169,779 research outputs found
Inhibition of HIV-1 transcription by cyclopentenone prostaglandin A1 in Jurkat T lymphocytes
No full textCyclopentenone prostaglandins inhibit virus replication in several DNA and RNA virus models. In this report we investigated the effect of prostaglandin A1 (PGA1) on HIV-1 transcription in human CD4+ Jurkat T lymphocyte cells. A dramatic reduction of HIV-1 RNA levels was detected up to seven days post infection in both unstimulated and phorbol 12-mystrate 13-acetate (PMA)-stimulated cells treated with PGA1. PGA1 treatment of cells was also effective in inhibiting the transcription of a chloramphenicol acetyltransferase (CAT) reporter gene, under the control of HIV-1 LTR, in Jurkat-Tat cells. We also show that PGA1 induced the synthesis of 70-kDa heat-shock protein (HSP70) in this cell system and the induction correlated with the drug-antiviral activity. PGA1 was also found to induce the loss of the tumor suppressor p53 protein, in the "proliferative" conformation, in a time correlation with the induction of the HSP70 As the "proliferative" p53 has been involved in the positive trans-activation of the HIV-1 LTR its depletion could contribute to the inhibitory mechanisms of PGA1 on virus transcription
Inhibition of herpesvirus-induced HIV-1 replication by cyclopentenone prostaglandins: role of I kappa B kinase (IKK)
No full textObjectives: Herpes simplex virus (HSV) infections have been associated with reactivation of HIV-1 replication and increases of HIV-1-load in plasma of co-infected individuals. The present authors have previously reported that in epithelial cells HSV-1 induces the IkappaB-kinase (IKK) causing persistent activation of NF-kappaB, a critical regulator of HIV-1 replication. The present study was performed to investigate whether HSV-1-infection could induce IKK-mediated NF-kappaB activation and enhance HIV-1 expression in human T cells, and to analyze the effect of the IKK-inhibitor prostaglandin A, (PGA(1)) and other prostanoids on the NF-kappaB-mediated HSV-HIV interaction. Design and methods: Induction of IKK and NF-kappaB activity was determined in lymphoblastoid Jurkat cells and HIV-1 chronically-infected H9 and ACH-2 cells by kinase assay and electrophoretic mobility shift assay, respectively. The effect of HSV-1 and different prostanoids on HIV-1 expression and replication was determined in Jurkat cells transfected with HIV-1-LTR-driven reporter genes, and in H9 and ACH-2 cells by p24-antigen level evaluation. The role of NF-kappaB in HSV-1-induced HIV-1 expression was investigated by using the IkappaBalpha dominant-negative IkappaBalpha-AA in cotransfection experiments. Results: In human T lymphoblastoid cells HSV-1 potently induces IKK activity, causing a persistent induction of NF-kappaB. HSV-1-induced IKK and NF-kappaB function results in transactivation of HIV-1-LTR-regulated genes and induction of HIV-1 replication in chronically-infected T cells. The cyclopentenone PGA(1) inhibits HSV-1-induced IKK and NF-kappaB activities, blocking HIV-1-LTR-driven expression and preventing HSV-1 -induced HIV-1 replication in co-infected cells. Conclusions: The results indicate that IKK is a key factor in triggering HSV-1 -induced HIV-1 transcription in chronically-infected cells and identify cyclopentenone prostanoids as potent inhibitors of HSV-1-induced HIV-1 reactivation. (C) 2004 Lippincott Williams Wilkins
Inhibition of HIV-1 replication by cyclopentenone prostaglandins in acutely infected human cells. Evidence for a transcriptional block.
