinsic phospholipase A2-like activity and parameters of LDL oxidation. LDL was exposed to a copper ion-dependent oxidising system and the kinetics of oxidation studied by monitoring formation of fatty acid conjugated dienes. The length of the lag phase of inhibited lipid peroxidation was measured as well as the rate of lipid peroxidation during the propagation phase. There was no significant correlation between LDL antioxidant vitamin or fatty acid composition and lag time to LDL oxidation. Oleic acid was negatively correlated with the rate of LDL oxidation (r = -0.41, P < 0.01) whilst linoleic acid was significantly correlated with the extent of LDL oxidation measured by the production of total dienes (r = 0.34, P < 0.05). Interestingly, LDL vitamin E content was positively correlated with both the rate (r = 0.28, P < 0.05) and extent of LDL oxidation (r = 0.43, P < 0.01). LDL isolated from this group of subjects showed significant intrinsic phospholipase-like activity. The phospholipase activity, whilst not correlated with lag time, was significantly correlated with both rate (r = 0.43, P < 0.01) and total diene production (r = 0.44, P < 0.01) of LDL oxidation. We conclude that antioxidant content, fatty acid composition and intrinsic phospholipase activity have little influence on the lag time of Cu-induced LDL oxidation. These components do however, significantly influence both the rate and extent of LDL oxidation, with increased vitamin E, linoleic acid content and phospholipase activity associated with faster and more extensive oxidation. The possible pro-oxidant effect of vitamin E has interesting implications for the postulated 'protective' effects of vitamin E on atherogenesis.

Antioxidants↗
PubMed1995

PGF2-isoprostanes formed during copper-induced oxidation of low-density lipoproteins are the prostaglandins that cross-react with PGE2 antibodies.

It has been previously shown that LDL oxidation can produce a prostaglandin artifact(s) which cross-reacts with PGE2 antibodies. The nature of this cross-reacting material had not been identified. In this study we have examined the products of LDL oxidation and found substances cross-reacting with both PGE2 and LTB4 antibodies. Lipid extracts of copper oxidised LDL were separated by reverse-phase HPLC and fractions cross-reacting with PGE2 antibody identified. Fractions were collected and examined by GC-MS as methyl ester TMS ether derivatives. 8-epi PGF2 alpha (8-isoprostane) was identified as one of the major metabolites eluting in fractions cross-reacting with PGE2. 8-epi-PGF2 alpha showed 4% cross-reactivity with a PGE2 antibody but very little with LTB4 or thromboxane B2 antibodies. Treatment of oxidised LDL with a specific 8-isoprostane antibody removed any detectable PGE2 levels in subsequent PGE2 RIA. The generation of cross-reacting material during LDL oxidation was not influenced by indomethacin. The generation of 8-isoprostanes by free radical oxidation of arachidonic acid in LDL may explain much of the cross-reactivity seen with PGE2 antibodies. The identity of substances cross-reacting with LTB4 have yet to be identified.

Chromatography, High Pressure Liquid↗
PubMed1994

Glucose turnover in pregnant women with acute malaria.

1. Hypoglycaemia is a serious complication of falciparum malaria, especially in pregnant patients. To investigate malaria-associated changes in glucose metabolism in pregnancy, steady-state [6,6-2H2] glucose turnover and clearance were measured in 10 women (eight with uncomplicated falciparum malaria and two with vivax malaria at 16-30 weeks gestation) before treatment, after intravenous quinine infusion (patients with falciparum malaria) and in convalescence. 2. Admission basal plasma glucose concentrations were higher than those in convalescence [median (range); 4.8 (3.6-7.0) versus 4.0 (3.6-4.6) mmol/l, P = 0.02], and there was a significant fall during initial quinine treatment in patients with falciparum malaria [5.0 (4.3-7.6) to 3.6 (3.2-5.4) mmol/l, P < 0.01]. Basal plasma insulin levels were comparable at presentation and follow-up (P = 0.35) and rose an average of only 2m-units/l during quinine infusion (P < 0.05). Pretreatment glucose turnover rates [3.37 (2.57-4.16) mg min-1 kg-1] were comparable with those found in a previously reported study of non-pregnant severely ill patients [3.22 (2.12-4.82) mg min-1 kg-1, n = 11] and correlated significantly with the admission parasitaemia (P < 0.025). In the eight patients with falciparum malaria, there was a significant fall in turnover during intravenous quinine infusion [3.42 (2.58-4.16) to 2.66 [1.94-3.94) mg min-1 kg-1] whereas clearance did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Platelet and neutrophil function and eicosanoid release in a subject with abetalipoproteinaemia.

