10 research outputs found

    Results of time kill studies with 7 strains of <i>Enterocossus faecalis</i> with a standard inoculum: 10<sup>5–6</sup> CFU/ml and chemically growth arrested bacteria.

    No full text
    a<p>A, amoxicillin; G, gentamicin; C, ceftriaxon; R, rifampicin, Te, teicoplanin; L, linezolid; D, daptomycin; Ti, tigecycline. Numbers in brackets give antibiotic concentration expressed in micrograms per milliliter.</p>b<p>Change from the starting inoculum expressed in log<sub>10</sub>CFU/ml modifications.</p>c<p>7 strains of <i>Enterococcus faecalis</i>: 5 clinical strains obtained from patients presenting endocarditis (OB, FAM, ME, LH, FG) and 2 referral strains (JH2-2, ATCC 11700).</p

    Results of time kill studies with 7 strains of <i>Enterocossus faecalis</i> with a standard inoculum: 10<sup>5–6</sup> CFU/ml and exponential growth phase bacteria.

    No full text
    a<p>A, amoxicillin; G, gentamicin; C, ceftriaxon; R, rifampicin, Te, teicoplanin; L, linezolid; D, daptomycin; Ti, tigecycline. Numbers in brackets indicate antibiotic concentration expressed in micrograms per milliliter.</p>b<p>Changes from the starting inoculum expressed in log<sub>10</sub>CFU/ml modifications.</p>c<p>7 strains of <i>Enterococcus faecalis</i>: 5 clinical strains obtained from patients presenting endocarditis (OB, FAM, ME, LH, FG) and 2 reference strains (JH2-2, ATCC 11700).</p

    Time kill studies with 9 strains of <i>Enterococcus faecalis</i> with a high inoculum and stationary growth phase bacteria.

    No full text
    <p>Nine strains of <i>Enterococcus faecalis</i> were used, including: 6 clinical strains obtained from patients presenting endocarditis (OB, FAM, ME, LH, FG, ZM); 1 clinical strain obtained from enterococcus bacteriemia without endocarditis (CR) and 2 reference strains (JH2-2, ATCC 11700). Daptomycin at 120 µg/ml and pH 5 (A) was bacteriostatic on all strains (1 to 2-log reduction). When pH was adjusted to 6 (B), the activity of daptomycin at 120 µg/ml increase with a 3 to 4-log reduction in 4 hours for 3/9 strains and a ≥4-log reduction for 4/9 strains. When pH was adjusted to 7 (C), daptomycin (120 µg/ml) bactericidal activity was optimum. At 4 hours 5/9 strains experienced a 2 to 4-log decrease and at 24 hours, a 3 to 6-log reduction was evidenced for 8/9 strains. Daptomycin at 60 µg/ml and pH 7 (D), alone or in combination did not reduce initial inoculum for 4/9 strains and was bacteriostatic for 5/9 strains after 24 hours (2-log reduction).</p

    Time kill studies with 9 strains of <i>Enterococcus faecalis</i> with a high inoculum and exponential growth phase bacteria.

    No full text
    <p>Nine strains of <i>Enterococcus faecalis</i> were used, including: 6 clinical strains obtained from patients presenting endocarditis (OB, FAM, ME, LH, FG, ZM); 1 clinical strain obtained from enterococcus bacteriemia without endocarditis (CR) and 2 reference strains (JH2-2, ATCC 11700). Daptomycin alone at 120 µg/ml (B) was bactericidal on 8/9 strains in 1 to 4 h with a 3 to 5-log decrease and showed only a 2 log decrease after 24 hours on 1/9 strains; whereas daptomycin alone at 60 µg/ml (A) and the combination amoxicillin-gentamicin were mainly not bactericidal (C).</p

    Daptomycin activity against nine strains of Enterococcus faecalis with a high inoculum and exponential or stationary growth phase bacteria, statistical analysis.

    No full text
    <p>Nine strains of <i>Enterococcus faecalis</i> were used, including: 6 clinical strains obtained from patients presenting endocarditis (OB, FAM, ME, LH, FG, ZM); 1 clinical strain obtained from enterococcus bacteriemia without endocarditis (CR) and 2 reference strains (JH2-2, ATCC 11700). In conditions of high inoculum and with exponential growth phase bacteria daptomycin activity at 120 µg/ml was significantly higher than daptomycin at 60 µg/ml (<i>p</i><0,0001) and than the combination amoxicillin-gentamicin (<i>p</i><0,0001) (A). In conditions of high inoculum and with stationary growth phase bacteria daptomycin activity at 120 µg/ml and pH 7 was significantly higher than daptomycin at 120 µg/ml and pH 5 (<i>p</i><0,0001), than daptomycin at 60 µg/ml and pH 7 (<i>p</i><0,0001), but not significantly higher than daptomycin at 120 µg/ml and pH 6 (<i>p</i> = 0,0537). Median changes in CFU/ml at 24 h were compared by Mann-Whitney <i>U</i>-test. A <i>p</i> value of ≤0.05 was considered significant. All statistical analyses were performed using GraphPad Prism software 6.0 (GraphPad, San Diego, CA, USA).</p

