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Jegatheesan P.,University of Lausanne | Jegatheesan P.,University of Paris Descartes | De Bandt J.-P.,University of Paris Descartes | De Bandt J.-P.,Hopitaux Universitaires Paris Center
Nutrients | Year: 2017

Among various factors, such as an unhealthy diet or a sedentarity lifestyle, excessive fructose consumption is known to favor nonalcoholic fatty liver disease (NAFLD), as fructose is both a substrate and an inducer of hepatic de novo lipogenesis. The present review presents some well-established mechanisms and new clues to better understand the pathophysiology of fructose-induced NAFLD. Beyond its lipogenic effect, fructose intake is also at the onset of hepatic inflammation and cellular stress, such as oxidative and endoplasmic stress, that are key factors contributing to the progression of simple steatosis to nonalcoholic steatohepatitis (NASH). Beyond its hepatic effects, this carbohydrate may exert direct and indirect effects at the peripheral level. Excessive fructose consumption is associated, for example, with the release by the liver of several key mediators leading to alterations in the communication between the liver and the gut, muscles, and adipose tissue and to disease aggravation. These multifaceted aspects of fructose properties are in part specific to fructose, but are also shared in part with sucrose and glucose present in energy- dense beverages and foods. All these aspects must be taken into account in the development of new therapeutic strategies and thereby to better prevent NAFLD. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.


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.


Pefura-Yone E.W.,University of Yaounde I | Pefura-Yone E.W.,Yaounde Jamot Hospital | Fodjeu G.,District Hospital of Bouda | Kengne A.P.,University of Cape Town | And 4 more authors.
Respiratory Medicine | Year: 2015

Background Little is known on the association between HIV infection and chronic obstructive pulmonary disease (COPD) in sub-Saharan Africa. We assessed the prevalence and investigated the determinants of COPD according to HIV status in a reference centre for HIV and tuberculosis (TB) management in Cameroon. Methods This case-control study involved 461 HIV-positive patients aged >18 years (cases) receiving care at the Yaounde Jamot Hospital (YJH) between November 2012 and February 2013, and in 461 age- and sex-matched HIV negative controls selected from the community through a multilevel stratified sampling. Logistic regression models were used to investigate the determinants of COPD. Results Each study group included 312 (67.7%) women. The mean age (standard deviation) was 42.6 (10.1) years in HIV positive group and 42.6 (10.2) years in HIV negative group. HIV infection was positively associated with COPD defined by the lower limit of normal FEV1/FVC ratio. In multivariable adjusted logistic regression, history of pulmonary TB, chronic respiratory symptoms and lower body mass index (BMI) were the main determinants of COPD in HIV infected patients (on antiretrovirals or not) regardless of the definition of COPD. Conclusions HIV infection is possibly a risk factor for COPD in this setting. The careful investigation of the determinants of COPD during routine diagnosis and care of people with HIV infection can aid the detection, further investigation, and improvement of the management of this group of patients. © 2014 Elsevier Ltd. All rights reserved.


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.

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