It has been suggested that plasma low density lipoprotein (LDL) may affect platelet and leukocyte activity and the release of biologically active eicosanoids which may contribute to the pathogenesis of coronary heart disease. To evaluate the possible biological effects of LDL further we have studied platelet aggregation, leukocyte function and eicosanoid release in a young woman with abetalipoproteinaemia (ABL) who totally lacks LDL. The subject showed decreased platelet response to threshold doses of ADP, collagen and arachidonic acid compared to a matched control measured in parallel or to a larger control group of 22 normal subjects. Aggregation was normal to higher doses of the same agonists. Thromboxane formation in clotted whole blood and in PRP stimulated with collagen was lower for the ABL subject than the control group. Neutrophil function assessed by chemiluminescence following stimulation with PMA, zymosan and FMLP was normal for the ABL subject, although the release of leukotriene B4 from calcium ionophore stimulated cells less than controls. Neutrophil platelet activating factor (PAF) formation and half life in plasma was not altered in ABL. The fatty acid composition of plasma, platelet and erythrocyte membrane phospholipids showed particularly low levels of linoleic acid in ABL compared to controls. Platelet phospholipids from the ABL subject also showed low levels of arachidonic acid. The decrease in eicosanoid formation seen in ABL may be the result of altered fatty acid composition of cell membrane phospholipids, or perhaps a defect in arachidonate mobilization. These results indicate that in a subject who lacks circulating LDL the behaviour of platelets and neutrophils in some in vitro tests is altered, although the extent to which these effects are reflected in vivo with regard to inflammatory and thrombotic mechanisms is not known.

Abetalipoproteinemia↗
PubMed1993

Neutrophil platelet-activating factor in normal and hypertensive pregnancy and in pregnancy-induced hypertension.

1. Platelet-activating factor is a phospholipid with potent vasodilator and platelet-activating properties. To test the hypothesis that a generalized change in cellular platelet-activating factor metabolism may be involved in the systemic vasodilatation of normal pregnancy or pregnancy-induced hypertension, we studied platelet-activating factor and eicosanoid synthesis in isolated leucocytes obtained from pregnant women before and after delivery compared with age-matched non-pregnant control subjects. Parallel observations were carried out in age- and gestation-matched women with uncomplicated hypertension in pregnancy and in women with pregnancy-induced hypertension and a further set of normotensive pregnant control subjects. 2. Leucocyte counts were higher in all pregnant groups compared with non-pregnant control subjects. Neutrophil production of platelet-activating factor and metabolites of prostacyclin, prostaglandin E2 and thromboxane in response to calcium ionophore stimulation were all lower in pregnant women compared with non-pregnant control subjects, but returned to similar levels 6 weeks post partum. There was no significant difference between essential hypertensive and normotensive groups. When women with pregnancy-induced hypertension were a priori sub-divided into those with or without proteinuria, subjects with proteinuria showed significantly lower levels of neutrophil platelet-activating factor synthesis. 3. Plasma levels of the platelet-activating factor metabolite (lyso-platelet-activating factor) were also lower in pregnancy, suggesting alterations in the activity of enzymes controlling synthesis or degradation of this phospholipid in pregnancy. In pregnancy-induced hypertension the levels of plasma lyso-platelet-activating factor were higher than in normal pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Enhancement of platelet 12-HETE production in the presence of polymorphonuclear leukocytes during calcium ionophore stimulation.

This study investigates the effect of platelet/neutrophil interactions on eicosanoid production. Human platelets and polymorphonuclear leukocytes (PMNs) were stimulated alone and in combination, with calcium ionophore A23187 and the resulting eicosanoids 12S-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoic acid (12-HETE), 12S-heptadecatrienoic acid (HHT), 5S,12R-dihydroxy-(6Z,8E,10E,14Z)-eicosatetraenoi c acid (LTB4) and 5S-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoic acid (5-HETE) were measured by HPLC. The addition of PMNs to platelet suspensions caused a 104% increase in 12-HETE, a product of 12-lipoxygenase activity, but had only a modest effect on the cyclooxygenase product HHT (increase of 18%). By using PMNs labelled with [14C]arachidonic acid it was shown that the increases in these platelet eicosanoids could be accounted for by translocation of released arachidonic acid from PMNs to platelets and its subsequent metabolism. The observation that 12-lipoxygenase was about five times more efficient than cyclooxygenase at utilising exogenous arachidonic acid during the platelet/PMN interactions was confirmed in experiments in which platelets were stimulated with A23187 in the presence of [14C]arachidonic acid. Stimulations of platelets with thrombin in the presence of PMNs resulted in a decrease in 12-HETE and HHT levels of 40% and 26%, respectively. The presence of platelets caused a small increase in neutrophil LTB4 output but resulted in a decrease in 5-HETE production of 43% during stimulation with A23187. This study demonstrates complex biochemical interactions between platelets and PMNs during eicosanoid production and provides evidence of a mechanism to explain the large enhancement in 12-HETE production.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1992

