Catherine I.A. Jack

UVR-induced oxidative stress in human skin in vivo: effects of oral vitamin C supplementation

Previous studies of cultured skin cells and murine skin in vivo have indicated that UVR-induced damage involves the generation of reactive oxygen species and depletion of endogenous antioxidant systems. In order to explore the relevance of this to UVR-induced damage to human skin, we have undertaken a detailed examination of the time-course of changes in markers of oxidative stress in human skin following exposure to physiological amounts of UVR in vivo. In addition, we have examined the skin bioavailability of a common nutritional antioxidant, vitamin C, and have assessed the effects of supplementation on markers of oxidative stress. Our hypothesis was that acute exposure of human skin to UVR in vivo would lead to oxidation of cellular biomolecules that could be prevented by prior vitamin C treatment. A UVR-challenge of 120 mJ/cm2 of broadband UVB (peak 310 nm, range 270-400 nm) was applied to buttock skin of 8 healthy volunteers. This caused a rapid and significant rise in activity of skin catalase at 1 h and an increase in the oxidized/total glutathione ratio at 6 h post-UVR. AP-1 DNA binding also peaked at 1-6 h post-UVR, then declined rapidly to baseline levels. No significant changes were seen in skin malonaldehyde content. Oral vitamin C supplements (500 mg/day) were taken by 12 volunteers for 8 weeks resulting in significant rises in plasma and skin vitamin C content. Supplementation had no effect on the UVR-induced erythemal response. The skin malonaldehyde content was reduced by vitamin C supplementation, but surprisingly, reductions in the skin content of total glutathione and protein thiols were also seen. We speculate that this apparently paradoxical effect could be due to regulation of total reductant capacity by skin cells, such that vitamin C may have been replacing other reductants in these cells. No evidence was obtained for an effect of the supplementary vitamin C on the mild oxidative stress seen in human skin following UVR exposure.

Use of Restraints and Bedrails in a British Hospital

To determine the prevalence of restraint and bedrail use in a British hospital.

Effect of antioxidant supplementation on the adaptive response of human skin fibroblasts to UV-induced oxidative stress

The effect of supplementation with substances having antioxidant properties on the adaptive responses of human skin fibroblasts to UV-induced oxidative stress was studied in vitro. UVR was found to induce a substantial oxidative stress in fibroblasts, resulting in an increased release of superoxide anions and an increase in lipid peroxidation (shown by an elevated malonaldehyde content). Sub-lethal doses of UVR were also found to induce adaptive responses in the fibroblast antioxidant defences, with a transient rise in catalase and superoxide dismutase activities followed by a slower, large increase in cellular glutathione content. Supplementation of the fibroblasts with the antioxidants, Trolox (a water soluble analogue of alpha-tocopherol), ascorbic acid or beta-carotene, had differential effects on these responses. Trolox supplementation reduced the UVR-induced cellular oxidative stress and adaptive response in a predictable concentration-dependent manner. This was in contrast to ascorbic acid which increased superoxide release from fibroblasts. At low doses, ascorbate supplements also reduced the magnitude of the adaptive increases in catalase and superoxide dismutase activities and increase in glutathione content. Beta-carotene had a similar effect to ascorbic acid, reducing the extent of the adaptations to UVR at lower doses while simultaneously increasing superoxide release and malonaldehyde content. These in vitro data indicate that only the vitamin E analogue suppressed UVR-induced oxidative stress in a predictable manner and suggest that common dietary antioxidants may not be equally effective in reducing the potential deleterious effects of UVR-induced oxidative stress in skin.

A comparison of two techniques for ankle Jerk assessment in elderly subjects

The reported prevalence of absent ankle jerks in elderly people varies greatly. This variation may be due to differences in the method of testing. Eight physicians examined 12 patients for the presence of ankle jerks using two techniques: plantar strike and tendon strike. Both intra-observer agreement (kappa 0.47 vs 0.20; p = 0.01) and inter-observer agreement (0.57 vs 0.21; p < 0.001) were greater with plantar strike. Reliability of ankle jerk assessment was greater for more experienced examiners. Differences in technique may explain some of the discrepancy between studies examining the prevalence of absent ankle jerks in elderly people.

