Specific ion channels contribute to key elements of pathology during secondary degeneration following neurotrauma

Background: Following partial injury to the central nervous system, cells beyond the initial injury site undergo secondary degeneration, exacerbating loss of neurons, compact myelin and function. Changes in Ca 2+ flux are associated with metabolic and structural changes, but it is not yet clear how flux through specific ion channels contributes to the various pathologies. Here, partial optic nerve transection in adult female rats was used to model secondary degeneration. Treatment with combinations of three ion channel inhibitors was used as a tool to investigate which elements of oxidative and structural damage related to long term functional outcomes. The inhibitors employed were the voltage gated Ca 2+ channel inhibitor Lomerizine (Lom), the Ca 2+ permeable AMPA receptor inhibitor YM872 and the P2X 7 receptor inhibitor oxATP. Results: Following partial optic nerve transection, hyper-phosphorylation of Tau and acetylated tubulin immunoreactivity were increased, and Nogo-A immunoreactivity was decreased, indicating that axonal changes occurred acutely. All combinations of ion channel inhibitors reduced hyper-phosphorylation of Tau and increased Nogo-A immunoreactivity at day 3 after injury. However, only Lom/oxATP or all three inhibitors in combination significantly reduced acetylated tubulin immunoreactivity. Most combinations of ion channel inhibitors were effective in restoring the lengths of the paranode and the paranodal gap, indicative of the length of the node of Ranvier, following injury. However, only all three inhibitors in combination restored to normal Ankyrin G length at the node of Ranvier. Similarly, HNE immunoreactivity and loss of oligodendrocyte precursor cells were only limited by treatment with all three ion channel inhibitors in combination. Conclusions: Data indicate that inhibiting any of a range of ion channels preserves certain elements of axon and node structure and limits some oxidative damage following injury, whereas ionic flux through all three channels must be inhibited to prevent lipid peroxidation and preserve Ankyrin G distribution and OPCs

Mise en place d'une procédure DMOS au sein des laboratoires Grünenthal

CHATENAY M.-PARIS 11-BU Pharma. (920192101) / SudocSudocFranceF

Pelloutier, Pouget, Hamon, Lazare et le retour de l’anarchisme au socialisme (1893-1900)

Le socialisme européen est secoué, dans les années 1890-1893, par l’éclosion d’une aile gauche de sensibilité antiparlementaire – SDB aux Pays-Bas, Jungen en Allemagne, POSR en France. Une fraction du mouvement anarchiste va s’y intéresser et tenter une alliance voire une recomposition avec ce courant socialiste, qui permettrait de contester l’hégémonie de la social-démocratie. Du congrès de Zurich (1893) à celui de Paris (1900), un groupe de militants – Pouget, Pelloutier, Lazare, Hamon – va être au cœur de ce processus. La tentative va échouer, mais est révélatrice d’une volonté de l’anarchisme français de « retour au socialisme » à cette époque, et constitue un prélude méconnu à sa période syndicaliste

In Vitro Inhibition of NFAT5-Mediated Induction of CCL2 in Hyperosmotic Conditions by Cyclosporine and Dexamethasone on Human HeLa-Modified Conjunctiva-Derived Cells.

To investigate the pro-inflammatory intracellular mechanisms induced by an in vitro model of dry eye disease (DED) on a Hela-modified conjunctiva-derived cells in hyperosmolarity (HO) stress conditions. This study focused on CCL2 induction and explored the implications of the nuclear factor of activated T-cells 5 (NFAT5) as well as mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NFĸB). This work was completed by an analysis of the effects of cyclosporine A (CsA), dexamethasone (Dex) and doxycycline (Dox) on HO-induced CCL2 and NFAT5 induction.A human HeLa-modified conjunctiva-derived cell line was cultured in NaCl-hyperosmolar medium for various exposure times. Cellular viability, CCL2 secretion, NFAT5 and CCL2 gene expression, and intracytoplasmic NFAT5 were assessed using the Cell Titer Blue® assay, enzyme-linked immunosorbent assay (ELISA), RT-qPCR and immunostaining, respectively. In selected experiments, inhibitors of MAPKs or NFκB, therapeutic agents or NFAT5 siRNAs were added before the hyperosmolar stimulations.HO induced CCL2 secretion and expression as well as NFAT5 gene expression and translocation. Adding NFAT5-siRNA before hyperosmolar stimulation led to a complete inhibition of CCL2 induction and to a decrease in cellular viability. p38 MAPK (p38), c-Jun NH2-terminal kinase (JNK) and NFĸB inhibitors, CsA and Dex induced a partial inhibition of HO-induced CCL2, while Dox and extracellular signal-regulated kinase (ERK) inhibitor did not. Dex also induced a partial inhibition of HO-induced NFAT5 gene expression but not CsA or Dox.These in vitro results suggest a potential role of CCL2 in DED and highlight the crucial role of NFAT5 in the pro-inflammatory effect of HO on HeLa-modified conjunctiva-derived cells, a rarely studied cellular type. This inflammatory pathway involving NFAT5 and CCL2 could offer a promising target for developing new therapies to treat DED, warranting further investigations to fully grasp the complete intracellular mechanisms

Système de surveillance à distance de la démarche humaine dans le cadre de maladies neurologiques

