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    Great reduction of human and avian type A Influenza virus multiplication by MESNA ( sodium-2 mercaptoethanesulfonate ) treatment.

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    7.3 Great reduction of human and avian type A Influenza virus multiplication by MESNA (sodium-2 mercaptoethanesulfonate ) treatment. G. Conti 1, P.Portincasa 1, F. Piazza (), G. Dieci 2, F. Zani () and C. Zini () 1 Department of Pathology and Laboratory Medicine, Microbiology Section 2 Department of Biochemistry and Molecular Biology Department of Pharmacy Department of Otorino-Odonto-Ophthalmology University of Parma, Gramsci 14, Parma, Italy The antiviral activity of MESNA, a thiol group compound, was evaluated in LLC-MK2 cells infected by Influenza virus. MESNA was able to inhibit viral multiplicaton in a dose-dependent fashion and virus yield, obtained both with HA and plaque assaies, were reduced at concentrations which did not suppress protein synthesis in mock-infected cells. Experiments of post-treatment performed at different times showed that addition of the drug was effective until 6 hours p.i. Removal of the compound at various times showed that the inhibition was not reversible at all times p.i. Also in this case haemagglutination assayes were carried out at 24, 48 and 72 hours of infection. Pre-treatment of uninfected LLC-MK2 cell monolayers were performed to gain informations on the possibility to render these cells resistant to viral infection. At 24,48 and 72 hours p.i. the presence of virus particles in maintenance medium without MESNA was evaluated by HA assayes . In these conditions no mature viral particles were detected at all times tested after infection.. Viral protein synthesis was studied in condition of treatment. At different interval-times monolayers of infected LLCMK2 cells were pulse-labeled with [35S]-methionine (30μCi/ml). MESNA-treatment determines a marked reduction of the normal synthesis of early and late viral proteins suggesting an action on viral transcriptase. “In vitro” assay of viral RNA dependent-RNA polymerase activity performed on purified Influenza virions showed negative results: MESNA is not able to determine an inhibition or block of the virus enzyme activity. This evidence leads us to hypothesise a possible involvement of a cellular factor (s). We are currently investigating the role / concentration level of the ratio Ox-Red glutathione, GSSG / GSH. Results obtained with human influenza virus strain, A, NWS, H1N1,were completely reproducible and comparable with those obtained with avian influenza virus strain, A, Ulster 73, H7N1. Furthermore, data obtained in MDCK cells were comparable to those, above described, obtained in LLC-MK2 cells. Corresponding Author: prof. Giorgio Cont

    Inhibition of human and avian type A Influenza virus multiplication performed by MESNA

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    The antiviral activity of MESNA, a thiol group compound, was evaluated in LLC-MK2 cells infected by Influenza virus. MESNA was able to inhibit viral multiplicaton in a dose-dependent fashion and virus yield, obtained both with HA and plaque assaies, was reduced at concentrations which did not suppress protein synthesis in mock-infected cells. MESNA treatment determined a marked reduction of the normal synthesis of early and late virus-induced proteins suggesting an action on viral transcriptase. However, “in vitro” assay of viral RNA dependent-RNA polymerase activity performed on purified virions showed negative results in that MESNA was not able to inhibit or block virus enzyme activity. This evidence led us to hypothesise a possible involvement of a cellular factor (s). We have investigated the role and the concentration of the ratio Ox-Red glutathione, GSSG / GSH. Results obtained demonstrate a correlation between the intracellular concentration of GSH and progression/ inhibition of viral infection. In particular, the results reported here demonstrate that the amounts of GSH reached into the cells are a direct consequence of MESNA treatments. Data obtained with human influenza virus strain, A, NWS, H1N1, were completely reproducible and comparable with those obtained with avian influenza virus strain, A, Ulster 73, H7N1. Furthermore, data obtained in MDCK cells were comparable to those, above described, obtained in LLC-MK2 cells. Corresponding Author: prof. Giorgio Cont

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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