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Biomedical subjects

S R Maxwell

Publications and source records attributed to S R Maxwell.

At least 19 recordsLinked to original sources
PubMed2001

Systemic uric acid administration increases serum antioxidant capacity in healthy volunteers.

Oxidative stress plays an important role in the development of atherosclerosis and contributes to tissue damage that occurs as a consequence, particularly in myocardial infarction and acute stroke. Antioxidant properties of uric acid have long been recognized and, as a result of its comparatively high serum concentrations, it is the most abundant scavenger of free radicals in humans. Elevation of serum uric acid concentration occurs as a physiologic response to increased oxidative stress-for example, during acute exercise-thus providing a counter-regulatory increase in antioxidant defenses. In view of its antioxidant properties, uric acid may have potentially important and beneficial effects within the cardiovascular system. We wished to investigate whether administration of uric acid was feasible and if it could have an impact on antioxidant function in vivo. We have, therefore, performed a randomized, placebo-controlled double-blind study of the effects of systemic administration of uric acid, 1,000 mg, in healthy volunteers, compared with vitamin C, 1,000 mg. We observed a significant increase in serum free-radical scavenging capacity from baseline during uric acid and vitamin C infusion, using two methodologically distinct antioxidant assays. The effect of uric acid was substantially greater than that of vitamin C.

Adult↗
PubMed2000

Coronary artery disease--free radical damage, antioxidant protection and the role of homocysteine.

Traditional risk factors for coronary artery disease (CAD) can only explain approximately two thirds of the observed clinical events. This has maintained interest in other nutritional and biochemical factors that might contribute to the underlying pathophysiology of vascular disease. Two such factors are dietary antioxidants and plasma homocysteine. Established risk factors such as hypertension, smoking and diabetes mellitus are all associated with increased oxidative stresses due to excess free radical activity in the vascular wall. This may facilitate the development of vascular disease because of (i) increased oxidation of low-density lipoprotein (LDL) particles which increases their propensity to deposition in the vascular wall, (ii) inactivation of endothelium-derived nitric oxide, and (iii) direct cytotoxicity to endothelial cells. Protective antioxidant molecules include vitamin C and vitamin E of which the latter is lipid soluble and is the primary antioxidant defence in circulating LDL particles. Epidemiological studies have suggested strongly that individuals who have high circulating concentrations or dietary intake of natural antioxidant vitamins are protected against vascular disease events (18). Furthermore, many studies have demonstrated a beneficial effect of natural and synthetic antioxidants on surrogate markers of vascular disease such as endothelial function and lipoprotein oxidation. However, large prospective randomized controlled intervention trials, mostly involving vitamin E (e.g. CHAOS, HOPE (22)), have failed to demonstrate any beneficial effect upon vascular mortality in high risk individuals. Possible reasons for these disappointing results include the pro-oxidant effects of high dose antioxidant supplements, particularly in patients with established vascular disease. Homocysteine is a sulphydryl-containing amino acid derived from the demethylation of dietary methionine. Epidemiological studies over 30 years have shown that increased concentrations of homocysteine are associated with vascular disease. This link is independent of other risk factors, is consistent across many studies and is strongly dose-related. Recently, evidence has accumulated to suggest that this link is also biologically plausible because homocysteine promotes oxidant injury to the vascular endothelium, impairs endothelium-dependent vasomotor regulation and may also alter the coagulant properties of the blood. Plasma homocysteine levels can be reduced by dietary supplements of folic acid and B vitamins. Studies are currently being undertaken to examine the impact of these vitamins in high risk patients and, thereby, establish a causative role for homocysteine in promoting vascular events.

Animals↗
PubMed1999

Antioxidant vitamin supplements: update of their potential benefits and possible risks.

