Reduced Plasma Levels of sCD14 and I-FABP in HIV-infected Patients with Mesalazine-treated Ulcerative Colitis

BACKGROUND: Microbial translocation (MT) is a shared feature of HIV infection and inflammatory bowel disease (IBD). AIMS: This study was conducted to assess the impact of IBD (and particularly ulcerative colitis, UC) on plasma markers of MT and immune activation in HIV+ subjects. METHODS: A cross-sectional study was conducted in 3 groups of patients: HIV+/UC+(group HIV/UC); HIV+/UC- (group HIV); HIV-/UC+(group UC). Plasma levels of soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), and endotoxin core antibodies (endoCAB) were measured as plasma markers of MT. Inflammation and immune activation were evaluated by measuring plasma levels of IL-6, IL-21, TNF-alpha, and high-sensitivity C-reactive protein (hs-CRP). T- and B-cells subpopulations were characterized by FACS analysis. RESULTS: Seven patients were enrolled in group HIV/UC, 9 in HIV, and 10 in UC. All HIV-positive patients had plasma values of HIV-1 RNA < 37 copies/mL for at least 12 months and good immunological recovery. All patients with UC were treated with oral mesalazine. Markers of MT, immune activation, and inflammation were not increased in subjects with HIV/UC. In fact, they had lower levels of I-FABP (p = 0.001) and sCD14 (p = 0.007) when compared to other patients groups. Positive correlations were found between I-FABP and sCD14 (r = .355, p = 0.076). Frequency of T- and B-cell subsets did not differ among groups. CONCLUSIONS: Our results suggest that UC does not worsen MT, inflammation, or immune activation in HIV-infected subjects. The anti-inflammatory activity of chronic mesalazine administration on intestinal mucosa may contribute to this finding

Nonintegrating Lentiviral Vector-Based Vaccine Efficiently Induces Functional and Persistent CD8+ T Cell Responses in Mice

CD8+ T cells are an essential component of an effective host immune response to tumors and viral infections. Genetic immunization is particularly suitable for inducing CTL responses, because the encoded proteins enter the MHC class I processing pathway through either transgene expression or cross-presentation. In order to compare the efficiency and persistence of immune response induced by genetic vaccines, BALB/c mice were immunized either twice intramuscularly with DNA plasmid expressing a codon-optimized HIV-1 gp120 Envelope sequence together with murine GM-CSF sequence or with a single immunization using an integrase defective lentiviral vector (IDLV) expressing the same proteins. Results strongly indicated that the schedule based on IDLV vaccine was more efficient in inducing specific immune response, as evaluated three months after the last immunization by IFNγ ELISPOT in both splenocytes and bone marrow- (BM-) derived cells, chromium release assay in splenocytes, and antibody detection in sera. In addition, IDLV immunization induced high frequency of polyfunctional CD8+ T cells able to simultaneously produce IFNγ, TNFα, and IL2

Successful Immunization with a Single Injection of Non-integrating Lentiviral Vector

We evaluated the ability of an integrase (IN)-defective self-inactivating lentiviral vector (sinLV) for the delivery of human immunodeficiency virus-1 (HIV-1) envelope sequences in mice to elicit specific immune responses. BALB/c mice were immunized with a single intramuscular injection of the IN-defective sinLV expressing the codon optimized HIV-1 JR-FL gp120 sequence, and results were compared with those for the IN-competent counterpart. The IN-defective sinLV elicited specific and long-lasting immune responses, as evaluated up to 90 days from the immunization by enzyme-linked immunosorbent spot (ELISPOT) and intracellular staining (ICS) for interferon- γ (IFN- γ ) assays in both splenocytes and bone marrow (BM) cells, chromium release assay in splenocytes, and antibody detection in sera, without integration of the vector into the host genome. These data provide evidence that a single administration of an IN-defective sinLV elicits a significant immune response in the absence of vector integration and may be a safe and useful strategy for vaccine development

Central Precocious Puberty: Treatment with Triptorelin 11.25 mg

Background. Few data are available on quarterly 11.25 mg GnRH analog treatment in central precocious puberty (CPP). Aim. To assess the efficacy of triptorelin 11.25 mg in children with CPP. Patients. 17 patients (16 females) with CPP (7.9 ± 0.9 years) were treated with triptorelin 11.25 mg/90 days. Methods. Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months, and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal oestradiol levels. Mean LH peak values after GnRH test significantly decreased from 25.7 ± 16.5 IU/L at baseline to 0.9 ± 0.5 IU/L at M3 (P < 0.0001); they did not significantly changed at M6 and M12. Conclusions. Triptorelin 11.25 mg/90 days efficiently suppressed the pituitary-gonadal axis in children with CPP from first administration

Circular viral DNA detection and junction sequence analysis from PBMC of SHIV-infected cynomolgus monkeys with undetectable virus plasma RNA

