Changes in the response to treatment against chronic hepatitis C between 1999 and 2015: data from a prospective cohort.

Background: The drug options and strategies for treatment against hepatitis C virus (HCV) infection have changed considerably in the last few years. The aim of this study was to compare the changes in the proportion of nonresponders and patients who achieved a sustained virologic response (SVR) from 1999 to 2015 in one single cohort.

Patients And Methods: A total of 522 patients treated against chronic hepatitis C were included prospectively.

Progression of liver stiffness predicts clinical events in HIV/HCV-coinfected patients with compensated cirrhosis.

Background: Our objective was to assess the predictive value of the changes of liver stiffness (LS) for clinical outcome in HIV/HCV-coinfected patients with compensated liver cirrhosis and a LS value < 40 kPa.

Methods: Prospective cohort of 275 HIV/HCV-coinfected patients with cirrhosis, no previous liver decompensation (LD) and LS < 40 kPa. The time from diagnosis to LD and/or hepatocellular carcinoma (HCC) and the predictors of this outcome were evaluated.

Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection.

Background: Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients.

Longitudinal evaluation of hepatitis C viral persistence in HIV-infected patients with spontaneous hepatitis C clearance.

Hepatitis C virus (HCV) viral persistence in patients with spontaneous viral clearance is controversial. Several studies have shown HCV-RNA in peripheral blood mononuclear cells (PBMCs) and/or liver tissue among patients who have cleared the virus spontaneously, suggesting that viral persistence is a common situation that could involve the entire population studied. Thus, our aim was to evaluate HCV-RNA persistence in PBMCs and hepatocytes in subjects infected with the human immunodeficiency virus (HIV).

Structural and Kinetic Characterization of Thymidine Kinase from Leishmania major.

Leishmania spp. is a protozoan parasite and the causative agent of leishmaniasis. Thymidine kinase (TK) catalyses the transfer of the γ-phosphate of ATP to 2'-deoxythymidine (dThd) forming thymidine monophosphate (dTMP).

[Prevalence and genotype distribution changes in hepatitis C virus co-infection among human immunodeficiency virus-infected patients].

Background: The prevalence of hepatitisC is decreasing among new diagnoses of HIV/HCV coinfection in Spain. The increasing use of the HCV treatment could have changed the HCV genotype distribution. The aim of this study is to analyze changes in the prevalence of HCV coinfection and in HCV genotype distribution among HIV-infected patients.

Maraviroc, a CCR5 antagonist, ameliorates the development of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD).

Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. The NAFLD spectrum ranges from simple steatosis to cirrhosis. The chemokine CCL5/RANTES plays an important role in the progression of hepatic inflammation and fibrosis.

Efficacy and safety of once-daily maraviroc plus ritonavir-boosted darunavir in pretreated HIV-infected patients in a real-life setting.

Objectives: Nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens may be needed in patients with NRTI toxicity. Maraviroc (MVC) plus ritonavir-boosted darunavir (DRV-r) or atazanavir is associated with slightly lower response rates than triple therapy in drug-naïve patients. No information is available on these combinations in pretreated patients.

Investigation of acyclic uridine amide and 5'-amido nucleoside analogues as potential inhibitors of the Plasmodium falciparum dUTPase.

Previously we have shown that trityl and diphenyl deoxyuridine derivatives and their acyclic analogues can inhibit Plasmodium falciparum dUTPase (PfdUTPase). We report the synthesis of conformationally restrained amide derivatives as inhibitors PfdUTPase, including both acyclic and cyclic examples. Activity was dependent on the orientation and location of the amide constraining group.

Interobserver concordance in controlled attenuation parameter measurement, a novel tool for the assessment of hepatic steatosis on the basis of transient elastography.

Background: The combination of transient elastometry with a controlled attenuation parameter (CAP) is available to evaluate hepatic steatosis (HS) along with liver stiffness.

Aims: To assess the concordance of CAP measurements between two independent observers in patients infected by HIV and/or hepatitis virus, as well as to determine the concordance of classification of the grade of HS using two cut-off values.

Materials And Methods: In a cross-sectional prospective study, CAP-enabled transient elastometry acquisitions were performed by two independent observers in patients with HIV or hepatitis virus infection.

No influence of antiretroviral therapy on the mutation rate of the HCV NS5B polymerase in HIV/HCV-coinfected patients.

Objectives: To assess the impact of antiretroviral treatment (ART), including nucleoside analogues retrotranscriptase inhibitors (NRTIs), on the mutation rate of hepatitis C virus (HCV) NS5B polymerase and on the ratio of substitution at synonymous and nonsynonymous sites (dN/dS) this polymerase in HIV/HCV-coinfected patients.

Patients And Methods: Sixty-one patients on defined ART were included in this study. The NS5B polymerase of HCV was sequenced at baseline and after at least two years of ART.

Destruction of chloroanisoles by using a hydrogen peroxide activated method and its application to remove chloroanisoles from cork stoppers.

A chemical method for the efficient destruction of 2,4,6-trichloroanisole (TCA) and pentachloroanisole (PCA) in aqueous solutions by using hydrogen peroxide as an oxidant catalyzed by molybdate ions in alkaline conditions was developed. Under optimal conditions, more than 80.0% TCA and 75.

Design, synthesis, and evaluation of 5'-diphenyl nucleoside analogues as inhibitors of the Plasmodium falciparum dUTPase.

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5'-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent.

