Bradykinin and adenosine receptors mediate desflurane induced postconditioning in human myocardium: role of reactive oxygen species

BACKGROUND: Desflurane during early reperfusion has been shown to postcondition human myocardium, in vitro. We investigated the role of adenosine and bradykinin receptors, and generation of radical oxygen species in desflurane-induced postconditioning in human myocardium. METHODS: We recorded isometric contraction of human right atrial trabeculae hanged in an oxygenated Tyrode's solution (34 degrees Celsius, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of N-mercaptopropionylglycine, a reactive oxygen species scavenger, 8-(p-Sulfophenyl)theophylline, an adenosine receptor antagonist, HOE140, a selective B2 bradykinin receptor antagonist. In separate groups, adenosine and bradykinin were administered during the first minutes of reoxygenation alone or in presence of N-mercaptopropionylglycine. The force of contraction of trabeculae was recorded continuously. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- standard deviation) between the groups by a variance analysis and post hoc test. RESULTS: Desflurane 6% (84 +/- 6% of baseline) enhanced the recovery of force after 60-min of reoxygenation as compared to control group (51 +/- 8% of baseline, P < 0.0001). N-mercaptopropionylglycine (54 +/- 3% of baseline), 8-(p-Sulfophenyl)theophylline (62 +/- 9% of baseline), HOE140 (58 +/- 6% of baseline) abolished desflurane-induced postconditioning. Adenosine (80 +/- 9% of baseline) and bradykinin (83 +/- 4% of baseline) induced postconditioning (P < 0.0001 vs control), N-mercaptopropionylglycine abolished the beneficial effects of adenosine and bradykinin (54 +/- 8 and 58 +/- 5% of baseline, respectively). CONCLUSIONS: In vitro, desflurane-induced postconditioning depends on reactive oxygen species production, activation of adenosine and bradykinin B2 receptors. And, the cardioprotective effect of adenosine and bradykinin administered at the beginning of reoxygenation, was mediated, at least in part, through ROS production

Ville et campagne de Fréjus romaine

En 2006, une fouille d’archéologie préventive, désignée sous le nom de « Villa Romana », a été réalisée dans le quartier de Villeneuve à Fréjus. Durant l’Antiquité il s’agit d’une zone périurbaine située entre la ville de Forum Iulii et le débouché de l’Argens. Connu depuis longtemps en raison de la présence d’un édifice thermal toujours en élévation, le quartier a été fouillé à plusieurs occasions et est interprété comme étant l’emplacement du camp de la flotte, établi après la bataille d’Actium. Celui-ci se transforme progressivement durant le Ier siècle apr. J.-C. en quartier suburbain au fur et à mesure que se développe Forum Iulii. Le secteur fouillé se situe dans la partie sud du camp, bordée par la mer durant les premiers temps de l’Antiquité. La fouille a permis de révéler la présence d’une plage aménagée. Les terrains ont ensuite été rapidement gagnés sur la mer, en raison d’une avancée rapide du littoral, que des études récentes ont permis de bien connaitre à Fréjus. Des jardins y sont alors aménagés. A partir du IIe siècle, cet espace est transformé en zone agricole, et constitue l’illustration de l’exploitation de la campagne aux portes de Fréjus, et cela, jusqu’à la fin de l’Antiquité. S’ensuit une longue période d’abandon de plusieurs siècles, avant que l’espace ne soit à nouveau voué à l’agriculture et ce jusqu’à l’orée des années soixante. Depuis, le développement de la ville actuelle de Fréjus a de nouveau transformé ce quartier en zone urbaine. Cet ouvrage, publié quelques années seulement après la fouille, présente l’ensemble des études archéologiques et paléoenvironnementales, réalisées à l’occasion de cette opération, largement pluridisciplinaire. Elles fournissent un contexte environnemental nouveau pour ce quartier antique et permettent de redéfinir un paysage à partir d’analyses bioarchéologiques et paléoécologiques récentes. L’étude de l’ensemble des mobiliers archéologiques est également présentée, en suivant la chronologie et l’évolution de ce quartier à travers l’Antiquité et l’époque moderne

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Altimetry for the future: building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the “Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Conditionnement pharmacologique par la ciclosporine A dans l’ischémie-reperfusion rénale

