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Biomedical subjects

A J Sinclair

Publications and source records attributed to A J Sinclair.

At least 145 records · Page 8Linked to original sources
PubMed1990

Free radicals and antioxidant systems in health and disease.

Free radical (FR) mechanisms have both beneficial and deleterious actions in vivo. Intensive scientific interest in FRs over the last 20 years has led to a clearer understanding of their roles and helped to clarify the contribution of our intrinsic defence systems (antioxidants) in limiting FR-induced tissue damage. As more and more conditions are shown to have a FR aetiology it becomes imperative to develop newer therapies to prevent and treat FR-induced disease.

Antioxidants↗
PubMed1990

Effects of single doses of a 20 mg frusemide/2.5 mg amiloride combination, 20 mg frusemide and placebo on plasma and urine electrolytes in healthy men.

The effects of single doses of a combination of 20 mg frusemide and 2.5 mg amiloride, of 20 mg frusemide and of placebo on plasma and urinary electrolytes were assessed in healthy volunteers using a randomized, crossover study. The combination significantly (P less than 0.001) increased the urinary volume compared with frusemide alone or placebo. Mean total urinary sodium was also significantly (P less than 0.001) increased by frusemide/amiloride compared with both frusemide and placebo. Mean total potassium excretion was reduced significantly (P less than 0.01) by frusemide/amiloride but total magnesium excretion was not significantly affected. The effects of frusemide/amiloride on plasma sodium, magnesium and potassium were similar to those of placebo. It is concluded that frusemide/amiloride has a greater diuretic and natriuretic effect than frusemide alone and does not increase potassium loss.

Adult↗
PubMed1989

Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty.

The effect of an eicosapentaenoic acid-rich encapsulated preparation of fish oil on the incidence of early restenosis after coronary angioplasty was assessed by a randomized double-blind placebo-controlled study. A total of 108 patients received either 10 capsules of fish oil (1.8 g eicosapentaenoic acid, 1.2 g docosahexaenoic acid) or 10 control capsules (50% olive oil, 50% corn oil), commencing the day before angioplasty and continuing for 4 months after angioplasty, in addition to treatment with aspirin and verapamil. In 101 (94%) of the 108 patients, follow-up angiographic or postmortem result was evaluated at a mean (+/- SD) of 100 (+/- 22) days. Angiographic restenosis was observed in 34% of patients (29% of lesions) in the fish oil-treated group and 33% of patients (31% of lesions) in the control group (no significant difference). The overall incidence of angiographic restenosis was significantly higher in patients with 1) recurrent angina pectoris, 2) a positive exercise test at follow-up after angioplasty, 3) residual stenosis greater than 30% immediately after angioplasty, and 4) dilation of the left anterior descending or right coronary artery. Biochemical investigations showed a greater decrease in the serum triglyceride levels in the fish oil-treated group versus the control group (p less than 0.05) but no differences between the two groups in cholesterol levels or platelet counts over the 4 month period. In conclusion, in this study, the administration of fish oil at a dose of 10 capsules/day did not reduce the incidence of early restenosis after coronary angioplasty.

Adult↗
PubMed1989

A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter.

A rat thyroglobulin promoter fragment, capable of directing thyroid-specific transcription, binds at least three different factors, TTF-1, TTF-2 and UFA, which are all present in nuclear extracts of the differentiated rat thyroid cell line FRTL-5. TTF-1 and TTF-2 are FRTL-5 specific, as demonstrated by their absence in nuclear extracts prepared from cell lines that do not express any thyroid-differentiated function, while UFA is present in all cell lines tested. TTF-1 has been extensively purified. It binds to the rat thyroglobulin promoter at three different sites which share sequence homology. Mutations in two of the three sites decrease both binding of TTF-1 in vitro and promoter function in vivo. This suggests that the tissue-specific expression of the thyroglobulin genes is mediated, at least in part, by the presence of a transcription factor exclusively in thyroid cells.

Animals↗
PubMed1989

Pre- and post-treatment distribution pattern of 123I-MIBG in patients with phaeochromocytomas and paragangliomas.

