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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jan Tuckermann; Anna Kleiman; Richard Moriggl; Rainer Spanbroek; +10 Authors

    Glucocorticoids (GCs) are widely used in the treatment of allergic skin conditions despite having numerous side effects. Here we use Cre/loxP-engineered tissue- and cell-specific and function-selective GC receptor (GR) mutant mice to identify responsive cell types and molecular mechanisms underlying the antiinflammatory activity of GCs in contact hypersensitivity (CHS). CHS was repressed by GCs only at the challenge phase, i.e., during reexposure to the hapten. Inactivation of the GR gene in keratinocytes or T cells of mutant mice did not attenuate the effects of GCs, but its ablation in macrophages and neutrophils abolished downregulation of the inflammatory response. Moreover, mice expressing a DNA binding-defective GR were also resistant to GC treatment. The persistent infiltration of macrophages and neutrophils in these mice is explained by an impaired repression of inflammatory cytokines and chemokines such as IL-1beta, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and IFN-gamma-inducible protein 10. In contrast TNF-alpha repression remained intact. Consequently, injection of recombinant proteins of these cytokines and chemokines partially reversed suppression of CHS by GCs. These studies provide evidence that in contact allergy, therapeutic action of corticosteroids is in macrophages and neutrophils and that dimerization GR is required.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Fachrepositorium Leb...arrow_drop_down
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    Europe PubMed Central
    Other literature type . 2007
    Data sources: PubMed Central
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    The Journal of Clinical Investigation
    Article . 2007 . Peer-reviewed
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Europe PubMed Central
      Other literature type . 2007
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      The Journal of Clinical Investigation
      Article . 2007 . Peer-reviewed
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  • Authors: Späth, Hans-Martin; Charavel, Marie; Morelle, Magali; Carrère, Marie-Odile;

    Objective: Qualitative interviews were conducted with pharmacists in hospitals and clinics in the Rhone-Alpes region of France to determine the role of economic data when selecting medicines for formularies, to identify barriers to the use of this information and to study to what degree a healthcare establishment's financing system influences the use of this data.Method: A stratified sample of healthcare establishments with over 100 short-stay beds were included: (1) thirteen public and semi-private hospitals financed through annual global budgets and (2) six private clinics financed on a fee-for-service basis. Interviews were carried out between October 1999 and January 2000, and coded independently by two researchers.Main outcome measure: A multiple correspondence analysis was performed to compare the two groups of healthcare establishments.Results: The influence of economic data in the decision-making process is limited, for other factors appear to have greater weight: (1) efficacy and safety of medicines (2) relations between decision-makers and the pharmaceutical industry and (3) patient quality of life. Economic data used was mainly related to medication prices and quantities consumed. This data was used in a large number of decisions and seemed to have more importance in hospitals than in clinics. Information related to resources that could be saved by the inclusion of a new medicine on formularies was seldom used and apparently considered less important in hospitals than in clinics. Pharmacoeconomic evaluations were very rarely used. Six barriers to the use of economic data were raised by the pharmacists, including: lack of time, which limits the collection and analysis of such information; insufficient health economics training, an obstacle to decision-makers' analytical capacity; and closed budgets within hospitals.Conclusion: Economic data concerning ‘medication budgets’ appears to have a greater impact in public and semi-private hospitals than in private clinics. Obstacles linked to the decision-making context itself were particularly highlighted, and it can be concluded that in order to increase the use of economic data, it is first necessary to create an environment that is more favourable to its application.

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    Authors: Monneuse, O.; Abdalla, S.; Pilleul, F.; Hervieu, V.; +3 Authors

    AbstractBackgroundThe clinical diagnosis of acute appendicitis in adults remains tricky, but radiological examinations are very helpful to determine the diagnosis even when the adult patient presents atypically. This study was designed to quantify the proportion of patients with a preoperative diagnosis of acute appendicitis that had isolated right lower quadrant pain without biological inflammatory signs and then to determine which imaging examination led to the determination of the diagnosis.MethodsIn this monocentric study based on retrospectively collected data, we analyzed a series of 326 patients with a preoperative diagnosis of acute appendicitis and isolated those who were afebrile and had isolated right lower quadrant pain and normal white blood cell counts and C‐reactive protein levels. We determined whether the systematic ultrasonography examination was informative enough or a complementary intravenous contrast media computed tomography scan was necessary to determine the diagnosis, and whether the final pathological diagnosis fit the preoperative one.ResultsA total of 15.6% of the patients with a preoperative diagnosis of acute appendicitis had isolated rebound tenderness in the right lower quadrant, i.e., they were afebrile and their white blood cell counts and C‐reactive protein levels were normal. In 96.1% of the cases, the ultrasonography examination, sometimes complemented by an intravenous contrasted computed tomography scan if the ultrasonography result was equivocal, fit the histopathological diagnosis of acute appendicitis.ConclusionsThe diagnosis of acute appendicitis cannot be excluded when an adult patient presents with isolated rebound tenderness in the right lower quadrant even without fever and biological inflammatory signs. In our study, ultrasonography and computed tomography were very helpful when making the final diagnosis.

