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Vinot C.,University of Paris Descartes | Gavard L.,Service de Gynecologie et Obstetrique | Treluyer J.M.,University of Paris Descartes | Treluyer J.M.,Hopitaux Universitaires Paris Center Cochin Broca Hotel Dieu | And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2013

Nowadays, antiretroviral therapy is recommended during pregnancy to prevent mother-to-child transmission of HIV. However, for many antiretroviral drugs, including maraviroc, a CCR5 antagonist, very little data exist regarding placental transfer. Besides, various factors may modulate this transfer, including efflux transporters belonging to the ATP-binding cassette (ABC) transporter superfamily. We investigated maraviroc placental transfer and the influence of ABC transporter expression on this transfer using the human cotyledon perfusion model. Term placentas were perfused ex vivo for 90 min with maraviroc (600 ng/ ml) either in the maternal-to-fetal (n=10 placentas) or fetal-to-maternal (n=6 placentas) direction. Plasma concentrations were determined by ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Fetal transfer rates (FTR) and clearance indexes (CLI) were calculated as ratios of fetal to maternal concentrations at steady state (mean values between 30 and 90 min) and ratios of FTR of maraviroc to that of antipyrine, respectively. ABC transporter gene expression levels were determined by quantitative reverse transcription (RT)-PCR and ABCB1 protein expression by Western blotting. For the maternal-to-fetal direction, the mean FTR and CLI were 8.0%±3.0 and 0.26±0.07, respectively, whereas the mean CLI was 0.52±0.23 for the fetal-to-maternal direction. We showed a significant inverse correlation between maraviroc CLI and ABCC2, ABCC10, and ABCC11 placental gene expression levels (P<0.05). To conclude, we report a low maraviroc placental transfer probably involving ABC efflux transporters and thus in all likelihood associated with a limited fetal exposition. Nevertheless, these results would need to be supported by in vivo data obtained from paired maternal and cord blood samples. Copyright © 2013, American Society for Microbiology.


Gendron N.,Hopitaux Universitaires Paris Center Cochin Broca Hotel Dieu | Joubrel C.,Hopitaux Universitaires Paris Center Cochin Broca Hotel Dieu | Joubrel C.,University of Paris Descartes | Nedellec S.,Assistance Publique Hopitaux de Paris | And 10 more authors.
Journal of Clinical Microbiology | Year: 2014

Medical abortion is not recognized as a high-risk factor for invasive pelvic infection. Here, we report two cases of group A Streptococcus (GAS; Streptococcus pyogenes) endometritis following medical abortions with a protocol of oral mifepristone and misoprostol.Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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