Overview of the current use of levosimendan in France: a prospective observational cohort study

Abstract Background Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. Method The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. Results The patients included ( n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock ( n = 250, 41.5%), decompensated heart failure ( n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment ( n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation ( n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. Conclusions We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied

Escherichia coli thioredoxin inhibition by cadmium

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Use of an Acellular Assay to Study Interactions between Actinides and Biological or Synthetic Ligands

International audienceSpeciation of actinides, and more particularly bioligand-binding ability, influences in vivo behavior. Understanding these interactions is essential for estimation of radiological dose and improvement of decorporation strategies for accidentally contaminated victims. Because the handling of actinides imposes overwhelming difficulties, in vitro assays carried out in physiological conditions are lacking and data regarding such interactions are scarce. In this study, we used a bi-compartmental and dynamic assay, providing physiological conditions (presence of inorganic ions, pH, temperature) to explore interactions between the actinides plutonium (Pu) and americium (Am) and endogenous (proteins transferrin and ferritin) or exogenous ligands (the chelating agent diethylenetriaminpentaacetic acid, DTPA). In this assay, an agarose gel represents the retention compartment of actinides and a dynamic fluid phase, the transfer compartment. The proportion of actinides transferred from static to dynamic phase reflects interactions between Pu/Am and various ligands. The results show differences in the formation of actinide-protein or actinide-DTPA complexes in physiologically relevant media depending on which ligand is present and where. We observed differential behavior for Pu and Am similar to in vivo studies. Thus, our assay may be used to determine the ability of various actinides to interact with specific proteins or with drug candidates for decorporation in complex physiologically relevant environments

Determination of drug efficacy to dissolve cobalt oxide particles in cellular models: Towards a therapeutic approach to decrease pulmonary retention

International audienceFollowing accidental inhalation of radioactive cobalt particles, the poorly soluble and highly radioactive Co3O4 particles are retained for long periods in lungs. To decrease their retention time is of crucial importance to minimize radiation-induced damage. As dissolved cobalt is quickly transferred to blood and eliminated by urinary excretion, enhancing the dissolution of particles would favor 60Co elimination. We evaluated the ability of ascorbic acid alone or associated with the chelating agents DTPA1, DFOB2 or EDTA3 to enhance dissolution of cobalt particles after macrophage engulfment, and the drug effects on the translocation of the soluble species CoCl2 through an epithelial barrier. We exposed differentiated THP-1 macrophage-like cells and Calu-3 lung epithelial cells cultured in a bicameral system to cobalt and selected molecules up to 7 days. DTPA, the recommended treatment in man, used alone showed no effect, whereas ascorbic acid significantly increased dissolution of Co3O4 particles. An additional efficacy in intracellular particles dissolution was observed for combinations of ascorbic acid with DTPA and EDTA. Except for DFOB, treatments did not significantly modify translocation of dissolved cobalt across the epithelial lung barrier. Our study provides new insights for decorporating strategies following radioactive cobalt particle intake

Toxicity mechanisms of cobalt oxide particles (Co 3 O 4 P) on human lung cells: impact of solubilization.

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MiR-22 deficiency fosters hepatocellular carcinoma development in fatty liver

MiR-22 is mostly considered as a hepatic tumor-suppressor microRNA based on in vitro analyses. Yet, whether miR-22 exerts a tumor-suppressive function in the liver has not been investigated in vivo. Herein, in silico analyses of miR-22 expression were performed in hepatocellular carcinomas from human patient cohorts and different mouse models. Diethylnitrosamine-induced hepatocellular carcinomas were then investigated in lean and diet-induced obese miR-22-deficient mice. The proteome of liver tissues from miR-22-deficient mice prior to hepatocellular carcinoma development was further analyzed to uncover miR-22 regulated factors that impact hepatocarcinogenesis with miR-22 deficiency. MiR-22 downregulation was consistently observed in hepatocellular carcinomas from all human cohorts and mouse models investigated. The time of appearance of the first tumors was decreased and the number of tumoral foci induced by diethylnitrosamine was significantly increased by miR-22-deficiency in vivo, two features which were further drastically exacerbated with diet-induced obesity. At the molecular level, we provide evidence that the loss of miR-22 significantly affects the energetic metabolism and mitochondrial functions of hepatocytes, and the expression of tumor-promoting factors such as thrombospondin-1. Our study demonstrates that miR-22 acts as a hepatic tumor suppressor in vivo by restraining pro-carcinogenic metabolic deregulations through pleiotropic mechanisms and the overexpression of relevant oncogenes.</p

La recherche publique en France en 2019 : Diagnostic et propositions du Comité national

International audienc

In vitro assessment of cobalt oxide particle dissolution in simulated lung fluids for identification of new decorporating agents

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