Oxidative damage to biological structures has been implicated in the pathophysiology of cardiovascular disease and cancer, the 2 most common causes of death in developed countries. This has stimulated interest in the possible role of natural antioxidant vitamins in preventing the development of these diseases. Epidemiological studies have offered support for the notion that high blood concentrations or dietary intake of antioxidant vitamins may have a protective effect. On the basis of these findings and powerful marketing strategies, many healthy members of the population are now voluntarily consuming antioxidant supplements. A number of long term, prospective, randomised, placebo-controlled trials examining the protective effect of antioxidant supplements have now been completed. Their results have been generally disappointing and have provided little evidence of efficacy. Of greater concern, they have unexpectedly raised concerns that antioxidants, notably betacarotene, might increase the rate of development of cancers in high risk individuals. For this reason regular consumption of antioxidant vitamins supplements cannot yet be advocated as a healthy lifestyle trait.

Antioxidants↗
PubMed1998

Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia.

OBJECTIVES: Oxygen-free radicals and lipid hydroperoxides may have an aetiological role in the development of lesions in the central nervous system in patients with Alzheimer's disease and in those with vascular dementia. This study aimed to make a cross-sectional comparison of blood markers of oxidative stress in two groups of patients with these disorders and a control group. DESIGN: Cross-sectional comparative study. SETTING: Established memory clinics in Cardiff organized by a University Department of Geriatric Medicine within an acute care NHS Trust. METHODS: Following a dietary assessment, postprandial venous blood samples were obtained from the following: 25 subjects with probable Alzheimer's disease (AD) (mean age 74.3; 10 F, 15 M); 17 subjects with probable vascular dementia (VD) (mean age 75.5; 5 F, 12 M); and 41 controls (mean age 73.4; 24 F, 17 M) for measurement of circulating lipid peroxides (LP), total antioxidant capacity (TAC), vitamin C (VitC), vitamin E (VitE) and beta-carotene (BC). RESULTS: Plasma levels of VitC were significantly lower in subjects with vascular dementia compared with controls (VD, 6.5 (4.8, 8.2); controls, 10.0 (8.38, 11.6); VD vs controls, p = 0.015), but no significant difference was seen between controls and patients with Alzheimer's disease (AD, mean 8.3 (6.2, 10.4)). VitE levels were significantly lower in subjects with AD compared with controls (31.1 (28.2, 34.0) vs 36.0 (32.8, 39.2), p = 0.035). BC levels were similar in subjects with AD and controls, but significantly elevated in those with VD (AD, 0.28 (0.2, 0.34); VD, 0.40, (0.27, 0.53); controls, 0.28 (0.22, 0.34); VD vs controls, p = 0.046). There were no significant differences in LP or TAC between the three groups. CONCLUSIONS: Subjects with dementia attributed to Alzheimer's disease or to vascular disease have a degree of disturbance in antioxidant balance which may predispose to increased oxidative stress. This may be a potential therapeutic area for antioxidant supplementation.

Aged↗
PubMed1998

Women and heart disease.

Coronary heart disease and other vascular diseases account for approximately half of all deaths in women. Although the underlying pathophysiological processes (atherosclerosis and thrombosis) are similar, deaths and other clinical end-points are significantly delayed compared to men. The reason for this sex-related delay in the expression of vascular disease remains a matter of debate but may be largely attributable to the actions of endogenous oestrogens: coronary heart disease manifestations are extremely rare in premenopausal women but increase after the menopause. These observations have lead to speculation that oestrogen-replacement therapy might continue to retard the development of cardiovascular disease in the post-menopausal years (primary prevention). The cardioprotective benefits of oestrogens include a favourable impact on plasma lipids, anti-platelet effects, preservation of endothelium-mediated vasodilatation and antioxidant effects. Several observational studies support this thesis but the results of prospective randomised controlled trials are still awaited. Secondary preventative measures such as aspirin, beta-blockade, ACE inhibition and HMG-CoA reductase inhibitors seem to be equally effective for women as men. However, there remains evidence that physicians are less likely to use such interventions in women at high risk.

