Biochemical analysis of α-synuclein extracted from control and Parkinson’s disease colonic biopsies

International audienceLewy bodies and neurites, the pathological hallmarks found in the brain of Parkinson’s disease (PD) patients, are primarily composed of aggregated and hyperphosphorylated alpha-synuclein. The observation that alpha-synuclein inclusions are also found in the gut of the vast majority of parkinsonian patients has led to an increasing number of studies aimed at developing diagnostic procedures based on the detection of pathological alpha-synuclein in gastrointestinal biopsies. The previous studies, which have all used immunohistochemistry for the detection of alpha-synuclein, have provided conflicting results. In the current survey, we used a different approach by analyzing the immunoreactivity pattern of alpha-synuclein separated by one- and two-dimensional electrophoresis, in colonic biopsies from PD subjects and healthy individuals. We did not observe any differences between controls and PD in the expression levels, phosphorylation or aggregation status of alpha-synuclein. Overall, our study suggests that the two biochemical methods tested here are not adequate for the prediction of PD using gastrointestinal biopsies. Further studies, using other biochemical approaches, are warranted to test whether there exists specific forms of pathological alpha-synuclein that distinguish PD from control subjects

Oxidative stress induction and genotoxicity of diesel exhausts on A549 lung cells continuously exposed at the air-liquid interface. Impact of rapeseed methyl ester supplementation and of after treatment devices: oxidation catalyst and particulate filter.

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Oxidative stress induction and genotoxicity of diesel exhausts on A549 lung cells continuously exposed at the air-liquid interface. Impact of rapeseed methyl ester supplementation and of after treatment devices: oxidation catalyst and particulate filter.

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An integrated functional and transcriptomic analysis reveals that repeated exposure to diesel exhaust induces sustained mitochondrial and cardiac dysfunctions

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Impact of after-treatment devices and biofuels on diesel exhausts genotoxicity in A549 cells exposed at air-liquid interface

International audienceUsing an air-liquid interface (ALI) device in dynamic conditions, we evaluated the efficiency of fuel after-treatment strategies (diesel oxidation catalysis, DOC, and diesel particulate filter, DPF, devices) and the impact of 7% and 30% rapeseed methyl esters (RME) blending on oxidative stress and genotoxicity induced in A549 lung cells after 3 h exposure to whole Diesel exhausts. Oxidative stress was studied using assays of ROS production, glutathione level, catalase and superoxide-dismutase (SOD) activities. No oxidative stress and no clear differences on cytotoxicity patterns between biodiesel and standard Diesel exhausts were found. A weak but significant genotoxicity (8-oxodGuo adducts) and, for standard Diesel only, a DNA damage response (DDR) as evidenced by ƔH2AX foci, remained after DOC + DPF flowing. All together, these data could contribute to the improvement of the after treatment strategies and to health risk assessment of current diesel exhausts

Bridging therapy or IV thrombolysis in minor stroke with large vessel occlusion

International audienceOBJECTIVE:Whether bridging therapy (intravenous thrombolysis [IVT] followed by endovascular treatment) is superior to IVT alone in minor stroke with large vessel occlusion (LVO) is unknown.METHODS:Multicentric retrospective observational study including, in intention-to-treat, consecutive IVT-treated minor strokes (NIHSS≤5) with LVO, with or without additional mechanical thrombectomy. Propensity-score (inverse probability of treatment weighting) was used to reduce baseline between-groups differences. The primary outcome was excellent outcome, i.e., modified Rankin score 0-1 at 3 months follow-up.RESULTS:Overall, 598 patients were included (214 and 384 in the bridging therapy and IVT groups, respectively). Following propensity-score weighting, the distribution of baseline clinical and radiological variables was similar across the two patient groups. Compared with IVT alone, bridging therapy was not associated with excellent outcome (OR=0.96; 95%CI=0.75-1.24; P=0.76), but was associated with symptomatic intracranial haemorrhage (OR=3.01; 95%CI=1.77-5.11; P<0.0001). Occlusion site was a strong modifier of the effect of bridging therapy on outcome (Pinteraction <0.0001), with bridging therapy associated with higher odds of excellent outcome in proximal M1 (OR=3.26; 95%CI=1.67-6.35; P=0.0006) and distal M1 (OR=1.69; 95%CI=1.01-2.82; P=0.04) occlusions, but with lower odds of excellent outcome for M2 (OR=0.53; 95%CI=0.38-0.75; P=0.0003) occlusions. Bridging therapy was associated with higher rates of symptomatic intracranial hemorrhage in M2 occlusions only (OR=4.40; 95%CI=2.20-8.83; P<0.0001).INTERPRETATION:Although overall outcomes were similar in intended bridging therapy as compared to intended IVT alone in minor strokes with LVO, our results suggest that intended bridging therapy may be beneficial in M1 occlusions, while the benefit-risk profile may favor IVT alone in M2 occlusions. This article is protected by copyright. All rights reserved

Comparative study of diesel and biodiesel exhausts on lung oxidative stress and genotoxicity in rats

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Comparative study of diesel and biodiesel exhausts repeated exposure on lung genotoxicity in rats

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Abstract Number ‐ 240: Association of intravenous thrombolysis and pre‐interventional reperfusion: a post‐hoc analysis of the SWIFT DIRECT trial

Introduction One potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre‐interventional reperfusion. Currently, there is a paucity of data regarding the occurrence of pre‐interventional reperfusion in patients randomized to IVT or no‐IVT before MT. Methods SWIFT DIRECT was a randomized controlled trial including acute ischemic stroke IVT‐eligible patients being directly admitted to a comprehensive stroke center, with allocation to either MT alone or IVT + MT. Primary endpoint of this analysis was the occurrence of pre‐interventional reperfusion defined as pre‐interventional expanded Thrombolysis in Cerebral Infarction score ≥ 2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results Out of the 396 patients analyzed, pre‐interventional reperfusion occurred in 20 (10.0%) of patients randomized to IVT+MT, and 7 (3.6%) of patients randomized to MT alone. Receiving IVT favored the occurrence of pre‐interventional reperfusion (aOR 2.91 [95% CI 1.23 – 6.87]). There was no IVT treatment effect heterogeneity on the occurrence of pre‐interventional reperfusion with different strata of Randomization‐to‐Groin‐Puncture (p for interaction = 0.33), although the effect tended to be stronger in patients with Randomization‐to‐Groin‐Puncture >28 minutes (aOR 4.65 [95% CI 1.16 – 18.68]). There were no significant difference in rates of functional outcomes between patients with and without pre‐interventional reperfusion. Conclusions Even for patients with proximal large vessel occlusions and direct access to MT, IVT leads towards an absolute increase of 6.9% (95% CI 1.7‐12.2%) in the rates of pre‐interventional reperfusion. The effect of IVT tended to be more pronounced when Randomization‐to‐Groin‐Puncture intervals were longer, but this heterogeneity did not reach statistical significance