Pleural Tuberculosis in Patients with Early HIV Infection Is Associated with Increased TNF-Alpha Expression and Necrosis in Granulomas

Although granulomas may be an essential host response against persistent antigens, they are also associated with immunopathology. We investigated whether HIV co-infection affects histopathological appearance and cytokine profiles of pleural granulomas in patients with active pleural tuberculosis (TB). Granulomas were investigated in pleural biopsies from HIV positive and negative TB pleuritis patients. Granulomas were characterised as necrotic or non-necrotic, graded histologically and investigated for the mRNA expression of IL-12, IFN-γ, TNF-α and IL-4 by in situ hybridisation. In all TB patients a mixed Th1/Th2 profile was noted. Necrotic granulomas were more evident in HIV positive patients with a clear association between TNF-α and necrosis. This study demonstrates immune dysregulation which may include TNF-α-mediated immunopathology at the site of disease in HIV infected pleural TB patients

Effect of Molecules’ Physicochemical Properties on Whey Protein/Alginate Hydrogel Rheology, Microstructure and Release Profile

International audienceThe encapsulation of molecules with different physicochemical properties (theophylline, blue dextran, salicylic acid and insulin) in whey protein (WP) and alginate (ALG) microparticles (MP) for oral administration was studied. MP based on WP/ALG were prepared by a cold gelation technique and coated with WP solution after reticulation. Molecules influenced polymer solution viscosity and elasticity, resulting in differences regarding encapsulation efficiency (from 23 to 100%), MP structure and swelling (>10%) and in terms of pH tested. Molecule release was due to diffusion and/or erosion of MP and was very dependent on the substance encapsulated. All the loaded MP were successfully coated, but variation in coating thickness (from 68 to 146 µm) and function of the molecules encapsulated resulted in differences in molecule release (5 to 80% in 1 h). Gel rheology modification, due to interactions between WP, ALG, calcium and other substances, was responsible for the highlighted differences. Measuring rheologic parameters before extrusion and reticulation appeared to be one of the most important aspects to study in order to successfully develop a vector with optimal biopharmaceutical properties. Our vector seems to be more appropriate for anionic high-molecular-weight substances, leading to high viscosity and elasticity and to MP enabling gastroresistance and controlled release of molecules at intestinal pH

Development of a new pediatric formulation of hydrophilic suppositories of pentobarbital and comparison with lipophilic formulations.

International audienc

Immunonutrition stimulates immune functions and antioxidant defense capacities of leukocytes in radiochemotherapy-treated head & neck and esophageal cancer patients: A double-blind randomized clinical trial

This clinical trial has been registered on ClinicalTrial.gov website: NCT00333099. (C) 2014 Elsevier Ltd and European Society for Clinical Nutrition and MetabolismThis work was supported by the Fonds National d'Amenagement et de Developpement du Territoire (FNADT) and European Regional Development Fund (ERDF)Background: Immunonutrition has been reported to improve the immune status of perioperative cancer patients, thereby reducing complications and length of hospital stay. Aim: This study aimed to assess whether immunonutrition enriched in arginine, EPA & DHA and nucleotides could impact the immune cells responses in head & neck and esophageal cancer patients treated by radiochemotherapy (RCT). Methods: A double-blind clinical trial was carried out in 28 patients randomized into two groups, receiving either an immunomodulating enteral nutrition formula (IEN, n = 13, Impact (R), Nestle) or an isoenergetic isonitrogenous standard enteral nutrition formula (SEN, n = 15) throughout RCT (5-7 weeks). After isolation from whole blood, immune cells metabolism and functions were assessed at the beginning (Db) and at the end (De) of RCT. Results: Immunonutrition maintained CD4(+)/CD8(+) T-Iymphocyte counts ratio and CD3 membrane expression between Db and De. Polymorphonuclear cells CD62L and CD15 densities and ROS production were increased in IEN patients. Peripheral blood mononuclear cells (PBMC) production of proinflammatory prostaglandin-E2 was stable in IEN patients and lower than in SEN patients at De. Genes coding for immune receptors, antioxidant enzymes and NADPH oxidase subunits were overexpressed in the PBMC of LEN vs SEN patients at De. Conclusion: Immunonutrition can enhance immune cell responses through the modulation of their phenotypes and functions. By modulating the gene expression of immune cells, immunonutrition could make it easier for the organism to adapt to the systemic inflammation and oxidative stress induced by RCT. Clinical trial registration: This clinical trial has been registered on ClinicalTrial.gov website: NCT00333099. (C) 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis

