Etude expérimentale de l'agrégation de microparticules dans un métal liquide

National audienceL'agrégation de petites particules dans un métal liquide est un phénomène gênant et mal connu, qui se produit dans les réacteurs sidérurgiques. La difficulté d'effectuer des expériences réalistes permettant de le quantifier se traduit par une absence de données expérimentales. Nous avons dimensionné et construit un réacteur de laboratoire compatible avec un métal liquide et adapté à l'étude de l'agrégation. Différents modes opératoires seront décrits et quelques résultats expérimentaux relatifs à l'état d'agrégation des particules seront présentés

Ethane-beta-Sultam Modifies the Activation of the Innate Immune System Induced by Intermittent Ethanol Administration in Female Adolescent Rats

Intermittent ethanol abuse or ‘binge drinking’ during adolescence induces neuronal damage, which may be associated with cognitive dysfunction. To investigate the neurochemical processes involved, rats were administered either 1 g/kg or 2 g/kg ethanol in a ‘binge drinking’ regime. After only 3 weeks, significant activation of phagocytic cells in the peripheral (alveolar macrophages) and the hippocampal brain region (microglia cells) was present,as exemplified by increases in the release of pro-inflammatory cytokines in the macrophages and of iNOS in the microglia. This was associated with neuronal loss in the hippocampus CA1 region. Daily supplementation with a taurine prodrug, ethane-β-sultam, 0.028 g/kg, during the intermittent ethanol loading regime, supressed the release of the pro-inflammatory cytokines and of reactive nitrogen species, as well as neuronal loss, particularly in the rats administered the lower dose of ethanol, 1 g/kg. Plasma, macrophage and hippocampal taurine levels increased marginally after ethane-β-sultam supplementation. The ‘binge drinking’ ethanol rats administered 1 g/kg ethanol showed increased latencies to those of the control rats in their acquisition of spacial navigation in the Morris Water Maze, which was normalised to that of the controls values after ethane-β-sultam administration. Such results confirm that the administration of ethane-β-sultam to binge drinking rats reduces neuroinflammation in both the periphery and the brain, suppresses neuronal loss, and improved working memory of rats in a water maze study

Dbx1-Expressing Cells Are Necessary for the Survival of the Mammalian Anterior Neural and Craniofacial Structures

Development of the vertebrate forebrain and craniofacial structures are intimately linked processes, the coordinated growth of these tissues being required to ensure normal head formation. In this study, we identify five small subsets of progenitors expressing the transcription factor dbx1 in the cephalic region of developing mouse embryos at E8.5. Using genetic tracing we show that dbx1-expressing cells and their progeny have a modest contribution to the forebrain and face tissues. However, their genetic ablation triggers extensive and non cell-autonomous apoptosis as well as a decrease in proliferation in surrounding tissues, resulting in the progressive loss of most of the forebrain and frontonasal structures. Targeted ablation of the different subsets reveals that the very first dbx1-expressing progenitors are critically required for the survival of anterior neural tissues, the production and/or migration of cephalic neural crest cells and, ultimately, forebrain formation. In addition, we find that the other subsets, generated at slightly later stages, each play a specific function during head development and that their coordinated activity is required for accurate craniofacial morphogenesis. Our results demonstrate that dbx1-expressing cells have a unique function during head development, notably by controlling cell survival in a non cell-autonomous manner

Transcriptome analyses based on genetic screens for Pax3 myogenic targets in the mouse embryo

<p>Abstract</p> <p>Background</p> <p>Pax3 is a key upstream regulator of the onset of myogenesis, controlling progenitor cell survival and behaviour as well as entry into the myogenic programme. It functions in the dermomyotome of the somite from which skeletal muscle derives and in progenitor cell populations that migrate from the somite such as those of the limbs. Few Pax3 target genes have been identified. Identifying genes that lie genetically downstream of <it>Pax3 </it>is therefore an important endeavour in elucidating the myogenic gene regulatory network.</p> <p>Results</p> <p>We have undertaken a screen in the mouse embryo which employs a <it>Pax3^GFP</it>allele that permits isolation of Pax3 expressing cells by flow cytometry and a <it>Pax3^PAX3-FKHR</it>allele that encodes PAX3-FKHR in which the DNA binding domain of Pax3 is fused to the strong transcriptional activation domain of FKHR. This constitutes a gain of function allele that rescues the <it>Pax3 </it>mutant phenotype. Microarray comparisons were carried out between <it>Pax3^GFP/+</it>and <it>Pax3^{GFP/PAX3-FKHR}</it>preparations from the hypaxial dermomyotome of somites at E9.5 and forelimb buds at E10.5. A further transcriptome comparison between Pax3-GFP positive and negative cells identified sequences specific to myogenic progenitors in the forelimb buds. Potential Pax3 targets, based on changes in transcript levels on the gain of function genetic background, were validated by analysis on loss or partial loss of function <it>Pax3 </it>mutant backgrounds. Sequences that are up- or down-regulated in the presence of PAX3-FKHR are classified as somite only, somite and limb or limb only. The latter should not contain sequences from Pax3 positive neural crest cells which do not invade the limbs. Verification by whole mount <it>in situ </it>hybridisation distinguishes myogenic markers. Presentation of potential Pax3 target genes focuses on signalling pathways and on transcriptional regulation.</p> <p>Conclusions</p> <p>Pax3 orchestrates many of the signalling pathways implicated in the activation or repression of myogenesis by regulating effectors and also, notably, inhibitors of these pathways. Important transcriptional regulators of myogenesis are candidate Pax3 targets. Myogenic determination genes, such as <it>Myf5 </it>are controlled positively, whereas the effect of <it>Pax3 </it>on genes encoding inhibitors of myogenesis provides a potential brake on differentiation. In the progenitor cell population, <it>Pax7 </it>and also <it>Hdac5 </it>which is a potential repressor of <it>Foxc2</it>, are subject to positive control by <it>Pax3</it>.</p

