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Biomedical subjects

S R Maxwell

Publications and source records attributed to S R Maxwell.

At least 37 records · Page 2Linked to original sources
PubMed1996

Antioxidant depletion during aortic aneurysm repair.

Ischaemia-reperfusion injury generates oxygen-derived free radicals leading to local and distant damage. A simple method of following oxidative activity is to measure the consumption of endogenous scavenging antioxidants; an enhanced chemiluminescent assay was used to study this phenomenon in 21 patients undergoing surgery for abdominal aortic aneurysm (AAA). Samples of peripheral venous blood were taken before induction of anaesthesia and then from a central venous line and the inferior mesenteric vein before, during, and after clamping of the aorta. Further specimens were taken from the central line at 2, 6 and 24 h after operation. Antioxidant concentration in the peripheral, central and inferior mesenteric blood were similar, indicating that anaesthesia and surgical dissection had no effect. Levels decreased significantly in central and inferior mesenteric blood during and after clamping, but returned to normal by 24 h. These results confirm ischaemia-reperfusion phenomena in AAA repair.

Aged↗
PubMed1996

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy.

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.

Adult↗
PubMed1995

Antioxidant consumption during exercise in intermittent claudication.

Twenty male claudicant patients and nine age-matched controls were exercised on a treadmill. Blood and urine samples were taken before and after exercise. Total antioxidant concentration was measured using an enhanced chemiluminescent assay and microalbuminuria determined by radioimmunoassay. Claudicants had increased microalbuminuria after exercise. Mean (s.e.m.) antioxidant concentrations were similar for patients and controls at rest: 479(28) and 438(23) mumol/l respectively. Claudicants showed a significant decrease in antioxidant concentration 1 min after exercise to 428(27) mumol/l; this returned to 470(30) mumol/l by 10 min. A correlation was found between the decrease in antioxidant concentration and the increase in microalbuminuria (rs = -0.496, P < 0.05). This study supports the concept of ischaemia-reperfusion injury in claudicant patients and has implications for treatment.

Adult↗
PubMed1995

Antioxidants, von Willebrand factor and endothelial cell injury in hypercholesterolaemia and vascular disease.

The relationship between antioxidants and endothelial cell injury was examined in 119 patients with (n = 48) or without (n = 71) vascular disease who were attending a hyperlipidaemia clinic. Serum levels of total antioxidant capacity, glutathione peroxidase (a protein antioxidant), von Willebrand factor (vWf, a specific endothelial cell product and marker of injury) and routine lipids were measured in the patients and from 58 healthy controls. Compared to controls, total antioxidant capacity (P < 0.01) and glutathione peroxidase (P < 0.0001) were lower whilst vWf was higher (P < 0.0001) amongst the patients. Comparing patients with and without vascular disease, glutathione peroxidase was lower (P < 0.03) and vWf was higher (P < 0.05) in the presence of vascular disease but there was no difference in levels of serum lipids or total antioxidant capacity. vWf and glutathione peroxidase were inversely correlated (r = -0.26, P < 0.005). We conclude that patients with hypercholesterolaemia have reduced antioxidant capacity and this is most severe in patients with clinically apparent vascular disease. This, linked to the finding of increased vWf in hypercholesterolaemia with highest levels in those patients with vascular disease, suggests that loss of antioxidant capacity may expose the vascular endothelium to excess oxidative damage. These results suggest a link between hypercholesterolaemia, impaired ability to resist free radical attack, and the development of atherosclerosis.

Antioxidants↗
PubMed1995

Prospects for the use of antioxidant therapies.

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. Natural antioxidant defences have been found to be defective in many of the same diseases. This has led to suggestions that oxidative damage and therefore disease progression may be retarded by supplementing natural antioxidant defences. Potential antioxidant therapy includes natural antioxidant enzymes and vitamins or synthetic agents with antioxidant activity. Diseases where antioxidant therapy may be beneficial include diabetes mellitus, reperfusion injury, inflammatory diseases and the prevention of chronic processes such as atherosclerosis and carcinogenesis. Further well controlled prospective clinical trials of antioxidants are required to establish the efficacy and tolerability of antioxidant therapy in the treatment of human diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Measurement of antioxidant activity in lipoproteins using enhanced chemiluminescence.

