Vitamin B12 inactivation may not be the only cause of acquired peripheral neuropathy in chronic nitrous oxide users

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What Is the Potential for Abuse of Lisdexamfetamine in Adults? A Preclinical and Clinical Literature Review and Expert Opinion

INTRODUCTION: Lisdexamfetamine dimesylate (LDX) is a prodrug approved for attention deficit/hyperactivity disorder and for moderate-to-severe binge eating disorder in adults in some countries. AREA COVERED: We aimed to specify the abuse potential of LDX in adults, using a review of pharmacokinetic/pharmacodynamic (PK/PD), animal, clinical, and pharmaco-epidemiological studies, through a PubMed search since inception until May 2021 using the following keywords: "lisdexamfetamine AND ('misuse' OR 'abuse' OR 'diversion' OR 'addiction')". EXPERT OPINION: Most of the studies highlighted a longer Tmax than dexamphetamine leading to a delayed onset of effects and a decreased Cmax. These PK parameters were often associated with a diminished feeling of euphoria, in comparison to immediate-release dexamphetamine. The potential for abuse was also limited by the prodrug property of LDX, thus reducing the risk of misuse. Nevertheless, all the data were not convergent, as some authors reported similar Cmax for LDX and dexamphetamine and reinforcing properties with a dose-dependent effect. Epidemiological studies found that abuse rates of LDX were substantially lower than those of immediate-release dexamphetamine. Overall, although LDX abuse seems possible, we did not find evidence concerning current safety signal. However, more long-term pharmaco-epidemiological studies are still needed to confirm this finding

The kinesin Kif21b regulates radial migration of cortical projection neurons through a non-canonical function on actin cytoskeleton

International audienceCompletion of neuronal migration is critical for brain development. Kif21b is a plus-end-directed kinesin motor protein that promotes intracellular transport and controls microtubule dynamics in neurons. Here we report a physiological function of Kif21b during radial migration of projection neurons in the mouse developing cortex. In vivo analysis in mouse and live imaging on cultured slices demonstrate that Kif21b regulates the radial glia-guided locomotion of newborn neurons independently of its motility on microtubules. We show that Kif21b directly binds and regulates the actin cytoskeleton both in vitro and in vivo in migratory neurons. We establish that Kif21b-mediated regulation of actin cytoskeleton dynamics influences branching and nucleokinesis during neuronal locomotion. Altogether, our results reveal atypical roles of Kif21b on the actin cytoskeleton during migration of cortical projection neurons

Fluorination of PVC medical devices to prevent plasticizers migration

International audienceMedical devices (MD) are often made of plasticized polyvinylchloride (PVC). However, plasticizers may leach out into infused solutions and expose the patients to a toxic risk. The aim of the present work is to fluorinate plasticized PVC tubular MDs to create a barrier layer on their internal surface, and to study the impact of such a chemical treatment on the migration of the plasticizers. Following fluorination by pure molecular fluorine, the physico-chemical characterization of these modified MDs was carried out using various spectroscopic and microscopic techniques or tensile tests, evidencing the formation of covalent C-F bonds on the surface of the treated samples without modification of their mechanical and optical properties. The migration of plasticizers from fluorinated MDs was assessed using gas chromatography coupled with mass spectrometry and was found considerably decreased in comparison with the pristine MDs. After 24 h, the amount of tri-octyltrimellitate plasticizer (TOTM) detected in migrates from fluorinated MDs was even lower than the limit of quantification. Complementary cytotoxicity assays were performed according to the ISO EN 10993-5 standard, showing that the new fluorinated material does not cause a cytotoxic effect on L929 cells

Les aspects actuels de l’usage de l’ecstasy/MDMA en France

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