Effet différentiel des produits finaux de glycosylation avancée ou AGE (Advanced Glycation End products) sur l infection par le virus de l immunodéficience humaine de type 1 (VIH-1) (évaluation des molécules à visée microbicides)

La formation des AGEs ( Advanced Glycation End products ) figure parmi les modifications irréversibles causées par l hyperglycémie observée chez les patients sous HAART. Les AGEs constituent un groupe hétérogène de molécules formées par la glycosylation non enzymatique de protéines, d ADN et de lipides. Nous avons étudié le rôle des AGEs sur l infection des cellules dendritiques et des macrophages. Nous avons montré que les AGEs sont capables d inhiber l infection des cellules dendritiques et des macrophages par Le VIH-1. En effet, les AGEs diminuent l expression de CD4, CXCR4 et CCR5 à la surface des cellules dendritiques alors qu ils diminuent seulement l expression de CD4 sur les macrophages. Les AGEs sont capables d induire une augmentation de la production virale par une lignée chroniquement infectée par le VIH. L ensemble de ces résultats montre que les AGE ont un rôle à la fois comme activateur et comme inhibiteur de la réplication virale. Ensuite, nous avons évalué l activité anti-VIH-1 des lectines dérivées des plantes Hippeastrum hybrid et Galanthus nivalis agglutinin sur les cellules dendritiques et les cellules épithéliales.The formation of Advanced Glycation End products (AGE) appears as one of the irreversible modifications caused by hyperglycaemia observed in patients controlled by antiretroviral combination therapies (HAART). AGE forms a heterogeneous group of complex molecules generated by the non enzymatic glycosylation between reducing sugar and the amino groups of proteins. We studied the impact of AGE on the susceptibility of dendritic cells and macrophages to HIV infection. AGE are able to inhibit in vitro HIV infection of dendritic cells and macrophages. In fact, the AGEs reduced CD4, CXCR4, and CCR5 membrane expression on dendritic cells, while CD4 expression is the only one reduced on macrophages. AGEs are able to activate HIV-1 replication in persistently infected cell lines of monocytic. All these results show that AGE play a role both as an activator and as an inhibitor of viral replication. Then, we evaluated anti-HIV-1 activity of the lectines derived from the plants Hippeastrum hybrid and Galanthus nivalis agglutinin on dendritic cells and epithelial cells.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Knowledge, attitudes, and practices of pediatricians in relation to breastfeeding support: A national survey in Lebanon

Background Rates of breastfeeding (BF) remain suboptimal despite overwhelming evidence for its benefits to the mother and child. Pediatricians play an important role in supporting breastfeeding (BF). In Lebanon, the rates of both exclusive and continued BF are critically low. The objective of this study is to examine the knowledge, attitudes and practices (KAP) of Lebanese pediatricians in relation to supporting BF. Methods A national survey of Lebanese pediatricians was conducted through Lime Survey (n = 100, response rate 9.5%). The list of pediatricians’ emails was obtained from the Lebanese Order of Physicians (LOP). Participants completed a questionnaire covering, in addition to sociodemographic characteristics, the KAP, related to supporting BF. Descriptive statistics and logistic regressions were used in data analysis. Results The most prevalent gaps in knowledge were related to the positioning of the baby during BF (71.9%) and the association between the mother’s fluid intake and her milk production (67.4%). With regards to attitudes, 34% of participants reported unfavorable attitudes towards BF in public and BF while working (25%). As for practices, more than 40% of pediatricians kept formula samples and 21% had formula-related advertising in their clinics. Half of the pediatricians reported rarely/never referring mothers to lactation consultants. After adjustment, both being a female pediatrician and having done the residency in Lebanon were significant predictors of better knowledge (OR = 4.51 (95%CI: 1.72–11.85) and OR = 3.93 (95%CI: 1.38,11.19) respectively. Conclusion This study revealed important gaps in the KAP related to BF support among Lebanese pediatricians. Coordinated efforts ought to be exerted to educate and equip pediatricians with needed knowledge and skills to support BF

Knowledge, attitudes, and practices of pediatricians in relation to breastfeeding support: A national survey in Lebanon.