123I-metaiodobenzylguanidine (MIBG) localizes in adrenergic neurones. A comparison of % washout of MIBG, during two time intervals, from various organs was carried out in seven normal volunteers and 11 patients with phaeochromocytoma and/or paraganglioma pre- and post-treatment using MIBG. % washout of MIBG during the time intervals of 30 min to 4 h were as follows: heart, controls 26.1 +/- 3.8 v. patients 51.5 +/- 9.1, (p less than 0.001), lungs, controls 36.5 +/- 5.3 v. patients 47.3 +/- 5.8, (p less than 0.05), liver, controls 26.5 +/- 5.7 v. patients 53.4 +/- 12.0 (p less than 0.01). Following treatment the % washout of MIBG from these tissues between 30 min and 4 h were similar in both groups of subjects. This observation coincided with the normalization of plasma catecholamine levels in most of the treatment group. There was no significant difference between the treatment and control groups, in the % washout of MIBG from these tissues during the 4 h and 22 h time intervals either before or after treatment. We conclude that quantitative scintigraphy 30 min to 4 h after MIBG administration is a useful technique to evaluate the pathophysiological effects of high circulating catecholamines in patients with phaeochromocytomas and/or paragangliomas.

3-Iodobenzylguanidine↗
PubMed1989

Alfuzosin and the venous reflex response: studies in normal subjects.

1. Alfuzosin is a post-synaptic alpha-adrenoceptor antagonist with antihypertensive and peripheral vasodilator properties. 2. We measured the effect of alfuzosin, 5 mg, on sympathetically-mediated venoconstriction by changes in the venous reflex response (VRR) in a randomised, double-blind, placebo-controlled, crossover study in a group of 10 healthy volunteers. 3. There was a significant inhibition of the VRR after alfuzosin compared with placebo (P less than 0.001) which was present 1 h after the dose and still evident at 6 h. 4. Supine blood pressure was significantly lower (P less than 0.01) and supine heart rate was significantly higher (P less than 0.001) after alfuzosin compared with placebo. 5. Inhibition of the VRR by alfuzosin was observed to precede the development of reflex tachycardia.

Adult↗
PubMed1989

Kinetics of digoxin and anti-digoxin antibody fragments during treatment of digoxin toxicity.

Anti-digoxin antibody fragments (ADAF, 80 mg) were infused intravenously to successfully treat severe digoxin toxicity in an 82 year old woman. During treatment, total and free digoxin were determined using an Abbot TDX analyser and an ultrafiltration technique. ADAF were measured by an enzyme-linked immunosorbent assay. By 1 h after ADAF, total serum digoxin concentrations had risen 12-fold from a pretreatment level of 15.4 nmol l-1 but free digoxin fell from 10 to 0.1 nmol l-1, indicating greater than 99.9% digoxin binding to ADAF. However, the low free levels had rebounded to 7.7 nmol l-1 by 12 h, but despite this rise the patient's condition had improved. A serum ADAF/digoxin molar ratio of around five was associated with the low concentration of free digoxin at 1 h, while at later times with ratios roughly between 3 and 4, the free digoxin concentrations ranged between 2.0 and 7.7 nmol l-1. ADAF were mainly confined to the plasma during the first hour, but subsequently distributed into an apparent volume of 193 ml kg-1. The elimination half-lives of ADAF and total digoxin were 96 and 55 h, respectively. More than 50% of the estimated digoxin load had been excreted in the urine by 5 days; for ADAF the equivalent figure was only about 3%. Renal and/or bacterial degradation may have contributed to the low detection of urinary ADAF.

Aged↗
PubMed1988

Effects of dietary butter enrichment on the fatty acid distribution of phospholipid fractions isolated from rat platelets and aortae.

