Oxidative stress is thought to play a major role in the pathogenesis of Alzheimer's disease (AD). Although there is strong post-mortem and experimental evidence of oxidative damage occurring in AD brains, the use of markers in the peripheral circulation to show oxidative stress is less convincing. We examined plasma from AD patients for markers of increased oxidative stress. We report elevated levels of 4-hydroxy-nonenal (4-HNE) in AD patients compared to controls (median 20.6, IQR 6.0-25.2 vs. 7.8, 3.3-14.5 micomol/l, respectively; p=0.001) but not malondialdehyde (MDA), and lower levels of ascorbate in AD plasma when compared to age-matched controls (9.9, 6.0-33.7 vs. 24.2, 13.9-48.6 micromol/l; p<0.05). Levels of 4-HNE in AD patients were inversely related to ascorbate (r=-0.337; p=0.07) and Folstein Mini-Mental State Examination (MMSE) (r=-0.474; p=0.015). The concentration of protein sulphydryls, free-radical scavengers, was directly related to the MMSE result (r=0.427; p=0.03). Increased production of 4-HNE indicates increased oxidative stress (lipid peroxidation), which is not evident using the more common marker MDA. This elevation of 4-HNE was related to the degree of cognitive impairment (MMSE).
Patients with cystic fibrosis (CF) experience a combination of chronic systemic oxidative stress, generation of free radicals in the lungs due to a hyperimmune response and a diminished ability to scavenge free radicals secondary to malabsorption and increased consumption. The authors asked the question, "Does breath isoprene content reflect systemic oxidative stress?"The study involved 12 CF patients and 12 matched healthy controls. The patients were sampled during acute respiratory exacerbation (increased respiratory symptoms, reduction in forced expiratory volume (FEV1) of >10%, and a decision to treat with intravenous antibiotics) and after two weeks of antibiotic treatment. Blood samples were examined for markers of oxidative stress. Breath samples were analysed for isoprene content.Malondialdehyde (MDA), erythrocyte membrane polyunsaturated fatty acids, protein sulphydryls and protein carbonyls all showed evidence of increased oxidative stress which was moderated by antibiotic treatment. Breath isoprene production rate was significantly lower in patients during exacerbation than in controls with a mean difference of -39 (95% confidence interval (CI) -11±57) pmol . min . kg -1 and increased to normal values following treatment (mean change 63 (95% CI 42±84) pmol . min . kg -1 ).In conclusion, breath isoprene cannot be considered a reliable marker of oxidative stress.
Two fluorescent probes were used for the measurement of membrane fluidity in patients on haemodialysis and continuous ambulatory peritoneal dialysis. 1,6-Diphenyl-1,3,5-hexatriene (DPH) anisotropy gives an indication of lipid order and pyrene measures lateral diffusion through the membrane. Pyrene dimer/monomer ratio was significantly lower than controls in both pre-dialysis and post-dialysis samples but DPH anisotropy was unchanged. Both methods showed an increase in membrane fluidity across a 4 hour haemodialysis session. There was an increase in membrane fluidity in CAPD patient samples which was more marked using DPH than pyrene. These results suggest that the two probes give different but complementary information about changes in membrane fluidity and may be more informative when used together rather than singly.
The following Table was omitted when published in the October issue TABLE I SUMMARY OF ALL CASES PUBLISHED SINCE 1966 Publications No. of Improved Deteriorated Postpartum Comment cases Preg. Preg. outcome.
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