Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>The aim of the present work was to assess i) <it>ex vivo </it>activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 <it>Plasmodium falciparum </it>isolates from African countries, India and Thailand, and iii) <it>in vitro </it>cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN).</p> <p>Methods</p> <p>The susceptibility of the 181 <it>P. falciparum </it>isolates to the nine anti-malarial drugs was assessed using the standard 42-hours ³H-hypoxanthine uptake inhibition method.</p> <p>Results</p> <p>The IC₅₀values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (<it>rho </it>= 0.46) and between PPQ and MDAQ (<it>rho </it>= 0.30). No significant correlation was shown between PPQ IC₅₀and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (<it>rho </it>= 0.37), PND and LMF (<it>rho </it>= 0.28), PND and QN (<it>rho </it>= 0.24), PND and AS (<it>rho </it>= 0.19), PND and DHA (<it>rho </it>= 0.18) and PND and CQ (<it>rho </it>= 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs.</p> <p>Conclusions</p> <p>In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs.</p

Unexpected Modulation of Recall B and T Cell Responses after Immunization with Rotavirus-like Particles in the Presence of LT-R192G

LT-R192G, a mutant of the thermolabile enterotoxin of E. coli, is a potent adjuvant of immunization. Immune responses are generally analyzed at the end of protocols including at least 2 administrations, but rarely after a prime. To investigate this point, we compared B and T cell responses in mice after one and two intrarectal immunizations with 2/6 rotavirus-like particles (2/6-VLP) and LT-R192G. After a boost, we found, an unexpected lower B cell expansion measured by flow cytometry, despite a secondary antibody response. We then analyzed CD4+CD25+Foxp3+ regulatory T cells (Tregs) and CD4+CD25+Foxp3− helper T cells after in vitro (re)stimulation of mesenteric lymph node cells with the antigen (2/6-VLP), the adjuvant (LT-R192G) or both. 2/6-VLP did not activate CD4+CD25+Foxp3− nor Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice, whereas they did activate both subsets from mice immunized with 2/6-VLP in the presence of adjuvant. LT-R192G dramatically decreased CD4+CD25+Foxp3+ T cells from non-immunized and 2/6-VLP immunized mice but not from mice immunized with 2/6-VLP and adjuvant. Moreover, in this case, LT-R192G increased Foxp3 expression on CD4+CD25+Foxp3+ cells, suggesting specific Treg activation during the recall. Finally, when both 2/6-VLP and LT-R192G were used for restimulation, LT-R192G clearly suppressed both 2/6-VLP-specific CD4+CD25+Foxp3− and Foxp3+ T cells. All together, these results suggest that LT-R192G exerts different effects on CD4+CD25+Foxp3+ T cells, depending on a first or a second contact. The unexpected immunomodulation observed during the recall should be considered in designing vaccination protocols

Secondary metabolites from Spirotropis longifolia (DC) Baill and their antifungal activity against human pathogenic fungi

A phytochemical study of the ethyl acetate extract of the roots and adventitious roots of Spirotropis longifolia, a monodominant tree species of the Guianan rainforest, has allowed the isolation of three compounds: 2- hydroxy-8,9-methylenedioxy-2',2'-dimethylpyrano-[5',6':4,3]-6a-prenyl-[6aS,11aS]-pterocarpan (spirotropin A), 2-hydroxy-8,9-methylenedioxy-2',2'-dimethy1-3',4'-dihydropyrano-[5',6':4,3]-6a-prenyl-(6aS,11aS]-pterocarpan (spirotropin B), and 5,7-dihydroxy-6.8-dipreny1-2 ''''.2 ''''-dimethylpyrano[5 '''',6 '''': 3',4]-isoflavone (spirotropone). In addition, 10 known compounds, trans-oxyresveratrol, trans-resveratrol, piceatannol, daidzein, genistein, isoprunetin, lupeol, latifolol, gnetin D and gnetin E, were also isolated. These compounds were evaluated for their antifungal activity and their cytotoxicity, and their structures were established by 1D and 2D NMR, HRMS, CD and optical rotation measurements. (C) 2011 Elsevier Ltd. All rights reserved.CNRS (France)CAPESCNPqFAPESPFAPDF (Brazil

Intérêts et limites du traitement médical dans la prise en charge des patients atteints d une hydatidose osseuse (revue des cas cliniques de la littérature)

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Le tourisme solidaire, acteur du développement au Burkina Faso (son rôle dans la santé publique)

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Hydatidose alvéolaire (à propos de deux cas au sud du Massif central)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Rôle du pharmacien d officine dans l information, le conseil et la prévention des pathologies infectieuses rencontrées en guyane

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF

Coinfection Leishmaniose viscérale-Sida (à propos d'un cas clinique sur une localisation bronchopulmonaire)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Pertinence et faisabilité d'une étude clinique et biologique sur les parasitoses intestinales en Casamance (Sénégal)

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Etat actuel des connaissances sur la bilharziose intestinale à Madagascar

MONTPELLIER-BU Pharmacie (341722105) / SudocSudocFranceF