National audienceLes maladies neurologiques deviennent de plus en plus courantes à mesure que la population vieillit et impliquent des dépenses de santé importantes. Une partie critique des soins est la surveillance des signes physiologiques des patients qui jouent un rôle important dans le processus de diagnostic. Cependant, moins d'attention est accordée aux soins à long terme, à domicile, qui sont considérés comme l'un des moyens les plus efficaces pour traiter les maladies neurologiques [1]. Un processus de surveillance prolongée est un aspect important dans l'évaluation à long terme du progrès et du rétablissement du patient. Cela implique des systèmes adaptés à l'usage domestique, avec accès à distance pour les professionnels de la santé [2]. Dans ce contexte, le téléphone mobile est l'outil d'accès facile mais il est entravé par des problèmes inhérents : limitation de la mémoire, de la puissance de traitement, de la batterie, de la taille de l’écran [3,4]. Ce travail propose une architecture pour un système d’analyse de la démarche humaine à base des capteurs d’un téléphone mobile, dont l’objectif principal est de réduire les verrous mentionnés ci-dessus

A Secured Smartphone-Based Architecture for Prolonged Monitoring of Neurological Gait

International audienc

Efficacy of Chlorhexidine Impregnated Wipes for the Local Dysbiosis in Atopic Dogs: A Multicentric Prospective Study

(1) Background: Dysbiosis is frequently observed in Canine Atopic Dermatitis (CAD). Antimicrobial treatment may be necessary to treat flare ups and the use of topical treatments is beneficial to prevent the development of bacterial resistance. Wipes are an easy way to apply antiseptic agents on the skin. The aim of this study was to evaluate the benefits of 3% chlorhexidine impregnated wipes (Pyoskin® wipes, MP Labo, France) on local areas of dysbiosis in dogs with CAD. (2) Methods: A total of 20 dogs suffering from CAD presented with localised areas of dysbiosis were included in this study. Affected areas were cleansed with the daily application of chlorhexidine wipes once a day for 14 days. Follow-up visits were scheduled after one and two weeks. Clinical signs (lesions and pruritus), dysbiosis scored by cytological counts (cocci and Malassezia) and investigator and owner global appreciation were evaluated. (3) Results: A statistically significant decrease in clinical scores and cytological counts were observed as soon as D7 and until D14. Both owner and investigator appreciation were considered high (4) Conclusions: The use of chlorhexidine impregnated wipes is a useful and easy way to manage localised dysbiosis in atopic dogs and allows limiting of systemic medication to prevent bacterial resistance

Hyperosmolar conditions, from 450 or 500 mOsM, induced cell death in an osmo-dependent manner, CCL2 secretion and gene expression, and NFAT5 gene expression and translocation in HeLa-modified conjunctiva-derived cells.

<p>Cells exposed to supplemented medium (340 mOsM) or different hyperosmolar conditions from 400 to 600 mOsM for 24 h were tested for cellular viability (A) with CellTiterBlue^® assay and CCL2 secretion (B) by ELISA, and cells treated for 4 h were lysed for mRNA expression by RT-qPCR to determine the CCL2 and NFAT5 gene expression (C, D). Data show mean ± SEM, <i>n</i> = 3 or more. Statistical analysis: one-way ANOVA followed by Dunnett's multiple comparison test. * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001, compared to 340 mOsM. Cells exposed to supplemented medium (340 mOsM) or hyperosmolar medium (500 mOsM) for 24 h were analyzed for NFAT5 translocation with NFAT5 immunofluorescent staining (E) in green. White scale bar: 20μm.</p

Hyperosmolar condition of 500 mOsM induced cell death, secretion and gene expression of CCL2 and NFAT5 gene expression in HeLa-modified conjunctiva-derived cells in a time-dependent manner.

<p>Cells exposed to supplemented medium (340 mOsM) or the hyperosmolar condition (500 mOsM) for different times from 30 min to 24 h were tested for cellular viability (A) with CellTiterBlue^® assay, CCL2 secretion (B) with ELISA and were lysed for mRNA expression using RT-qPCR to determine CCL2 and NFAT5 gene expression (C, D). Data showing mean ± SEM, <i>n</i> = 3 or more. Statistical analysis: two-way ANOVA followed by Sidak’s multiple comparison test. * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001, compared to 340 mOsM at the same time.</p

NFAT5 siRNA increased HO-induced cell death and inhibited HO-induced CCL2 secretion and CCL2 and NFAT5 gene expression in HeLa-modified conjunctiva-derived cells.

<p>Cells treated for 24 h with negative control siRNA or NFAT5 siRNA were then exposed to supplemented medium (340 mOsM) or hyperosmolar condition (500 mOsM). Cells exposed for 24 h were tested for cellular viability (A) with CellTiterBlue^® assay, CCL2 secretion (B) by ELISA and cells exposed for 4 h were lysed for mRNA expression using RT-qPCR to determine the CCL2 and NFAT5 gene expression (C, D). Data showing mean ± SEM, <i>n</i> = 3 or more. Statistical analysis: two-way ANOVA followed by Tukey’s multiple comparison test. § <i>p</i> ≤ 0.05; §§ <i>p</i> ≤ 0.01; §§§ <i>p</i> ≤ 0.001; §§§ <i>p</i> ≤ 0.0001, compared to respective 340 mOsM. * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001, compared to respective control siRNA.</p