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Biomedical subjects

R Vandongen

Publications and source records attributed to R Vandongen.

At least 19 recordsLinked to original sources

Measurement of ascorbic acid in platelets and its relationship to polymorphonuclear leukocyte levels.

A simplified method for measuring ascorbic acid (AA) concentrations in platelets is described. Platelet ascorbate was determined as the difference in concentrations between platelet rich plasma and platelet free plasma. In 20 healthy individuals concentrations of AA in platelets and polymorphonuclear leukocytes were found to be significantly correlated (r = 0.72, P < 0.01). Measurement of platelet ascorbate may provide an estimate of tissue AA status.

Adult

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

Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive oil supplementation.

This double-blind study was designed to examine and compare the effects of supplementing the existing diet with fish oil or olive oil on lipids and cell function in patients with peripheral vascular disease. Thirty-two patients with symptomatic and angiographically demonstrated peripheral vascular disease were screened, matched, and randomly allocated to take either 15 g/d fish oil or olive oil for 4 weeks. Fish oil reduced serum triglyceride levels by 26%, but increased total cholesterol levels due to a significant increase in both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein-2 cholesterol (HDL2-C). There was a nonsignificant decrease in HDL3-C levels. Olive oil reduced total cholesterol levels, accountable to a significantly decrease in LDL-C levels. Serum thromboxane B2 (TXB2) levels remained unchanged following fish oil, but were significantly increased by olive oil. Urinary excretion of TXB2 and 6-keto-PGF1 alpha was unaffected by either oil supplement. Platelet aggregation, which was measured in platelet-rich plasma in response to two doses of collagen or platelet-activating factor (PAF), was significantly reduced after fish oil, but was increased by olive oil. Following fish oil, there was a significant increase in eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) levels and a decrease in arachidonic acid content of platelet phospholipids. The platelet fatty acid composition after olive oil was unchanged. Fish oil decreased neutrophil leukotriene B4 (LTB4) generation following calcium ionophore stimulation by 33%, while leukotriene B5 levels increased significantly. Neutrophil PAF production and plasma lyso-PAF were unaffected by either oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Relationships between blood pressure and measures of dietary energy intake, physical fitness, and physical activity in Australian children aged 11-12 years.

STUDY OBJECTIVE: The aim was to examine associations between blood pressure and dietary energy intake, physical activity, and physical fitness in Australian children. DESIGN: The study was a survey of year 7 children attending schools in metropolitan Perth. SETTING: Survey schools were located in suburbs representative of the range of socioeconomic strata in metropolitan Perth. PARTICIPANTS: Data were obtained on 1311 out of 2045 eligible children (64%). The sample included 681 boys and 630 girls. Mean age was 12.0 (SD 0.4) years. MEASUREMENTS AND MAIN RESULTS: Triplicate blood pressure measurements were obtained using a Dinamap oscillometric recorder. Dietary energy intakes were computed from two week day 24 h records. Physical activity was assessed using questionnaires. Physical fitness was measured using a shuttle run test. Additional measurements included weight, height, and skinfold thickness at four sites. A previous observation of an inverse relationship between diastolic blood pressure and dietary energy intake in boys was confirmed. There was evidence of an inverse relationship in girls but not in boys between blood pressure and physical activity. There was little evidence of relationships between blood pressure and physical fitness. CONCLUSIONS: Compared with weight and body mass index, dietary energy intake and the chosen measures of physical activity and physical fitness are poor predictors of blood pressure in the population studied.

Blood Pressure

Effects of alcohol and caloric restrictions on blood pressure and serum lipids in overweight men.