Low density lipoprotein composition and oxidizability in coronary disease--apparent favourable effect of beta blockers.

The oxidative modification of LDL in vivo may have an important role in atherogenesis. To determine whether LDL fatty acid, anti-oxidant composition and sensitivity to oxidation in vitro is different in subjects with established atherosclerosis we compared 20 men with angiogram proven coronary disease with 25 controls without clinical evidence of arterial disease. LDL-cholesterol, total triglycerides and LDL fatty acid composition did not differ significantly between the groups. LDL oxidation lag time and oxidation rate in coronary patients (132 min, 0.02 absorbance units/min) and controls (140, 0.017) were not significantly different. However coronary disease subjects taking beta-blockers had evidence for reduced LDL oxidizability (lag time 148 +/- 7 min; oxidation rate 0.017 +/- 0.002 abs units/min) compared with those not on beta-blockers (lag time 114 +/- 7 min, rate 0.025 +/- 0.003, P < 0.005). LDL beta-carotene was significantly lower in coronary patients (0.92 mumol/mmol LDL cholesterol; controls 1.58; P = 0.001). LDL alpha-tocopherol appeared lower in coronary patients (2.8 mumol/mmol LDL cholesterol; controls 3.3; P = 0.056) and was significantly lower in smokers (2.56; non-smokers 3.24; P = 0.04). LDL oxidation rate was negatively correlated with LDL alpha-tocopherol (r = -0.51, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

Effects of alcohol intake on plasma fatty acids assessed independently of diet and smoking habits.

1. This study was designed to determine prospectively whether changing alcohol consumption influenced the proportion of plasma linoleic acid independently of diet or smoking habits, and to evaluate changes in the plasma linoleic acid concentration as a potential marker of changes in alcohol consumption. 2. Fasting plasma fatty acid profiles were investigated in 72 male drinkers who were randomly assigned to drink low-alcohol beer or to maintain their usual drinking habits for a period of 4 weeks. 3. At entry to the study, a higher alcohol intake was associated with lower proportions of plasma linoleic acid, arachidonic acid and dihomolinolenic acid and higher proportions of plasma palmitoleic acid, independently of changes in body mass index. Smoking habits were unchanged and there were no major changes in diet during the period of the intervention. 4. Because the plasma palmitoleic acid concentration has been suggested as a possible marker of 'at risk' drinking, we investigated plasma fatty acid concentrations as indicators of alcohol intake. The plasma palmitoleic acid concentration was not a useful discriminator. Indices determined using logistic regression and combining plasma apolipoprotein A-II and linoleic acid concentrations gave better discrimination than either variable alone.

Adult↗
PubMed1991

The effect of lipoproteins on the release of some eicosanoids by stimulated human leukocytes. A possible role in atherogenesis.

Changes in eicosanoid generation have been examined in stimulated human peripheral leukocytes incubated with plasma lipoprotein fractions. Leukocytes (2.5 X 10(7) cells/ml, 90% neutrophils) were incubated with physiological concentrations of low density lipoprotein (LDL), high density lipoprotein (HDL) and very low density lipoprotein (VLDL). No release of leukotriene B4 (LTB4) or platelet activating factor (PAF) was noted prior to cell stimulation with either calcium ionophore, opsonized zymosan or FMLP. After stimulation with ionophore, LDL led to a 40% enhancement of LTB4 release compared to control incubations while there was no effect on PAF production. HDL caused a small but not significant increase in LTB4 while VLDL had no effect on the release of LTB4. The formation of the other major lipoxygenase product 5-hydroxy-eicosatetraenoic acid (5-HETE) was decreased by 20% following LDL incubation and by more than 50% after VLDL incubation compared to controls. LTB4 release was also enhanced by 27% after incubation with LDL and stimulation with opsonized zymosan. LDL did not cause any increase in superoxide production by leukocytes stimulated with opsonized zymosan or PMA. PGE2 release was stimulated directly in cells incubated with lipoproteins, particularly LDL and VLDL. Oxidised LDL enhanced LTB4 production to an even greater extent than native LDL. The observed enhancement of LTB4 by LDL is not the result of LDL oxidation during incubation, the provision of arachidonic acid substrate by the lipoprotein nor the uptake of cholesterol by the cell. The effect is most likely associated with the binding of LDL to the cell membrane, since LTB4 enhancement was partially blocked by dextran sulphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid↗
PubMed1990

Leukocyte and platelet function and eicosanoid production in subjects with hypercholesterolaemia.

