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Biomedical subjects

R Vandongen

Publications and source records attributed to R Vandongen.

At least 37 records · Page 2Linked to original sources

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↗

Mechanisms of platelet activating factor-induced aggregation and secretion in human platelets.

The role of TXA2 in PAF-induced aggregation and secretion of human platelets is unclear. We have studied the relationship between aggregation, synthesis of TXA2 and release of 5-HT during the time course of aggregation induced by PAF and collagen. For PAF-induced aggregation there was strong aggregation and secretion with minimal production of TXA2 in contrast to collagen in which a surge in TXA2 synthesis preceded both aggregation and secretion. To determine the role of calcium flux in PAF-induced aggregation we have similarly studied the temporal relationships between aggregation, secretion and TXA2 synthesis for calcium ionophore A23187 induced aggregation but found these to be distinctly different from those determined for PAF. A method for measuring absolute amounts of 5HT released from platelets in small volumes of plasma is described. We conclude that TXA2 is not important in the mechanism of PAF induced aggregation and that an increase in the level of intraplatelet calcium per se is not sufficient to explain the mediation of PAF-induced aggregation.

Adult↗

Controlled comparison of effects of exercise and alcohol on blood pressure and serum high density lipoprotein cholesterol in sedentary males.

1. Seventy-two sedentary male drinkers, aged 20-45 years, and with mean blood pressure (BP) at entry of 132 +/- 1.2/73 +/- 0.9 mmHg, completed a 4 week study during which they were assigned randomly to either drink a low alcohol beer (effectively reducing their weekly alcohol intake from 481 +/- 47 mL to 52 +/- 5 mL) or to continue their normal drinking habits. 2. Within these two groups subjects were further assigned to either a moderate exercise programme of three 30 min sessions per week of stationary cycling at 60-70% maximum workload or to a control light exercise programme where they pedalled against zero or minimal resistance. 3. Both alcohol restriction and moderate exercise were associated with mean falls in bodyweight of 0.5 kg. After adjustment for bodyweight a significant main effect of alcohol restriction on systolic BP (-4.1 +/- 1.7 mmHg, P less than 0.05) and diastolic BP (-1.6 +/- 0.8 mmHg, P = 0.05) was demonstrated. There was no significant main effect of moderate exercise on systolic or diastolic blood pressure despite a significant improvement in physical fitness (maximal oxygen uptake increasing from 33.2 +/- 0.8 mL/kg per min to 35.5 +/- 0.1 mL/kg per min). 4. Significant falls in high density lipoprotein cholesterol (HDLC) and triglyceride levels seen with alcohol restriction were unaffected by the increase in fitness, the magnitude of the fall being similar in both the moderate and light exercise groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Platelet activating factor and one-kidney, one clip hypertension.

The reduction in blood pressure to normotensive levels within 3 hours of unclipping the one-kidney, one clip Goldblatt hypertensive rat has been attributed to the release of potent blood pressure-lowering lipids, one of which is thought to be identical to platelet activating factor. The specific platelet activating factor receptor antagonist WEB 2086 was infused intravenously into hypertensive one-kidney, one clip rats, and the mean arterial blood pressure changes after unclipping were examined. Before infusion, blocking doses of WEB 2086 were confirmed to effectively abolish the fall in blood pressure induced by exogenous platelet activating factor. Serotonin release in response to exogenous platelet activating factor was also inhibited in platelets preincubated with plasma from rats infused with the antagonist. Hypertensive rats were given a bolus blocking dose of WEB 2086 (5 mg/kg i.v.) and the same dose by infusion (5 mg/kg/hr i.v.) before they were unclipped. A control group was given a bolus volume of saline and infused with saline before unclipping. In WEB 2086-treated rats, blood pressure fell from a baseline mean of 181 +/- 13.0 to 125 +/- 23 mm Hg after 4 hours, a fall of 28%. Saline-treated rats fell from a mean of 194 +/- 23 to 127 +/- 25 mm Hg (33%). There was no significant difference in the blood pressure fall between the two groups. Therefore, platelet activating factor is unlikely to be responsible for the restoration of normal blood pressure after unclipping the Goldblatt hypertensive rat. We attribute the fall in blood pressure to other presently unidentified renomedullary lipids.

Animals↗

Two-way factorial study of alcohol and salt restriction in treated hypertensive men.

The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a "low sodium" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fish oil-induced changes in apolipoproteins in IDDM subjects.