BackgroundRates of breastfeeding (BF) remain suboptimal despite overwhelming evidence for its benefits to the mother and child. Pediatricians play an important role in supporting breastfeeding (BF). In Lebanon, the rates of both exclusive and continued BF are critically low. The objective of this study is to examine the knowledge, attitudes and practices (KAP) of Lebanese pediatricians in relation to supporting BF.MethodsA national survey of Lebanese pediatricians was conducted through Lime Survey (n = 100, response rate 9.5%). The list of pediatricians' emails was obtained from the Lebanese Order of Physicians (LOP). Participants completed a questionnaire covering, in addition to sociodemographic characteristics, the KAP, related to supporting BF. Descriptive statistics and logistic regressions were used in data analysis.ResultsThe most prevalent gaps in knowledge were related to the positioning of the baby during BF (71.9%) and the association between the mother's fluid intake and her milk production (67.4%). With regards to attitudes, 34% of participants reported unfavorable attitudes towards BF in public and BF while working (25%). As for practices, more than 40% of pediatricians kept formula samples and 21% had formula-related advertising in their clinics. Half of the pediatricians reported rarely/never referring mothers to lactation consultants. After adjustment, both being a female pediatrician and having done the residency in Lebanon were significant predictors of better knowledge (OR = 4.51 (95%CI: 1.72-11.85) and OR = 3.93 (95%CI: 1.38,11.19) respectively.ConclusionThis study revealed important gaps in the KAP related to BF support among Lebanese pediatricians. Coordinated efforts ought to be exerted to educate and equip pediatricians with needed knowledge and skills to support BF

Knowledge, attitudes, and practices of pediatricians in relation to breastfeeding support: A national survey in Lebanon

Background Rates of breastfeeding (BF) remain suboptimal despite overwhelming evidence for its benefits to the mother and child. Pediatricians play an important role in supporting breastfeeding (BF). In Lebanon, the rates of both exclusive and continued BF are critically low. The objective of this study is to examine the knowledge, attitudes and practices (KAP) of Lebanese pediatricians in relation to supporting BF. Methods A national survey of Lebanese pediatricians was conducted through Lime Survey (n = 100, response rate 9.5%). The list of pediatricians' emails was obtained from the Lebanese Order of Physicians (LOP). Participants completed a questionnaire covering, in addition to sociodemographic characteristics, the KAP, related to supporting BF. Descriptive statistics and logistic regressions were used in data analysis. Results The most prevalent gaps in knowledge were related to the positioning of the baby during BF (71.9%) and the association between the mother's fluid intake and her milk production (67.4%). With regards to attitudes, 34% of participants reported unfavorable attitudes towards BF in public and BF while working (25%). As for practices, more than 40% of pediatricians kept formula samples and 21% had formula-related advertising in their clinics. Half of the pediatricians reported rarely/never referring mothers to lactation consultants. After adjustment, both being a female pediatrician and having done the residency in Lebanon were significant predictors of better knowledge (OR = 4.51 (95%CI: 1.72-11.85) and OR = 3.93 (95%CI: 1.38,11.19) respectively. Conclusion This study revealed important gaps in the KAP related to BF support among Lebanese pediatricians. Coordinated efforts ought to be exerted to educate and equip pediatricians with needed knowledge and skills to support BF. Copyright

Differential in vitro inhibitory activity against HIV-1 of alpha-(1-3)- and alpha-(1-6)-D-mannose specific plant lectins : Implication for microbicide development

<p>Abstract</p> <p>Background</p> <p>Plant lectins such as <it>Galanthus nivalis </it>agglutinin (GNA) and <it>Hippeastrum hybrid </it>agglutinin (HHA) are natural proteins able to link mannose residues, and therefore inhibit HIV-target cell interactions. Plant lectins are candidate for microbicide development.</p> <p>Objective</p> <p>To evaluate the activity against HIV of the mannose-specific plant lectins HHA and GNA at the cellular membrane level of epithelial cells and monocyte-derived dendritic cells (MDDC), two potential target cells of HIV at the genital mucosal level.</p> <p>Methods</p> <p>The inhibitory effects of HHA and GNA were evaluated on HIV adsorption to genital epithelial HEC-1A cell line, on HIV transcytosis throughout a monolayer of polarized epithelial HEC-1A cells, on HIV adsorption to MDDC and on transfer of HIV from MDDC to autologous T lymphocytes.</p> <p>Results</p> <p>HHA faintly inhibited attachment to HEC-1A cells of the R5-tropic HIV-1_Ba-Lstrain, in a dose-dependent manner, whereas GNA moderately inhibited HIV adsorption in the same context, but only at high drug doses. Only HHA, but not GNA, inhibited HIV-1_JR-CSFtranscytosis in a dose-dependent manner. By confocal microscopy, HHA, but not GNA, was adsorbed at the epithelial cell surface, suggesting that HHA interacts specifically with receptors mediating HIV-1 transcytosis. Both plant lectins partially inhibited HIV attachment to MDDC. HHA inhibited more efficiently the transfer of HIV from MDDC to T cell, than GNA. Both HHA and GNA lacked toxicity below 200 μg/ml irrespective the cellular system used and do not disturb the monolayer integrity of epithelial cells.</p> <p>Conclusion</p> <p>These observations demonstrate higher inhibitory activities of the lectin plant HHA by comparison to GNA, on HIV adsorption to HEC-1A cell line, HIV transcytosis through HEC-1A cell line monolayer, HIV adsorption to MDDC and HIV transfer from MDDC to T cells, highlighting the potential interest of HHA as effective microbicide against HIV.</p

