Actively contractile cardiomyocyte (CM) monolayer represents an interesting tool to study both cardiac diseases and injuries. However, this model is poorly transfectable with conventional agents. Consequently, there is a need to develop new carriers that could overcome this problem. Titanate nanotubes (TiONts) could be a potential candidate due to possibly higher cell uptake as a direct consequence of their shape. On the basis of this rationale, TiONts were assessed for their cytotoxicity and internalization pathways. Cytotoxicity was assessed for TiONts either functionalized with PEI or unfunctionalized and its spherical counterpart P25 TiO2. No cytotoxic effect was observed under TiONts, TiONts-PEI1800 and P25 TiO2 exposed conditions. The tubular morphology was found to be an important parameter promoting internalization while reversing the charge was assessed as non-additional. Internalization was found to occur by endocytosis and diffusion through the membrane. A preliminary transfection study indicated the potential of TiONts as a nanocarrier.
BackgroundFew data are available on the impact of levosimendan in refractory cardiogenic shock patients undergoing peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO). The aim of this study was to evaluate the impact of levosimendan on VA-ECMO weaning in patients hospitalized in intensive care unit (ICU).MethodsThis retrospective cohort study was conducted in a French university hospital from 2010 to 2017. All patients hospitalized in ICU undergoing VA-ECMO were consecutively evaluated.ResultsA total of 150 patients undergoing VA-ECMO were eligible for the study. Thirty-eight propensity-matched patients were evaluated in the levosimendan group and 65 in the non-levosimendan group. In patients treated with levosimendan, left ventricular ejection fraction had increased from 21.5 ± 9.1% to 30.7 ± 13.5% (P < 0.0001) and aortic velocity–time integral from 8.9 ± 4 cm to 12.5 ± 3.8 cm (P = 0.002) 24 h after drug infusion. After propensity score matching, levosimendan was the only factor associated with a significant reduction in VA-ECMO weaning failure rates (hazard ratio = 0.16; 95% confidence interval 0.04–0.7; P = 0.01). Kaplan–Meier survival curves showed that survival rates at 30 days were 78.4% for the levosimendan group and 49.5% for the non-levosimendan group (P = 0.02). After propensity score matching analysis, the difference in 30-day mortality between the two groups was not significant (hazard ratio = 0.55; 95% confidence interval 0.27–1.10; P = 0.09).ConclusionsOur results suggest that levosimendan was associated with a beneficial effect on VA-ECMO weaning in ICU patients.
Oxidative stress induced by a glucose/glucose oxidase (G/GO) generator system dose-dependently decreased the viability of cultured vascular smooth muscle cells (VSMC) as estimated by MTT assay. Cell death was induced in 40% of cells exposed to 0.2 IU/ml of the free radical generating mixture. Annexin-V labeling, Hoechst staining together with DNA laddering demonstrated that apoptosis was responsible for this cell loss. Pretreatment of the cells with 10(-8) M calcitonin gene-related peptide (CGRP) significantly attenuated the damaging effect of the oxidative stress. Indeed, cell viability was estimated to be 80% in CGRP-treated group, instead of 60% in absence of CGRP treatment. This protective effect of CGRP was antagonized by 8-37 CGRP, an antagonist of CGRP-1 receptors, whereas it was not reproduced by amylin, a CGRP analogue. As indicated by the reduction in Hoechst staining and in DNA laddering, CGRP prevented the onset of apoptosis. We also demonstrated that the peptide significantly up-regulated the activation of ERK1/2 and P38 kinases. Inhibitors of the kinases prevented the protective effect of CGRP. We conclude that CGRP antagonizes oxidative stress-induced apoptosis by up-regulating MAP kinase activation and that activation of these kinases was necessary to protection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.