Ischemia-reperfusion (IR) is a situation encountered in transplantation or during aortic surgery, which can result in renal damages, requiring sometimes transient or definitive dialysis. Mitochondria play a crucial role in the pathophysiology of IR causing cell death. Previous studies of cardiac IR highlighted the role of mitochondrial permeability transition pore (mPTP). Cyclosporin A (CsA) has been proposed as a treatment to protect the kidney from IR by the delay of the opening of the mPTP. However, CsA has acute renal hemodynamic effects and a long-term toxicity, requiring an experimental validation of its protection in the renal IR. In this work, we developed a mouse model of renal IR. In a first study, we showed that the post-conditioning with CsA and ischemic postconditioning improve renal function with a delay of the opening of the mPTP. In a second study, we showed that a high dose of CsA injected just before the ischemia improves renal function and leads to the delay of the opening of mPTP mediated by an increase of HSP70. Our results open new perspectives in renal protection, especially for reducing episodes of acute renal failure in aortic surgery or in renal transplantationL'ischémie-reperfusion (IR) rénale entraîne des lésions de nécrose tubulaire aigue, nécessitant parfois une épuration extra rénale transitoire voir définitive. La mitochondrie joue un rôle important dans la physiopathologie de ces lésions d'IR en entrainant la mort cellulaire. L'étude de l'IR dans la cellule cardiaque a permis de mettre en évidence le rôle central du pore de transition de perméabilité mitochondriale (mPTP) dans le déclenchement de cette mort cellulaire. La ciclosporine (CsA) a été proposée comme thérapeutique pour protéger la cellule des lésions d'IR en retardant l'ouverture de ce mPTP. Cependant la CsA a des effets rénaux vasoconstricteurs aigus, nécessitant une validation expérimentale de sa protection dans l'IR rénale. Au cours de ce travail de thèse, nous avons mis au point un modèle murin d'IR rénale. Ensuite nous avons montré que le post-conditionnement à la CsA, ainsi que le post-conditionnement ischémique, permettent d'améliorer la fonction rénale avec un retard à l'ouverture du mPTP. Dans un deuxième travail, nous montrons que le pré conditionnement à la CsA est dose et temps dépendant, et médié en partie par l'augmentation d'expression d'une protéine chaperonne, l'Heat Shock Protéine 70 (HSP70). L'injection en bolus de CsA permet également d'améliorer la fonction rénale dans ce modèle d'IR avec un retard à l'ouverture du mPTP. Nos résultats ouvrent de nouvelles perspectives dans la protection rénale, notamment dans la réduction des épisodes d'insuffisance rénale aigue après chirurgie aortique ou en transplantation rénal

Pharmacological conditionning with Cyclosporin A in renal ischemia reperfusion

L'ischémie-reperfusion (IR) rénale entraîne des lésions de nécrose tubulaire aigue, nécessitant parfois une épuration extra rénale transitoire voir définitive. La mitochondrie joue un rôle important dans la physiopathologie de ces lésions d'IR en entrainant la mort cellulaire. L'étude de l'IR dans la cellule cardiaque a permis de mettre en évidence le rôle central du pore de transition de perméabilité mitochondriale (mPTP) dans le déclenchement de cette mort cellulaire. La ciclosporine (CsA) a été proposée comme thérapeutique pour protéger la cellule des lésions d'IR en retardant l'ouverture de ce mPTP. Cependant la CsA a des effets rénaux vasoconstricteurs aigus, nécessitant une validation expérimentale de sa protection dans l'IR rénale. Au cours de ce travail de thèse, nous avons mis au point un modèle murin d'IR rénale. Ensuite nous avons montré que le post-conditionnement à la CsA, ainsi que le post-conditionnement ischémique, permettent d'améliorer la fonction rénale avec un retard à l'ouverture du mPTP. Dans un deuxième travail, nous montrons que le pré conditionnement à la CsA est dose et temps dépendant, et médié en partie par l'augmentation d'expression d'une protéine chaperonne, l'Heat Shock Protéine 70 (HSP70). L'injection en bolus de CsA permet également d'améliorer la fonction rénale dans ce modèle d'IR avec un retard à l'ouverture du mPTP. Nos résultats ouvrent de nouvelles perspectives dans la protection rénale, notamment dans la réduction des épisodes d'insuffisance rénale aigue après chirurgie aortique ou en transplantation rénaleIschemia-reperfusion (IR) is a situation encountered in transplantation or during aortic surgery, which can result in renal damages, requiring sometimes transient or definitive dialysis. Mitochondria play a crucial role in the pathophysiology of IR causing cell death. Previous studies of cardiac IR highlighted the role of mitochondrial permeability transition pore (mPTP). Cyclosporin A (CsA) has been proposed as a treatment to protect the kidney from IR by the delay of the opening of the mPTP. However, CsA has acute renal hemodynamic effects and a long-term toxicity, requiring an experimental validation of its protection in the renal IR. In this work, we developed a mouse model of renal IR. In a first study, we showed that the post-conditioning with CsA and ischemic postconditioning improve renal function with a delay of the opening of the mPTP. In a second study, we showed that a high dose of CsA injected just before the ischemia improves renal function and leads to the delay of the opening of mPTP mediated by an increase of HSP70. Our results open new perspectives in renal protection, especially for reducing episodes of acute renal failure in aortic surgery or in renal transplantatio