Estrogens↗
PubMed1997

Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options.

Lack of blood supply or ischaemia underlies many of the most important cardiovascular and cerebrovascular diseases faced by clinicians in their daily practice. Many of these ischaemic episodes can be reversed at an early stage by surgical or pharmacological means with the ultimate aim of preventing infarction and cell necrosis in the ischaemic tissues. However, reperfusion of ischaemic areas, in particular the readmission of oxygen, may contribute to further tissue damage (reperfusion injury). For example, the use of thrombolytic therapy in acute myocardial infarction and other revascularisation procedures, such as percutaneous transluminal angioplasty and coronary artery bypass surgery, may be associated with reperfusion of ischaemic myocardium. Such ischaemia and reperfusion may result in injury to one of more of the biochemical, cellular and microvascular components of the heart. Our understanding of the significance of reperfusion injury is however restricted by the profuse literature in animal models and limited literature in the clinical situation. This article reviews the pathophysiology, clinical manifestations of reperfusion injury to the heart and discusses the possible therapeutic approaches to avoiding any adverse effects.

Animals↗
PubMed1997

Free radicals and antioxidants in cardiovascular disease.

Several lines of evidence suggest that free radical-mediated oxidative damage to lipoproteins may be an important factor predisposing them to uptake into the vascular wall. This has led to interest in the factors that determine the susceptibility of lipoproteins to oxidation and their relationship to the development of coronary heart disease. Of these factors, the lipoprotein content of natural antioxidant vitamins such as vitamin E, and beta-carotene have aroused particular interest. Studies in animal models of atherosclerosis suggest that natural and synthetic antioxidants can retard the development of atheroma. Epidemiological comparisons between populations and studies within populations also support the contention that high plasma levels or dietary intake of natural antioxidant vitamins may protect against the development of coronary disease in man. Prospective randomized controlled trials of antioxidants in high risk groups are underway to test whether the theoretical promise of a beneficial role for antioxidants in coronary heart disease prevention will be fufilled.

Animals↗
PubMed1997

Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus.

Oxidative damage by free radicals has been implicated in the pathogenesis of vascular disease in diabetes. We compared the radical-scavenging antioxidant activity of serum from 28 patients with insulin-dependent diabetes mellitus and 24 patients with non-insulin-dependent diabetes mellitus uncomplicated by vascular disease with age-matched non-diabetic control subjects. Patients with insulin-dependent diabetes had significantly reduced total antioxidant activity (320.2 +/- 11.3 vs. 427.5 +/- 19.2 mumol L-1; P < 0.001). This was attributable to lower urate (209.4 +/- 10.4 vs. 297.1 +/- 16.7 mumol L-1; P < 0.001) and vitamin C levels (63.6 +/- 6.0 vs. 87.5 +/- 4.9 mumol L-1; P < 0.01). Patients with non-insulin-dependent diabetes had lower total antioxidant activity than age-matched control subjects (433.8 +/- 25.4 vs. 473.9 +/- 30.2 mumol L-1; NS), reflecting lower urate (299.5 +/- 19.4 vs. 324.8 +/- 21.4 mumol L-1; NS) and vitamin C levels (38.6 +/- 5.7 vs. 58.5 +/- 5.3 mumol L-1; P < 0.05). Multiple regression analysis showed that urate, vitamin C and vitamin E were the major contributors to serum total antioxidant activity. These results show that diabetic patients have significant defects of antioxidant protection, which may increase vulnerability to oxidative damage and the development of diabetic complications.

Adult↗
PubMed1997

Enhanced chemiluminescent assay for measuring the total antioxidant capacity of serum, saliva and crevicular fluid.