Carbapenem and colistin-resistant bacteria in North Lebanon: Coexistence of mcr-1 and NDM-4 genes in Escherichia coli

International audienceIntroduction: The increasing incidence of infections caused by multidrug-resistant bacteria is considered a global health problem. This study aimed to investigate this resistance in Gram-negative bacteria isolated from patients hospitalized in North-Lebanon. Methodology: All isolates were identified using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antibiotic susceptibility testing was achieved using disk diffusion, E-test and Broth microdilution methods. Phenotypic detection of carbapenemase was carried out using the CarbaNP test. RT-PCR, standard-PCR and sequencing were performed to detect resistance genes and oprD gene. Conjugal transfer was carried out between our isolates and Escherichia coli J53 to detect the genetic localization of resistance genes. MLST was conducted to determine the genotype of each isolate. Results: Twenty-three carbapenem-resistant Enterobacterales of which eight colistin-resistant Escherichia coli, and Twenty carbapenem-resistant Pseudomonas aeruginosa were isolated. All isolates showed an imipenem MIC greater than 32 mg/mL with MICs for colistin greater than 2 mg/L for E. coli isolates. All the Enterobacterales isolates had at least one carbapenemase-encoding gene, with E. coli isolates coharboring blaNDM-4 and mcr-1 genes. Moreover, 16/20 Pseudomonas aeruginosa harbored the blaVIM-2 gene and 18/20 had mutations in the oprD gene. MLST revealed that the isolates belonged to several clones. Conclusions: We report here the first description in the world of clinical E. coli isolates coharboring blaNDM-4 and mcr-1 genes, and K. pneumoniae isolates producing NDM-6 and OXA-48 carbapenemases. Also, we describe the emergence of NDM-1-producing E. cloacae in Lebanon. Screening for these isolates is necessary to limit the spread of resistant microorganisms in hospitals

Inhibition of HIV-1 transmission in trans from dendritic cells to CD4+ T lymphocytes by natural antibodies to the CRD domain of DC-SIGN purified from breast milk and intravenous immunoglobulins

The present study demonstrates that human breast milk and normal human polyclonal immunoglobulins purified from plasma [intravenous immunoglobulins (IVIg)] contain functional natural immunoglobulin A (IgA) and IgG antibodies directed against the carbohydrate recognition domain (CRD) domain of the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) molecule, which is involved in the binding of human immunodeficiency virus (HIV)-1 to dendritic cells (DCs). Antibodies to DC-SIGN CRD were affinity-purified on a matrix to which a synthetic peptide corresponding to the N-terminal CRD domain (amino-acid 342–amino-acid 371) had been coupled. The affinity-purified antibodies bound to the DC-SIGN peptide and to the native DC-SIGN molecule expressed by HeLa DC-SIGN+ cells and immature monocyte-derived dendritic cells (iMDDCs), in a specific and dose-dependent manner. At an optimal dose of 200 µg/ml, natural antibodies to DC-SIGN CRD peptide purified from breast milk and IVIg stained 25 and 20% of HeLa DC-SIGN+ cells and 32 and 12% of iMDDCs, respectively. Anti-DC-SIGN CRD peptide antibodies inhibited the attachment of virus to HeLa DC-SIGN by up to 78% and the attachment to iMDDCs by only 20%. Both breast milk- and IVIg-derived natural antibodies to the CRD peptide inhibited 60% of the transmission in trans of HIV-1JRCSF, an R5-tropic strain, from iMDDCs to CD4+ T lymphocytes. Taken together, these observations suggest that the attachment of HIV to DCs and transmission in trans to autologous CD4+ T lymphocytes occur through two independent mechanisms. Our data support a role of natural antibodies to DC-SIGN in the modulation of postnatal HIV transmission through breast-feeding and in the natural host defence against HIV-1 in infected individuals