Glances in Immunology of HIV and HCV Infection

Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies

Review Article Glances in Immunology of HIV and HCV Infection

Since the identification of HIV and HCV much progress has been made in the understanding of their life cycle and interaction with the host immune system. Despite these viruses markedly differ in their virological properties and in their pathogenesis, they share many common features in their immune escape and survival strategy. Both viruses have developed sophisticated ways to subvert and antagonize host innate and adaptive immune responses. In the last years, much effort has been done in the study of the AIDS pathogenesis and in the development of efficient treatment strategies, and a fatal infection has been transformed in a potentially chronic pathology. Much of this knowledge is now being transferred in the HCV research field, especially in the development of new drugs, although a big difference still remains between the outcome of the two infections, being HCV eradicable after treatment, whereas HIV eradication remains at present unachievable due to the establishment of reservoirs. In this review, we present current knowledge on innate and adaptive immune recognition and activation during HIV and HCV mono-infections and evasion strategies. We also discuss the genetic associations between components of the immune system, the course of infection, and the outcome of the therapies

Impaired NK-cell-mediated cytotoxic activity and cytokine production in patients with endometriosis: A possible role for PCBs and DDE

Endometriosis is a gynaecological disorder characterized by the presence and growth of endometrial tissue in ectopic sites. In this study we examined the immunological functions of patients with endometriosis and serum level of PCBs and p,p'-DDE to verify the impact of these environmental contaminants on the dysregulation of immune functions. We found that proliferative responses and immunoglobulin production were not dysregulated in patients with endometriosis while NK cell activity was significantly down-regulated in these patients. Moreover, a significant down-regulation of IL-1 beta and IL-12 production was found in patients with respect to controls. Serum levels of PCBs and p,p'-DDE were found to be significantly higher in women with endometriosis than in the control group, with respect to the sum of the congeners most prominent in human tissues. In particular, total PCBs concentration in patients with endometriosis and controls was respectively 330 and 160 ng/g fat with respect to the most abundant congeners, while pp-DDE concentration was of 770 and 3 10 ng/g fat. Moreover, we found that normal human PBMC pulsed with PCBs p,p'-DDE and their combination showed a significant down-regulation of NK cell cytotoxic activity and IL-1 beta and IL-12 production. These findings suggest that changes in specific immune parameters correlate with elevated serum PCBs and DDE levels and endometriosis. (c) 2006 Elsevier Inc. All rights reserved

Role of interferon lambda 4 and ALT levels in optimising treatment of HCV for patients with low-stage fibrosis

The use of new anti-HCV drugs is currently limited by high costs and dual therapy; pegylated interferon and ribavirin (peg-IFN+RBV) still represents the only affordable treatment in patients with low-stage fibrosis. We evaluated the role of Interferon lambda4 (IFNL4) polymorphisms and its combination with on-treatment alanine transaminase (ALT) modification in predicting sustained virological response (SVR) in HCV genotype 1 and 4 patients with low-stage fibrosis. We retrospectively analysed 124 patients with Metavir ≤F2, who received dual therapy at our centre. Genotyping for IFNL4 polymorphisms was assessed at baseline, as well as ALT levels (baseline and week 2, 4, 12 and 24 of therapy). Thirty patients (24%) were TT/TT, 74 (60%) TT/DG and 20 (16%) DG/DG. The SVR rate was significantly higher in TT/TT genotype compare to TT/DG and DG/DG (97% vs. 53% and 50%, respectively, p=0.001). Patients that achieved a 60% reduction of ALT baseline value after 4 weeks of therapy had a significantly higher SVR rate (94% vs. 52%, p<0.001). Factors significantly associated with SVR were TT/TT genotype (p=0.029), RVR (p=0.019) and 60% ALT reduction at 4 week of therapy (p=0.005). The absence of both TT/TT genotype and 60% ALT reduction were negative predictors of SVR (p<0.001). In conclusion, the combined use of IFNL4 polymorphisms and ALT reduction at 4 week of treatment is able to optimize candidates’ selection for peg-IFN+RBV, discriminating those that could still benefit from dual therapy from the ones that need the new regimen

An overview on nature-inspired optimization algorithms for Structural Health Monitoring of historical buildings

Structural Health Monitoring (SHM) of historical building is an emerging field of research aimed at the development of strategies for on-line assessment of structural condition and identification of damage in the earliest stage. Built heritage is weak against operational and environmental condition and preservation must guarantee minimum repair and non-intrusiveness. SHM provides a cost-effective management and maintenance allowing prevention and prioritization of the interventions. Recently, in computer science, mimicking nature to address complex problems is becoming more frequent. Nature-inspired approaches turn out to be extremely efficient in facing optimization, commonly used to analyze engineering processes in SHM, providing interesting advantages when compared with classic methods. This paper begins with an introduction to Natural Computing. Then, focusing on its applications to SHM, possible improvements in built heritage conservation are shown and discussed suggesting a general framework for safety assessment and damage identification of existing structures.This work was financed by FEDER funds through the Competitiveness Factors Operational Programme COMPETE and by national funds through FCT - Foundation for Science and Technology within the scope of the project POCI-01-0145-FEDER-007633info:eu-repo/semantics/publishedVersio

