Hopitaux Universitaires Paris Center
Hopitaux Universitaires Paris Center
Chenevier-Gobeaux C.,Hopitaux Universitaires Paris Center
Leukemia | Year: 2017
Alterations in metabolic activities are cancer hallmarks that offer a wide range of new therapeutic opportunities. Here we decipher the interplay between mTORC1 activity and glucose metabolism in acute myeloid leukemia (AML). We show that mTORC1 signaling that is constantly overactivated in AML cells promotes glycolysis and leads to glucose addiction. The level of mTORC1 activity determines the sensitivity of AML cells to glycolysis inhibition as switch-off mTORC1 activity leads to glucose-independent cell survival that is sustained by an increase in mitochondrial oxidative phosphorylation. Metabolic analysis identified the pentose phosphate pathway (PPP) as an important pro-survival pathway for glucose metabolism in AML cells with high mTORC1 activity and provided a clear rational for targeting glucose-6-phosphate dehydrogenase (G6PD) in AML. Indeed, our analysis of the cancer genome atlas AML database pinpointed G6PD as a new biomarker in AML, as its overexpression correlated with an adverse prognosis in this cohort. Targeting the PPP using the G6PD inhibitor 6-aminonicotinamide induces in vitro and in vivo cytotoxicity against AML cells and synergistically sensitizes leukemic cells to chemotherapy. Our results demonstrate that high mTORC1 activity creates a specific vulnerability to G6PD inhibition that may work as a new AML therapy.Leukemia advance online publication, 28 March 2017; doi:10.1038/leu.2017.81. © 2017 Macmillan Publishers Limited, part of Springer Nature.
Hyon C.,Groupe Hospitalier University Of Lest Parisien |
Dode C.,Hopitaux Universitaires Paris Center
Medecine Therapeutique Medecine de la Reproduction, Gynecologie et Endocrinologie | Year: 2017
Premature ovarian insufficiency (POI), clinically characterized by cessation of ovarian function before the age of 40 years, occurs in approximately 1-5% of women. POI may be secondary to chemotherapy, radiotherapy or environmental factors but genetic causes are identified in 20-25% of cases. Among genetic causes abnormal chromosome numbers, such as monosomy X that is responsible for Turner syndrome, or chromosomal rearrangements are the most frequent causes of POI. The development of array-CGH or SNP array and Next Generation Sequencing (NGS) during the past decades has allowed to identify new causes of POI. However, karyotype and FMR1 gene premutation analyses are the first genetic investigations that have to be conducted in patients with POI. For further genetic investigations, patients can be referred to a reference center where a second line of genetic analysis can be performed. Copyright © 2017 John Libbey Eurotext.
Bafeta A.,French Institute of Health and Medical Research |
Yavchitz A.,French Institute of Health and Medical Research |
Riveros C.,French Institute of Health and Medical Research |
Batista R.,Hopitaux Universitaires Paris Center |
Ravaud P.,French Institute of Health and Medical Research
Annals of Internal Medicine | Year: 2017
Background: Fecal microbiota transplantation (FMT) could be a novel treatment option for several chronic diseases associated with altered gut microbiota. Purpose: To examine the conduct and reporting of studies assessing FMT. Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science from inception to 31 January 2017. Study Selection: Two reviewers independently examined titles and abstracts to identify all English-language reports of human clinical studies assessing the safety or efficacy of FMT. Data Extraction: Three reviewers independently assessed study types and characteristics and the reporting of important methodological components of the FMT intervention. Data Synthesis: Most (84%) of the 85 published reports found addressed the use of FMTs for Clostridium difficile infection or inflammatory bowel disease, and most (87%) were non-randomized controlled trials. Important methodological components that were not reported in published studies included the following: eligibility criteria for donors (47%), materials used for collecting stools and the period of collection (96%), methods used for conservation of stools (76%), the amount and type of stools used (for example, fresh or frozen), and duration of stool conservation (67%). Many (58%) did not report an analysis of microbiota composition. Limitations: Lack of universal consensus regarding the most important methodological components of FMT and inability to assess the actual conduct of studies and whether the publication process affected the completeness of reporting. Conclusion: Key components of FMT interventions, which are necessary to replicate and understand study findings about efficacy and safety, are poorly reported. © 2017 American College of Physicians.
Gaucher S.,University of Paris Descartes |
Gaucher S.,Hopitaux Universitaires Paris Center |
Jarraya M.,Hopitaux Universitaires Saint Louis Lariboisiere
Cell and Tissue Banking | Year: 2015
MTT assay is the gold standard for assessing skin sample viability but it is time-consuming. Here we compared the MTT test with two other assays for the assessment of skin viability. The MTT, PrestoBlue (colorimetric method) and LDH release assays were applied to fresh and cryopreserved skin. Skin viability was considered proportional to the optical density values of the relevant analytes. PrestoBlue did not reliably distinguish between fresh and cryopreserved skin. The LDH release assay did not allow us to establish a viability index. We recommend the MTT assay for assessing skin viability. © 2014, Springer Science+Business Media Dordrecht.