Rats were maintained for 2 weeks on a low-fat basal diet (5% energy) and a diet from which 50% of the energy was derived from butter. Lipids were extracted from aortae and platelets and the fatty acid profiles of individual phospholipids were examined. Similar responses to dietary butter enrichment occurred in PI, PS, PE and PC fractions from either tissue: 20:4(n - 6) and all other n - 6 series longer-chain polyunsaturated fatty acids except 20:3(n - 6) decreased in percentage; all n - 3 series polyunsaturated fatty acids increased, including 20:5(n - 3) and 22:6(n - 3); n - 9 series polyunsaturated fatty acids, derived from 18:1(n - 9), increased. Despite the considerable redistribution of polyunsaturated fatty acids, the percentages of total polyunsaturated fatty acids in each phospholipid were, in every case, independent of diet. None of the changes were localized in a particular phospholipid fraction. Quantitation of fatty acids using heptadecanoic acid as an internal standard revealed that the concentrations of 20:4(n - 6) in platelet and aortic PE and PC was higher than in PI fractions. Therefore, in terms of substrate amount, it appears that PC and PE as well as PI have the potential to provide endogenous 20:4(n - 6) for oxygenation to the prostanoids thromboxane A2 and prostacyclin I2.

Animals↗
PubMed1988

An investigation of nutrition-related risk factors in an isolated Aboriginal community in northern Australia: advantages of a traditionally-orientated life-style.

Australian Aborigines develop a high frequency of type-2 diabetes mellitus when they make the transition from a traditional to an urban life-style. Preliminary studies were conducted at an outstation in northeastern Arnhem Land where the Aborigines have been exposed to Western influence for approximately 20 years only and where they continue to follow a life-style that is largely traditional. At the time of the study 31 persons were resident at the outstation, 20 persons were over 15 years of age (adults) and 11 persons were under 15 years of age (children). Eighteen adults and six children were tested. By standard criteria for body mass index these persons were all underweight (less than 20 kg/m2). In spite of this, they displayed no biochemical evidence of malnutrition. Their plasma fatty-acid profiles were consistent with a low dietary fat intake and a high consumption of lean meat. Levels of linoleic acid were much lower and those of arachidonic acid were much higher than are those in persons who consume a Western diet. Fasting glucose and cholesterol concentrations were low relative to those of urbanized Aborigines and white Australians. However, their fasting insulin and triglyceride levels were inappropriately high for their very low body mass index and fasting glucose levels. The mild elevation of triglyceride and fasting insulin levels is consistent with insulin resistance and suggests that these Aborigines (in common with other Aborigines) may become susceptible to obesity and diabetes if they became urbanized further.

Adolescent↗
PubMed1988

Increased vascular reactivity induced by essential fatty acid deficiency in rat autoperfused hindquarters.

The effects of essential fatty acid deficiency (EFAD) on vascular reactivity to vasoconstrictor stimuli were studied in rat autoperfused hindquarters. Weanling male Sprague-Dawley rats (aged 21 days) were fed diets containing 8% (weight/weight) of stearax plus 2% safflower oil (control diet) or 10% stearax (EFAD diet) for 8 weeks. There was no difference in systemic blood pressure or body weight between the two groups. Basal production of immunoreactive 6-keto-PGF1 alpha by aortic segments was much less in EFAD aortae than in control aortae. In contrast, immunoreactive 6-keto-PGF1 alpha produced by incubating aortic segments with exogenous arachidonic acid (12 mumol/l) was much greater in EFAD aortae than in control aortae. Moreover, conversion of [14C]-arachidonate to [14C]-6-keto-PGF1 alpha was more pronounced in EFAD aortae than in control aortae. Vasoconstrictor responses to noradrenaline (0.01-1.0 mumol/l) and angiotensin II (0.001-1.0 mumol/l) infused into the blood perfused hindquarters were then examined. The rats on the EFAD diet were more sensitive to both noradrenaline and angiotensin II than rats on the control diet (P less than 0.05, two-way ANOVA). Thus, a deficiency of essential fatty acids can lead to increased vascular sensitivity to vasoconstrictor stimuli. Deficiency of arachidonic acid in phospholipid stores is also accompanied by augmented cyclo-oxygenase activity in the vessel wall, similar to that observed previously in spontaneously hypertensive rats (SHR) and rats with one kidney renovascular hypertension.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Effects on plasma lipids and fatty acid composition of very low fat diets enriched with fish or kangaroo meat.

