Search results for "FOSB"
showing 10 items of 42 documents
Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrho…
2018
Background: In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this “real-life” study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). Methods: All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). Results: Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ±…
Aminopyrine breath test predicts liver-related events and death in HCV-related cirrhosis on SVR after DAA therapy
2019
Background & Aims: In patients with hepatitis C virus (HCV)-related advanced cirrhosis, the effects of sustained virological response (SVR) by direct antiviral agents (DAAs) on decompensation and liver deaths are less clearcut, since up to 30% of patients do not improve, and no predictors of outcome have been identified. We used 13C-aminopyrine breath test (ABT) to assess whether its changes can predict liver-related outcomes after DAA treatment in patients with HCV cirrhosis. Methods: Fifty consecutive patients with HCV cirrhosis were enrolled. Patients were included if they had Child A cirrhosis at risk for decompensation – defined as Child A6 (N = 22, 44%) or previous decompensation …
Involvement of TLR4 in the long-term epigenetic changes, rewarding and anxiety effects induced by intermittent ethanol treatment in adolescence
2016
Studies in humans and experimental animals have demonstrated the vulnerability of the adolescent brain to actions of ethanol and the long-term consequences of binge drinking, including the behavioral and cognitive deficits that result from alcohol neurotoxicity, and increased risk to alcohol abuse and dependence. Although the mechanisms that participate in these effects are largely unknown, we have shown that ethanol by activating innate immune receptors, toll-like receptor 4 (TLR4), induces neuroinflammation, impairs myelin proteins and causes cognitive dysfunctions in adolescent mice. Since neuroimmune signaling is also involved in alcohol abuse, the aim of this study was to assess whethe…
Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy
2018
AbstractNatural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mai…
Multiclass HCV resistance to direct-acting antiviral failure in real-life patients advocates for tailored second-line therapies
2017
Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N= 200) and w…
A model-based meta-analysis of sofosbuvir-based treatments in chronic hepatitis C patients.
2016
The objective of this study was to compare the efficacy of sofosbuvir-based treatments in patients with chronic hepatitis C virus (HCV) infection using a model-based meta-analysis (MBMA). A bibliographic search was performed to identify clinical trials involving sofosbuvir as a unique direct-acting antiviral (DAA) agent or together with daclatasvir, ledipasvir or simeprevir for the treatment of diagnosed HCV infection. The time course of the virological response (VR) was modelled to estimate the effect of treatment and the influence of population characteristics on the longitudinal efficacy profile. The model was validated and simulations of 10 different treatment schedules were performed. …
Resistance analysis and treatment outcomes in hepatitis C virus genotype 3-infected patients within the Italian network VIRONET-C
2021
Aim: This study aimed to investigate the role of resistance-associated substitutions (RASs) to direct-acting-antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET-C network, a total of 539 GT3-infected patients (417 DAA-naïve and 135 DAA-failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home-made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co-infected. Phylogenetic analysis classified sequences as GT3a-b-g-h (98%-0.4%-0.2%-1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SO…
Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Respons…
2015
UNLABELLED Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoin…
Changes in histone acetylation in the prefrontal cortex of ethanol-exposed adolescent rats are associated with ethanol-induced place conditioning
2012
Alcohol drinking during adolescence can induce long-lasting effects on the motivation to consume alcohol. Abnormal plasticity in reward-related processes might contribute to the vulnerability of adolescents to drug addiction. We have shown that binge-like ethanol treatment in adolescent rats induces alterations in the dopaminergic system and causes histone modifications in brain reward regions. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced alterations in gene expression and behavior, we addressed the hypothesis that ethanol is capable of inducing transcriptional changes by histone modifications in specific gene promoters in adolescen…
Hypertrophic agonists induce the binding of c-Fos to an AP-1 site in cardiac myocytes: implications for the expression of GLUT1
2003
Objectives: Serum is among the agents known to induce hypertrophy of cardiac myocytes, which occurs concomitant with an increase in AP-1-mediated transcription. We have examined if this effect correlates with changes in the relative abundance of particular AP-1 heterodimers, as their exact composition under these conditions is unknown. Furthermore, we obtained insight on the specific role of c-Fos from studying the induction of the glucose transporter GLUT1 by serum in fibroblasts. Methods: We characterised the AP-1 heterodimers expressed in neonatal cardiac myocytes by supershift electrophoretic mobility shift assay (EMSA) analysis. Quantitative changes in transcription were measured using…