    Chemical structure of 1R-Chl, imatinib, dasatinib, and their effects on BCR-ABL unmutated and mutated genes transduced into murine BM cells.

    No full text
    <p>(A) 1R-Chl (left) targets the DNA sequences 5′-WGGWGW-3′. Bold, imidazole rings. imatinib (middle) targets Bcr-Abl kinase, and dasatinib (right) targets 14 out of 15 Bcr-Abl mutants. (B) Murine BM cells transduced with unmutated BCR-ABL and single point mutation Y253H, E255K, and T315I genes were tested for the effectiveness of 1R-Chl (125 nM to 1000 nM), 1S-Chl (500 nM and 1000 nM), imatinib (500 nM and 5000 nM; IC<sub>50</sub> = 260 nM for the native BCR-ABL transduced cells) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003593#pone.0003593-OHare1" target="_blank">[6]</a>, and dasatinib (10 nM and 100 nM; IC<sub>50</sub> = 0.8 nM for the native BCR-ABL transduced cells) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003593#pone.0003593-OHare1" target="_blank">[6]</a>. Triplicate experiments were done, and the numbers of colonies were quantified 7 days after initial plating.</p

    Additive effects of 1R-Chl and imatinib treatments.

    No full text
    <p>(A) Murine BM cells transduced with unmutated BCR-ABL were treated with 500 nM imatinib, 500 nM 1R-Chl, and 500 nM 1S-Chl individually, or in combination of either 500 nM 1R-Chl or 500 nM 1S-Chl with 500 nM imatinib. (B) Same treatment routines were used on CML patient MNCs. The CML patient MNCs were treated 500 nM imatinib, 500 nM 1R-Chl, and 500 nM 1S-Chl individually, or 500 nM 1R(S)-Chl in combination with 500 nM imatinib. (C) Same experiments were done on normal blood donor MNCs.</p

    Effects of 1R-Chl on colony formation of CML patient MNCs and normal human MNCs.

    No full text
    <p>(A) MNCs from CML patients were cultured with rh stem cell factor, rh IL-3, rh GM-CSF with or without erythropoietin which lead to CFU-GM or BFU-E cell lineages. The experiments were done in duplicate with 1R-Chl ranging from 125 to 1000 nM, 1S-Chl at 500 and 1000 nM, and imatinib at 500 and 5000 nM. The colonies were counted and results were calculated as the percentage of the control plates (without treatment) after 2 weeks. (B) MNCs from normal donors were cultured and plated under the same condition as CML patient cells. The cells were exposed to 500 and 1000 nM 1R-Chl, 500 and 1000 nM 1S-Chl, and 500 and 5000 nM imatinib. The colonies were counted and percent growth inhibition was calculated after 2 weeks.</p

    Cytotoxicity (MTS) assays on resting murine BM cells and human MNCs.

    No full text
    <p>(A) Ficoll-Hypaque-separated murine BM cells were plated in triplicate with 1R-Chl (10, 100, 500, and 1000 nM) without any growth factors or mitogens. After 72 and 96 hours, 20 µL of Celltiter 96 Aqueous One solution (Promega, WI) was added. The absorbances of the MTS metabolites were read corresponding to the numbers of metabolically active cells. (B) Ficoll-Hypaque-separated human MNCs were treated as above, and the viabilities of the cells were assessed after 72 and 96 hours.</p

    Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator

    No full text
    A novel series of alkoxyimino derivatives as S1P<sub>1</sub> agonists were discovered through de novo design using FTY720 as the chemical starting point. Extensive structure–activity relationship studies led to the discovery of (<i>E</i>)-1-(4-(1-(((4-cyclohexyl-3-(trifluoromethyl)­benzyl)­oxy)­imino)­ethyl)-2-ethylbenzyl)­azetidine-3-carboxylic acid (<b>32</b>, BAF312, Siponimod), which has recently completed phase 2 clinical trials in patients with relapsing–remitting multiple sclerosis
    corecore