Asthma in the Elderly Patient

Asthma is common in old age and carries significant morbidity and mortality. Most deaths due to asthma occur in old people. Often the diagnosis of asthma is overshadowed by other medical problems such as heart failure and emphysema, and thus elderly people may not receive optimal treatment. The treatment of an elderly patient with asthma is further complicated by concomitant disease and pharmacological interactions.

Differential free-radical activity after successful and unsuccessful thrombolytic reperfusion in acute myocardial infarction.

BackgroundFree-radical generation after successful thrombolysis in acute myocardial infarction may jeopardise ischaemic but viable myocardium, thus limiting the optimal benefits of reperfusion. MethodsCirculating free-radical activity was assessed in 25 consecutive patients with acute myocardial infarction. Those who successfully reperfused (Group A) were compared with those who did not (Group B). We also compared patients who had or had not developed Q waves and patients with and without previous angina or myocardial infarction. All patients presented within 6 h of the onset of chest pain and received standard intravenous streptokinase therapy. Free-radical activity in serial serum samples collected over 72 h was measured using the percentage molar ratio (PMR) of the concentrations of 9,11-linoleic acid to 9,12-linoleic acid, and malonaldehyde concentration. ResultsThroughout the study period Group A (n = 11 ) showed significantly greater change in serum PMR and malonaldehyde levels compared with Group B (n = 14) (P< 0.01). PMR differences between the two groups were most pronounced at 3 and 12 h (P< 0.001). Patients with non-Q-wave myocardial infarction (n = 5) showed significantly greater changes in serum PMR and malonaldehyde levels (P< 0.01) compared with those with Q-wave infarction (n=20). A history of previous infarction or angina had no apparent effects on the changes in serum free-radical activity. ConclusionsSuccessful early reperfusion and non-Q-wave myocardial infarction are both associated with a significantly greater increase in the levels of markers of serum free-radical activity immediately after infarction. The results support present concepts of free-radical-mediated reperfusion injury. Use of these assays may identify those patients who may be at risk from free-radical-mediated reperfusion injury.

Serum octadeca-9,11 dienoic acid — an assay of free radical activity or a result of bacterial production?

The diene conjugated linoleic acid isomer is currently used as an assay of free radical activity, but recent studies have cast doubt on the specificity of the assay. Therefore, 180 strains of common bacterial lung pathogens were studied to determine whether they could produce the diene conjugated isomer of linoleic acid in vitro. The various strains were grown in tissue culture fluid spiked with linoleic acid. Concentrations of the diene conjugated 18:2 [9,11] linoleic acid isomer and the parent compound, 18:2 [9,12] linoleic acid were then determined using a high performance liquid chromatography method. The percentage molar ratio of these two isomers was found to be significantly elevated in 12.8% of all bacterial strains examined. In contrast the thiobarbituric acid reactivity, a non-specific measure of lipid peroxidation, was not elevated in any of the strains incubated in an identical fashion. These results suggest that the diene conjugated linoleic assay may not be a reliable marker of the free radical processes in the lung in the presence of certain bacterial infections.

Lack of protection of prior heat shock against UV-induced oxidative stress in human skin fibroblasts.

Abstract The effect of prior hyperthermia on UV-induced oxidative stress was studied in human skin fibroblasts. UV radiation alone induced an increased release of superoxide anions and increased lipid peroxidation in skin fibroblasts accompanied by a rise in catalase and superoxide dismutase activities. Hyperthermia was found to induce a significant rise in the cell content of heat-shock proteins, HSP60 and HSP70, but this treatment prior to UV radiation did not influence any indicators of oxidative stress in the fibroblasts. In contrast, the combination of heat shock prior to UV-exposure reduced fibroblast cell viability compared with UV radiation-exposure alone.