The effects of very low fat diets (less than 7% energy) enriched with different sources of long chain (C20 and C22) polyunsaturated fatty acids (PUFA) on plasma lipid levels and plasma fatty acid composition were studied in 13 healthy volunteers. Three diets provided 500 g/day of tropical Australian fish (rich in arachidonic acid and docosahexaenoic acid), southern Australian fish (rich in docosahexaenoic acid) or kangaroo meat (rich in linoleic and arachidonic acids). The fourth diet was vegetarian, similarly low in fat but containing no 20- and 22-carbon PUFA. Subjects ate their normal or usual diets on weeks 1 and 4 and the very low fat diets in weeks 2 and 3. Weighed food intake records were kept, and weeks 2, 3 and 4 were designed to be isoenergetic with week 1. Plasma cholesterol levels fell significantly on all diets within one week. There were reductions in both low density (LDL) and high density lipoprotein (HDL) cholesterol levels, with effects on HDL cholesterol being more consistent. There were no consistent or significant effects on total triglyceride levels despite the high carbohydrate content of the diets. On all diets the percentage of linoleic acid fell in the plasma phospholipid and cholesteryl ester fractions, while the percentage of palmitic acid in the phospholipids and cholesteryl esters and palmitoleic acid in the cholesteryl ester fraction rose on all diets. The percentage of arachidonic acid rose in the phospholipid and cholesteryl esters on the two diets that were good sources of this fatty acid (tropical fish and kangaroo meat).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

In vivo kinetics of 123I-labelled insulin: studies in normal subjects and patients with diabetes mellitus.

Radioactive tracer techniques using 131I- and 125I-insulin have been applied to study insulin metabolism. A simple method to label human insulin with 123I to a high specific activity is described. We have used this radiotracer to study insulin kinetics in vivo in normal subjects and in two groups of diabetic patients. The rate of decline in plasma radioactivity was shown to be significantly reduced in patients with diabetes. There were no significant differences in the time-activity profiles of liver and kidneys between the groups studied. This technique may provide insight into the mechanism of some forms of insulin resistance.

Adult↗
PubMed1987

Effects of arachidonate deficiency on endothelium-dependent vascular reactions.

1. The release of endothelium-derived relaxing factor (EDRF), which appears to be impaired in vessels chronically exposed to hypertension, may involve mobilization of arachidonate from phospholipids. In this study the effects of arachidonate deficiency on endothelium-dependent responses were examined in rat isolated aorta. 2. Weanling rats were fed an essential fatty acid-deficient (EFAD) diet for 8 weeks which reduced plasma and aortic phospholipid arachidonate content from 17 to 1.8% and from 21 to 8%, respectively. After this time the rats were killed and the reactivity of aortic rings was studied in organ baths. 3. In aortic rings from control rats the concentration-response curves for the contractile action of phenylephrine were shifted to the left 3.5-fold by removal of the endothelium, and the maximum was not altered. 4. In contrast, in EFAD rings with endothelium, the maximal vasoconstriction to phenylephrine was less than in control rings, and removal of the endothelium increased the maximum (from 1.9 +/- 0.2 to 3.2 +/- 0.1 g, P less than 0.05) and reduced the EC50 7-fold. 5. In EFAD rings precontracted with phenylephrine (0.3 mumol/l) the relaxations produced by the endothelium-dependent dilator acetylcholine were not significantly different from those produced in control rings. The dilator actions of sodium nitroprusside were also similar in EFAD and control rings. 6. Thus, endothelium-dependent dilatation in the aorta is not impaired by partial depletion of phospholipid arachidonate. However, contractile responses to alpha-adrenoceptor agonists are depressed by spontaneously released EDRF in rat aorta, so that the results suggest that depletion of phospholipid arachidonate either augments spontaneous release of EDRF, or impairs EDRF inactivating mechanisms.

Animals↗