    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao World Journal of Sur...arrow_drop_down
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    World Journal of Surgery
    Article . 2009 . Peer-reviewed
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    Authors: Perinel, Julie; Mariette, Christophe; Dousset, Bertrand; Sielezneff, Igor; +10 Authors

    Postoperative complications occurred in 77.5% [95% confidence interval (95% CI) 68.1-85.1] patients in the NJEEN group versus 64.4% (95% CI 54.2-73.6) in TPN group (P = 0.040). NJEEN was associated with higher frequency of postoperative pancreatic fistula (POPF) (48.1% vs 27.7%, P = 0.012) and higher severity (grade B/C 29.4% vs 13.9%; P = 0.007). There was no significant difference in the incidence of post-pancreatectomy hemorrhage, delayed gastric emptying, infectious complications, the grade of postoperative complications, and the length of postoperative stay. A successful NJEEN was achieved in 63% patients. In TPN group, average energy intake was significantly higher (P < 0.001) and patients had an earlier recovery of oral feeding (P = 0.0009). Multicenter, randomized, controlled trial was conducted between 2011 and 2014. Nine centers in France analyzed 204 patients undergoing PD to NJEEN (n = 103) or TPN (n = 101). Primary outcome was the rate of postoperative complications according to Clavien-Dindo classification. Successful NJEEN was defined as insertion of a nasojejunal feeding tube, delivering at least 50% of nutritional needs on PoD 5, and no TPN for more than consecutive 48 hours. In patients undergoing PD, NJEEN was associated with an increased overall postoperative complications rate. The frequency and the severity of POPF were also significantly increased after NJEEN. In terms of safety and feasibility, NJEEN should not be recommended. Current nutritional guidelines recommend the use of enteral over parenteral nutrition in patients undergoing gastrointestinal surgery. However, the NJEEN remains controversial in patients undergoing PD. The aim of this study was to compare nasojejunal early enteral nutrition (NJEEN) with total parenteral nutrition (TPN), after pancreaticoduodenectomy (PD), in terms of postoperative complications.

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    HPB
    Article . 2019 . Peer-reviewed
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    Article . 2019 . Peer-reviewed
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    Annals of Surgery
    Article . 2016 . Peer-reviewed
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    Other literature type . Article . 2016
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      Article . 2019 . Peer-reviewed
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      Annals of Surgery
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    Authors: Alexis Saintamand; Pauline Rouaud; Faten Saad; Géraldine Rios; +2 Authors

    International audience; In mature B cells, class switch recombination (CSR) replaces the expressed constant Cμ gene with a downstream C(H) gene. How the four transcriptional enhancers of the IgH 3' regulatory region (3'RR) control CSR remains an open question. We have investigated IgG1 CSR in 3'RR-deficient mice. Here we show that the 3'RR enhancers target the S(γ1) acceptor region (and poorly the S(μ) donor region) by acting on epigenetic marks, germline transcription, paused RNA Pol II recruitment, R loop formation, AID targeting and double-strand break generation. In contrast, location and diversity of S(μ)-S(γ1) junctions are not affected by deletion of the 3'RR enhancers. Thus, the 3'RR controls the first steps of CSR by priming the S acceptor region but is not implicated in the choice of the end-joining pathway.

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    Nature Communications
    Article . 2015 . Peer-reviewed
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    Authors: E, Marthinet; G, Divita; J, Bernaud; D, Rigal; +1 Authors

