The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform
Lars L. Gustafsson - One of the best experts on this subject based on the ideXlab platform.
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Discrepancy in plasma melarsoprol concentrations between HPLC and bioassay methods in patients with T. Gambiense sleeping sickness indicates that melarsoprol is metabolized
Tropical medicine & international health : TM & IH, 1998Co-Authors: Ulf Bronner, Reto Brun, Doua F, Örjan Ericsson, Christian Burri, Keiser J, Lars Rombo, Lars L. GustafssonAbstract:Summaryobjective With the use of a specific high-performance liquid chromatography (HPLC) method and a bioassay which determines trypanocidal activity concentrations of melarsoprol were assassed in plasma, urine and cerebrospinal fluid (CSF) from 8 patients with late-stage Trypanosoma Gambiense sleeping sickness. The aim was to unravel to what extent the bioassay codetermines biologically active metabolites of melarsoprol. methods Subjects were given one dose of melarsoprol i.v. per day for 4 days (1.2, 2.4, 3.0–3.6, 3.0–3.6 mg per kg b.w., respectively). Plasma samples were obtained before the first melarsoprol injection, immediately after and at 1 h, 24 h and 5 days after the 4th injection. Urine was collected before melarsoprol therapy and at 24 h after the 4th injection. CSF samples were taken once before treatment and at 24 h after the 4th injection. results HPLC analyses showed that plasma concentrations immediately after the 4th injection varied from 2200 to 15 900 nmol/l; dropping to 0–1800 nmol/l at 1 h; and to undetectable levels at 24 h. In urine small amounts of melarsoprol were recovered. Melarsoprol could not be detected in CSF by HPLC. Immediately after injection, bioassay analyses showed plasma concentrations of the same magnitude as HPLC assays but at 1 h they were 4–65-fold higher than the levels assessed by HPLC. Even 24 h and 5 days after the 4th injection there was significant but decreasing activity. Urine levels were 40–260-fold higher than the measured HPLC concentrations, whereas there was low but detectable activity in CSF. conclusion Results indicate that melarsoprol is rapidly eliminated from plasma. The significant trypanocidal activity determined by bioassay and simultaneuos low or undetectable levels of melarsoprol assayed by HPLC indicate that the compound is transformed into metabolites with parasiticidal activity.
Paulo César Cotrim - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport
Parasitology Research, 2009Co-Authors: J. I. Aoki, E. H. Yamashiro-kanashiro, D. C. C. Ramos, Paulo César CotrimAbstract:Tubercidin (TUB) is an adenosine analog with potent antiparasite action, unfortunately associated with severe host toxicity. Prevention of TUB toxicity can be reached associating nitrobenzylthioinosine (NBMPR), an inhibitor of the purine nucleoside transport, specifically target to the mammal cells. It was demonstrated that this nucleoside transport inhibitor has no significant effect in the in vitro uptake of TUB by Schistosoma mansoni and Trypanosoma Gambiense . Seeking to evaluate if the association of these compounds is also effective against leishmania, we analyzed the TUB–NBMPR combined treatment in in vitro cultures of promastigote forms of Leishmania ( L .) amazonensis , Leishmania ( L .) chagasi , Leishmania ( L .) major , and Leishmania ( V .) braziliensis as well as in cultures of amastigote forms of L . ( L .) amazonensi s, mice macrophages infected with L . ( L .) amazonensis , and in vivo tests in BALB/c mice infected with L . ( L .) amazonensis . We demonstrated that TUB–NBMPR combined treatment can be effective against leishmania cells protecting mammalian cells from TUB toxicity.
Etienne Pays - One of the best experts on this subject based on the ideXlab platform.
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Adaptation of Trypanosoma rhodesiense to hypohaptoglobinaemic serum requires transcription of the APOL1 resistance gene in a RNA polymerase I locus.
