Hepatitis B virus impairs TLR9 expression and function in plasmacytoid dendritic cells.

Plasmacytoid dendritic cells (pDCs) play a key role in detecting pathogens by producing large amounts of type I interferon (IFN) by sensing the presence of viral infections through the Toll-Like Receptor (TLR) pathway. TLR9 is a sensor of viral and bacterial DNA motifs and activates the IRF7 transcription factor which leads to type I IFN secretion by pDCs. However, during chronic hepatitis B virus (HBV) infection, pDCs display an impaired ability to secrete IFN-α following ex vivo stimulation with TLR9 ligands.

The e-Bug project in France.

The high rates of antibiotic prescriptions and antimicrobial resistance in France motivated its participation in the European e-Bug school project concerning microbes, and infection transmission, prevention and treatment. The prospect of raising awareness among children, helping them to adopt suitable attitudes and behaviour towards infection transmission and treatment starting from childhood, generated enthusiastic support from relevant national educational and health institutions throughout the Project. France was actively involved in every stage: background research showed that the subject matter was best suited to the national science curricula of the fourth and fifth forms in junior schools, and the sixth and ninth forms in senior schools; a focus group study with junior and senior teachers elicited teachers' needs concerning teaching resources; and a qualitative and quantitative evaluation, after translation and pack review, enabled further adaptation of the packs.

Hepatitis B virus replication in primary macaque hepatocytes: crossing the species barrier toward a new small primate model.

Unlabelled: The development of new anti-hepatitis B virus (HBV) therapies, especially immunotherapeutic approaches, has been limited by the lack of a primate model more accessible than chimpanzees. We have previously demonstrated that sylvanus and cynomolgus macaques are susceptible to in vivo HBV infection after intrahepatic HBV DNA inoculation. In this study, we evaluated the susceptibility of primary macaque hepatocytes (PMHs) to HBV infection with a highly efficient HBV genome-mediated transfer system via a recombinant baculovirus (Bac-HBV).

Oral cholic acid for hereditary defects of primary bile acid synthesis: a safe and effective long-term therapy.

Background & Aims: Oral bile acid replacement has been shown to be an effective therapy in primary bile acid synthesis defects, but to date there have been no reports of the long-term effects of this therapy. The aim of the study was to evaluate the long-term effectiveness and safety of cholic acid (CA) therapy.

Methods: Fifteen patients with either 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (3beta-HSD) (n = 13) or Delta(4)-3-oxosteroid 5beta-reductase (Delta(4)-3-oxo-R) (n = 2) deficiency confirmed by mass spectrometry and gene sequencing received oral CA and were followed up prospectively.

Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro.

Background: Currently approved antiviral monotherapies against chronic hepatitis B fail to eradicate hepatitis B virus (HBV), to overcome the defects in HBV-specific immune responses and to prevent HBV relapse after cessation of therapy. CpG oligodesoxynucleotides (CpG ODN) are synthetic agonists of Toll-like receptor 9 and potent inducers of innate and acquired immunity. Our aim was to establish the proof of concept of the antiviral benefit of combining a nucleoside analogue with CpG-induced cytokines on HBV replication in vitro.

Immunohistochemical detection of HCV proteins in liver tissue.

Detection and localization of HCV in liver tissue are vital for diagnostic purposes and clinical management of HCV-infected patients, as well as for the elucidation of viropathological mechanisms. The fragility of HCV RNA and the low levels of viral expression in infected tissues are a constant limitation in molecular assays for HCV characterization. HCV antigen detection, by immunochemistry, in liver biopsies is an attractive option for precise localization and quantification of viral proteins with direct access to histological patterns.

[How to practice health education in a general medicine or a pharmacy setting? Results from an experiment among pregnant women, adolescents and elderly people].

This experiment evaluated the development and implementation of 5 pilot health education activities using a comprehensive and population-based approach in general medicine practice and in pharmacies. These interventions involved 185 patients, and they were developed and carried out by 35 general practitioners and pharmacists in 5 sites in France between 2001 and 2004. Health professionals often demonstrated and argued for a comprehensive approach to health: positive vision of health, integration of different aspects of health, and personalized, tailored efforts.

Essential role of antigen-presenting cell-derived BAFF for antibody responses.

Antigen-presenting cells (APC) are directly involved in survival, growth and differentiation of naive B cells and in immunoglobulin class switch recombination. Less is known about the contribution of APC to memory B cell responses. We employed an in vitro model to investigate the secondary humoral response against foot-and-mouth disease virus, with cells from a natural host of the virus - the pig.

Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.

Objective: To characterise the interactions between tacrolimus and antiretroviral drug combinations in hepatitis C virus-HIV co-infected patients who had received a liver transplant.

Design: An observational, open-label, multiple-dose, two-period, one-sequence design clinical trial in which patients received tacrolimus as an immunosuppressive therapy during the postoperative period and then had an antiretroviral drug regimen added. Tacrolimus pharmacokinetics were evaluated at steady state during these two periods.

TLR9 expression and function is abolished by the cervical cancer-associated human papillomavirus type 16.

Cervical cancer development is linked to the persistent infection by high-risk mucosal human papillomaviruses (HPVs) types. The E6 and E7 major oncoproteins from this dsDNA virus play a key role in the deregulation of the cell cycle, apoptosis, and adaptive immune surveillance. In this study, we show for the first time that HPV type 16 (HPV16), the most carcinogenic type among the high-risk subgroup, interferes with innate immunity by affecting the expression of TLRs.

Silencing of natural interferon producing cell activation by porcine circovirus type 2 DNA.

