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Your search keyword '"Dumas, Michel"' showing total 16 results
Start Over Author "Dumas, Michel" Topic trypanosoma brucei
16 results on '"Dumas, Michel"'

1. Pharmacokinetics, metabolism and excretion of megazol in a Trypanosoma brucei gambiense primate model of human African trypanosomiasis - Preliminary study

Author

Enanga, Bertin, Ndong, Jerôme Mezui Me, Boudra, Hamid, Debrauwer, Laurent, Dubreuil, Guy, Bouteille, Bernard, Chauviere, Gérard, Labat, Christian, Dumas, Michel, Perie, Jacques, Houin, Georges, Faculte des Sciences Pharmaceutiques, Centre International de Recherches Médicales de Franceville (CIRMF), Xénobiotiques, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut d'Epidémiologie Neurologique et de Neurologie Tropicale, Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
suramin, mice, [SDV]Life Sciences [q-bio], Megazol, Pharmacokinetics, Trypanosoma brucei, gambiense
Abstract

International audience; The pharmacokinetics of megazol (2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1,3,4-thiadiazol, CAS 19622-55-0) was investigated after a 100 mg/kg oral administration to six primates infected with Trypanosoma brucei gambiense. The plasma levels of megazol were between 0.2 mu g/ml and 46 mu g/ml 24 h after dosing in all animals. In animals with prolonged infection, megazol absorption was accelerated (T-max was 4 h compared with 8 h, for day 53 and day 39 post inoculation) but the amount absorbed was not modified. The megazol concentrations in the cerebrospinal fluid represented between 5.5 % and 10.6 %, of the plasma levels at the same rimes. Unchanged megazol was eliminated predominantly via the kidneys: 46-96 % of the ingested dose was recovered in the urine, compared with 0-5 % in the faeces. Furthermore, this urinary elimination of megazol was altered in animals with prolonged infections. In the urine, 4 unknown metabolites were observed, unchanged megazol was characterized by LC-MS/MS. This study indicates that megazol crosses the blood-brain barrier after oral administration. Prolonged infections affect the absorption of megazol and its urinary elimination.

Published
2000
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2. In vitro induction of nitric oxide synthase in astrocytes and microglia by Trypanosoma brucei brucei.

Author

Girard, Murielle, Ayed, Zoulikha, Preux, Pierre-Marie, Bouteille, Bernard, Preud'homme, Jean-Louis, Dumas, Michel, Jauberteau, Marie-Odile, and Jauberteau

Subjects
NITRIC-oxide synthases, TRYPANOSOMA brucei, ASTROCYTES
Abstract

In stage II human african trypanosomiasis (HAT), which is characterized by central nervous system (CNS) involvement, neurones and oligodendrocytes might be targets of dysimmune processes. Nitric oxide (NO) production by peripheral macrophages is documented in HAT. We studied the production of NO by murine astrocytes and microglia cocultured with Trypanosoma brucei(T. b.) brucei AnTat 1.9. Purified astrocytes or microglia from mouse brains were cocultured with T. b. brucei, and in some instances with interferon (IFN)-γ, which is known to be released during the disease and also to be a growth factor for trypanosomes. Inducible NO synthase (iNOS) expression was studied by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. NO production was determined by measuring nitrite generation in culture. Detection of iNOS in astrocytes and microglia in the presence of T. b. brucei, was closely associated with nitrite production and was strongly enhanced by the addition of IFN-γ to the culture medium. The stimulation of iNOS activity required parasite–cell contact and likely occurred at the transcriptional level. This study demonstrates the induction of iNOS in CNS-related macrophage cells in the presence of trypanosomes and its potentiation by IFN-γ. [ABSTRACT FROM AUTHOR]

Published
2000
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16. Plasma kinetics and efficacy of oral megazol treatment in Trypanosoma brucei brucei-infected sheep

Author

Boda, Caroline, Enanga, Bertin, Dumet, Hélène, Chauviere, Gérard, Labrousse, François, Couquet, Claude, Saivin, Sylvie, Houin, Georges, Perie, Jacques, Dumas, Michel, and Bouteille, Bernard

Subjects
*TRYPANOSOMA brucei, *DISEASE complications, *BLOOD plasma, *CHROMATOGRAPHIC analysis
Abstract

Experimentally infected sheep have been previously developed as an animal model of trypanosomosis. We used this model to test the efficacy of megazol on eleven Trypanosoma brucei brucei-infected sheep. When parasites were found in blood on day 11 post-infection, megazol was orally administered at a single dose of 40 or 80 mg/kg. After a transient aparasitaemic period, all animals except two relapsed starting at day 2 post-treatment, which were considerated as cured on day 150 post-treatment and showed no relapse after a follow-up period of 270 days. In order to understand the high failure of megazol treatment to cure animals, a kinetic study was carried out. Plasma concentrations of megazol determined, by reverse-phase high-performance liquid chromatography at 8 h post-treatment in these animals, were lowered, suggesting slow megazol absorption, except in cured animals. However, megazol plasma profiles in uninfected sheep after a single oral dose of megazol showed a fast megazol lowered absorption associated with a short plasma half-life of drug. Inter-individual variation of megazol pharmacokinetic properties was also observed. These findings suggested that the high failure rates of megazol treatment were related to poor drug availability after oral administration in sheep. In conclusion, megazol could cure sheep with T. b. brucei infection but oral administration was not an effective route. [Copyright &y& Elsevier]

Published
2004
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