Microvascular vasodilator properties of the angiotensin II type 2 receptor in a mouse model of type 1 diabetes

Diabetes Mellitus is associated with severe cardiovascular disorders involving the renin-angiotensin system, mainly through activation of the angiotensin II type 1 receptor (AT1R). Although the type 2 receptor (AT2R) opposes the effects of AT1R, with vasodilator and anti-trophic properties, its role in diabetes is debatable. Thus we investigated AT2R-mediated dilatation in a model of type 1 diabetes induced by streptozotocin in 5-month-old male mice lacking AT2R (AT2R). Glucose tolerance was reduced and markers of inflammation and oxidative stress (cyclooxygenase-2, gp91phox p22phox and p67phox) were increased in AT2R mice compared to wild-type (WT) animals. Streptozotocin-induced hyperglycaemia was higher in AT2R than in WT mice. Arterial gp91phox and MnSOD expression levels in addition to blood 8-isoprostane and creatinine were further increased in diabetic AT2R mice compared to diabetic WT mice. AT2R-dependent dilatation in both isolated mesenteric resistance arteries and perfused kidneys was greater in diabetic mice than in non-diabetic animals. Thus, in type 1 diabetes, AT2R may reduce glycaemia and display anti-oxidant and/or anti-inflammatory properties in association with greater vasodilatation in mesenteric arteries and in the renal vasculature, a major target of diabetes. Therefore AT2R might represent a new therapeutic target in diabetes

Hydroxychloroquine partially prevents endothelial dysfunction induced by anti-beta-2-GPI antibodies in an in vivo mouse model of antiphospholipid syndrome

Background Antiphospholipid syndrome is associated with endothelial dysfunction, which leads to thrombosis and early atheroma. Given that hydroxychloroquine has anti-thrombotic properties in lupus, we hypothesized that it could reduce endothelial dysfunction in an animal model of antiphospholipid syndrome. We evaluated the effect of hydroxychloroquine in preventing endothelial dysfunction in a mouse model of antiphospholipid syndrome. Methods Antiphospholipid syndrome was induced by an injection of monoclonal anti-beta-2-GPI antibodies. Vascular reactivity was evaluated in mesenteric resistance arteries isolated from mice 3 weeks (APL3W) after receiving a single injection of anti-beta-2-GPI antibodies and after 3 weeks of daily oral hydroxychloroquine treatment (HCQ3W) compared to control mice (CT3W). We evaluated endothelial dysfunction by measuring acetylcholine-mediated vasodilation. A pharmacological approach was used to evaluate NO synthase uncoupling (tetrahydrobiopterin) and the generation of reactive oxygen species (Tempol). Results Impaired acetylcholine-mediated dilation was evidenced in mice 3 weeks after anti-beta-2-GPI antibodies injection compared to CT3W, by reduced maximal dilation (p<0.0001) and sensitivity (pKd) (p = 0.01) to acetylcholine. Hydroxychloroquine improved acetylcholine-dependent dilation, on pKd (p = 0.02) but not maximal capacity compared to untreated mice. The addition of tetrahydrobiopterin (p = 0.02) and/or Tempol (p = 0.0008) improved acetylcholine-mediated dilation in APL3W but not in HCQ3W. Conclusions We demonstrated that endothelial dysfunction in mouse resistance arteries persisted at 3 weeks after a single injection of monoclonal anti-beta-2-GPI antibodies, and that hydroxychloroquine improved endothelium-dependent dilation at 3 weeks, through improvement of NO synthase coupling and oxidative stress reduction

Historique de l'origine des matières en suspension dans le Rhône (France) en utilisant la signature géochimique non-réactive des particules

International audienceSuspended particulate matter (SPM) conveyed by rivers contribute to the transport of numerous contaminants that can affect water quality through their desorption from particles or during diagenesis processes. In order to assess to SPM deliveries and associated contaminants to the Rhône River then to the Mediterranean Sea, it is essential to identify SPM sources at the scale of the whole Rhône watershed. We present a first study on the determination the historical SPM inputs from the tributaries in the Upper Rhône River. We apply an original geochemical mixing model onto two sediment cores collected in a same deposit area. To prevent chemical transformations which can occur during particles transport and after settlement of SPM, we use concentrations of key trace elements in the conservative fraction of SPM. Data acquired were integrated into a mixing model coupled to Monte Carlo simulation to assess uncertainties. In addition, the spatial heterogeneity was scrutinized using data from both sediment cores. To improve accuracy and precision of historical sediment source contributions, we compared mixing model data output using geochemical signatures of SPM from the various samples and from well characterizes flood events. Finally, historical sediment source contributions were compared to hydrological time series and SPM deliveries to the Rhone River