L'évolution politique et l'enracinement local d'un radical-socialiste du Nord : Daniel Vincent

Sandrine Lemoine-Rodrigues, From national responsibilities to local mandates : the enrooting of a Nord "Radical", Daniel Vincent. Elected to everybody's surprise in the Avesnes area, in the 1910 legislative elections, after rising against his party's establishment, Daniel Vincent, a "Radical-Socialiste», relies mostly upon a popular and urban electorate, displaying his concern for social issues by having, for example, the law on social insurances passed. In 1939, having become a "Sénateur", he moves away from his original electorate, now attracted by socialism and relies on a progressively acquired notoriety. Between the two poles of his career, one can discern a human and political evolution stretching over nearly thirty years. Can't this evolution, which one should try to assess, give us a key to the evolution of a whole political current, through a nonetheless fully original career ?Elu à la surprise générale dans l'Avesnois, lors des élections législatives de 1910, après avoir bravé les notables de son parti, Daniel Vincent, radical- socialiste, s'appuie surtout sur un électorat populaire et citadin, se préoccupant des problèmes sociaux, en faisant voter, par exemple, la loi sur les assurances sociales. En 1939, sénateur, il délaisse son électorat de base conquis par le socialisme et s'appuie sur une notoriété progressivement acquise. Entre les deux pôles de sa carrière, se situe une évolution humaine et politique, couvrant près de trente années. Au travers de cette évolution qu'il faut chercher à cerner, n'est-ce pas l'évolution de tout un courant politique que l'on peut appréhender, derrière une carrière néanmoins originale ?Sandrine Lemoine-Rodrigues, Van de nationale verantwoordelijkheid naar het lokaal mandaat : de verankering van een radikaal van het Noorden, Daniel Vincent. Daniel Vincent werd tot ieders verbazing verkozen tijdens de wetgevende verkiezingen van 1910, na een conflict met de notabelen van zijn partij. Hij steunde als radikaal socialist op een volks en stedelijk electoraat en droeg zorg voor sociale problemen : zo deed hij de wet op de sociale verzekeringen stem- men. In 1939 is hij senator en verwaarloost zijn vroeger electoraat dat geheel socialistisch geworden is, maar steunt op een groter geworden bekendheid. Tussen de twee polen van zijn loopbaan ligt een menselijke en politieke evolutie die meer dan dertig jaar overspant. Achter deze evolutie die men nauwkeurig moet omschrijven schuilt die van een politieke strekking die een neerslag vindt in een originele loopbaan.Lemoine-Rodrigues Sandrine. L'évolution politique et l'enracinement local d'un radical-socialiste du Nord : Daniel Vincent. In: Revue du Nord, tome 75, n°302, Juillet-septembre 1993. Le personnel politique. pp. 701-729

Evaluation of renal function in patients with cirrhosis: where are we now?

International audienceIn the clinical context of the patients with liver cirrhosis, accurate evaluation of the renal function is potentially crucial. Indeed, it can lead to early diagnosis of both acute kidney injury and chronic kidney disease and to reliable characterization of the renal status of the patient before performing a liver transplantation. Despite some limitations, the assay of serum creatinine (SCr) is universally used to estimate glomerular filtration rate (GFR) because of its wide availability, its simplicity and because it is inexpensive. Nevertheless, several reports show that the value of this assay to estimate GFR is strongly challenged in cirrhotic patients, especially in patients with liver failure and/or severely impaired renal function. This has led to seek new alternatives to estimate more reliably the GFR in these patients. Although the reference methods, based on the utilization of exogenous markers, allow measuring GFR and thereby constitute the "gold standard" to evaluate renal function, they are not feasible in routine clinical practice. Several studies have shown that a cystatin C (CysC) based formula perform better than the SCr-based estimates in cirrhotic patients and the estimation of GFR by these formulas could therefore lead to optimize the management of the patients. A new estimate based on CysC has been recently developed using a large number of patients and the first results regarding the evaluation of its performance are promising, making this new formula the best candidate for a reference estimate of the renal function in cirrhotic patients

Une inscription fragmentaire découverte à Néoules (Var), sur le territoire d'Arles antique

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