We have examined the independent and combined effects on blood pressure and blood lipids of alcohol restriction and weight loss in overweight male drinkers with a view to assessing overall effects on cardiovascular risk of two widely promoted nonpharmacological approaches for hypertension. Eighty-six men with a mean age of 44.3 years, a mean regular alcohol intake of 440 ml/wk (five or six standard drinks per day), a mean blood pressure of 137.4 mm Hg systolic and 84.8 mm Hg diastolic, and a mean body mass of 92.5 kg entered a controlled two-way factorial study. The subjects were randomly assigned to four groups for an 18-week intervention in which members of two groups drank only low-alcohol beer, thereby reducing their alcohol intake by 374 ml/wk, while those of the other two groups continued their normal alcohol intake. Within the low and normal alcohol intake groups subjects either continued their usual diet or reduced their caloric intake by 4,200-6,300 kJ/day (1,000-1,500 kcal/day) (with protein, fat, and carbohydrate provided as 15%, 30%, and 55% of total calories, respectively). Calorie reduction and alcohol restriction caused weight losses of 7.5 (p less than 0.001) and 2.1 (p less than 0.01) kg, respectively. Calorie reduction and alcohol restriction were associated with decreases in systolic blood pressure of 5.4 (p less than 0.001) and 4.8 (p less than 0.01) mm Hg, respectively, and in diastolic blood pressure of 4.2 (p less than 0.001) and 3.3 (p less than 0.01) mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Differential effect of aspirin on platelet aggregation in IDDM.

Diabetes mellitus is associated with a high incidence of cardiovascular diseases not directly attributable to hyperlipidemia, smoking, or hypertension, but which in part may be explained by an enhanced tendency to thrombosis due to increased platelet activity. The aim of this study was to evaluate platelet function and compare the effectiveness of the antiplatelet drug aspirin on platelet aggregation in diabetic and nondiabetic subjects. Platelet aggregation and composition were examined in 20 male insulin-dependent diabetes mellitus (IDDM) patients and 20 nondiabetic control subjects matched for age and body mass index. All were normotensive with serum total cholesterol less than 6.5 mM. Although within the clinically acceptable normal range, blood pressure was significantly higher in diabetic patients (130/75 mmHg) than in control subjects (123/70 mmHg) (P less than 0.05). Serum thromboxane B2 and ex vivo aggregation of platelets in response to two doses of the agonists collagen and platelet-activating factor (PAF) were similar to nondiabetic subjects. However, after taking 100 mg/day aspirin for 5 days, platelet aggregation to collagen was reduced by 76% in control subjects compared to 56% in IDDM patients (P less than 0.001). Aspirin treatment also reduced the slope of the aggregation curve and increased the lag time (the period between the addition of collagen and the start of irreversible aggregation) significantly more in control than in diabetic platelets. This difference in platelet aggregation could not be attributed to differences in platelet serotonin or thromboxane A2 secretion, the latter being almost completely suppressed by aspirin in each group. Platelet aggregation to PAF was similar in both groups and was not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Changes in markers of alcohol intake in man below 'safe' drinking levels.

In a group of 343 working men, only 34 of whom regularly drank more than 60 ml of ethanol per day, logistic regression was used to determine the combination of biomarkers which best discriminated between those who regularly drank less than 30 ml or 30 ml or more of ethanol daily. The index consisted of apolipoprotein A-II, uric acid, gamma-glutamyl transpeptidase and mean corpuscular volume. Even with the relatively low level of alcohol intake reported in these subjects (assessed using a 7-day retrospective alcohol diary), the groups with higher or lower intake of alcohol were separated with a sensitivity of 68%, a specificity of 74% and a positive predictive value of 71%. Systolic blood pressure, adjusted for age and body mass index, was also linearly related to alcohol intake, and when included in the biomarker index improved the proportion correctly classified from 71% to 75%. Using the biomarkers only, 94% of subjects regularly drinking at least 80 ml of ethanol equivalent per day and 100% of the non-drinkers were correctly classified.

Adult

Blood pressure and body composition in children: importance of allowing for cuff size.

A cross-sectional study of blood pressure (BP) was conducted in a sample of 1312 Australian school children aged 11-12 yrs. In line with current recommendations for the measurement of BP, a cuff of appropriate size was chosen for each subject based on his or her arm circumference. Analyses revealed statistically significant independent relationships between measured BP and cuff size. Observed relationships in the sample between measured BP and body composition variables were substantially affected when BP measurements were adjusted to remove the effect of cuff size. Cuff-associated biases in estimates of relationships between BP and body composition variables may still exist even though cuffs are carefully chosen to suit arms of different circumferences. It would appear that this potential problem is largely unrecognised. Some previous studies of relationships between BP and body composition may have been affected.

Anthropometry

Reflotron cholesterol measurements in 1112 Australian children aged 10-12 years.