A group of 22 subjects with type IIA hypercholesterolaemia (mean serum cholesterol = 8.3 +/- 0.3 mmol/l) were sex, age and weight matched with 22 control subjects (mean serum cholesterol = 4.5 +/- 0.1 mmol/l). Diastolic blood pressure was significantly higher in hypercholesterolaemic subjects (79.2 +/- 1.4 mm Hg) than in control subjects (71.9 +/- 1.4 mm Hg). While the high cholesterol group had 52% greater thromboxane production in clotted whole blood than controls this difference was not significant, and the platelet aggregation and serotonin secretion response to doses of collagen, ADP and arachidonic acid were similar between the 2 groups. Polymorphonuclear leukocyte (PMN) chemiluminescence (used as a measure of reactive oxygen species production) in response to low doses of the chemotactic-peptide FMLP and opsonized zymosan was significantly greater in high cholesterol subjects compared to their matched controls. The production of platelet activating factor (PAF) by calcium ionophore (2.5 micrograms) stimulated PMN isolated from hypercholesterolaemic subjects (11.5 +/- 1.4 ng/10(6) cells) was significantly greater than PAF production by cells from the control group (8.3 +/- 1.0 ng/10(6) cells). Leukotriene B4 release by PMN in response to calcium ionophore did not differ between the 2 groups. These data suggest a degree of leukocyte activation in hypercholesterolaemic subjects compared to controls with normal cholesterol. In addition, plasma levels of lyso-PAF were higher in high cholesterol subjects (317 +/- 21 ng/ml) compared to their matched controls (271 +/- 18 ng/ml) perhaps indicating increased plasma acetylhydrolase activity in subjects with raised cholesterol levels. Recently described biological activity for lyso PAF suggests a possible role for this substance in atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1990

Inhibition of leukotriene and platelet activating factor synthesis in leukocytes by the sesquiterpene lactone scandenolide.

The sesquiterpene lactone scandenolide, isolated from the Philippines medicinal plant Mikania cordata, at a dose of 100 microM completely inhibited whole blood chemiluminescence in response to the activators PMA and zymosan. In isolated inflammatory rat leukocytes this compound inhibited both leukotriene B4 and 5-HETE production with IC50 of 15 microM and 30 microM, respectively. The formation of the cyclooxygenase product thromboxane B2 was not inhibited in the concentration range 10 to 200 microM of scandenolide. The formation of the potent inflammatory mediator platelet activating factor (PAF) was suppressed by microM concentrations of scandenolide with an IC50 of less than 20 microM. The presence of a compound in M. cordata which inhibits some of the inflammatory mediators such as leukotrienes and PAF may explain at least in part some of its medicinal properties.

Animals↗
PubMed1988

Effect of pure eicosapentaenoic acid feeding on blood pressure and vascular reactivity in spontaneously hypertensive rats.

1. This study examined the effects of eicosapentaenoic acid (EPA) treatment on vascular reactivity and blood pressure in spontaneously hypertensive rats (SHR). 2. Twenty SHR were given pure EPA as the methyl ester (280 mg/kg) by gavage for 10 days. An equal number of control rats received vehicle alone. EPA treatment had no effect on blood pressure compared with control rats. 3. Aortic rings from EPA-treated rats, precontracted with PGF2 alpha showed increased endothelium-dependent relaxations to acetylcholine. Endothelium-independent relaxations to sodium nitroprusside were not altered. Rings from rats fed pure EPA did not show any differences in vasoconstrictor responses to noradrenaline or serotonin. 4. Serum thromboxane B2 (TXB2) levels fell 17% in animals given pure EPA, but prostacyclin production was not affected. These responses are less than those seen following Max EPA fish oil. 5. Thus, pure EPA treatment did not lower blood pressure, but may have a direct effect on aortic endothelia and cause increased endothelium-dependent relaxations in response to acetylcholine in SHR.

6-Ketoprostaglandin F1 alpha↗