Historique de l'origine des matières en suspension dans le Rhône (France) en utilisant la signature géochimique non-réactive des particules

International audienceSuspended particulate matter (SPM) conveyed by rivers contribute to the transport of numerous contaminants that can affect water quality through their desorption from particles or during diagenesis processes. In order to assess to SPM deliveries and associated contaminants to the Rhône River then to the Mediterranean Sea, it is essential to identify SPM sources at the scale of the whole Rhône watershed. We present a first study on the determination the historical SPM inputs from the tributaries in the Upper Rhône River. We apply an original geochemical mixing model onto two sediment cores collected in a same deposit area. To prevent chemical transformations which can occur during particles transport and after settlement of SPM, we use concentrations of key trace elements in the conservative fraction of SPM. Data acquired were integrated into a mixing model coupled to Monte Carlo simulation to assess uncertainties. In addition, the spatial heterogeneity was scrutinized using data from both sediment cores. To improve accuracy and precision of historical sediment source contributions, we compared mixing model data output using geochemical signatures of SPM from the various samples and from well characterizes flood events. Finally, historical sediment source contributions were compared to hydrological time series and SPM deliveries to the Rhone River

Anthropisation of the Rhône River during the last century: case of main pollutants measured in sediment cores

International audienc

Historique de l'origine des matières en suspension dans le Rhône (France) en utilisant la signature géochimique non-réactive des particules

International audienceSuspended particulate matter (SPM) conveyed by rivers contribute to the transport of numerous contaminants that can affect water quality through their desorption from particles or during diagenesis processes. In order to assess to SPM deliveries and associated contaminants to the Rhône River then to the Mediterranean Sea, it is essential to identify SPM sources at the scale of the whole Rhône watershed. We present a first study on the determination the historical SPM inputs from the tributaries in the Upper Rhône River. We apply an original geochemical mixing model onto two sediment cores collected in a same deposit area. To prevent chemical transformations which can occur during particles transport and after settlement of SPM, we use concentrations of key trace elements in the conservative fraction of SPM. Data acquired were integrated into a mixing model coupled to Monte Carlo simulation to assess uncertainties. In addition, the spatial heterogeneity was scrutinized using data from both sediment cores. To improve accuracy and precision of historical sediment source contributions, we compared mixing model data output using geochemical signatures of SPM from the various samples and from well characterizes flood events. Finally, historical sediment source contributions were compared to hydrological time series and SPM deliveries to the Rhone River

Origine et historique des apports de matières en suspension (MES) des affluents du Rhône : utilisation de la signature géochimique non-réactive des particules

International audienceSuspended particulate matter (SPM) flows in rivers are mainly due to soil erosion and anthropogenic activities. They contribute to the transport of a large amount of contaminants and can induce impacts on water quality and river ecosystem. To better manage these inputs in river systems, it is essential to identify the origin of sediments. In that way, SPM fluxes monitoring or fingerprinting approaches in rivers are increasingly addressed. In the frame of the Rhône sediment observatory (OSR) program, the Rhône River, which is the main sediment input to the Mediterranean Sea, is studied through several stations of measurement. Since 7 years, SPM were collected on the Rhône River and its tributaries for contrasting hydrological conditions allowing developing fingerprinting approaches. The aims of this study were to use major and trace element concentrations in the conservative fraction of SPM from the Rhône and its tributaries in order (i) to determine the actual relative contribution of SPM fluxes, with uncertainty, from tributaries to the Rhône River and (ii) to determine the historical SPM inputs of the tributaries by applying this approach on a sediment core. To determine the origin of sediment at given time and space, the use of conservative parameters is essential to avoid any tracer's transformations during particles transport. To assess element concentrations in the conservative fraction of SPM, samples were extracted by a total mineralization (HNO3, HCl, HF) and a soft extraction (HCl 1M). The discrimination of SPM and sediment sources were realized by using a Kruskal-Wallis test and a Discriminatory Factory Analysis to select element concentrations that could discriminate the main tributaries of the Rhône (Ain, Arve, Bourbre, Fier, Guiers, Saône, Isère, Durance). 17 discriminant elements were then integrated into a mixing model with uncertainty analysis using the Monte Carlo method. Our method allowed to correctly determining SPM origin in the Upper Rhône and downstream the confluence of the Rhône and Saône rivers, for contrasting hydrological conditions. These results were successfully confronted to SPM dynamics estimated by a hydro-sedimentary 1-D model or by using SPM and discharges data obtained via the OSR stations network. Determination of the SPM origin at the outlet of the Rhône is in progress in order to, first, integrate tributaries signatures from the downstream part of the Rhône and, second, to apply this method on a sediment core sampled at the outlet of the Rhône River. The results of the core analyses will allow defining a historical profile of sediment inputs at the outlet of the Rhône catchment