OBJECTIVE: To study the distribution of blood cholesterol concentration in a sample of Western Australian schoolchildren. DESIGN: The Reflotron dry-chemistry system (Boehringer Mannheim, Germany) was used to measure cholesterol in finger-prick blood samples obtained from Year 6 children aged 10-12 years attending government schools in metropolitan Perth. Recruitment methods ensured that children from different socioeconomic strata were represented. PARTICIPANTS: For the 1239 children enrolled in Year 6 in 30 government schools, parental consent to participate was obtained for 1144; of these cholesterol concentration was measured in 1112. RESULTS: The measurement method proved practicable and was generally well accepted. Cholesterol levels were somewhat lower than those obtained using a laboratory reference method and a bias, relative to national quality assurance standards, was estimated to be -0.32 mmol/L. Mean cholesterol level in boys (4.28 mmol/L, SD 0.69) was not significantly different from that in girls (4.35 mmol/L, SD 0.72). Allowing for measurement bias, 52% of boys and 57% of girls had cholesterol levels exceeding the National Heart Foundation's designated "desirable" level of 4.5 mmol/L for children. CONCLUSIONS: The distribution of cholesterol levels in Australian children compares unfavourably with distributions in children in countries with low rates of cardiovascular disease and indicates a need for widespread, appropriate diet and lifestyle changes.

Australia

Comparison of diets supplemented with fish oil or olive oil on plasma lipoproteins in insulin-dependent diabetics.

This study was designed to compare changes in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol in normolipidaemic male insulin-dependent diabetics (IDD) following dietary supplementation with either the fish oil concentrate Max EPA or olive oil. The contribution of the small quantity of cholesterol in Max EPA to these changes was also examined. Twenty-seven subjects were matched in groups of three and randomly allocated to one of three treatment groups of nine subjects each. Subjects were given 15 1-g capsules of oil daily for 3 weeks, consisting of either Max EPA, olive oil, or olive oil to which was added the same amount of cholesterol as contained in Max EPA, respectively. There was a significant increase in eicosapentaenoic acid, and a decrease in arachidonic acid, in the platelet membrane phospholipids of subjects taking Max EPA. In this group, there was an approximately 30% increase in serum HDL2-cholesterol (0.59 +/- 0.07 to 0.77 +/- 0.11 mmol/L, mean +/- SEM; P less than .01) and a corresponding decrease in HDL3-cholesterol (0.79 +/- 0.03 to 0.71 +/- 0.03 mmol/L; P less than .05). Although total and LDL-cholesterol concentrations were also higher after Max EPA, the changes were not significant. Triglycerides were significantly decreased by Max EPA. There were no significant changes in lipids in the groups given olive oil. These results show that compared with olive oil, dietary supplementation with Max EPA substantially increases HDL2-cholesterol in insulin-dependent diabetics. This is most likely due to a selective effect of omega 3 fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

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

A double-blind placebo-controlled trial of the effects of short-term potassium supplementation on blood pressure and atrial natriuretic peptide in normotensive women.

To determine the early effect of potassium loading on blood pressure regulatory mechanisms, the effect of 4 days' supplementation with 80 mmol/day KCl on blood pressure and vasodilator hormone release was examined using a double-blind crossover design in normotensive women with a baseline potassium excretion of 51.8 +/- 2.7 mmol/day. Systolic blood pressure fell 1.7 +/- 0.6 mm Hg, (P less than .01) in association with a mean increase in sodium excretion of 14.7 +/- 4.5 mmol/day and an increase in urine volume of 122.6 +/- 57.0 mL/day. There was a small but significant fall in plasma atrial natriuretic peptide (ANP) over the 4 days of potassium supplementation, while significant increases were seen in the levels of plasma potassium (P less than .01) and aldosterone (P less than .01). After 4 days of KCl, urinary 6-keto-PGF1 alpha was significantly elevated and correlated positively with urinary sodium excretion. Plasma renin activity was unchanged. The results suggest that increased vasodilator prostanoid synthesis and a mild natriuresis may contribute to the transient fall in systolic blood pressure. The increase in aldosterone and reduction in ANP probably represent homeostatic responses to this natriuresis, and could account for the failure of potassium supplementation to induce a long-term reduction in blood pressure in other studies in normotensive subjects.

