Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Les ligands amidines N-phosphorées (synthèse, structure, réactivité, coordination et catalyse)

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Silver-modification of ZnO thin films deposited on Zn-electroplated Cu substrate by thermal shock method for the enhanced photocatalytic performance

Ag-modified ZnO thin films on Zn-electroplated Cu substrate with different Ag-contents were prepared via a simple sol–gel spin-coating procedure followed by a thermal shock method with AgNO3, and then characterized by XRD, Raman, FTIR, FESEM, EDX, and UV-visible absorption spectroscopy. Their photocatalytic performance was evaluated by the degradation of methylene blue. Due to the sol–gel spin-coating process, the film was successfully immobilized on mechanically robust Zn/Cu plates, making it promising for applications in harsh practical conditions and facilitating recovery. When our ZnO thin films were surface-modified with AgNO3 at 1 and 2 mol%, they exhibited the best photocatalytic activity under UVA light and visible light, respectively, which can be explained by the appearance of maze-like architecture on their surface with vertical ZnO walls, surface defects and metallic silver nanoparticles. However, when the Ag-content was increased to 3 mol%, the maze-like structure collapsed, leading to decreases in photocatalytic performance

Flash vacuum thermolysis of N-(3- and 4-pyridylmethylidene)-tert-butylamines: mechanisms of formation of pyrrolopyridines and naphthyridines

Pyrrolopyridines and naphthyridines are formed by flash vacuum thermolysis (FVT) of 3-and 4-pyridylmethylidene-tert-butylimines 8 and 15. Elimination of a methyl radical generates resonance stablized 2-azaallyl radicals a1 and b1. The formation of pyrrolopyridines 9, 16 and 17 is rationalized in terms of cyclization of 1-aziridinyl radicals a2 and b2. Formation of naphthyridine 10 from imine 8, and of 11 and 18 from imine 15, are in accord with cyclization of 1-azaallyl radicals a6 and b9. Formation of naphthyridine 11 from 8, and of 10 and 19 from 15, indicate the operation of the spiro-cyclization pathways forming intermediates a9 and b14. Formation of the 1,8-naphthyridine 20 (3%) indicates a rearrangement through aziridine b22 and biradical b23. DFT calculations at the CAM-B3LYP/6-311G(d,p) level support the proposed reaction mechanisms

Antiproliferative, Anti-Inflammatory Activities, and Molecular Docking Studies of Secondary Metabolites from Macrosolen tricolor

In Vietnam, Macrosolen tricolor is used for the treatment of bloating, broken bones, cough, diarrhea, diuretic, rheumatism, and laxative effects. The study aimed to identify the in vitro antiproliferation and anti-inflammation of all fractions and purified compounds from the M. tricolor whole plants, as well as the in silico molecular docking of the potentially cytotoxic compounds. As the results, fractions (MTH.I, MTH.II, MTE.I, and MTE.II) strongly demonstrated antiproliferative properties against three tested cells, MDA-MB-231, RD, and HepG2 (IC50 values ranged from 4.00 ± 0.20 to 70.60 ± 1.44 μg/mL), as well as anti-inflammatory effects (IC50 values ranged from 4.45 ± 0.08 to 23.00 ± 1.18 μg/mL), whereas other fractions meaningfully evidenced selective cytotoxicity and/or anti-inflammation. Therefore, the phytochemical compositions of the active fractions were illuminated, leading to the characterization of eighteen compounds. Compounds (3–5) revealed the most cytotoxic effects towards all examined cells (IC50 values ranged from 6.88 ± 0.12 to 71.64 ± 1.17 μM) and the strongest anti-inflammatory properties (IC50 values of 16.30 ± 0.92, 7.31 ± 0.55, and 9.23 ± 0.60 μM, respectively). Compound 11 showed potential cytotoxicity against MDA-MB-231, RD, and HepG2 cells (IC50 values of 24.42 ± 0.28, 20.60 ± 0.25, and 3.20 ± 0.02 μM, respectively). Furthermore, compounds (4, 5, and 11) interacted with the active site of the apoptosis regulator Bcl-2 protein (PDB ID: 2O2F), were comparable to PAC, and were compatible with their anticancer activity. This project suggests that M. tricolor is a good source of natural antiproliferative and anti-inflammatory agents and contributes to understanding the biological activities of Macrosolen species in traditional Vietnamese medicine