Origine et historique des apports de matières en suspension (MES) des affluents du Rhône : utilisation de la signature géochimique non-réactive des particules

International audienceSuspended particulate matter (SPM) flows in rivers are mainly due to soil erosion and anthropogenic activities. They contribute to the transport of a large amount of contaminants and can induce impacts on water quality and river ecosystem. To better manage these inputs in river systems, it is essential to identify the origin of sediments. In that way, SPM fluxes monitoring or fingerprinting approaches in rivers are increasingly addressed. In the frame of the Rhône sediment observatory (OSR) program, the Rhône River, which is the main sediment input to the Mediterranean Sea, is studied through several stations of measurement. Since 7 years, SPM were collected on the Rhône River and its tributaries for contrasting hydrological conditions allowing developing fingerprinting approaches. The aims of this study were to use major and trace element concentrations in the conservative fraction of SPM from the Rhône and its tributaries in order (i) to determine the actual relative contribution of SPM fluxes, with uncertainty, from tributaries to the Rhône River and (ii) to determine the historical SPM inputs of the tributaries by applying this approach on a sediment core. To determine the origin of sediment at given time and space, the use of conservative parameters is essential to avoid any tracer's transformations during particles transport. To assess element concentrations in the conservative fraction of SPM, samples were extracted by a total mineralization (HNO3, HCl, HF) and a soft extraction (HCl 1M). The discrimination of SPM and sediment sources were realized by using a Kruskal-Wallis test and a Discriminatory Factory Analysis to select element concentrations that could discriminate the main tributaries of the Rhône (Ain, Arve, Bourbre, Fier, Guiers, Saône, Isère, Durance). 17 discriminant elements were then integrated into a mixing model with uncertainty analysis using the Monte Carlo method. Our method allowed to correctly determining SPM origin in the Upper Rhône and downstream the confluence of the Rhône and Saône rivers, for contrasting hydrological conditions. These results were successfully confronted to SPM dynamics estimated by a hydro-sedimentary 1-D model or by using SPM and discharges data obtained via the OSR stations network. Determination of the SPM origin at the outlet of the Rhône is in progress in order to, first, integrate tributaries signatures from the downstream part of the Rhône and, second, to apply this method on a sediment core sampled at the outlet of the Rhône River. The results of the core analyses will allow defining a historical profile of sediment inputs at the outlet of the Rhône catchment

Anti-terrorism laws in the Maghreb countries: the mirror of a transition that never was

This article sheds light on the counter-terrorism measures enacted by the Maghreb countries, with a comparative approach of the laws in Algeria, Mauritania, Morocco and Tunisia. Carried out by comparing the Arabic and French original versions, the analysis revealed a common attitude that tended to preserve national security at the expenses of civil freedoms and human rights. In almost all cases, anti-terrorism laws strayed away from their supposed initial finality, fighting terrorism, tackling other issues such as the maintenance of public order or indirectly the control of dissidence and political opposition, with no or scarce legal checks and balances that could restrict possible police or judiciary abuses towards civil and political rights. The legal measures significantly delayed both the first transition to democracyin the region in the 2000s as well as the promising development after the 'Arab spring