Recovery of interleukin-17 production from interleukin-15-stimulated CD4+ mononuclear cells in HIV-1-infected patients with sustained viral suppression

Interleukin-17 (IL-17) is a pro-inflammatory cytokine that is mainly produced by CD4 + T cells. The role of Th17 during the human immunodeficiency virus (HIV)-1 infection is still unclear, but HIV-1 infection can cause a preferential depletion of Th17 cells. It has been shown that IL-15 elicits IL-17 production from human peripheral blood mononuclear cells. We studied the effect of IL-15 stimulation in vitro on IL-17 production from CD4 + mononuclear cells of HIV-infected patients. We observed that IL-15 triggers, in a dose-dependent manner, IL-17 secretion. This effect was blocked by anti-IL-15 monoclonal antibody (P = 0.01). Interestingly, IL-17 production was significantly lower in patients with detectable plasma viremia when compared with successfully treated HIV-infected patients (P = 0.02) and healthy controls, respectively (P < 0.001). We also noticed a significant difference in IL-17 production between naive HIV-infected patients and patients with virological failure on combined antiretroviral therapy (cART) (P = 0.02). Our results suggest that IL-15 can induce IL-17 production from peripheral CD4 + mononuclear cells of HIV-infected patients. Persistent HIV plasma viremia could cause a severe perturbation of IL-17 production from CD4 + mononuclear cells. IL-17 production in HIV-infected patients could be recovered through a sustained suppression of the viral replication in the peripheral blood through cART

Persistent high plasma levels of sCD163 and sCD14 in adult patients with measles virus infection

Background and aims: Measles is an infectious disease that represents a serious public health problem worldwide, being associated with increased susceptibility to secondary infections, especially in the respiratory and gastrointestinal tracts. The aim of this study was to evaluate sCD163 and sCD14 levels in measles virus (MV) infected patients, as markers of immune activation, in order to better understand their role in the pathogenesis of the disease. TNF-α plasma levels were also evaluated. Methods: sCD163, sCD14 and TNF-α were measured by ELISA in plasma samples of 27 MV infected patients and 27 healthy donors (HD) included as controls. Results: At the time of hospital admission, sCD163 and sCD14 levels were significantly higher in MV infected patients than in HD, while a decrease in TNF-α levels were found even if without statistical significance. sCD163 and sCD14 levels were significantly decreased after two months from acute infection compared to hospital admission although they remained significantly higher compared to HD. TNF-α levels increased significantly during the follow-up period. Considering clinical parameters, sCD163 levels positively correlated with aspartate aminotransferase, white blood cell count and neutrophils rate, while negatively correlated with the lymphocyte percentage. sCD14 levels positively correlated with the neutrophil and lymphocyte percentages. Conclusions. These results indicate that, despite the resolution of symptoms, an important macrophage/ monocyte activation persists in measles patients, even after two months from infection

Changes in inflammatory biomarkers in HCV-infected patients undergoing direct acting antiviral-containing regimens with or without interferon

Background and aims Increased levels of chemokine interferon-gamma (IFN-γ)-inducible protein-10 (CXCL10), soluble CD163 (sCD163) and soluble CD14 (sCD14) have been reported in HCV infection. The aim of this study was to compare, sCD163 and sCD14 levels in HCV-infected patients undergoing direct acting antiviral (DAA)-containing regimens with or without interferon (IFN). Methods sCD163, sCD14 and CXCL10 were longitudinally measured by ELISA in 159 plasma samples from 25 HCV-infected patients undergoing IFN-based treatment plus telaprevir or boceprevir and 28 HCV infected subjects treated with DAA IFN-free regimens. Twenty-five healthy donors (HD) were included as controls. Results At baseline CXCL10, sCD163 and sCD14 levels were higher in HCV-infected patients than in HD. CXCL10 and sCD163 levels were significantly decreased in responder (R) patients who achieved sustained virological response (SVR), with both IFN-based and IFN-free regimens, while they were persistently elevated in non-responders (NR) patients who stopped IFN-based treatments because of failure or adverse events. Conversely, sCD14 levels were apparently unchanged during therapy, but at the end of treatment the levels reached normal ranges. Comparing the two regimens, the extent of CXCL10 reduction was more pronounced in patients undergoing DAA IFN-free therapies, whereas sCD163 and sCD14 reduction was similar in the two groups. Interestingly, only in IFN-based regimens baseline sCD163 levels were significantly higher in NR than in R patients, while in the IFN-free treatment group also patients with highsCD163 plasma levels obtained SVR. At the end of therapy, even if the biomarkers were largely decreased, their levels remained significantly higher compared to HD. Only in the early fibrosis stages, sCD163 values tended to normalize. Conclusions These results indicate that IFN-free regimens including newer DAA induce an early and marked decrease in circulating inflammatory biomarkers. However, the full normalization of biomarkers was not obtained, especially in patients with advanced fibrosis, thus underlying the need for a treatment in the early stages of HCV infection

