Telomerase Deficiency Predisposes to Heart Failure and Ischemia-Reperfusion Injury

Introduction: Elevated levels of mitochondrial reactive oxygen species (ROS) contribute to the development of numerous cardiovascular diseases. TERT, the catalytic subunit of telomerase, has been shown to translocate to mitochondria to suppress ROS while promoting ATP production. Acute overexpression of TERT increases survival and decreases infarct size in a mouse model of myocardial infarct, while decreased telomerase activity predisposes to mitochondrial defects and heart failure. In the present study, we examined the role of TERT on cardiac structure and function under basal conditions and conditions of acute or prolonged stress in a novel rat model of TERT deficiency.Methods: Cardiac structure and function were evaluated via transthoracic echocardiogram. Langendorff preparations were used to test the effects of acute global ischemia reperfusion injury on cardiac function and infarction. Coronary flow and left ventricular pressure were measured during and after ischemia/reperfusion (I/R). Mitochondrial DNA integrity was measured by PCR and mitochondrial respiration was assessed in isolated mitochondria using an Oxygraph. Angiotensin II infusion was used as an established model of systemic stress.Results: No structural changes (echocardiogram) or coronary flow/left ventricle pressure (isolated hearts) were observed in TERT−/− rats at baseline; however, after I/R, coronary flow was significantly reduced in TERT−/− compared to wild type (WT) rats, while diastolic Left Ventricle Pressure was significantly elevated (n = 6 in each group; p < 0.05) in the TERT−/−. Interestingly, infarct size was less in TERT−/− rats compared to WT rats, while mitochondrial respiratory control index decreased and mitochondrial DNA lesions increased in TERT−/− compared to WT. Angiotensin II treatment did not alter cardiac structure or function; however, it augmented the infarct size significantly more in TERT−/− compared to the WT.Conclusion: Absence of TERT activity increases susceptibility to stress like cardiac injury. These results suggest a critical role of telomerase in chronic heart disease

Characterization of the inflammatory cell infiltrate and expression of costimulatory molecules in chronic echinococcus granulosus infection of the human liver

Background: The local immune responses to chronic echinococcal infections in various organs are largely unknown. Since the liver is the most frequently involved organ in such infections in human we aimed to characterize the inflammatory as well as immune cell infiltrate around hydatid cysts in the liver and compared to common inflammatory processes of the liver. Method: Surgical samples from the liver of 21 cystic echinococcosis (CE) patients were studied and the distribution of different types of inflammatory and immune cells were determined by immunohistochemistry. Furthermore, expression levels of costimulatory CTLA4, CD28, CD80 and CD86 molecules were measured at RNA level by PCR. Liver biopsy samples from patients with steatohepatitis (SH, n = 11) and chronic hepatitis (CH, n = 11) were used as non-inflammatory and chronic inflammatory controls, respectively. The composition and density of the inflammatory and immune cell infiltrates have been compared by using morphometry. Results: CD3+ T cells predominated the inflammatory infiltrate in all pathological processes, while in CE samples CD20+ B cells, in CH samples CD68+ macrophages were also frequent. Both myeloperoxidase (MPO) + leukocytes and CD68+ macrophages were found to be significantly decreased in CE as compared to either SH or CH samples. Concerning T cell subtypes, only CD8+ T cells were found to be significantly decreased in SH samples. CD1a + dendritic cells were almost completely missing from CE biopsies unlike in any other sample types. There were no differences detected in the mRNA expression of costimulatory molecules except decreased expression of CD28 in CE samples. Conclusion: In the hydatid lesions of the liver of chronic echinococcal infections T cell-mediated immunity seems to be impaired as compared to other types of chronic inflammatory processes, suggesting an immunosuppressive role for Echinococcus granulosus, which deserve further attentions

AlN films deposited by dc magnetron sputtering and high power impulse magnetron sputtering for SAW applications

International audienceIn this work, aluminium nitride (AlN) films were deposited on silicon substrates buffered by an epitaxial AlN thin film for surface acoustic wave (SAW) applications. The films were deposited by dc magnetron sputtering (dcMS) and high power impulse magnetron sputtering (HiPIMS) deposition techniques. The structural properties of AlN films were investigated using x-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy and atomic force microscopy. In both cases of films deposited by dcMS and HiPIMS, the XRD results showed that the obtained films are oriented, with full width at half maximum rocking curves of around 1 degrees. Raman spectroscopy revealed higher residual stress relaxation in the AlN epilayers grown by HiPIMS compared to AlN grown by dcMS, highlighted by a blue shift in the E2(high) Raman mode. The SAW measurements indicated an insertion loss of AlN-SAW devices of about 53 and 35 dB for the AlN films deposited by dcMS and HiPIMS respectively. The relation between the structural properties of AlN and the characteristics of AlN-SAW devices were correlated and discussed

Développement et validation d'une méthode ELISA de détection immunochimique de l'induction de la vitellogénine chez la truite juvénile après exposition au Nonylphenol

There is increasing concern about man-made chemicals in the aquatic environment that mimic the action of the steroid hormone, 17b-oestradiol. One of the most sensitive responses to the xenobiotics oestrogens in fish is the induction of the egg-yolk precursor vitellogenin which is normally synthetised by female under oestrogen stimulation. In immature or male fish, vitellogenin may thus serve as a reliable biomarker for xenobiotic oestrogen. In this study, a competitive enzyme linked immunosorbent assay (ELISA) using anti-salmon vitellogenin antibodies (Biosense Laboratories) was developed for the quantification of plasma vitellogenin in rainbow trout. Cross-reactivity and specificity of the antibodies with rainbow trout Vitellogenin was assessed by western blotting and ELISA and no cross-reactivity was observed with juvenile plasma. Vitellogenin was purified from plasma of oestradiol-treated juvenile fish by anion exchange chromatography followed by gel filtration. Purity was confirmed by silver staining Native PAGE, and hence the purified vitellogenin was used as standard in the ELISA. The sensitivity range of the ELISA was 16-175 ng/ml and the detection limit was 7,5 ng/ml. The repetability and the reproductibility were 5-9,5% andChez des poissons juveniles ou des mâles on peut utiliser la mesure de la vitellogenine comme biomarqueur aux xénobiotiques oestrogenes. Nous avons developpé une méthode immunochimique de type ELISA avec un anticorps anti-saumon (laboratoire Biosense). Cet essai a permis d'estimer les effets de la durée d'exposition et de la dose sur l'induction par le 17b oestradiol et le 4 nonylphenol. Les différences observées pour les deux composés sont certainement dues à la métabolisation. Le 4nonylphenol semble beaucoup moins capable d'effet oestrogénique que le 17 beta oestradiol

Effect of (xeno)-estrogens on zebrafish P450c17 (C17, 17 alpha-hydroxylase/17, 20-lyase) mRNA and protein expression in gonadal tissue.

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Interference between estrogen (ER) and aryl hydrocarbon receptors (AhR) signalling pathways in two fish models: the PELN cell line and zebrafish embryos.

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