We describe a new assay for antioxidant activity (AOA) in lipoprotein solutions based upon their potential to quench light emission from a glowing horseradish peroxidase-catalyzed enhanced chemiluminescent reaction. By comparison with the quenching activity of the tocopherol-analogue trolox the AOA can be quantified. These measurements suggest that all lipoprotein fractions have significant AOA and that this has a non-linear relationship with lipoprotein concentration increasing significantly on a per particle basis at higher concentrations. Mean AOA in very low density, low density and high density lipoprotein fractions were 39.9 +/- 5.3, 20.3 +/- 4.0 and 5.3 +/- 1.0 mumol of trolox equivalents per litre, respectively, when measured at 1 mg protein/ml. Using known values for the protein content of the lipoprotein fractions, these values correspond to 79.8 +/- 10.7, 10.3 +/- 2.0 and 0.84 +/- 0.15 equivalents per particle. Parallel measurements of light emission and conjugated diene formation suggest that the oxidative stress imposed by the peroxidase-catalyzed reaction leads to lipid peroxidation but only after all AOA has been exhausted. AOA was significantly correlated with the alpha-tocopherol content in 30 lipoprotein samples (r = 0.764). This assay offers a rapid and simple method for investigating the effects of diseases, drugs or dietary manipulation on lipoprotein AOA.

Antioxidants↗
PubMed1994

Therapeutic progress. III: Diabetic nephropathy.

Diabetic nephropathy is a common cause of end stage renal failure. Patients ultimately require dialysis or transplantation and endure a poor quality of life in association with increased mortality. Due to the quantitative significance of this problem there is also a considerable financial burden. It has been generally accepted that once nephropathy is established it is irreversible although aggressive anti-hypertensive treatment can delay its progression. More recently there have been numerous reports proposing a specific renal protective role of certain drugs. In this article we review the current literature on the use of angiotensin converting enzyme inhibitors in diabetic nephropathy. There is strong evidence that the use of ACE inhibitors in diabetic nephropathy (in the presence or absence of hypertension) slows the progression of deterioration in renal function and may even arrest its progression if detected at the microproteinuric stage.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Evidence for downregulation of hypothalamic 5-hydroxytryptamine receptor function in endurance-trained athletes.

Serum prolactin (PRL) was used as a hormone marker of serotoninergic function following oral administration of an acute dose of a serotoninergic agonist. Five male endurance-trained athletes (ET) and five healthy non-endurance-trained controls (NT) were studied. The peak PRL concentration was lower (P = 0.031) for the ET athletes (486 +/- 208 mU l-1; mean +/- S.D.) than for the NT controls (1000 +/- 385 mU l-1); the total release of PRL was also lower (P = 0.042) for the ET subjects. The lower neuroendocrine response to a serotoninergic agonist in the endurance-trained athletes suggests a downregulation of central serotoninergic receptor function in response to endurance training in man.

Adult↗
PubMed1994

Corticosteroids: do they damage the cardiovascular system?

Since their introduction for the treatment of rheumatoid arthritis, corticosteroids have become widely used as effective agents in the control of inflammatory diseases. Although there have been undoubted benefits upon mortality in diseases such as systemic lupus erythematosus, many patients survive only to suffer a high incidence of premature atherosclerosis. There is also evidence of increased rates of vascular mortality in other corticosteroid-treated diseases, such as rheumatoid arthritis, reversible airways obstruction and transplant recipients. Possible mechanisms of damage include elevated blood pressure, impaired glucose tolerance, dyslipidaemia, and imbalances in thrombosis and fibrinolysis. This paper reviews the clinical evidence supporting the contention that there is an excess cardiovascular mortality in steroid-treated patients and the underlying mechanisms, and points to further areas of research.

Adrenal Cortex Hormones↗
PubMed1994

Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage.

