Biomarkers of oxidative stress in overweight men are not influenced by a combination of antioxidants

The effect of antioxidant supplementation on biomarkers of oxidative stress was investigated in a 6-week intervention study in 60 overweight men. The supplement contained a combination of antioxidants aiming to correspond to the antioxidant content found in a diet rich in fruit and vegetables. Placebo, single or double dose of antioxidants was provided to the subjects. Metabolic variables, plasma antioxidants and biomarkers of oxidative stress (lipid peroxidation and DNA damage) were measured. No effect of supplementation on biomarkers of oxidative stress was observed. Both intervention groups showed substantial increases of plasma antioxidants. This study demonstrated that supplementation with a combination of antioxidants did not affect lipid peroxidation and DNA damage in overweight men, despite increased concentrations of plasma antioxidants. The absence of antioxidant supplement effect might possibly be explained by the chosen study group having a normal level of oxidative stress, duration of the intervention and/or doses of antioxidants

Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients

One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved

Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration

Background Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. Methods Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. Results In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. Conclusion This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.Peer reviewe

Positive end-expiratory pressure during induction of general anesthesia increases duration of nonhypoxic apnea in morbidly obese patients.

Positive end-expiratory pressure (PEEP) applied during induction of anesthesia prevents atelectasis formation and increases the duration of nonhypoxic apnea in nonobese patients. PEEP also prevents atelectasis formation in morbidly obese patients. Because morbidly obese patients have difficult airway management more often and because arterial desaturation develops rapidly, we studied the clinical benefit of PEEP applied during anesthesia induction. Thirty morbidly obese patients were randomly allocated to one of two groups. In the PEEP group, patients breathed 100% O(2) through a continuous positive airway pressure device (10 cm H(2)O) for 5 min. After induction of anesthesia, they were mechanically ventilated with PEEP (10 cm H(2)O) for another 5 min until tracheal intubation. In the control group, the sequence was the same but without any continuous positive airway pressure or PEEP. We measured apnea duration until Spo(2) reached 90% and we performed arterial blood gases analyses just before apnea and at 92% Spo(2). Nonhypoxic apnea duration was longer in the PEEP group compared with the control group (188 +/- 46 versus 127 +/- 43 s; P = 0.002). Pao(2) was higher before apnea in the PEEP group (P = 0.038). Application of positive airway pressure during induction of general anesthesia in morbidly obese patients increases nonhypoxic apnea duration by 50%