Sélection et évaluation de prodrogues hydrosolubles de cyclosporine A en vue d'une administration oculaire

La cyclosporine A est une molécule particulièrement efficace dans le traitement de certaines pathologies oculaires. Sa faible solubilité aqueuse ne lui permet pas d'être administrée facilement sous forme de collyre. La synthèse d'une prodrogue hydrosoluble de cyclosporine A a permis la formulation d'une solution aqueuse à 0,2% en principe actif. La prodrogue est hydrolysée par les enzymes lacrymales dès les premières minutes de contact avec les larmes. De plus, après administration dans l'oeil du lapin, la prodrogue s'est révélée bien tolérée et a généré des concentrations thérapeutiques lacrymales. Appliquée sur un modèle de greffe de cornée chez le rat, la prodrogue a empêché le rejet aussi bien que des injections intramusculaires de cyclosporine A. L'étude par spectrométrie de masse du mécanisme de conversion a mis en évidence un double mécanisme de conversion de la prodrogue dans les larmes. Malgré un problème de stabilité chimique, la prodrogue demeure prometteuse pour le traitement topique de maladies oculaires

Alcohol-non-preferring Sardinian rats exhibit a higher ethanol-induced taurine increase compared to alcohol-preferring Sardinian rats: a microdialysis study

It is well known that ethanol injections induce increases in the extracellular taurine concentration from various rat brain regions. Furthermore, recent studies have shown that taurine supplementation modulates the ethanol reinforcing effects in a place conditioning experiment. However, it is unknown whether there is a relationship between this taurine increase and the ethanol drinking behaviors. In the present microdialysis experiments, we compared the effects of ethanol injections (1.0 and 2.0 g/kg) on the extracellular taurine concentration from the nucleus accumbens of either Sardinian alcohol-preferring or Sardinian alcohol-non-preferring rats which have been selectively bred for their differential ethanol preference. The results show that acute ethanol produces an immediate increase in the taurine microdialysate content from both rat lines. However, this increase in taurine microdialysate content was more potent in the alcohol-non-preferring rats. Since taurine has been postulated to be released by brain cells to modulate some of the adverse effects of ethanol, the higher increase in taurine microdialysate content in the alcohol-non-preferring rats is probably related to their higher vulnerability to ethanol aversive effects

Taurine concentration in the brain and in the plasma following intraperitoneal injections.

Summary.The effect of different taurine doses (0.050, 0.125, 0.250, 0.500 and 1.000 g/kg) administered intraperitoneally to Wistar rats was studied in both the plasma and the hippocampal microdialysate content.The samples were analyzed by reverse phased HPLC for the microdialysate samples and by HPLC with ion-exchange post-column derivatization (ninhydrin) for the plasma samples.In both plasma and microdialysate, we observed a dose dependent increase of taurine concentration. The AUC curves obtained from both microdialysate and plasma samples showed that the increase of taurine concentrations were linear. The mean ratio between AUC's microdialysate and plasma was 1.63+/-0.21 showing thus an unbalance between plasma and brain taurine content; a mechanism which enhance taurine transfer from the plasma to the brain was assumed

L-NNA decreases cortical vascularization, alcohol preference and withdrawal in alcoholic rats.

Rats, which were made chronically alcoholic in combination with L-N(o)-nitro-arginine (L-NNA) treatment (5 mg/kg/day), a nitric oxide (NO) synthase inhibitor, showed a significant decrease in their alcohol preference and hypermotility during the withdrawal period by comparison with chronically alcoholic rats. However, no difference in the global liquid consumption between treated and untreated rats during the withdrawal stage was identified. In addition, the hypervascularization of the cortical area observed after chronic alcoholism was significantly decreased in the rats that had received L-NNA during the alcoholism procedure and was comparable to control rats. Thus, L-NNA alters both the behavioral preference for alcohol after alcoholism and the hypermotility during alcohol withdrawal, thus supporting the hypothesis of a direct implication of NO in alcohol abuse and its withdrawal

SR147778, a CB1 cannabinoid receptor antagonist, suppresses ethanol preference in chronically alcoholized Wistar rats.

This study investigated the effect of the new CB1 cannabinoid receptor antagonist, SR147778, on ethanol preference in chronically alcoholized Wistar rats. In study 1, SR147778, at doses of 0.3, 1, or 10 mg/kg/day (mg/kg/d) intraperitonealy (ip), was administered during chronic pulmonary ethanol intoxication for 30 days. The rats were then exposed to a two-bottle choice (ethanol 10% v/v vs. water) for at least 30 days. Neither 0.3 nor 1 mg/kg/d had any effect on ethanol preference. In contrast, the high dose induced a significant transient increase in ethanol intake between days 6 and 10. In study 2, SR147778, at doses of 0.3, 1, or 10 mg/kg/d ip, was administered during the free-choice period after chronic alcoholization. Both ethanol preference and intake were significantly reduced only for 1 and 10 mg/kg/d. These results reinforce the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate mediating alcohol intake and the motivational properties of alcohol. When these results are compared with those obtained with SR141716 (Rimonabant) on ethanol preference, we observed that (1) coadministration of 10 mg/kg/d SR147778 during chronic alcoholization induced a shorter transient increase of ethanol intake than Rimonabant and (2) SR147778 treatment during the free-choice period at doses of 1 and 10 mg/kg/d decreased ethanol intake more dramatically than SR141716 which, furthermore, continued for the duration of the free choice