The aim of this study was to examine the effect of Max EPA (a commercially available fish oil preparation) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic (IDDM) men with dosages that were likely to be acceptable to patients. Twenty-two male IDDM patients aged 20-41 yr, 6 of whom had retinopathy, were recruited from the Royal Perth Hospital diabetic clinic. After screening, subjects were divided into three groups. Six of the subjects without retinopathy were randomly selected and allocated to a control group. The remaining 16 patients (10 without and 6 with retinopathy) received a fish oil supplement. All subjects were advised to maintain their usual dietary patterns. Sixteen patients, including the 6 with retinopathy, were instructed to take 15 Max EPA fish oil capsules/day with meals. Patients in the control group did not take Max EPA. Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol (P less than 0.01), which could be accounted for by increases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. The increase in HDL cholesterol was explained by a 33% rise (P less than 0.001) in its HDL2 subclass. Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-I increased after ingestion of fish oil and correlated significantly (P less than 0.05) with the rise in HDL cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Dietary fish oils increase serum lipids in insulin-dependent diabetics compared with healthy controls.

The effect of daily dietary supplementation with fish oil on serum lipids and platelet total phospholipid fatty acids was examined in male normolipidemic insulin-dependent diabetics and normal controls. They were given 15 g/d of fish oil as Max EPA (equivalent to 2.7 g/d of eicosapentaenoic acid) for 3 weeks. The diabetics showed a rise in total cholesterol, attributable to increases in LDL- and HDL-cholesterol. The increase in HDL-cholesterol was largely due to a rise in its HDL2 subclass. There was also a decrease in triglycerides in both groups. Similar changes in lipids were seen in the normal controls, although these were not significant. The more pronounced effect in diabetics suggests an altered metabolic response to omega-3 fatty acids in that disorder. However, the results indicate that the possible detrimental effect of the rise in total and LDL-cholesterol following fish oil may be offset by the increase in the protective HDL2 subclass.

Adult↗

Plasma levels of the lyso-derivative of platelet-activating factor are related to age.

1. The effect of age on the plasma level of the lyso-derivative of platelet-activating factor (lyso-PAF) was studied in 72 normal subjects, (32 females, 40 males) aged 12-64 years. Lyso-PAF was acetylated in vitro to PAF which was measured by bioassay using 5-[14C]hydroxytryptamine-labelled rabbit platelets. 2. Under 40 years there were similar direct relations between plasma lyso-PAF and age in both sexes (linear regression; males, P less than 0.001; females, P less than 0.002), the level approximately doubling from the adolescent level around 100 ng/ml. However, in the later years the levels fell, the fall seeming to commence earlier in females, so that between 40 and 65 years the level was greater in males [169 +/- 47 (SD) vs 120 +/- 30 ng/ml; P less than 0.01]. 3. The increase in plasma lyso-PAF up to middle-age may be related to the reported increase in prostanoid production with age, since these platelet and vasoactive compounds can have a common origin in membrane phospholipid. This would be consistent with increasing phospholipase A2 activity and decreasing stability of cell membranes with age, but the later fall in lyso-PAF is then unexplained; the lesser values in females than males in the more advanced years could be related to females' generally lesser vascular disease. However, knowledge of the biological roles and metabolism of PAF is still very limited and the real significance of the findings remains to be determined.

Adolescent↗

Role of thromboxane A2 as a mediator of platelet-activating-factor-induced aggregation of human platelets.

1. At present it is unclear whether platelet-activating-factor (PAF)-induced aggregation is mediated by thromboxane. To obtain further information about this event we have compared the affects of aspirin on platelet aggregation and secretion induced by PAF and collagen. 2. Collagen and PAF induced aggregation and secretion in human platelets in a dose-related manner. 3. Aspirin inhibited the magnitude of both platelet aggregation and secretion induced by PAF and collagen, but the degree of inhibition was much greater for collagen. 4. Aspirin strongly inhibited the aggregation rate of collagen-induced platelet aggregation, but had no measurable effect on the rate of PAF-induced aggregation. 5. Inconsistencies reported in previous studies of the effect of aspirin on PAF-induced platelet aggregation may be explained, in part, by the doses of PAF used and the method of inactivating cyclo-oxygenase (in vitro compared with in vivo). 6. Our results suggest that the initial events of PAF-induced aggregation are independent of thromboxane A2 formation and that thromboxane A2 plays only a minor role in the later phase of PAF-induced aggregation.

Adult↗