Anti-infectious properties of the probiotic Saccharomyces cerevisiae CNCM I-3856 on enterotoxigenic E. coli (ETEC) strain H10407

International audienceEnterotoxigenic Escherichia coli (ETEC) are major food-borne pathogens responsible for traveler's diarrhea. The production of adhesins and the secretion of enterotoxins constitute the major virulence traits of the bacteria. Treatments are mainly symptomatic and can involve antibiotherapy. However, given the rise of antibiotic resistance worldwide, there is an urgent need for the development of new preventive strategies for the control of ETEC infections. Among them, a promising approach is the use of probiotics. The aim of this study was to investigate, using complementary in vitro and in vivo approaches, the inhibitory potential of the yeast Saccharomyces cerevisiae CNCM I-3856 against the human ETEC reference strain H10407. In conventional culture media, S. cerevisiae significantly reduced ETEC growth and toxin production. The yeast also inhibited bacterial adhesion to mucin-agar and intestinal Caco-2/TC7 cells in a dose-dependent manner. Lastly, pre-treatment with S. cerevisiae inhibited interleukin-8 production by ETEC-infected intestinal cells. In streptomycin-treated mice, the probiotic yeast decreased bacterial colonization, mainly in the ileum, the main site of ETEC pathogenesis. For the first time, this study shows that the probiotic yeast S. cerevisiae CNCM I-3856 can exert an anti-infectious activity against a human ETEC strain through a multi-targeted approach, including inhibition of bacterial growth and toxin production, reduction of bacterial adhesion to mucins and intestinal epithelial cells, and suppression of ETEC-induced inflammation. Interestingly, the highest activity was obtained with a prophylactic treatment. Further studies will aim to assess the effect of the yeast on ETEC survival and virulence under human simulated digestive conditions

Mycobacterium avium complex augments macrophage HIV-1 production and increases CCR5 expression

Infection with HIV-1 results in pronounced immune suppression and susceptibility to opportunistic infections (OI). Reciprocally, OI augment HIV-1 replication. As we have shown for Mycobacterium avium complex (MAC) and Pneumocystis carinii, macrophages infected with opportunistic pathogens and within lymphoid tissues containing OI, exhibit striking levels of viral replication. To explore potential underlying mechanisms for increased HIV-1 replication associated with coinfection, blood monocytes were exposed to MAC antigens (MAg) or viable MAC and their levels of tumor necrosis factor α (TNFα) and HIV-1 coreceptors monitored. MAC enhanced TNFα production in vitro, consistent with its expression in coinfected lymph nodes. Using a polyclonal antibody to the CCR5 coreceptor that mediates viral entry of macrophage tropic HIV-1, a subset of unstimulated monocytes was shown to be CCR5-positive by fluorescence-activated cell sorter analysis. After stimulation with MAg or infection with MAC, CCR5 expression was increased at both the mRNA level and on the cell surface. Up-regulation of CCR5 by MAC was not paralleled by an increase in the T cell tropic coreceptor, CXCR4. Increases in NF-κB, TNFα, and CCR5 were consistent with the enhanced production of HIV-1 in MAg-treated adherent macrophage cultures as measured by HIV-1 p24 levels. Increased CCR5 was also detected in coinfected lymph nodes as compared with tissues with only HIV-1. The increased production of TNFα, together with elevated expression of CCR5, provide potential mechanisms for enhanced infection and replication of HIV-1 by macrophages in OI-infected cells and tissues. Consequently, treating OI may inhibit not only the OI-induced pathology, but also limit the viral burden