Lactobacillus rhamnosus R11 consommé dans un complément alimentaire a survécu au transit digestif humain sans modifier l'équilibre du microbiote évalué par PCR en temps réel

International audienceThe aim of this study was to evaluate the survival of Lactobacillus rhamnosus R11 and Lactobacillus acidophilus R52 in the human digestive tract and their effects on the microbiota homeostasis. We designed an open human trial including 14 healthy volunteers. A 3-week exclusion period of fermented products was followed by a 12-day consumption period of 4 capsules daily containing 2 × 109L. rhamnosus R11 and 1 × 108L. acidophilus R52, and a 12-day wash-out period. The 2 strains and dominant bacterial groups of the microbiota were quantified by real-time polymerase chain reaction. At the end of the capsule consumption period, high levels of L. rhamnosus R11 were detected in faecal samples from all volunteers, reaching a mean value of 7.1 log10 colony-forming unit (CFU) equivalents/g of stool. L. acidophilus R52 was detected in the stools of only 1 volunteer, reaching a maximum level of 6.1 log10 CFU equivalents/g of stool. Dilution plating enumerations performed in parallel provided less consistent and generally lower levels. No significant effect of capsule consumption was observed on microbiota homeostasis for the dominant faecal populations. Mean values of 8.8, 9.2, 9.9 and 10.6 log10 CFU equivalents/g of stool were obtained for the Clostridium coccoides, Bifidobacterium sp., Bacteroides sp. and Clostridium leptum groups, respectively.Le but de cette étude était d'évaluer la survie de Lactobacillus rhamnosus R11 et Lactobacillus acidophilus R52 dans le tube digestif humain et leurs effets sur l'homéostasie du microbiote. Nous avons conçu un essai humain ouvert incluant 14 volontaires sains. Une période d'exclusion de 3 semaines des produits fermentés a été suivie d'une période de consommation de 12 jours de 4 gélules par jour contenant 2 × 10 9 L. rhamnosus R11 et 1 × 10 8 L. acidophilus R52, et d'une période de sevrage de 12 jours . Les 2 souches et groupes bactériens dominants du microbiote ont été quantifiés par réaction en chaîne par polymérase en temps réel. À la fin de la période de consommation de la capsule, des niveaux élevés de L. rhamnosusR11 ont été détectés dans les échantillons fécaux de tous les volontaires, atteignant une valeur moyenne de 7,1 log 10 équivalents d'unités formant colonies (UFC)/g de selles. L. acidophilus R52 a été détecté dans les selles d'un seul volontaire, atteignant un niveau maximum de 6,1 log 10 équivalents UFC/g de selles. Les dénombrements par étalement par dilution effectués en parallèle ont fourni des niveaux moins cohérents et généralement inférieurs. Aucun effet significatif de la consommation de capsules n'a été observé sur l'homéostasie du microbiote pour les populations fécales dominantes. Des valeurs moyennes de 8,8, 9,2, 9,9 et 10,6 log 10 équivalents UFC/g de selles ont été obtenues pour Clostridium coccoides , Bifidobacterium sp., Bacteroides sp. etGroupes Clostridium leptum , respectivement

High Levels and Safety of Oseltamivir Carboxylate Plasma Concentrations after Nasogastric Administration in Critically Ill Children in a Pediatric Intensive Care Unit▿

During the 2009 H1N1 influenza pandemics, the concentrations of oseltamivir (O) and its active metabolite (oseltamivir carboxylate [OC]) were determined in 11 children (1 month to 16 years of age) admitted to intensive care units for presumed severe H1N1 infection. They received oseltamivir phosphate (OP) nasogastrically at doses between 1.5 and 6.8 mg/kg of body weight. High OC concentrations were found, with a mean level of 678 ± 535 μg/liter. The mean OP concentration was 27 ± 52 μg/liter. No marked side effect was reported

Survival of Lactobacillus casei in the Human Digestive Tract after Consumption of Fermented Milk

A human trial was carried out to assess the ileal and fecal survival of Lactobacillus casei DN-114 001 ingested in fermented milk. Survival rates were up to 51.2% in the ileum and 28.4% in the feces. The probiotic bacterium has the capacity to survive during its transit through the human gut

Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis.