No full textCyclopentenone prostaglandins (PGs) inhibit virus replication in several DNA and RNA virus models, in vitro and in vivo. In the present report we demonstrate that the cyclopentenone prostaglandins PGA1 and PGJ2 at nontoxic concentrations can dramatically suppress HIV-I replication during acute infection in CEM-SS cells. PGs did not affect HIV-1 adsorption, penetration, reverse transcriptase activity nor viral DNA accumulation in HIV-1 infected cells. A dramatic reduction in HIV-1 mRNA levels was detected up to 48-72 h after infection (p.i.) in PG-treated cells, and HIV-1 protein synthesis was greatly reduced by a single PG-treatment up to 96 h p.i. Repeated PGA,-treatments were effective in protecting CEM-SS cells by the cytopathic effect of the virus, and in dramatically reducing HIV-1 RNA levels up to 7 d after infection. The antiviral effect was not mediated by alterations in the expression of α-, β-, or γ-interferon, TNFα, TNFβ, IL6, and IL10 in HIV-infected CEM-SS cells. The fact that prostaglandins are used clinically in the treatment of several diseases, suggests a potential use of cyclopentenone PGs in the treatment of HIV-infection
Innovare nell'ottica della sostenibilità: l'esempio dell'albergo diffuso come progetto di valorizzazione per il territorio
No full textLa sostenibilità rappresenta una fondamentale leva per la competitività e una vera sfida per il turismo. Il turismo sostenibile e il turismo responsabile si legano quindi alle problematiche dell'innovazione delle attività turistiche. In questo lavoro si intende analizzare la dimensione di eventuali innovazioni nel comparto alberghiero. In particolare, è oggetto di attenzione scientifica il fenomeno dell' "albergo diffuso" con l'obiettivo di verificare se questo modello di ospitalità risponde alle caratteristiche di innovazione in chiave di sostenibilità, costituendo perciò un buon esempio di valorizzazione del territorio. Secondariamente, vengono analizzate le condizioni secondo le quali questa forma di ospitalità possa effettivamente svilupparsi e diffondersi in Italia, favorendone la competitività. Il presupposto dell'indagine è che non basta innovare per la sostenibilità, ma anche riuscire a mantenere nel tempo l'innovazione e la dimensione della sostenibilità. Turismo, innovazione, sostenibilità e competitività non sono in antitesi, ma elementi tra loro strettamente connessi e legati da rapporti di interdipendenza
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Induction of the heat-shock response by antiviral prostaglandins in human cells infected with human immunodeficiency virus type 1
No full textCyclopentenone prostaglandins inhibit the replication of several DNA and RNA viruses, including retroviruses. The antiviral activity has been associated with the induction of a 70-kDa heat-shock protein (HSP70), via activation of the heat-shock transcription factor (HSF) in infected cells. In the present study we investigated the effect of prostaglandin A1 (PGA1) on the regulation of HSP70 gene expression as well as on viral RNA and protein synthesis in CEM-SS cells during acute infection with human immunodeficiency virus type 1 (HIV-1). We report that HIV-1 infection does not alter HSF activation by PGA1, whereas it causes an increase in intracellular HSP70 mRNA levels, as a result of enhanced HSP70 mRNA stability. We also show that, as reported in studies of different virus/host cell models, PGA1 inhibits HIV-1 replication by acting at multiple levels during HIV-1 infection. In addition to the previously reported block of HIV-1 mRNA transcription, PGA, was also found to inhibit viral protein synthesis. These results, together with the fact that prostaglandins are used clinically in the treatment of several diseases, open new perspectives in the search for novel antiretroviral drugs
Mitomycin C in highly myopic eyes - Author reply
No full textOphthalmology. 2005 Feb;112(2):208-18; discussion 219.
Mitomycin C modulation of corneal wound healing after photorefractive keratectomy in highly myopic eyes.
Gambato C, Ghirlando A, Moretto E, Busato F, Midena E.
SourceRefractive Surgery Service and Antimetabolite Therapy Research Unit, Department of Ophthalmology, University of Padova, Padova, Italy.
Abstract
PURPOSE: To evaluate the role of topical mitomycin C in corneal wound healing (CWH) after photorefractive keratectomy (PRK) in highly myopic eyes.
DESIGN: Prospective, double-masked, randomized clinical trial.
PARTICIPANTS: Seventy-two eyes of 36 patients affected by high (>7 diopters) myopia.
METHODS: In each patient, one eye was randomly assigned to PRK with intraoperative topical 0.02% mitomycin C application, and the fellow eye was treated with a placebo. Postoperatively, mitomycin C-treated eyes received artificial tears (3 times daily, tapered in 3 months), whereas the fellow eye was treated with fluorometholone sodium 2% and artificial tears (3 times daily, tapered in 3 months).
MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), contrast sensitivity, manifest refraction, and biomicroscopy. Contrast sensitivity was determined using the Pelli-Robson chart. Corneal confocal microscopy documented CWH.
RESULTS: Mean follow-up was 18 months (range, 12-36). No side effects or toxic effects were documented. At 12-month follow-up examination, UCVAs (logarithm of the minimum angle of resolution) were 0.4+/-0.48 and 0.5+/-0.53 (P = .03) in mitomycin C-treated eyes and corticosteroid-treated eyes, respectively. At 1 year, corneal haze developed in 20% of corticosteroid-treated eyes, versus 0% of mitomycin C-treated eyes. At 12, 24, and 36 months, corneal confocal microscopy showed activated keratocytes and extracellular matrix significantly more evident in untreated eyes (Ps = 0.004, 0.024, and 0.046, respectively).
CONCLUSION: Topical intraoperative application of 0.02% mitomycin C can reduce haze formation in highly myopic eyes undergoing PRK.
Comment in
Ophthalmology. 2006 Feb;113(2):357; author reply 357-8
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Interferon (IFN)-beta Gene Transfer into TS/A Adenocarcinoma Cells and Comparison with IFN-alpha. Differential Effects on Tumorigenicity and Host Response
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