... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute ... more ... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute tension. b) Depuis Victor Hugo et Y Homme qui rit, la substitution d'une relative au déterminatif est devenue commune. Mais alors ...
A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the abili... more A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the ability of 5(6)-carboxyfluorescein diacetate (CFDA) to indicate the worm's viability. It is shown for the first time that the treatment of a suspension of worms with a solution of 5(6)-carboxyfluorescein diacetate (4.2%) for 30min transiently induces fluorescence in dead worms only, allowing a fast and efficient determination of the proportion of dead worms by fluorescence microscopy. The proposed test has been validated using mixtures of populations of living and killed C. elegans and proved to be selective, linear in the range 0-100%, accurate and precise. The suitability of the assay to detect anthelmintic activity was then evaluated by studying the toxicity against C. elegans of a series of known anthelmintic compounds (mebendazole, levamisole, niclosamide, pyrantel, piperazine, and thiabendazole) with various modes of action. The worms were exposed to each drug at two concentrations, 50 and 100microg/ml for piperazine, niclosamide, pyrantel and 5 and 10microg/ml for the others. We observed that, in the tested range of doses, piperazine and niclosamide were only moderately toxic, yielding 13.1 and 17.5% of dead worms; due to their mode of action and/or specificity, the low toxicity of these compounds was as expected. The marked activities of all the other compound fully agree with those described in the literature and obtained by other more laborious techniques. These validation data indicate that the proposed in vitro anthelmintic assay using 5(6)-carboxyfluorescein diacetate allows for sensitive measurement of worm viability.
Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities aga... more Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities against six distinct cancer cell lines. Several of these natural products were found to have low micromolar antiproliferative potencies. The log P values of these compounds did not influence their observed activity. When active, the compounds displayed cytostatic, not cytotoxic activity, with the exception of pseudolycorine (3), which exhibited cytotoxic profiles. The active compounds showed similar efficacies toward cancer cells irrespective of whether the cell lines were responsive or resistant to proapoptotic stimuli. Altogether, the data from the present study revealed that lycorine (1), amarbellisine (6), haemanthamine (14), and haemanthidine (15) are potentially useful chemical scaffolds to generate further compounds to combat cancers associated with poor prognoses, especially those naturally resistant to apoptosis, such as glioblastoma, melanoma, non-small-cell lung, and metastatic cancers.
The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and... more The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories received samples of different concentrations of 8-oxodG for analysis. About half the results returned (for 8-oxodG) were within 20% of the median values. Coefficients of variation (for three identical samples) were commonly around 10%. A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8-oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the reported results were within 20% of the median value, and half obtained a CVof less than 10%. In order to test sensitivity, as well as precision, DNA was treated with photosensitiser and light to introduce increasing amounts of 8-oxoGua and samples were sent to members. Median values calculated from all returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10(6) Gua; only seven laboratories detected the increase over the whole range, while all but one detected a dose response over two concentration intervals. Results in this trial reflect a continuing improvement in precision and accuracy. The next challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue, where the concentration is much lower than in calf thymus DNA.
To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic system... more To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein-water gels incorporating gentamicin sulfate could be used as local, bioresorbable,and sustained-release implants. For this purpose, four formulations were examined with regard to their physicochemical and in vitro drug release characteristics. Hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA),and X-ray diffraction showed cubic liquid crystalline and eutectic structures. The more suitable formulation consisting of 80-15-5%wt/wt monoolein-water-gentamicin sulfate progressively released the antibiotic for a period of 3 weeks without burst effect. Moreover, the content and the release profile of gentamicin sulfate were not significantly changed after storage at 2-6 degrees C for a period of 10 months.
A series of 33 novel divanillates and trivanillates were synthesized and found to possess promisi... more A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies.
... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute ... more ... tonnerre. Parmi les autres, relevons : la Femme spectacle, Compartiment tueurs, Filles haute tension. b) Depuis Victor Hugo et Y Homme qui rit, la substitution d'une relative au déterminatif est devenue commune. Mais alors ...