This paper reports the development of an enhanced chemiluminescent (ECL) assay for measuring the total antioxidant (AO) capacity of serum, saliva and a fluid collectable from the gum margin called gingival crevicular fluid (GCF). The theory behind the assay is explained, and the optimum conditions for the assay, and for storage of reagents and clinical samples is described. Calibration lines were linear (R > or = 0.99; P < 0.0001) and the within batch coefficient of variations for a water soluble vitamin E analogue (Trolox), serum and saliva samples were < 5%. In saliva and GCF, a characteristic AO response not seen in serum of the same patients, was identified. Total peripheral (serum) and local (saliva) AO capacities (mumol/L Trolox) were investigated in patients with (n = 18) and without (n = 16) adult periodontitis. Serum AO status did not differ between groups. Salivary total AO concentrations were lower in the peridontitis (P) group [175 (53) mumol/L] than in the non-periodontitis (NP) group [254 (110) mumol/L1: P < 0.01], as were saliva:serum AO ratio's [0.37 (0.11) versus 0.5 (0.18): P < 0.01]. Periodontitis patients may have a reduced salivary AO concentration, which could result from, or predispose to, the damaging effects of reactive oxygen species (ROS). The potential for ROS production in the oral and periodontal environment may explain the presence of a specific antioxidant in oral fluids that is not detectable in serum. The ECL assay described provides a rapid, simple and reproducible method of measuring total antioxidant defence in small volumes of biological fluids.

Adult↗
PubMed1997

Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus.

The diabetic patient is at significantly increased risk of developing vascular disease. Its aetiology may involve oxidative damage by free radicals and protection against such damage can be offered by radical-scavenging antioxidants. We investigated whether there was a relationship between glycaemic control as assessed by measurement of glycated haemoglobin (HbA1c) and serum antioxidant status in a population of 118 diabetic outpatients with either insulin-dependent or non-insulin-dependent diabetes. Amongst patients with non-insulin-dependent diabetes mellitus there was a significant inverse correlation between levels of glycated haemoglobin and total free radical scavenging activity (r = -0.456, P < 0.0001). This association resulted primarily because of a similar correlation with uric acid (r = -0.421, P = 0.0003). There was also a weak inverse correlation with vitamin A but no significant association with vitamin C or vitamin E levels. There were no significant associations found amongst the patients with insulin-dependent diabetes. These results indicate that poor diabetic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. By implication improved glycaemic control may preserve serum antioxidant status in diabetes.

Adult↗
PubMed1997

Anti-oxidant therapy: does it have a role in the treatment of human disease?

Free radical oxidative stress has been implicated in the pathogenesis of a variety of human diseases. Natural anti-oxidant defences have also been found to be defective in many of the same diseases. Many researchers have concluded that, if the imbalance between the oxidative stresses and anti-oxidant defence can be corrected by supplementing natural anti-oxidant defences, it may be possible to prevent or retard disease progression. Potential anti-oxidant therapies include natural anti-oxidant enzymes and vitamins or synthetic agents with anti-oxidant activity. Diseases where anti-oxidant therapy may be beneficial can be divided into those involving acute intervention, such as reperfusion injury or inflammation, and those involving chronic preventative therapy, such as atherosclerosis, carcinogenesis and diabetic vascular disease. The pharmaceutical considerations are different in each case. The principles guiding the development, use and assessment of anti-oxidant therapies are discussed in this review.

Journal Article↗
PubMed1997

An investigation of the antioxidant activity of black tea using enhanced chemiluminescence.

Antioxidants are important species which possess the ability to protect the body from damage caused by free radical-induced oxidative stress. A variety of free radical-scavenging antioxidants exist within the body many of which are derived from dietary sources. There is currently much interest in the antioxidant role of flavonoids and other polyphenols found in tea, wine, fruit and vegetables. Enhanced chemiluminescence is a simple technique which can be used as a rapid and sensitive assay for measuring the antioxidant activity of beverages such as green and black tea. This article examines the impact of water temperature, stewing time, leaf concentration and the addition of milk upon the antioxidant activity of black tea solutions. The antioxidant activity of a range of commercially available black and green teas has also been measured.

Animals↗