    International audience; Multidrug resistance of cancer (MDR) is the major cause of failure of chemotherapy. The typical MDR phenotype is due to the overexpression of membrane proteins among which the main representative is P-glycoprotein (Pgp) encoded by the MDR1 gene. Many attempts to modulate MDR by chemosensitizers have been unsuccessful in human therapy due to their intrinsic toxic effects. In an effort to modulate the MDR phenotype efficiently we designed an antisense and a transcriptional decoy strategy targeting the TATA-less human MDR1 gene promoter. The choice of the start point of transcription in a multiple start site window is related to an upstream MED-1 cis-element, the sequence and configuration of which are specific to human MDR1 gene expressed in Pgp-overproducing cancer cells. A 12mer antisense oligodeoxynucleotide (ODN) and a 12mer double-stranded ODN, both containing the MED-1 sequence, were designed and efficiently vectorized into the nucleus with the chimerical MPG peptide. A synthetic cellular model (NIH-EGFP) and highly resistant human CEM/VLB0.45 leukemia cells, significantly responded to transfection with the ODN/MPG complex. The level of EGFP fluorescence in NIH-EGFP cells decreased, and thus its production, and viability of CEM/VLB0.45 cells decreased by 63% in the presence of vinblastine, revealing that their resistance to the anticancer drug was reversed. These results open new insights into transcriptional decoy and anti-gene therapies of MDR cancers that overproduce Pgp. Gene Therapy (2000) 7, 1224-1233.Multidrug resistance of cancer (MDR) is the major cause of failure of chemotherapy. The typical MDR phenotype is due to the overexpression of membrane proteins among which the main representative is P-glycoprotein (Pgp) encoded by the MDR1 gene. Many attempts to modulate MDR by chemosensitizers have been unsuccessful in human therapy due to their intrinsic toxic effects. In an effort to modulate the MDR phenotype efficiently we designed an antisense and a transcriptional decoy strategy targeting the TATA-less human MDR1 gene promoter. The choice of the start point of transcription in a multiple start site window is related to an upstream MED-1 cis-element, the sequence and configuration of which are specific to human MDR1 gene expressed in Pgp-overproducing cancer cells. A 12mer antisense oligodeoxynucleotide (ODN) and a 12mer double-stranded ODN, both containing the MED-1 sequence, were designed and efficiently vectorized into the nucleus with the chimerical MPG peptide. A synthetic cellular model (NIH-EGFP) and highly resistant human CEM/VLB0.45 leukemia cells, significantly responded to transfection with the ODN/MPG complex. The level of EGFP fluorescence in NIH-EGFP cells decreased, and thus its production, and viability of CEM/VLB0.45 cells decreased by 63% in the presence of vinblastine, revealing that their resistance to the anticancer drug was reversed. These results open new insights into transcriptional decoy and anti-gene therapies of MDR cancers that overproduce Pgp. Gene Therapy (2000) 7, 1224-1233.

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    Gene Therapy
    Article . 2000 . Peer-reviewed
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  • Authors: Zolesio, Emmanuelle;

    National audience; La pratique chirurgicale vise à repousser les frontières de la mort (Adam, Herzlich, 2007 ; Pouchelle, 2008). Toutefois, il arrive que les chirurgiens ne parviennent pas à éviter celle-ci et qu'ils soient confrontés à la mort d'un de leur patient suite à un déchoquage, à une mort sur table due à une erreur opératoire ou encore à des complications post-opératoires. Charles L. Bosk (1979) s'est attaché à voir comment les chirurgiens identifiaient, classifiaient ces échecs et comment ils les sanctionnaient collégialement. Nous aimerions pour notre part voir comment ils se prémunissent face à ces échecs à " sauver des vies ". Nous verrons dans un premier temps que tous les décès de patients ne pèsent pas de la même façon sur le moral des opérateurs (la mort d'un patient opéré en urgence n'affecte pour ainsi dire que peu le praticien qui n'a eu aucun contact préalable avec le patient) et qu'un travail de distanciation d'avec le patient est opéré dès la période de formation qu'est l'internat. Autrement dit, le chirurgien apprend progressivement à ne plus s'identifier avec le patient et à occulter la personne pour ne voir qu'un " cas " opératoire, une " structure anatomique " au moment où il opère. La faible place du relationnel avec le patient (au regard d'autres pratiques médicales comme celle de la médecine générale par exemple), célèbre en chirurgie (Pouchelle, 2008), apparaît comme une première façon de mettre à distance le potentiel décès de patients et la souffrance qu'il induit pour le praticien. Si les chirurgiens apprennent à ne pas aimer la relation avec le patient, c'est semble-t-il avant tout pour se protéger. Les observations de terrain et les entretiens conduits avec le personnel chirurgical ont fait apparaître également le rôle joué par l'humour noir dans la gestion individuelle et collective de ces morts que l'on n'a pu éviter. Autant nous ne souscrivons pas au fait que les plaisanteries sexuelles fassent partie des stratégies collectives de défense virile (Dejours, 2000) - du moins en ce qui concerne la chirurgie - autant l'humour noir semble effectivement une façon de gérer la souffrance du praticien suite au décès d'un de ses patients. Ceci aide à comprendre en partie les conduites transgressives et l'humour carabin (Godeau, 2007), apparemment plus développé en chirurgie que dans d'autres spécialités médicales.

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    Authors: Tommasino, L.; Thomazeau, C.; Touchard, F.; Lemaire, M.;

    Abstract The asymmetric reduction of phenylglyoxylate methyl ester with molecular hydrogen and catalytic amounts of cationic chiral diamine and dithiourea complexes of rhodium and iridium is reported. The catalytic activity of the complexes is rather different if the C 2 -symmetric ligand is a diamine or a dithiourea, even if enantioselectivity is always observed, with ee values up to 72%.