Characterization of an autoinducer of penicillin biosynthesis in Penicillium chrysogenum.

Filamentous fungi produce an impressive variety of secondary metabolites; many of them have important biological activities. The biosynthesis of these secondary metabolites is frequently induced by plant-derived external elicitors and appears to also be regulated by internal inducers, which may work in a way similar to that of bacterial autoinducers. The biosynthesis of penicillin in Penicillium chrysogenum is an excellent model for studying the molecular mechanisms of control of gene expression due to a good knowledge of the biochemistry and molecular genetics of β-lactam antibiotics and to the availability of its genome sequence and proteome.

Site-directed mutagenesis provides insights into the selective binding of trityl derivatives to Plasmodium falciparum dUTPase.

We have previously identified a series of triphenylmethane derivatives of deoxyuridine with antimalarial activity in vitro which selectively inhibit Plasmodium falciparum deoxyuridine triphosphate nucleotidohydrolase (PfdUTPase) compared to the human enzyme. The crystal structure of PfdUTPase in complex with one of these inhibitors suggested that the triphenylmethane derivative was selective due to a series of interactions between the trityl group and the side chains of residues Phe(46), Ile(117) and Lys(96) located in a hydrophobic pocket distinct from the phosphate binding site. Here we show by site-directed mutagenesis that the hydrophobic nature of the trityl binding site and in particular aromatic interactions established between the inhibitor and residue Phe(46) contribute significantly to the binding of uracil-based derivatives containing trityl groups in the 5'-position.

Spn1 regulates the GNBP3-dependent Toll signaling pathway in Drosophila melanogaster.

The Drosophila genome encodes 29 serpins, most of unknown function. We show here that Spn1 is an active protease inhibitor of the serpin superfamily. Spn1 inhibits trypsin in vitro and regulates the Toll-mediated immune response in vivo.

Reduced metribuzin pollution with phosphatidylcholine-clay formulations.

Background: Metribuzin is a widely used herbicide that has been identified as a groundwater contaminant. In this study, slow-release formulations of metribuzin were designed by encapsulating the active ingredient in phosphatidylcholine (PC) vesicles and adsorbing the vesicles onto montmorillonite.

Results: The maximum active ingredient content in the slow-release formulations was 246 g kg(-1) .

Kinetic properties and specificity of trimeric Plasmodium falciparum and human dUTPases.

Deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTPase, EC 3.6.1.

Interobserver concordance in the assessment of liver fibrosis in HIV/HCV-coinfected patients using transient elastometry.

Objectives: Although the reproducibility of transient elastometry (TE) in hepatitis C virus (HCV)-monoinfected patients seems to be high, this may not be the case in HIV/HCV-coinfected patients because of different degrees of steatosis and/or inflammation. This study was aimed to determine the interobserver concordance of TE measurements in HIV/HCV-coinfected patients.

Methods: A total of 188 patients were evaluated in a cross-sectional, prospective study in two hospitals.

Liver stiffness as a predictor of esophageal varices requiring therapy in HIV/hepatitis C virus-coinfected patients with cirrhosis.

Background: Liver stiffness (LS) measured by transient elastometry is associated with portal pressure in hepatitis C virus (HCV)-monoinfected patients and could predict the presence of esophageal varices in these subjects. The aim of this study was to assess the ability of LS to predict esophageal varices requiring preventive therapy for bleeding in HIV/HCV-coinfected patients.

Methods: One hundred two HIV/HCV-coinfected patients with liver cirrhosis (LS >or= 14 kPa) underwent an upper gastrointestinal endoscopy (UGE) examination.

Application of transient elastometry to differentiate mild from moderate to severe liver fibrosis in HIV/HCV co-infected patients.

Background/aims: Transient elastometry (TE) is accurate for detecting cirrhosis (F=4) in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients. However, this procedure is less precise to differentiate mild (F < or = 1) from moderate to severe (F > or = 2) fibrosis using the cut-off value of 7.2kPa, a level previously proposed by some authors.

Biodegradation of 2,4,6-TCA by the white-rot fungus Phlebia radiata is initiated by a phase I (O-demethylation)-phase II (O-conjugation) reactions system: implications for the chlorine cycle.

Thirteen species of white-rot fungi tested have been shown to efficiently biodegrade 1 mM 2,4,6-trichloroanisole (2,4,6-TCA) in liquid cultures. The maximum biodegradation rate (94.5% in 10-day incubations) was exhibited by a Phlebia radiata strain.

Topical 5-aminolevulinic acid photodynamic therapy for the treatment of unilesional mycosis fungoides: a report of two cases and review of the literature.

Background: Unilesional mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL), characterized clinically by a solitary lesion and by histopathological features indistinguishable from multilesional MF. The photodynamic therapy (PDT) is a new and effective treatment of precancerous lesions and non-melanoma skin cancers. In recent years it has been used successfully for the treatment of MF.

Environmental significance of O-demethylation of chloroanisoles by soil bacterial isolates as a mechanism that improves the overall biodegradation of chlorophenols.

The biodegradation rate of chlorophenols in the environment seems to be limited by a competitive mechanism of O-methylation which produces chloroanisoles with a high potential of being bioconcentrated in living organisms. In this work we report for the first time the isolation of three soil bacterial strains able to efficiently degrade 2,4,6-trichloroanisole (2,4,6-TCA). These strains were identified as Xanthomonas retroflexus INBB4, Pseudomonas putida INBP1 and Acinetobacter radioresistens INBS1.