Exogenous HIV-1 Nef Upsets the IFN-γ-Induced Impairment of Human Intestinal Epithelial Integrity

The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions

Study of GaAs detectors characteristics for medical imaging

In this work we present the results of a systematic study about SI GaAs detectors as a function of substrate and contact type, geometry and thickness. This study has been stimulated from the interest in using GaAs as a detector for medical imaging applications. GaAs detectors have been produced using crystals grown with different techniques and changing both the thickness (in the range 200 μm-1 mm) and the contacts type and geometry. We have measured the current-voltage characteristics and, using radioactive sources (109Cd, 20 keV photons, 241Am, 60 keV photons, 99mTc, 140 keV photons), we have studied the performance of our detectors in terms of charge collection efficiency and energy resolution as a function of the bias voltage. Besides we have also studied the electrical and spectroscopic properties of GaAs detectors with different types and concentrations of the dopants in the substrate. So we have found the optimal doping type and concentration to have the best spectroscopic performances and the higher breakdown voltage. Simulation programs made with Monte Carlo methods have been developed to describe the electric field distribution and the transport of charge carriers toward the electrodes in GaAs detectors. In these simulations we have considered the presence of deep energy levels in the bandgap, the thickness, the bias voltage and the charge deposition in the crystal after photon interaction

Advanced liver disease outcomes after hepatitis C eradication by human immunodeficiency virus infection in PITER cohort

Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated

Real-life data on potential drug-druginteractions in patients with chronic hepatitis C viral infection undergoing antiviral therapy with interferon-free DAAs in the PITER Cohort Study

Background There are few real-life data on the potential drug-drug interactions (DDIs) between anti-HCV direct-acting antivirals (DAAs) and the comedications used. Aim To assess the potential DDIs of DAAs in HCV-infected outpatients, according to the severity of liver disease and comedication used in a prospective multicentric study. Methods Data from patients in 15 clinical centers who had started a DAA regimen and were receiving comedications during March 2015 to March 2016 were prospectively evaluated. The DDIs for each regimen and comedication were assigned according to HepC Drug Interactions (www.hep-druginteractions.org) Results Of the 449 patients evaluated, 86 had mild liver disease and 363 had moderate-to-severe disease. The use of a single comedication was more frequent among patients with mild liver disease (p = 0.03), whereas utilization of more than three drugs among those with moderate- to-severe disease (p = 0.05). Of the 142 comedications used in 86 patients with mild disease, 27 (20%) may require dose adjustment/closer monitoring, none was contraindicated. Of the 322 comedications used in 363 patients with moderate-to-severe liver disease, 82 (25%) were classified with potential DDIs that required only monitoring and dose adjustments; 10 (3%) were contraindicated in severe liver disease. In patients with mild liver disease 30% (26/86) used at least one drug with a potential DDI whereas of the 363 patients with moderate-to-severe liver disease, 161 (44%) were at risk for one or more DDI. Conclusions Based on these results, we can estimate that 30 - 44% of patients undergoing DAA and taking comedications are at risk of a clinically significant DDI. This data indicates the need for increased awareness of potential DDI during DAA therapy, especially in patients with moderate- to-severe liver disease. For several drugs, the recommendation related to the DDI changes from "dose adjustment/closer monitoring", in mild to moderate liver disease, to "the use is contraindicated" in severe liver disease

Legionella Infection Risk from Domestic Hot Water

We investigated Legionella and Pseudomonas contamination of hot water in a cross-sectional multicentric survey in Italy. Chemical parameters (hardness, free chlorine, and trace elements) were determined. Legionella spp. were detected in 33 (22.6%) and Pseudomonas spp. in 56 (38.4%) of 146 samples. Some factors associated with Legionella contamination were heater type, tank distance and capacity, water plant age, and mineral content. Pseudomonas presence was influenced by water source, hardness, free chlorine, and temperature. Legionella contamination was associated with a centralized heater, distance from the heater point >10 m, and a water plant >10 years old. Furthermore, zinc levels of <20 μg/L and copper levels of >50 μg/L appeared to be protective against Legionella colonization. Legionella species and serogroups were differently distributed according to heater type, water temperature, and free chlorine, suggesting that Legionella strains may have a different sensibility and resistance to environmental factors and different ecologic niches