Significant coronary stenosis detected by coronary computed angiography in asymptomatic HIV infected subjects

Objectives: increased incidence of acute coronary events, high rate of abnormal surrogate markers of atherosclerosis and increased amount of coronary calcium have been described in HIV infected population. To expand knowledge on coronary artery disease (CAD) in HIV patients, cardiac CT scan was performed in asymptomatic subjects with low cardiovascular (CV) risk. Methods: A cross-sectional study using dual-source CT (MDCT) coronary angiography. was conducted in HIV-infected subjects with the following characteristics: Framingham Risk Score (FRS) <= 10, absence of metabolic syndrome, negative echocardiographic and ECG stress-test. A luminal narrowing exceeding 50% was defined as a clinically significant coronary stenosis. Calcium score was quantified using the Agatston Calcium Score method. Results: Fifty-five subjects were enrolled. Significant coronary stenoses, requiring coronary angiography, were found in 16/55 (29.1%). At multivariate analysis older age was the only variable independently associated with the presence of significant luminal narrowing (p = 0.011). Conclusions: MDCT showed an unexpected, age-associated high rate of significant coronary stenosis in asymptomatic HIV positive subjects with low CV risk. These findings suggest that aggressive screening programs for coronary artery disease may be appropriate in this population; further studies are recommended to assess the appropriateness of MDCT for this purpose. (C) 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved

Seroprevalencija virusa hepatitisa E u krava s ruralnih područja južne Italije

Hepatitis E virus (HEV) is considered to be an emerging zoonotic disease, which causes numerous cases of hepatitis and deaths worldwide each year. Pigs are a host reservoir of HEV, but numerous other wild and domestic species can be infected. The aim of this study was to carry out serological screening of anti-HEV antibodies in cattle in the Sicily region (Southern Italy). Between April and December 2018, 231 serum samples were collected from cows and analysed with enzyme-linked immunosorbent assay (ELISA), for detection of HEV antibodies (IgG). The overall prevalence of anti-HEV antibodies was 36.36% (84/231; 95% CI 30-43). There were statistically significant differences in the HEV seroprevalence in animals of different ages (12 months: 39.30%; >24 months: 54.10%) (P0.05). This study shows that further investigation of HEV in cattle is required to understand better the epidemiology in farm animals and the potential zoonotic risks for humans. This is the first report of HEV seroprevalence for cows in Italy, which provides baseline data for further studies and for control of HEV infection in cattle.Virus hepatitisa E (HEV) smatra se emergentnom zoonozom koja uzrokuje brojne slučajeve hepatitisa i uginuća širom svijeta svake godine. Svinja je rezervoar HEV-a, no mogu se zaraziti i brojne druge divlje i domaće vrste. Cilj ovog istraživanja bio je provesti serološki probir anti-HEV protutijela u goveda na Siciliji (južna Italija). Od travnja do prosinca 2018. prikupljen je ukupno 231 uzorak seruma krava i analiziran testom ELISA za detekciju protutijela na HEV (IgG). Prevalencija anti-HEV protutijela bila je 36,36 % (84/231; 95 % CI 30 – 43). Pronađena je statistički znakovita razlika (P 12 mjeseci: 39,30 %; > 24 mjeseci: 54,10 %). Nije zabilježena statistički znakovita razlika (P> 0,05) s obzirom na spol (31,37 % u mužjaka i 37,38 % u ženki). Rezultati ukazuju na potrebu daljnjih istraživanja HEV-a u goveda kako bi se bolje razumjela epidemiologija u farmskih životinja i potencijalan zoonotski rizik za ljude. Ovo je prvo izvješće o seroprevalenciji HEV-a u krava u Italiji, kojim se pružaju referentni podaci za daljnja istraživanja i kontrolu infekcije HEV-om u goveda