AbstractExtrachromosomal forms of human immunodeficiency virus (HIV)-1 can be detected in peripheral blood mononuclear cell (PBMC) from HIV-infected patients in the absence of detectable viral replication and are thought to be a sign of active but cryptic virus replication. No information, however, are available on whether these forms are also present in animal models for acquired immunodeficiency syndrome (AIDS) and on their relation with other methods of detection of virus replication. To this aim, a polymerase chain reaction (PCR) approach was used to detect and analyze unintegrated circular 2-LTR-containing forms in PBMC of simian human immunodeficiency virus (SHIV)89.6P infected cynomolgus monkeys with RNA levels ranging between 1.8 × 106 and less than 50 copies/ml of plasma. 2-LTR forms were detected in 96.5% of monkeys' samples above 50 copies/ml of plasma, whereas they were present in 75.8% of monkeys' samples below 50 copies/ml of plasma. Persistence of unintegrated viral DNA in monkeys with undetectable plasma RNA could indicate either stability in non-dividing cells or ongoing low levels of viral replication in dividing cells

Dried blood spots for the quantitative evaluation of IgG isotypes and correlation with serum samples in HIV-exposed uninfected (HEU) infants

Background: The determination of IgG levels and their subclasses can provide clinically relevant information on the status of the immune system. Here we determined the sensitivity and reproducibility of the quantification of IgG subclasses from Dried Blood Spots (DBS) in Malawian uninfected infants exposed to HIV (HEU). Methods: Sixty paired samples of serum and DBS from HEU infants were used. Samples were collected from 1, 6, and 24-month old infants. IgGs concentrations from both serum and DBS were analyzed by BN ProSpec Siemens assay, using a different setting for sample dilutions. The reproducibility of the DBS method was tested on 10 samples run twice, starting from the DBS extraction process. To assess the systematic, proportional, and random differences, we computed the Passing-Bablok regression, and the Bland-Altman analysis to estimate the total mean bias between the two tests. Results: The IgG isotypes concentrations from serum and DBS showed significant differences in all the comparisons. Generally, the DBS method underestimated IgG subclasses' values showing a recovery range between 51.2% and 77.6%. Passing Bablok regression on age-based groups showed agreement for IgG, IgG1, and IgG2, but not for IgG3 and IgG4. The mean bias obtained with the Bland Altman test varied largely depending on IgG isotypes (−0.02–2.21 g/l) Coefficient of variation <7.0% was found in the repeated tests for IgG, IgG1, IgG3, and IgG4, while it was 12.4% for IgG2. Conclusions: Varying degrees of differences were seen in the IgGs measurement in the two different matrices. In IgGs analysis, the DBS method offers promise for population-based research, but the results should be carefully evaluated and considered as a relative value since they are not equivalent to the serum concentrations

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

Markers of microbial translocation during pregnancy: differences among HIV+ women of African and European provenance.

Introduction: Microbial translocation (MT) markers are indicators of HIV-related immune activation, but reference values are mostly derived from European or North American populations and could be substantially different in populations living in developing countries. Here we evaluate possible differences in MT markers levels in HIV+ pregnant women of different geographical provenance. Methodology: This study is nested within an observational study of pregnant women with HIV in Italy. Women were dichotomized on the basis of provenance in two groups of European (n = 14) and African (n = 26) origin. Soluble CD14, lipopolysaccharide-binding protein (LBP) and intestinal-fatty acid binding protein (I-FABP) were measured in plasma samples collected between the first and second trimester of pregnancy. Results: Demographic and viroimmunological characteristics were similar between groups, although European women were more commonly smokers and HCV-coinfected. Irrespective of origin, LBP plasma levels were positively correlated with I-FABP (r = 0.467, p = 0.004) and sCD14 levels (r = 0.312 p = 0.060). Significantly higher levels of sCD14 (1885 vs. 1208 ng/mL, p = 0.005) LBP (28.5 vs. 25.3 µg/mL, p = 0.050) and I-FABP (573.4 vs. 358.2 pg/mL, p = 0.002) were observed in European compared with African women. A multivariable linear regression analysis, adjusted for smoking and HCV coinfection confirmed the association between sCD14 levels and women provenance (p = 0.03). Conclusions: Our observations indicate significant differences in soluble markers among women of different provenance. In the design and analysis of studies evaluating MT markers, population-specific reference values should be considered

Observations of the Crab Nebula and Pulsar with the Large-sized Telescope Prototype of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is a next-generation ground-based observatory for gamma-ray astronomy at very high energies. The Large-Sized Telescope prototype (LST-1) is located at the CTA-North site, on the Canary Island of La Palma. LSTs are designed to provide optimal performance in the lowest part of the energy range covered by CTA, down to ≃20 GeV. LST-1 started performing astronomical observations in 2019 November, during its commissioning phase, and it has been taking data ever since. We present the first LST-1 observations of the Crab Nebula, the standard candle of very-high-energy gamma-ray astronomy, and use them, together with simulations, to assess the performance of the telescope. LST-1 has reached the expected performance during its commissioning period—only a minor adjustment of the preexisting simulations was needed to match the telescope’s behavior. The energy threshold at trigger level is around 20 GeV, rising to ≃30 GeV after data analysis. Performance parameters depend strongly on energy, and on the strength of the gamma-ray selection cuts in the analysis: angular resolution ranges from 0.°12-0.°40, and energy resolution from 15%-50%. Flux sensitivity is around 1.1% of the Crab Nebula flux above 250 GeV for a 50 hr observation (12% for 30 minutes). The spectral energy distribution (in the 0.03-30 TeV range) and the light curve obtained for the Crab Nebula agree with previous measurements, considering statistical and systematic uncertainties. A clear periodic signal is also detected from the pulsar at the center of the Nebula