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    Tetrahedron Asymmetry
    Article . 1999 . Peer-reviewed
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    Authors: Nataliya, Zelisko; Dmytro, Atamanyuk; Olexandr, Vasylenko; Philippe, Grellier; +1 Authors

    A series of novel 6,6,7-trisubstituted thiopyrano[2,3-d][1,3]thiazoles-based molecules have been synthesized and evaluated as potential antitrypanosomal agents. The most active analogue 3b inhibited Trypanosoma brucei brucei and Trypanosoma brucei gambiense with an IC50 of 0.26 and 0.42 mu M, respectively. They could be considered as potent hits for further antitrypanosomal drug discovery efforts. (C) 2012 Elsevier Ltd. All rights reserved.

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    Aperta - TÜBİTAK Açık Arşivi
    Other literature type . 2012
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    Bioorganic & Medicinal Chemistry Letters
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    Authors: Fache, F.; Lehuede, S.; Lemaire, M.;

    Abstract Various substituted aromatics have been reduced using colloidal ruthenium under H 2 pressure with good stereoselectivity (cis/trans up to 60). Interesting chemoselectivities are also observed.

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    Tetrahedron Letters
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      Tetrahedron Letters
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jan Tuckermann; Anna Kleiman; Richard Moriggl; Rainer Spanbroek; +10 Authors

    Glucocorticoids (GCs) are widely used in the treatment of allergic skin conditions despite having numerous side effects. Here we use Cre/loxP-engineered tissue- and cell-specific and function-selective GC receptor (GR) mutant mice to identify responsive cell types and molecular mechanisms underlying the antiinflammatory activity of GCs in contact hypersensitivity (CHS). CHS was repressed by GCs only at the challenge phase, i.e., during reexposure to the hapten. Inactivation of the GR gene in keratinocytes or T cells of mutant mice did not attenuate the effects of GCs, but its ablation in macrophages and neutrophils abolished downregulation of the inflammatory response. Moreover, mice expressing a DNA binding-defective GR were also resistant to GC treatment. The persistent infiltration of macrophages and neutrophils in these mice is explained by an impaired repression of inflammatory cytokines and chemokines such as IL-1beta, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and IFN-gamma-inducible protein 10. In contrast TNF-alpha repression remained intact. Consequently, injection of recombinant proteins of these cytokines and chemokines partially reversed suppression of CHS by GCs. These studies provide evidence that in contact allergy, therapeutic action of corticosteroids is in macrophages and neutrophils and that dimerization GR is required.

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    Europe PubMed Central
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    The Journal of Clinical Investigation
    Article . 2007 . Peer-reviewed
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      Europe PubMed Central
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      The Journal of Clinical Investigation
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  • Authors: Späth, Hans-Martin; Charavel, Marie; Morelle, Magali; Carrère, Marie-Odile;

    Objective: Qualitative interviews were conducted with pharmacists in hospitals and clinics in the Rhone-Alpes region of France to determine the role of economic data when selecting medicines for formularies, to identify barriers to the use of this information and to study to what degree a healthcare establishment's financing system influences the use of this data.Method: A stratified sample of healthcare establishments with over 100 short-stay beds were included: (1) thirteen public and semi-private hospitals financed through annual global budgets and (2) six private clinics financed on a fee-for-service basis. Interviews were carried out between October 1999 and January 2000, and coded independently by two researchers.Main outcome measure: A multiple correspondence analysis was performed to compare the two groups of healthcare establishments.Results: The influence of economic data in the decision-making process is limited, for other factors appear to have greater weight: (1) efficacy and safety of medicines (2) relations between decision-makers and the pharmaceutical industry and (3) patient quality of life. Economic data used was mainly related to medication prices and quantities consumed. This data was used in a large number of decisions and seemed to have more importance in hospitals than in clinics. Information related to resources that could be saved by the inclusion of a new medicine on formularies was seldom used and apparently considered less important in hospitals than in clinics. Pharmacoeconomic evaluations were very rarely used. Six barriers to the use of economic data were raised by the pharmacists, including: lack of time, which limits the collection and analysis of such information; insufficient health economics training, an obstacle to decision-makers' analytical capacity; and closed budgets within hospitals.Conclusion: Economic data concerning ‘medication budgets’ appears to have a greater impact in public and semi-private hospitals than in private clinics. Obstacles linked to the decision-making context itself were particularly highlighted, and it can be concluded that in order to increase the use of economic data, it is first necessary to create an environment that is more favourable to its application.