6-Ketoprostaglandin F1 alpha

Urinary steroid profiles and alcohol-related blood pressure elevation.

1. From an earlier cross-sectional survey of 343 public servants, 15 pairs of non-smoking teetotallers and heavy drinkers (alcohol intake more than 350 mL/week) were matched for age and adiposity and utilized for a case-control study of the effects of alcohol on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity and blood pressure. 2. Two successive 24 h urine collections were analysed by radio-immunoassay (RIA) for cortisol excretion, and for the cortisol and cortisone metabolites, tetrahydrocortisol (THC), allo-tetrahydrocortisol (allo-THC) and tetrahydrocortisone (THE), by capillary column gas chromatography. 3. Heavy drinkers had higher systolic and diastolic blood pressure (BP) than teetotallers (132.6 +/- 2.5 vs 123.2 +/- 1.3 and 78.7 +/- 1.6 vs 71.7 +/- 1.4, respectively; unpaired t-test, P less than 0.01). Twenty-four-hour urinary sodium and cortisol excretion were similar in the two groups. 4. The THC plus allo-THC:THE ratio was similar in drinkers and teetotallers (1.81 +/- 0.20 vs 2.03 +/- 0.20), consistent with no effect of alcohol on 11 beta-OHSD activity. The ratio of THC to allo-THC was increased in drinkers compared with teetotallers (1.49 +/- 0.18 vs 1.05 +/- 0.13; unpaired t-test, P less than 0.05), consistent with either a decrease in 5 alpha-reductase activity or an increase in 5 beta-reductase activity. 5. This study provides no evidence for alcohol-related inhibition of 11 beta-OHSD, despite substantially higher blood pressures in heavy drinkers compared to teetotallers. Such an effect is, therefore, unlikely to contribute significantly to the mechanism of alcohol-related hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of smoking cessation on serum apolipoprotein A-I and A-II concentrations.

This study investigated the effects of 6 weeks' smoking cessation on serum levels of total-cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C) and apolipoproteins A-I and A-II (apo A-I and apo A-II) in 64 subjects of both sexes. Smoking cessation was associated with an increase in levels of apo A-II. Concurrent changes in weight and alcohol consumption during attempted smoking cessation, together with change in thiocyanate level, were entered as predictor variables into a multiple regression analysis. The change in apo A-II was found to be best accounted for by change in plasma thiocyanate level, and, in women, change in HDL-C and apo A-I by change in weight. The changes induced by smoking cessation may be due, at least in part, to associated changes in alcohol consumption and/or dietary intake, but in the case of apo A-II there is evidence of a more direct effect.

Adult

Release of platelet activating factor by the isolated kidney is not linked to the production of prostaglandins.

In many isolated tissues, including glomerular mesangial cells and endothelial cells, the synthesis of platelet activating factor (PAF) occurs by remodeling the phospholipids so that the production of PAF results in the release of arachidonic acid with subsequent production of cyclooxygenase or lipoxygenase products. In some tissues, including the renal medulla, another pathway for PAF biosynthesis (the de novo pathway) has been found in which the production of PAF is not linked to the production of arachidonic acid products. We tested the hypothesis that the remodeling pathway was active in the release of PAF into renal venous effluent of the isolated kidney. Isolated rat kidneys perfused at constant flow with albumin-containing buffer were stimulated to produce prostaglandin by an infusion of angiotensin II or bradykinin. Some kidneys were also challenged with the calcium ionophore A23187. Perfusate was collected for bioassay of PAF and radioimmunoassay of prostaglandin (PG) E2; urine was collected for PAF bioassay. Angiotensin II (10(-9) to 10(-8) M) increased renal vascular resistance, and bradykinin (10(-8) to 10(-7) M) and A23187 (3 x 10(-6) M) reduced renal vascular resistance. PGE2 production was increased significantly by bradykinin and angiotensin II but not by A23187. Only A23187 increased the release of PAF into the perfusate. Urine PAF was not changed by any of the stimuli. These data indicate that the release of PGE2 by the isolated, perfused rat kidney can be dissociated from the release of PAF. The findings support the suggestion that PAF released by the kidney into the renal venous effluent is not produced by remodeling the lipids that are the source of renally released prostaglandins.

Angiotensin II

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