489 research outputs found

    Comparative antiviral activity of integrase inhibitors in human monocyte-derived macrophages and lymphocytes

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    The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; MK-2048, L870,810 and IN5 showed a potent anti-HIV-1 activity in macrophages, while in lymphocytes only MK-2048 and L870,810 showed an inhibitory effect comparable to raltegravir. IN2 was a poorly effective anti-HIV-1 compound in all cellular systems. All effective integrase inhibitors exhibited a potent antiviral activity against both X4 and R5 HIV-1 strains. In general, raltegravir, MK-2048, L870,810 and IN5 showed anti HIV activity similar or slightly higher in macrophages compared to PBMC and C8166 T cells: for MK-2048, the EC(50) was 0.4, 0.9, 11.5nM in macrophages, in PBMCs and T cells, respectively; for L870,810, the EC(50) was 1.5, 14.3, and 10.6nM, respectively; for IN5 the EC(50) was 0.5, 13.7, and 5.7nM, respectively

    Swallowing evaluation with videofluoroscopy in the paediatric population

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    Paediatric swallowing disorders can have several causes, from prematurity and congenital anomalies to gastro-oesophageal reflux and infective or inflammatory pathologies of the upper digestive tract. In neonates, the swallowing process is reflexive and involuntary. Later in infancy, the oral phase comes under voluntary control, while the pharyngeal phase and oesophageal phases remain involuntary. Swallowing difficulties can severely compromise pulmonary health and nutritional intake of paediatric patients. Videofluoroscopic Swallow Study (VFSS) is a radiographic procedure that provides a dynamic view of the swallowing process and is frequently considered to be definitive evaluation for objective assessment of dysphagia in paediatric patients. This review focuses on the different possible aetiologies of paediatric swallowing disorders and related videofluoroscopic swallowing study procedures and appearances

    Behavior of a forest of NiFe nanowires in KOH and NaCl solution for water electrolysis

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    The present work investigates the behavior of nanostructured electrodes consisting of an array of nanowires of NiFe alloy in KOH + 0.5 M NaCl solution. The aim is to explore the possibility of using these electrodes for hydrogen production by seawater electrolysis. Seawater splitting requires a highly selective electrode on the anode side, where the evolution of molecular chlorine or the formation of other active chlorine compounds can compete with the oxygen evolution reaction. Nanostructured electrodes, obtained by template electrosynthesis, were tested at room temperature in KOH + 0.5 M NaCl solution, and the results were compared with those obtained in pure KOH. The results showed that the presence of NaCl does not affect the electrocatalytic behavior of the nanostructured NiFe alloy. Furthermore, the chemical–physical characterizations carried out after the long-term galvanostatic tests, have shown that the nanostructured electrodes are also stable in terms of morphology and composition. In addition, the solution used to perform the long-term galvanostatic tests was analyzed to investigate the possible formation of chlorine compounds. The absence of these compounds, together with the measured potential value measured for the oxygen evolution reaction, which was always lower than the thermodynamic redox potential for the hypochlorite formation reaction, leads us to conclude that these electrodes are potentially suitable for seawater electrolysis

    Mitochondrial enzyme GLUD2 plays a critical role in glioblastoma progression

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    Background: Glioblastoma (GBM) is the most frequent and malignant primary brain tumor in adults and despite the progress in surgical procedures and therapy options, the overall survival remains very poor. Glutamate and α-KG are fundamental elements necessary to support the growth and proliferation of GBM cells. Glutamate oxidative deamination, catalyzed by GLUD2, is the predominant pathway for the production of α-KG. Methods: GLUD2 emerged from the RNA-seq analysis of 13 GBM patients, performed in our laboratory and a microarray analysis of 77 high-grade gliomas available on the Geo database. Thereafter, we investigated GLUD2 relevance in cancer cell behavior by GLUD2 overexpression and silencing in two different human GBM cell lines. Finally, we overexpressed GLUD2 in-vivo by using zebrafish embryos and monitored the developing central nervous system. Findings: GLUD2 expression was found associated to the histopathological classification, prognosis and survival of GBM patients. Moreover, through in-vitro functional studies, we showed that differences in GLUD2 expression level affected cell proliferation, migration, invasion, colony formation abilities, cell cycle phases, mitochondrial function and ROS production. In support of these findings, we also demonstrated, with in-vivo studies, that GLUD2 overexpression affects glial cell proliferation without affecting neuronal development in zebrafish embryos. Interpretation: We concluded that GLUD2 overexpression inhibited GBM cell growth suggesting a novel potential drug target for control of GBM progression. The possibility to enhance GLUD2 activity in GBM could result in a blocked/reduced proliferation of GBM cells without affecting the survival of the surrounding neurons
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