Molecular microbiology, 2015Co-Authors: Laurence Lecordier, Pierrick Uzureau, Patricia Tebabi, Jonathan Brauner, Fleur Samantha Benghiat, Benoit Vanhollebeke, Etienne PaysAbstract:Human apolipoprotein L1 (APOL1) kills African trypanosomes except Trypanosoma rhodesiense and Trypanosoma Gambiense, the parasites causing sleeping sickness. APOL1 uptake into trypanosomes is favoured by its association with the haptoglobin-related protein-haemoglobin complex, which binds to the parasite surface receptor for haptoglobin-haemoglobin. As haptoglobin-haemoglobin can saturate the receptor, APOL1 uptake is increased in haptoglobin-poor (hypohaptoglobinaemic) serum (HyHS). While T. rhodesiense resists APOL1 by RNA polymerase I (pol-I)-mediated expression of the serum resistance-associated (SRA) protein, T. Gambiense resists by pol-II-mediated expression of the T. Gambiense-specific glycoprotein (TgsGP). Moreover, in T. Gambiense resistance to HyHS is linked to haptoglobin-haemoglobin receptor inactivation by mutation. We report that unlike T. Gambiense, T. rhodesiense possesses a functional haptoglobin-haemoglobin receptor, and that like T. Gambiense experimentally provided with active receptor, this parasite is killed in HyHS because of receptor-mediated APOL1 uptake. However, T. rhodesiense could adapt to low haptoglobin by increasing transcription of SRA. When assayed in Trypanosoma brucei, resistance to HyHS occurred with pol-I-, but not with pol-II-mediated SRA expression. Similarly, T. Gambiense provided with active receptor acquired resistance to HyHS only when TgsGP was moved to a pol-I locus. Thus, transcription by pol-I favours adaptive gene regulation, explaining the presence of SRA in a pol-I locus.
Ulf Bronner - One of the best experts on this subject based on the ideXlab platform.
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Discrepancy in plasma melarsoprol concentrations between HPLC and bioassay methods in patients with T. Gambiense sleeping sickness indicates that melarsoprol is metabolized
Tropical medicine & international health : TM & IH, 1998Co-Authors: Ulf Bronner, Reto Brun, Doua F, Örjan Ericsson, Christian Burri, Keiser J, Lars Rombo, Lars L. GustafssonAbstract:Summaryobjective With the use of a specific high-performance liquid chromatography (HPLC) method and a bioassay which determines trypanocidal activity concentrations of melarsoprol were assassed in plasma, urine and cerebrospinal fluid (CSF) from 8 patients with late-stage Trypanosoma Gambiense sleeping sickness. The aim was to unravel to what extent the bioassay codetermines biologically active metabolites of melarsoprol. methods Subjects were given one dose of melarsoprol i.v. per day for 4 days (1.2, 2.4, 3.0–3.6, 3.0–3.6 mg per kg b.w., respectively). Plasma samples were obtained before the first melarsoprol injection, immediately after and at 1 h, 24 h and 5 days after the 4th injection. Urine was collected before melarsoprol therapy and at 24 h after the 4th injection. CSF samples were taken once before treatment and at 24 h after the 4th injection. results HPLC analyses showed that plasma concentrations immediately after the 4th injection varied from 2200 to 15 900 nmol/l; dropping to 0–1800 nmol/l at 1 h; and to undetectable levels at 24 h. In urine small amounts of melarsoprol were recovered. Melarsoprol could not be detected in CSF by HPLC. Immediately after injection, bioassay analyses showed plasma concentrations of the same magnitude as HPLC assays but at 1 h they were 4–65-fold higher than the levels assessed by HPLC. Even 24 h and 5 days after the 4th injection there was significant but decreasing activity. Urine levels were 40–260-fold higher than the measured HPLC concentrations, whereas there was low but detectable activity in CSF. conclusion Results indicate that melarsoprol is rapidly eliminated from plasma. The significant trypanocidal activity determined by bioassay and simultaneuos low or undetectable levels of melarsoprol assayed by HPLC indicate that the compound is transformed into metabolites with parasiticidal activity.
J. I. Aoki - One of the best experts on this subject based on the ideXlab platform.
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Efficacy of the tubercidin antileishmania action associated with an inhibitor of the nucleoside transport
Parasitology Research, 2009Co-Authors: J. I. Aoki, E. H. Yamashiro-kanashiro, D. C. C. Ramos, Paulo César CotrimAbstract:Tubercidin (TUB) is an adenosine analog with potent antiparasite action, unfortunately associated with severe host toxicity. Prevention of TUB toxicity can be reached associating nitrobenzylthioinosine (NBMPR), an inhibitor of the purine nucleoside transport, specifically target to the mammal cells. It was demonstrated that this nucleoside transport inhibitor has no significant effect in the in vitro uptake of TUB by Schistosoma mansoni and Trypanosoma Gambiense . Seeking to evaluate if the association of these compounds is also effective against leishmania, we analyzed the TUB–NBMPR combined treatment in in vitro cultures of promastigote forms of Leishmania ( L .) amazonensis , Leishmania ( L .) chagasi , Leishmania ( L .) major , and Leishmania ( V .) braziliensis as well as in cultures of amastigote forms of L . ( L .) amazonensi s, mice macrophages infected with L . ( L .) amazonensis , and in vivo tests in BALB/c mice infected with L . ( L .) amazonensis . We demonstrated that TUB–NBMPR combined treatment can be effective against leishmania cells protecting mammalian cells from TUB toxicity.
