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

Probiotics Reduce Inflammation in Antiretroviral Treated, HIV-Infected Individuals: Results of the "Probio-HIV" Clinical Trial

BACKGROUND: HIV infection results in damage to the gastrointestinal (GI) tract, microbial translocation and immune activation. These are not completely normalized with combined antiretroviral therapy (cART). Moreover, increate morbidity and mortality of cART-treated HIV-infected individuals is associated with inflammation. METHODS: In order to enhance GI tract immunity, we recruited and treated 20 HIV-infected humans with cART supplemented with probiotics and followed inflammation and immunological parameters (clinical trial number NCT02164344). 11 HIV seronegative subjects were included as control group. The enumeration of CD4+, CD8+, CD38+ and HLA-DR+ lymphocytes were evaluated on peripheral blood; HIV-RNA levels, sCD14, d-dimer, C-reactive protein (CRP) high sensitivity C-reactive protein (hsCRP), IL-6 and Lipopolysaccharide Binding Protein (LBP) were assayed on plasma. RESULTS: We observe that cART does not normalize the levels of immune activation in HIV positive patients anyway inflammation and markers of microbial translocation were significantly reduced with probiotic supplementation. Patients show a clear and statistically significant reduction in the levels of immune activation on CD4 T-lymphocytes, for both markers CD38 and HLA-DR and their simultaneous expression, LBP and hsCRP plasma levels after probiotic diet supplementation settling to values comparable to controls. CONCLUSIONS: Supplementing cART with probiotics in HIV-infected individuals may improve GI tract immunity and there by mitigate inflammatory sequelae, ultimately improving prognosis

5-S-Cysteinyl-dopamine effect on the human dopaminergic neuroblastoma cell line SH-SY5Y

In recent years a catechol-thioether metabolite of dopamine, 5-S-cysteinyl-dopamine, has been identified in certain dopaminergic regions of the brain, notably the Substantia Nigra. 5-S-Cysteinyl-dopamine has received great attention in view of its possible significance as an index of oxidative stress in aging and in neurodegenerative processes, particularly in Parkinson's disease. In the present study the effect of 5-S-cysteinyldopamine on human dopaminergic neuroblastoma SH-SY5Y cells is investigated. The substance is highly cytotoxic, even at a concentration as low as 30 mu M. Treatment of the cells with 5-S-cysteinyl-dopamine induce the following intracellular responses: a decrease of the mitochondrial transmembrane potential, an increase in reactive oxygen species such as superoxide anion and peroxides, a marked decrease of reduced glutathione and an inhibition of the complex I activity. Caspase-3-like protease activation and oligonucleosomal DNA fragmentation have also been observed. These data are indicative of the onset of apoptotic processes due to 5-S-cysteinyl-dopamine. (c) 2006 Elsevier Ltd. All rights reserved

Modulation of apoptosis and improved redox metabolism with the use of a new antioxidant formula

Abstract Oxidative stress is involved in the pathogenesis of a wide spectrum of diseases, implicating that strategies directed at counterbalancing oxidative processes could have a role in clinical medicine. There is also an evidence that oxidative stress acts as a major determinant of apoptotic cell death. Many studies have reported favourable effects of antioxidant formulas on several parameters of the oxidant-antioxidant balance, but none of them has focused whether antioxidant formulas could modulate apoptosis. We investigated in 20 healthy individuals the effect of supplementation with a formula containing alpha-tocopherol, alpha-lipoic acid, coenzyme Q(10), carnitines, and selenomethionine, on plasma oxidant status and peroxide levels, erythrocyte antioxidant enzymes, lymphocyte apoptosis, and generation of ROS at the mitochondrial level. Control subjects received only carnitines or an incomplete formula with alpha-tocopherol, alpha-lipoic acid, coenzyme Q(10), and selenomethionine. Supplementation with the complete formula resulted in a significant increase in the plasma antioxidant status that was mirrored by a decrease in blood peroxide levels and a reduced generation of ROS at the mitochondrial level. This was associated with a significant decrease in the frequency of peripheral blood lymphocytes, with either CD4 or CD8 phenotype, undergoing apoptosis. Less consistent results were found when either incomplete formula was used. Our study suggests that supplementation with antioxidant formulas can modulate the process of apoptosis under in vivo conditions. The clinical potential of this strategy in the treatment of diseases with an elevated commitment to apoptosis should be explored

Gastric metastasis from ovarian adenocarcinoma presenting as a subepithelial tumor and diagnosed by endoscopic ultrasound-guided tissue acquisition

none8noWe describe an uncommon case of a patient with a metastatic adenocarcinoma of ovarian origin presented as a gastric subepithelial tumor (SET) and that was diagnosed by endoscopic ultrasound fine-needle biopsy (EUS-FNB). Malignant gastric lesions are rarely metastatic and the primary tumor is mainly breast, lung, esophageal cancer or cutaneous melanoma. Gastric metastasis from ovarian cancer is unusual, presenting synchronously with the primary tumor but also several years later than the initial diagnosis. From an endoscopic point of view, gastric metastasis does not present specific features. They may mimic both a primary gastric tumor or, less frequently, an SET. This case demonstrates the importance of EUS-FNB in distinguishing SETs and how this may alter treatment and prognosis.openAntonini, Filippo*; Laterza, Liboria; Fuccio, Lorenzo; Marcellini, Massimo; Angelelli, Lucia; Calcina, Sonia; Rubini, Corrado; Macarri, GiampieroAntonini, Filippo*; Laterza, Liboria; Fuccio, Lorenzo; Marcellini, Massimo; Angelelli, Lucia; Calcina, Sonia; Rubini, Corrado; Macarri, Giampier

Demographic, immunological and virological characteristics of the 20 HIV-infected patients and 11 controls included in the study.

<p>Demographic, immunological and virological characteristics of the 20 HIV-infected patients and 11 controls included in the study.</p

The CONSORT flow diagram of the clinical trial.

<p>Experimental design of the study.</p