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Chevtzoff C.,French National Center for Scientific Research | Chevtzoff C.,University of Bordeaux Segalen | Yoboue E.D.,French National Center for Scientific Research | Yoboue E.D.,University of Bordeaux Segalen | And 9 more authors.
Journal of Biological Chemistry | Year: 2010

Mitochondrial biogenesis is a complex process. It necessitates the participation of both the nuclear and the mitochondrial genomes. This process is highly regulated, and mitochondrial content within a cell varies according to energy demand. In the yeast Saccharomyces cerevisiae, the cAMP pathway is involved in the regulation of mitochondrial biogenesis. An overactivation of this pathway leads to an increase in mitochondrial enzymatic content. Of the three yeast cAMP protein kinases, we have previously shown that Tpk3p is the one involved in the regulation of mitochondrial biogenesis. In this paper, we investigated the molecular mechanisms that govern this process. We show that in the absence of Tpk3p, mitochondria produce large amounts of reactive oxygen species that signal to the HAP2/3/4/5 nuclear transcription factors involved in mitochondrial biogenesis. We establish that an increase in mitochondrial reactive oxygen species production down-regulates mitochondrial biogenesis. It is the first time that a redox sensitivity of the transcription factors involved in yeast mitochondrial biogenesis is shown. Such a process could be seen as a mitochondria quality control process. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. Source


Bardet S.,Center Francois Baclesse | Chamontin B.,Center Hospitalo University Rangueil | Douillard C.,Lille University Hospital Center | Pagny J.-Y.,Hopital Europeen Georges Pompidou | And 4 more authors.
Annales d'Endocrinologie | Year: 2016

To establish the cause of primary aldosteronism (PA), it is essential to distinguish unilateral from bilateral adrenal aldosterone secretion, as adrenalectomy improves aldosterone secretion and controls hypertension and hypokalemia only in the former. Except in the rare cases of type 1 or 3 familial hyperaldosteronism, which can be diagnosed genetically and are not candidates for surgery, lateralized aldosterone secretion is diagnosed on adrenal CT or MRI and adrenal venous sampling. Postural stimulation tests and 131I-norcholesterol scintigraphy have poor diagnostic value and 11C-metomidate PET is not yet available. We recommend that adrenal CT or MRI be performed in all cases of PA. Imaging may exceptionally identify adrenocortical carcinoma, for which the surgical objectives are carcinologic, and otherwise shows either normal or hyperplastic adrenals or unilateral adenoma. Imaging alone carries a risk of false positives in patients over 35 years of age (non-aldosterone-secreting adenoma) and false negatives in all patients (unilateral hyperplasia). We suggest that all candidates for surgery over 35 years of age undergo adrenal venous sampling, simultaneously in both adrenal veins, without ACTH stimulation, to confirm the unilateral form of the hypersecretion. Sampling results should be confirmed on adrenal vein cortisol assay showing a concentration at least double that found in peripheral veins. Aldosterone secretion should be considered lateralized when aldosterone/cortisol ratio on the dominant side is at least 4-fold higher than contralaterally. © 2016. Source


Marijon E.,University of Paris Descartes | Trinquart L.,University of Paris Descartes | Trinquart L.,French Institute of Health and Medical Research | Otmani A.,University of Paris Descartes | And 21 more authors.
American Heart Journal | Year: 2010

Background: Sudden cardiac death (SCD) is the predominant cause of mortality in patients with mild heart failure (HF). This 2-year follow-up, multicenter, cohort study aimed to assess the extent to which implantable cardioverter defibrillators (ICDs), by reducing SCD, lead to predominant progressive HF death in mildly symptomatic HF patients at baseline in daily medical practice. Methods: Between June 2001 and June 2003, 1,030 New York Heart Association II patients received an ICD in 22 French centers. Sudden cardiac death and progressive HF mortality rates were assessed using competing risk methodology, and predictors for progressive HF at baseline were tested in a multivariate regression model. Results: During a mean follow-up of 22 ± 6 months, 114 deaths occurred: 12 (10.5%) due to SCD and 52 (45.6%) due to progressive HF (24-month cause-specific mortality rates of 1.2% [95% CI 0.6-1.9] and 5.4% [95% CI 4.0-6.8], respectively). Diuretics use (hazard ratio [HR] 2.8, 95% CI 1.5-5.5, P = .002), history of atrial fibrillation (HR 2.09, 95% CI 1.2-3.65, P = .01), and low ejection fraction (HR 2.7, 95% CI 1.4-4.8, P = .0008) were independent predictors for progressive HF death, whereas β-blocker therapy was a protector (HR 0.6, 95% CI 0.3-0.9, P = .04). Half of the patients (48%) who died from progressive HF within 2 years of ICD implant initially presented with enlarged QRS (≥120 milliseconds). Conclusions: Because of ICD efficiency, progressive HF is the main cause of death within 2 years of implant, although these patients are only mildly symptomatic at implantation. In addition to optimal pharmacologic therapy, these results raise the question of systematically implanting ICDs with cardiac resynchronization therapy in patients with electrical asynchronism at baseline. © 2010 Mosby, Inc. All rights reserved. Source


Le Brun J.-F.,University Paul Sabatier | Ferron G.,University Paul Sabatier | Vaysse C.,Center Hospitalo University Rangueil | Baujat M.,Center Hospitalo University Paule Of Viguier | And 3 more authors.
European Journal of Obstetrics Gynecology and Reproductive Biology | Year: 2012

Objectives: Endoscopy is a key tool in the diagnosis and management planning of peritoneal carcinomatosis. The aim of this study was to determine which type of endoscope is the most efficient for comprehensive staging of the upper abdomen peritoneal surface. Methods: From April 2010 to February 2011, endoscopies were performed on five human female fresh-frozen cadavers. Three endoscopes (rigid 0°, 30° and flexible) were used consecutively and compared. Results: The diaphragmatic areas explored with the flexible endoscope were significantly larger than those with the other two. On average, 135 (range 66-225), 168 (range 96-306), and 201 (range 128-399) cm2 were observed using the 0°, 30°, and flexible laparoscopes, respectively. The p value obtained using the exact Wilcoxon test for paired data was 0.0019 between the 0° and 30° endoscopes and between the 30° and flexible endoscopes. The 30° endoscope was consistently better than the 0° endoscope for the observation of the diaphragm and spleen undersurface. Conclusion: Flexible endoscopy seemed to be the most efficient for the evaluation of peritoneal carcinomatosis. However, due to a poorer image, the need for considerable practice, and the high equipment and maintenance cost of the flexible endoscope, the rigid 30° endoscope seems to be the best compromise. © 2012 Elsevier Ireland Ltd. All rights reserved. Source


Amar L.,University of Paris Descartes | Baguet J.P.,Center dexcellence en hypertension | Bardet S.,Center Francois Baclesse | Chaffanjon P.,Grenoble University Hospital Center | And 28 more authors.
Annales d'Endocrinologie | Year: 2016

The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations > 550 pmol/L (200 pg/mL) on 2 measurements, and rejected for aldosterone concentration < 240 pmol/L (90 pg/mL) and/or subthreshold ARR. The diagnostic threshold applied is different if certain medication cannot be interrupted. In intermediate situations, dynamic testing is performed. Genetic forms of PA are screened for in young subjects and/or in case of familial history. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated. © 2016 Elsevier Masson SAS Source

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