Hypertension is associated with an increased risk of atherosclerosis. Free radical oxidative damage has been implicated in the atherogenic process. We measured levels of the antioxidants uric acid, thiols, vitamins C, A and E as well as the total antioxidant capacity in 21 normotensive controls, 22 patients whose hypertension was controlled on drugs and 30 patients with uncontrolled hypertension. Mean BPs in the groups were 125/76, 132/80 and 181/98 mmHg, respectively. When compared with controls, both hypertensive groups had significantly lower serum ascorbic acid (54 +/- 5 vs. 37 +/- 6 vs. 38 +/- 5 mumol/l, P < 0.05) and albumin-corrected thiol levels (9.91 +/- 0.18 vs. 8.69 +/- 0.20 vs. 8.92 +/- 0.19 mumol/g, P < 0.05). The levels of the other antioxidants did not differ significantly between the groups. Levels of von Willebrand factor, a marker of endothelial damage, were correlated with SBP but not with antioxidant status. We conclude that hypertensive subjects have lower levels of the antioxidants vitamin C and thiols and this may reflect greater oxidative consumption. The implications for atherogenesis and endothelial function and integrity in hypertension are discussed.

Adult↗
PubMed1993

Can anti-oxidants prevent ischaemic heart disease?

Ischaemic heart disease remains a major cause of mortality in developed countries. A number of important risk factors for the development of coronary atherosclerosis have been identified including hypertension, hypercholesterolaemia, insulin resistance and smoking. However, these factors can only partly explain variations in the incidence of ischaemic heart disease either between populations or within populations over time. In addition, population interventions based upon these factors have had little impact in the primary prevention of heart disease. Recent evidence suggests that one of the important mechanisms predisposing to the development of atherosclerosis is oxidation of the cholesterol-rich low-density lipoprotein particle. This modification accelerates its uptake into macrophages, thereby leading to the formation of the cholesterol-laden 'foam cell'. In vitro, low-density lipoprotein oxidation can be prevented by naturally occurring anti-oxidants such as vitamin C, vitamin E and beta-carotene. This article explores the evidence that these dietary anti-oxidants may influence the rate of progression of coronary atherosclerosis in vivo and discusses the need for formal clinical trials of anti-oxidant therapy.

Animals↗
PubMed1993

A comparison of the beta 1-selectivity of conventional metoprolol and metoprolol CR during exercise in healthy volunteers.

This paper reports on a randomized double-blind crossover study to compare the effects of daily treatment with 100 mg conventional metoprolol (M100), 50 or 100 mg slow-release metoprolol CR (CR50, CR100) and placebo on the response to treadmill walking exercise in 12 healthy volunteers. Twenty minutes of exercise was undertaken at 1.5 h post-dose (Ex1) and again at 4 h (Ex2). During Ex1 all metoprolol preparations caused a reduction in the exercise-induced increase in heart rate when compared to placebo (P < 0.001). The exercise-induced increase in plasma glycerol, an indicator of lipolysis, was diminished by all metoprolol preparations but to a greater extent by M100 (P < 0.05). Rises in plasma ammonia were used to assess the net degradation of energy-rich adenine nucleotides by skeletal muscle during exercise. When compared to placebo, a significant elevation in plasma ammonia was seen only during exercise with M100 (P < 0.05). The perceived exertion at the end of exercise was also greatest on conventional metoprolol. The differences between the effects of conventional and CR formulations of metoprolol were less when exercise was repeated 4 h post dosing. We conclude that metoprolol CR may offer advantages over the conventional preparation, in subjects regularly engaging in exercise, by reducing the metabolic stress imposed upon skeletal muscle.

Adult↗
PubMed1993

Changes in plasma antioxidant status during eccentric exercise and the effect of vitamin supplementation.

Twenty-four healthy students undertook one hour of box-stepping exercise. Prior to exercise eight had received no medication (Group A), eight received 400 mg of vitamin C daily for three weeks before and one week after exercise (Group C) and eight received 400 mg of vitamin E for the same period (Group E). Groups C and E had significantly higher levels of vitamin C (p < 0.01) and vitamin E (p < 0.01) respectively than group A at the commencement of exercise. Plasma total antioxidant capacity rose significantly during exercise in all group (A - p < 0.05; C - p < 0.001; E - p < 0.001). This rise was accounted for by increases in plasma uric acid in all groups. In addition there were significant increases in vitamin C in group C (p < 0.001) and vitamin E in group E (p < 0.05). There were no significant changes in plasma malondialdehyde following exercise in any group. It is concluded that plasma antioxidant capacity rises in response to one hour of eccentric exercise and that the contribution of individual antioxidants to this change can be influenced by vitamin supplementation. The possible mechanisms of the antioxidant changes during exercise and their implications are discussed.

Adolescent↗