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- Clausen, Bettina Hjelm, et al.
(författare)
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Systemically administered anti-TNF therapy ameliorates functional outcomes after focal cerebral ischemia
- 2014
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: The innate immune system contributes to the outcome after stroke, where neuroinflammation and post-stroke systemic immune depression are central features. Tumor necrosis factor (TNF), which exists in both a transmembrane (tm) and soluble (sol) form, is known to sustain complex inflammatory responses associated with stroke. We tested the effect of systemically blocking only solTNF versus blocking both tmTNF and solTNF on infarct volume, functional outcome and inflammation in focal cerebral ischemia. Methods: We used XPro1595 (a dominant-negative inhibitor of solTNF) and etanercept (which blocks both solTNF and tmTNF) to test the effect of systemic administration on infarct volume, functional recovery and inflammation after focal cerebral ischemia in mice. Functional recovery was evaluated after one, three and five days, and infarct volumes at six hours, 24 hours and five days after ischemia. Brain inflammation, liver acute phase response (APR), spleen and blood leukocyte profiles, along with plasma microvesicle analysis, were evaluated. Results: We found that both XPro1595 and etanercept significantly improved functional outcomes, altered microglial responses, and modified APR, spleen T cell and microvesicle numbers, but without affecting infarct volumes. Conclusions: Our data suggest that XPro1595 and etanercept improve functional outcome after focal cerebral ischemia by altering the peripheral immune response, changing blood and spleen cell populations and decreasing granulocyte infiltration into the brain. Blocking solTNF, using XPro1595, was just as efficient as blocking both solTNF and tmTNF using etanercept. Our findings may have implications for future treatments with anti-TNF drugs in TNF-dependent diseases.
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- Karimi, Mahssa, et al.
(författare)
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Driving habits and risk factors for traffic accidents among sleep apnea patients - a European multi-centre cohort study
- 2014
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 23:6, s. 689-699
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Tidskriftsartikel (refereegranskat)abstract
- Obstructive sleep apnea is associated with increased motor vehicle accident risk, and improved detection of patients at risk is of importance. The present study addresses potential risk factors in the European Sleep Apnea Database and includes patients with suspected obstructive sleep apnea [n = 8476, age 51.5 (12.5) years, body mass index 31.0 (6.6) kg m-2 , 82.4% driver's licence holders]. Driving distance (km year-1 ), driver's licence type, sleep apnea severity, sleepiness and comorbidities were assessed. Previously validated risk factors for accident history: Epworth Sleepiness Scale ≥16; habitual sleep time ≤5 h; use of hypnotics; and driving ≥15 000 km year-1 were analysed across European regions. At least one risk factor was identified in male and female drivers, 68.75 and 51.3%, respectively. The occurrence of the risk factors was similar across Europe, with only a lower rate in the eastern region (P = 0.001). The mean number of risk factors increased across classes of sleep apnea severity. Frequent driving was prevalent [14.0 (interquartile range 8.0-20.0) × 103 km year-1 ] and 32.7% of drivers had severe obstructive sleep apnea [apnea-hypopnea index 50.3 (38.8-66.0) n h-1 ]. Obesity, shorter sleep time and younger age were associated with increased traffic exposure (P ≤ 0.03). In conclusion, the risk factors associated with accident history were common among European patients with suspected obstructive sleep apnea, but varied between geographical regions. There was a weak covariation between occurrence of risk factors and clinically determined apnea severity but frequent driving, a strong risk factor for accidents, was over-represented. Systematic evaluation of accident-related risk factors is important to detect sleep apnea patients at risk for motor vehicle accidents.
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