Tetracycline Residues in Bovine Muscle and Liver Samples from Sicily (Southern Italy) by LC-MS/MS Method: A Six-Year Study

We examined a total of 369 bovine liver and muscle samples for the detection of oxytetracycline (OTC), tetracycline (TC), chlortetracycline (CTC), and doxycycline (DOX) residues by implementation and validation of a LC-MS/MS method. The method showed good recovery values between 86% and 92% at three levels of concentrations. The linearity tests revealed r2 > 0.996 for all the tetracyclines examined. Furthermore, the Youden test revealed that the method was robust. Only 14.4% of the samples showed OTC and TC residues in a concentration range of 10.4–40.2 g kg1. No CTC and DOX residues were found in all the samples analyzed. Liver samples showed the highest average values (31.5 20.6 and 21.8 18.9 for OTC and TC, respectively). The results showed a low incidence of TCs in all the samples examined, in comparison with other studies reported in the literature. A significant decrease in TC residues frequency was found from 2013 (p < 0.05). This work reports for the first time epidemiological data on the presence of TC residues in liver and muscle samples of cattle farmed in Sicily (Southern Italy). The very low incidence of TC residues indicates a continuous improvement in farming techniques in Southern Italy, which is essential to ensure consumers’ protection

The Biobank of the ‘Istituto Zooprofilattico Sperimentale’ of Sicily: an important resource in medical research for safe and quality storage of biological specimens

The Mediterraean Biobank has been recently launched at the ‘Istituto Zooprofilattico Sperimentale’ (IZS) of Sicily in Palermo. The main aim of the Biobank is to collect and store, under standardised conditions and in a centralised system, several types of certified animal and zoonotic biological resources such as bacterial and viral strains, parasites, nucleic acids, positive/negative sera, cell cultures and tissues, in accordance to quality System procedures as regulated by UNI CEI EN ISO/IEC 17025:2005.peer-reviewe

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA &lt;50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Parietal resting-state EEG alpha source connectivity is associated with subcortical white matter lesions in HIV-positive people

Objective Parietal resting-state electroencephalographic (rsEEG) alpha (8–10 Hz) source connectivity is abnormal in HIV-positive persons. Here we tested whether this abnormality may be associated with subcortical white matter vascular lesions in the cerebral hemispheres. Methods Clinical, rsEEG, and magnetic resonance imaging (MRI) datasets in 38 HIV-positive persons and clinical and rsEEG datasets in 13 healthy controls were analyzed. Radiologists visually evaluated the subcortical white matter hyperintensities from T2-weighted FLAIR MRIs (i.e., Fazekas scale). In parallel, neurophysiologists estimated the eLORETA rsEEG source lagged linear connectivity from parietal cortical regions of interest. Results Compared to the HIV participants with no/negligible subcortical white matter hyperintensities, the HIV participants with mild/moderate subcortical white matter hyperintensities showed lower parietal interhemispheric rsEEG alpha lagged linear connectivity. This effect was also observed in HIV-positive persons with unimpaired cognition. This rsEEG marker allowed good discrimination (area under the receiver operating characteristic curve &gt; 0.80) between the HIV-positive individuals with different amounts of subcortical white matter hyperintensities. Conclusions The parietal rsEEG alpha source connectivity is associated with subcortical white matter vascular lesions in HIV-positive persons, even without neurocognitive disorders. Significance Those MRI-rsEEG markers may be used to screen HIV-positive persons at risk of neurocognitive disorders