8-modified-2\u27-deoxyadenosine analogues induce delayed polymerization arrest during HIV-1 reverse transcription

The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix &alpha;H in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2&prime;-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2&prime;-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication.<br /

V. Auguste Norga, 1830-1905. Souvenirs patriotiques, avec preface et notes par Guillaume Aubertin.

OPLADEN-RUG0

Evolution des pleurésies de l'enfant (rôle du drainage sous thoracoscopie et de la corticothérapie orale)

ST QUENTIN EN YVELINES-BU (782972101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Et si l’on plantait plus de vignes et d’oliviers pour limiter la propagation des incendies

Interview de F. Pimont par Guillaume Aubertin de Var Matin le 6/9/2017 pour un article intitulé « Et si l’on plantait plus de vignes et d’oliviers pour limiter la propagation des incendies », pour publication le 9/9/2017La Région n’avait pas connu de feux de forêts aussi importants depuis 2003. Certains élus et chercheurs proposent de planter des espèces précises qui feraient office de coupe-feu, Même les docteurs le disent: il y a du bon dans la vigne. Si les spécialistes de la santé reconnaissent qu’un petit verre de vin de temps en temps peut être bénéfique pour la santé, certains élus de la région ont eux aussi tendance à promouvoir la culture du raisin sur leursterres. C’est qu’en plus de donner du bon vin, les vignes pourraient faire o!ce de coupe-feu encas de gros incendie

Nocturnal hypoventilation in Down syndrome children with or without sleep apnea

International audienceBackground: There is a high prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS), sometimes associated with alveolar hypoventilation.Objective: To compare transcutaneous partial pressure of carbon dioxide (PtcCO2 ) and pulse oximetry (SpO2 ) in children with DS and in control children with OSA.Patients and methods: This retrospective case-control study involved children followed in Trousseau Hospital (Paris) Sleep Center. Polysomnography (PSG) recordings and clinical files of children with DS were reviewed to identify clinical signs of OSA and comorbidities associated with DS. Controls were children who presented with OSA of ENT origin without other comorbidities (exceptions: two overweight, one obese, and three with well-controlled asthma). DS subjects and controls were matched for age and apnea hypopnea index.Results: There were 28 children in each group. Mean PtcCO2 during sleep was significantly higher in patients with DS compared to controls (44 mm Hg vs 42 mm Hg, P = .001). Five (21%) patients with DS met the American Academy of Sleep medicine criteria for hypoventilation, compared to one (4%) in the control group. The mean PtcO2 during sleep was significantly lower in patients with DS (77 mm Hg vs 82 mm Hg, P = .003).Conclusions: This is the first study to compare nocturnal gas exchange in children with DS to a control group of children with similar OSA. Our data demonstrate that children with DS have increased PtcCO2 regardless of the presence of OSA and its severity. This may be due to respiratory muscle hypotonia and/or ventilatory control alteration in patients with DS

Nocturnal hypoventilation in Down syndrome children with or without sleep apnea

International audienceBackground: There is a high prevalence of obstructive sleep apnea (OSA) in children with Down syndrome (DS), sometimes associated with alveolar hypoventilation.Objective: To compare transcutaneous partial pressure of carbon dioxide (PtcCO2 ) and pulse oximetry (SpO2 ) in children with DS and in control children with OSA.Patients and methods: This retrospective case-control study involved children followed in Trousseau Hospital (Paris) Sleep Center. Polysomnography (PSG) recordings and clinical files of children with DS were reviewed to identify clinical signs of OSA and comorbidities associated with DS. Controls were children who presented with OSA of ENT origin without other comorbidities (exceptions: two overweight, one obese, and three with well-controlled asthma). DS subjects and controls were matched for age and apnea hypopnea index.Results: There were 28 children in each group. Mean PtcCO2 during sleep was significantly higher in patients with DS compared to controls (44 mm Hg vs 42 mm Hg, P = .001). Five (21%) patients with DS met the American Academy of Sleep medicine criteria for hypoventilation, compared to one (4%) in the control group. The mean PtcO2 during sleep was significantly lower in patients with DS (77 mm Hg vs 82 mm Hg, P = .003).Conclusions: This is the first study to compare nocturnal gas exchange in children with DS to a control group of children with similar OSA. Our data demonstrate that children with DS have increased PtcCO2 regardless of the presence of OSA and its severity. This may be due to respiratory muscle hypotonia and/or ventilatory control alteration in patients with DS

Value of gas exchange recording at home in children receiving noninvasive ventilation: Gas exchange during noninvasive ventilation

International audienceNoninvasive positive pressure ventilation (NPPV) is preferentially performed at home. The objectives of the study were to evaluate the feasibility of an overnight gas exchange recording at home and to compare recordings performed in the hospital and at home. Twenty nine pairs of overnight gas exchange recordings during NPPV were performed at home and in the hospital in 11 children with neuromuscular disease and 13 children with other disorders treated with long term NPPV. No technical problem occurred during the recordings performed at home and one pulse oximetry (SpO2) recording failed in the hospital. For the two groups, SpO2 and transcutaneous carbon dioxide (PtcCO2) values did not differ significantly between the hospital and the home. However, correlations between SpO2 and PtcCO2 values obtained in the hospital and at home were better for mean values than for minimal and maximal values, and in patients with other disorders as compared to patients with neuromuscular disease. Overnight gas exchange recordings with NPPV by a combined PtcCO2/SpO2 monitor are feasible at home and show results comparable to hospital recordings. Home PtcCO2/SpO2 recordings may be integrated in the care of children treated with domiciliary NPPV and are associated with less disruption of family life and decreased health care costs