Nonsense (premature stop codon) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) in approximately 10% of patients. Ataluren (PTC124) is an oral drug that permits ribosomes to readthrough premature stop codons in mRNA to produce functional protein.Journal ArticleRandomized Controlled TrialResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Polymorphisms of coding trinucleotide repeats of homeogenes in neurodevelopmental psychiatric disorders.

International audienceOBJECTIVES: Autism (MIM#209850) and schizophrenia (MIM#181500) are both neurodevelopmental psychiatric disorders characterized by a highly genetic component. Homeogenes and forkhead genes encode transcription factors, which have been involved in brain development and cell differentiation. Thus, they are relevant candidate genes for psychiatric disorders. Genetic studies have reported an association between autism and DLX2, HOXA1, EN2, ARX, and FOXP2 genes whereas only three studies of EN2, OTX2, and FOXP2 were performed on schizophrenia. Interestingly, most of these candidate genes contain trinucleotide repeats coding for polyamino acid stretch in which instability can be the cause of neurodevelopmental disorders. Our goal was to identify variations of coding trinucleotide repeats in schizophrenia, autism, and idiopathic mental retardation. METHODS: We screened the coding trinucleotide repeats of OTX1, EN1, DLX2, HOXA1, and FOXP2 genes in populations suffering from schizophrenia (247 patients), autism (98 patients), and idiopathic mental retardation (56 patients), and compared them with control populations (112 super controls and 202 healthy controls). RESULTS: Novel deletions and insertions of coding trinucleotide repeats were found in the DLX2, HOXA1, and FOXP2 genes. Most of these variations were detected in controls and no difference in their distribution was observed between patient and control groups. Two different polymorphisms in FOXP2 were, however, found only in autistic patients and the functional consequences of these variations of repeats have to be characterized and correlated to particular clinical features. CONCLUSION: This study did not identify specific disease risk variants of trinucleotide repeats in OTX1, EN1, DLX2, HOXA1, and FOXP2 candidate genes in neurodevelopmental psychiatric disorders

Molecular Analyte Profiling of the Early Events and Tissue Conditioning Following Intravesical Bacillus Calmette-Guerin Therapy in Patients With Superficial Bladder Cancer

International audiencePURPOSE:We characterized the innate immune response to intravesical bacillus Calmette-Guerin therapy using a systems approach based on proteomic and cytometric screens.MATERIALS AND METHODS:Blood and urine were collected from patients receiving intravesical bacillus Calmette-Guerin therapy before, and 2 and 4 hours after bacillus Calmette-Guerin treatment, at the first and third instillation. Proteomic and cytometry based screens were performed.RESULTS:Molecular analyte profiling revealed a prime/boost pattern to the innate response to intravesical bacillus Calmette-Guerin. We identified 36 statistically significant changes in the proteins induced during the third instillation compared to the initial treatment. These analytes were classified into 3 categories of 1) plasma proteins that leaked into the urine, 2) cytokines/chemokines produced locally during the first hours of inflammation and 3) other innate molecules that modulate the bladder microenvironment. To characterize the marked increase in the inflammatory response after multiple treatments we evaluated the cells present in the urine and again a prime/boost response was revealed. For the locally produced analytes it was possible to define the cell source(s) and, thus, provide a first generation map of what occurs during the initial phase of bacillus Calmette-Guerin therapy.CONCLUSIONS:This study provides in vivo information concerning the ability of bacillus Calmette-Guerin to sensitize the tissue microenvironment to enhance innate responses and establishes a framework for improving vaccination strategies while decreasing adverse events