Les amants de Nevers dans Hiroshima mon amour: passion et compassion

En la película Hiroshima mon amour, el episodio que titulamos «Los amantes de Nevers» es una reminiscencia del pasado de la protagonista. Cuando publica Duras el texto del guión en 1960, le añade unas treinta páginas de anejos dedicados casi totalmente al episodio de Nevers. Nuestro análisis enfoca el texto bajo una doble perspectiva; estilística (la dimensión poética de la escritura del amor) y genética (el episodio de Nevers que inicia de modo solapado la temática autobiográfica desarrollada en La Douleur)

Electrophysiological and arrhythmogenic effects of 5-hydroxytryptamine on human atrial cells are reduced in atrial fibrillation

5-Hydroxytryptamine (5-HT) is proarrhythmic in atrial cells from patients in sinus rhythm (SR) via activation of 5-HT<sub>4</sub> receptors, but its effects in atrial cells from patients with atrial fibrillation (AF) are unknown. The whole-cell perforated patch-clamp technique was used to record L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>), action potential duration (APD) and arrhythmic activity at 37 °C in enzymatically isolated atrial cells obtained from patients undergoing cardiac surgery, in SR or with chronic AF. In the AF group, 5-HT (10 μM) produced an increase in <i>I</i><sub>CaL</sub> of 115 ± 21% above control (<i>n</i> = 10 cells, 6 patients) that was significantly smaller than that in the SR group (232 ± 33%; <i>p</i> 0.05; <i>n</i> = 27 cells, 12 patients). Subsequent co-application of isoproterenol (1 μM) caused a further increase in <i>I</i><sub>CaL</sub> in the AF group (by 256 ± 94%) that was greater than that in the SR group (22 ± 6%; p < 0.05). The APD at 50% repolarisation (APD<sub>50</sub>) was prolonged by 14 ± 3 ms by 5-HT in the AF group (<i>n</i> = 37 cells, 14 patients). This was less than that in the SR group (27 ± 4 ms; <i>p</i> < 0.05; <i>n</i> = 58 cells, 24 patients). Arrhythmic activity in response to 5-HT was observed in 22% of cells in the SR group, but none was observed in the AF group (p < 0.05). Atrial fibrillation was associated with reduced effects of 5-HT, but not of isoproterenol, on <i>I</i><sub>CaL</sub> in human atrial cells. This reduced effect on <i>I</i><sub>CaL</sub> was associated with a reduced APD<sub>50</sub> and arrhythmic activity with 5-HT. Thus, the potentially arrhythmogenic influence of 5-HT may be suppressed in AF-remodelled human atrium

The role of thrombin and thrombin receptors in ischemic, hemorrhagic and traumatic brain injury: deleterious or protective?

In the last two decades it has become apparent that thrombin has many extravascular effects that are mediated by a family of protease-activated receptors (PARs). PAR-1, -3 and -4 are activated via cleavage by thrombin. The importance of extravascular thrombin in modulating ischemic, hemorrhagic and traumatic injury in brain has recently become clear. Thus, in vitro , thrombin at low concentration protects neurons and astrocytes from cell death caused by a number of different insults. In vivo , pretreating the brain with a low dose of thrombin (thrombin preconditioning), attenuates the brain injury induced by a large dose of thrombin, an intracerebral hemorrhage or by focal cerebral ischemia. Thrombin may also be an important mediator of ischemic preconditioning. In contrast, high doses of thrombin kill neurons and astrocytes in vitro and cause disruption of the blood–brain barrier, brain edema and seizures in vivo . This review examines the role of thrombin in brain injury and the molecular mechanisms and signaling cascades involved.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66277/1/j.1471-4159.2003.01268.x.pd

5-Hydroxytryptamine Modulates Migration, Cytokine and Chemokine Release and T-Cell Priming Capacity of Dendritic Cells In Vitro and In Vivo

Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR1 and 5-HTR2 receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR3, 5-HTR4 and 5-HTR7 receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders

Current and prospective pharmacological targets in relation to antimigraine action

Migraine is a recurrent incapacitating neurovascular disorder characterized by unilateral and throbbing headaches associated with photophobia, phonophobia, nausea, and vomiting. Current specific drugs used in the acute treatment of migraine interact with vascular receptors, a fact that has raised concerns about their cardiovascular safety. In the past, α-adrenoceptor agonists (ergotamine, dihydroergotamine, isometheptene) were used. The last two decades have witnessed the advent of 5-HT1B/1D receptor agonists (sumatriptan and second-generation triptans), which have a well-established efficacy in the acute treatment of migraine. Moreover, current prophylactic treatments of migraine include 5-HT2 receptor antagonists, Ca2+ channel blockers, and β-adrenoceptor antagonists. Despite the progress in migraine research and in view of its complex etiology, this disease still remains underdiagnosed, and available therapies are underused. In this review, we have discussed pharmacological targets in migraine, with special emphasis on compounds acting on 5-HT (5-HT1-7), adrenergic (α1, α2, and β), calcitonin gene-related peptide (CGRP 1 and CGRP2), adenosine (A1, A2, and A3), glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and female hormone (estrogen and progesterone) receptors. In addition, we have considered some other targets, including gamma-aminobutyric acid, angiotensin, bradykinin, histamine, and ionotropic receptors, in relation to antimigraine therapy. Finally, the cardiovascular safety of current and prospective antimigraine therapies is touched upon

L’Après-midi de M. Andesmas de Marguerite Duras : topogenèse d’un univers fictionnel

Dans son ouvrage Le Nouveau roman – une césure dans l’histoire du récit, Francine Dugast-Portes choisit, à juste titre, d’intégrer Marguerite Duras sinon au groupe des « Nouveaux Romanciers », stricto sensu, du moins au champ du « roman nouveau », parmi les écrivains « qui se retrouvaient sur des positions esthétiques communes, et surtout des refus communs ». En effet, quand Nathalie Sarraute affirme : « Nous étions tous d’accord pour dire que le personnage, l’intrigue, étaient des choses dép..

Du subjectile au sujet Duras : « C’est moi Agatha »

Travailler sur les manuscrits de Marguerite Duras, c’est être confronté, plus que pour tout autre écrivain, à l’empreinte du vécu sur la création. La masse hétérogène des supports matériels de l’archive durassienne fait du chercheur un archéologue ramenant au jour le geste scriptural lui-même, saisi dans l’espace-temps de sa genèse. Consciente de ce que les manuscrits pouvaient révéler de l’intimité de sa création, Marguerite Duras a longtemps été réticente à leur conservation : Pendant quinz..

La voix adressée de Marguerite Duras dans le cycle atlantique : une voix fantôme

Spécial Topic/Dossier spécial : Marguerite Duras, une voix fantôme : roman, théâtre, cinéma (Textes réunis par Atsuo Morimoto et Gilles Philippe)III. Vers une perspective nouvell