Porcine circovirus type 2 (PCV2) infection of natural interferon producing cells (NIPCs) impairs the induction of interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha by cytosine-phosphorothioate-guanine (CpG) oligodeoxynucleotides (ODNs), thereby preventing both their autocrine maturation and the paracrine maturation of myeloid dendritic cells (DCs). The present study shows that the PCV2-mediated inhibition of NIPCs was mediated by viral DNA, although it was independent of virus replication. The inhibitory effect of PCV2 DNA was more diversified than if it had simply targeted CpG-ODN-induced cytokines (IFN-alpha, TNF-alpha, interleukin-6, IL-12).

Cytokine and C-reactive protein profiles induced by porcine circovirus type 2 experimental infection in 3-week-old piglets.

The purpose of this study was to determine serum profiles of cytokines at a protein level and Creactive protein (CRP) during the development of postweaning multisystemic wasting syndrome (PMWS) in experimentally inoculated pigs. Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined for a 35-day period in 10 piglets experimentally infected with PCV2 at 3 weeks of age. Four of the infected piglets developed severe PMWS at 14 to 21 days post-infection (d.

Life-threatening interaction between antiretroviral therapy and vinblastine in HIV-associated multicentric Castleman's disease.

Background: HIV-infected patients still present a high risk of developing lymphoproliferative malignancies, despite the fact that their prognosis has been considerably improved by highly active antiretroviral therapy (HAART). Potential interactions exist between antiretroviral drugs, in particular protease inhibitors, and anti-neoplastic ones, but their impact in terms of clinical and haematological adverse events remains unclear.

Methods: We report a case of potentially life-threatening interaction between vinblastine and antiretroviral therapy in a patient presenting with HIV-associated multicentric Castleman's disease (MCD).

Determination of amprenavir total and unbound concentrations in plasma by high-performance liquid chromatography and ultrafiltration.

Amprenavir is an HIV-1 protease inhibitor with high protein binding (90%) in human plasma. This study was designed to develop an assay to measure the concentration of unbound amprenavir, to study variation with time in patients, and to investigate whether ritonavir and lopinavir, other protease inhibitors that could be combined, interact with amprenavir protein binding in vitro. A reverse-phase high-performance liquid chromatography assay to UV detection was developed and validated to measure total amprenavir in plasma, and this method was adapted to quantitate low concentrations of unbound amprenavir in ultrafiltrate aqueous fluid.

High variability of indinavir and nelfinavir pharmacokinetics in HIV-infected patients with a sustained virological response on highly active antiretroviral therapy.

Objectives: To describe plasma concentrations of indinavir alone or combined with ritonavir, and of nelfinavir and its active metabolite M8, and to measure their variabilities in HIV-infected patients treated with a stable antiretroviral regimen and experiencing a sustained virological response for at least 12 months.

Patients And Methods: In this prospective trial, blood samples were drawn during a 6-hour time interval between two doses at enrolment to assess protease inhibitor (PI) pharmacokinetic parameters, and 4 months later to assess plasma trough and peak concentrations. Safety and adherence assessments and laboratory data were collected during an 8-month period.

Fc gamma RII-dependent sensitisation of natural interferon-producing cells for viral infection and interferon-alpha responses.

Natural interferon-producing cells (NIPC), also called plasmacytoid dendritic cells, are the most potent producers of IFN-alpha in response to viral and bacterial components, serving an important function in innate immune defences. The present work demonstrates that NIPC responsiveness can be primed by immunisation, increasing their capacity to produce IFN-alpha after viral infection. NIPC isolated from pigs immunised against classical swine fever virus (CSFV), a member of the Flaviviridae, were more receptive to viral infection and produced higher levels of IFN-alpha than NIPC from immunologically naive animals.

Subset-dependent modulation of dendritic cell activity by circovirus type 2.

Viral interactions with dendritic cells (DCs) have important consequences for immune defence function. Certain single-stranded DNA viruses that associate with a number of species, including humans and pigs, exhibit interesting characteristics in this context. Porcine circovirus type 2 (PCV2) can persist within myeloid DCs in the absence of virus replication.

Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients.

The aim of the present study was to assess the pharmacokinetic behavior of atazanavir-ritonavir when it is coadministered with tenofovir disoproxil fumarate (DF) in human immunodeficiency virus (HIV)-infected patients. Eleven patients enrolled in Agence Nationale de Recherche sur le SIDA (National Agency for AIDS Research, Paris, France) trial 107 were included in this pharmacokinetic study. They received atazanavir at 300 mg and ritonavir at 100 mg once a day (QD) from day 1 to the end of study.

Interactions between amprenavir and the lopinavir-ritonavir combination in heavily pretreated patients infected with human immunodeficiency virus.

Objective: This pharmacokinetic study was designed to characterize interactions between amprenavir and the lopinavir-ritonavir combination in patients infected with human immunodeficiency virus in whom previous antiretroviral therapy had failed.

Methods: Twenty-seven patients included in a randomized clinical trial (ANRS [National Agency for AIDS Research] Protocol 104) participated in this study. They were randomized to receive ritonavir at a dose of either 100 mg twice daily or 200 mg twice daily.

Steady-state pharmacokinetics of amprenavir coadministered with ritonavir in human immunodeficiency virus type 1-infected patients.

The protease inhibitor (PI) ritonavir is used as a strong inhibitor of cytochrome P450 3A4, which boosts the activities of coadministered PIs, resulting in augmented plasma PI levels, simplification of the dosage regimen, and better efficacy against resistant viruses. The objectives of the present open-label, multiple-dose study were to determine the steady-state pharmacokinetics of amprenavir administered at 600 mg twice daily (BID) and ritonavir administered at 100 mg BID in human immunodeficiency virus type 1 (HIV-1)-infected adults treated with different antiretroviral combinations including or not including a nonnucleoside reverse transcriptase inhibitor (NNRTI). Nineteen patients completed the study.