A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the abili... more A new in vitro assay for anthelmintic activity using Caenorhabditis elegans is based on the ability of 5(6)-carboxyfluorescein diacetate (CFDA) to indicate the worm's viability. It is shown for the first time that the treatment of a suspension of worms with a solution of 5(6)-carboxyfluorescein diacetate (4.2%) for 30min transiently induces fluorescence in dead worms only, allowing a fast and efficient determination of the proportion of dead worms by fluorescence microscopy. The proposed test has been validated using mixtures of populations of living and killed C. elegans and proved to be selective, linear in the range 0-100%, accurate and precise. The suitability of the assay to detect anthelmintic activity was then evaluated by studying the toxicity against C. elegans of a series of known anthelmintic compounds (mebendazole, levamisole, niclosamide, pyrantel, piperazine, and thiabendazole) with various modes of action. The worms were exposed to each drug at two concentrations, 50 and 100microg/ml for piperazine, niclosamide, pyrantel and 5 and 10microg/ml for the others. We observed that, in the tested range of doses, piperazine and niclosamide were only moderately toxic, yielding 13.1 and 17.5% of dead worms; due to their mode of action and/or specificity, the low toxicity of these compounds was as expected. The marked activities of all the other compound fully agree with those described in the literature and obtained by other more laborious techniques. These validation data indicate that the proposed in vitro anthelmintic assay using 5(6)-carboxyfluorescein diacetate allows for sensitive measurement of worm viability.
Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities aga... more Fifteen Amaryllidaceae alkaloids (1-15) were evaluated for their antiproliferative activities against six distinct cancer cell lines. Several of these natural products were found to have low micromolar antiproliferative potencies. The log P values of these compounds did not influence their observed activity. When active, the compounds displayed cytostatic, not cytotoxic activity, with the exception of pseudolycorine (3), which exhibited cytotoxic profiles. The active compounds showed similar efficacies toward cancer cells irrespective of whether the cell lines were responsive or resistant to proapoptotic stimuli. Altogether, the data from the present study revealed that lycorine (1), amarbellisine (6), haemanthamine (14), and haemanthidine (15) are potentially useful chemical scaffolds to generate further compounds to combat cancers associated with poor prognoses, especially those naturally resistant to apoptosis, such as glioblastoma, melanoma, non-small-cell lung, and metastatic cancers.
The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and... more The aim of ESCODD, a European Commission funded Concerted Action, is to improve the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8-oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories received samples of different concentrations of 8-oxodG for analysis. About half the results returned (for 8-oxodG) were within 20% of the median values. Coefficients of variation (for three identical samples) were commonly around 10%. A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8-oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the reported results were within 20% of the median value, and half obtained a CVof less than 10%. In order to test sensitivity, as well as precision, DNA was treated with photosensitiser and light to introduce increasing amounts of 8-oxoGua and samples were sent to members. Median values calculated from all returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10(6) Gua; only seven laboratories detected the increase over the whole range, while all but one detected a dose response over two concentration intervals. Results in this trial reflect a continuing improvement in precision and accuracy. The next challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue, where the concentration is much lower than in calf thymus DNA.
To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic system... more To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein-water gels incorporating gentamicin sulfate could be used as local, bioresorbable,and sustained-release implants. For this purpose, four formulations were examined with regard to their physicochemical and in vitro drug release characteristics. Hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA),and X-ray diffraction showed cubic liquid crystalline and eutectic structures. The more suitable formulation consisting of 80-15-5%wt/wt monoolein-water-gentamicin sulfate progressively released the antibiotic for a period of 3 weeks without burst effect. Moreover, the content and the release profile of gentamicin sulfate were not significantly changed after storage at 2-6 degrees C for a period of 10 months.
A series of 33 novel divanillates and trivanillates were synthesized and found to possess promisi... more A series of 33 novel divanillates and trivanillates were synthesized and found to possess promising cytostatic rather than cytotoxic properties. Several compounds under study decreased by >50% the activity of Aurora A, B, and C, and WEE1 kinase activity at concentrations <10% of their IC(50) growth inhibitory ones, accounting, at least partly, for their cytostatic effects in cancer cells and to a lesser extent in normal cells. Compounds 6b and 13c represent interesting starting points for the development of cytostatic agents to combat cancers, which are naturally resistant to pro-apoptotic stimuli, including metastatic malignancies.
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