Breuillard C.,University of Paris Descartes |
Cynober L.,University of Paris Descartes |
Cynober L.,Hopitaux Universitaires Paris Center |
Moinard C.,University of Paris Descartes
Amino Acids | Year: 2015
Citrulline (Cit) is a non-essential amino acid whose metabolic properties were largely ignored until the last decade when it began to emerge as a highly promising nutrient with many regulatory properties, with a key role in nitrogen homeostasis. Because Cit is not taken up by the liver, its synthesis from arginine, glutamine, ornithine and proline in the intestine prevents the hepatic uptake of the two first amino acids which activate the urea cycle and so prevents amino acid catabolism. This sparing effect may have positive spin-off for muscle via increased protein synthesis, protein content and functionality. However, the mechanisms of action of Cit are not fully known, even if preliminary data suggest an implication of mTOR pathway. Further exploration is needed to gain a complete overview of the role of Cit in the control of nitrogen homeostasis. © 2015 Springer-Verlag Wien.
Cynober L.,Hopitaux Universitaires Paris Center |
Cynober L.,University of Paris Pantheon Sorbonne |
De Bandt J.-P.,Hopitaux Universitaires Paris Center |
De Bandt J.-P.,University of Paris Pantheon Sorbonne
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2014
PURPOSE OF REVIEW: To analyze the recent literature (2011-2013) on glutamine supplementation of parenteral and enteral nutrition in critically ill patients. Potential confounding factors that may explain conflicting results are suggested. RECENT FINDINGS: Some recent, prospective, multicenter trials and two small trials yielded conflicting results that weigh heavily in the conclusions of a recent meta-analysis. Heterogeneity of the patients enrolled (especially in terms of injury severity, age, and basal nutritional status) and difficulties in identifying patients truly in need of glutamine supplementation may explain the discrepancies. SUMMARY: Glutamine supplementation has been recognized as beneficial in acutely injured patients. However, recent conflicting results in either 'real-life conditions' or very severe situations suggest that its indications need to be more precisely determined. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Auger J.,Hopitaux Universitaires Paris Center
Proceedings. Biological sciences / The Royal Society | Year: 2013
Digit length ratios, especially the second-to-fourth digit ratio (2D : 4D), are associated with various pathological and behavioural conditions in many species including humans and are dependent upon prenatal androgen to oestrogen balance. It is unknown whether digit ratios are modified by environmental exposure to ubiquitous endocrine disruptors. We studied the effect on adult male Wistar rat digit ratios of a gestational exposure to the oestrogenic and antiandrogenic compounds bisphenol A (BPA), genistein and vinclozolin, in low doses, and in combination with investigating in parallel a possible sexual dimorphism of this trait. We also investigated the effects on the male progeny not exposed during gestation. X-rays were taken of the left and right forepaws, and 2D-5D proximal to distal phalanx distances were measured by a standardized procedure based on semi-automatic image analysis. We provide evidence that there is a sexual dimorphism of digit ratios in the Wistar rat, and we found that BPA alone or in combination with genistein and vinclozolin significantly feminized digit ratios in male rats. Intriguingly, significant feminization of digit ratios was also found in the unexposed male progeny of males that had been exposed to compound mixtures. In conclusion, prenatal environmental levels of endocrine-active substances permanently disrupt digit ratios. Digit ratio measurement in adults is thus a promising biomarker of prenatal exposure to low-dose endocrine disruptors in rodents, with potential implications for future studies in humans.
Caira L.,Hopitaux Universitaires Paris Center
Soins Cadres de Sante | Year: 2012
Keeping people with disabilities in employment is part of human resources policy. As hospital staff members age, many are concerned about the decline of their capability, which requires a reorganisation of their workplace. The disability adviser plays a pivotal role in employment and expertise planning. © 2012 Elsevier Masson SAS.
Charpentier S.,University Paul Sabatier |
Chenevier-Gobeaux C.,hopitaux universitaires Paris Center
Presse Medicale | Year: 2016
High sensitivity cardiac troponins must be used in first intention.H0/H3 algorithm is recommended in the diagnostic strategy.In total, 75% of emergency patients can be early discharged with the H0/H1 algorithm.Interpretation of troponin values requires taking into account the clinical context and electrocardiogram.The algorithm H0/H1 cannot be used for early presenters in ED after onset of chest pain.Further validation studies are needed before widespread application of H0/H1 algorithm. © 2016 Elsevier Masson SAS.
Badin de Montjoye B.,Hopitaux universitaires Paris Center
Ethique et Sante | Year: 2013
Addiction corresponds to the use and abuse of potentially harmful toxics. It also includes dependence to psychoactive drugs or to practices of dangerous behaviours. Consensus now defines these concepts using international classifications (Diagnostic and Statistical Manual of Mental Disorders [DSM-IV]; CIM. X). A possibility exists to build a link with these so-called inaccessible patients, since the visit in the emergency department. The author develops a comprehensive approach that includes two cornerstone steps: on the one hand, the obstacles to be overcome in order to share confidence with the patient, on the other hand, addiction as a specific disorder. © 2012 Elsevier Masson SAS.