1,720,983 research outputs found
Pinosilvin administered in monotherapy and in combination with methotrexate reduces oxidative stress in adjuvant arthritis rat model
No full textRheumatoid arthritis (RA) is a common severe joint disease that involves all age groups. This is one of the conditions in which oxidative stress (OS) has been shown to play a role by regulating the progression of the inflammatory response. Adjuvant arthritis (AA) is a rat model of autoimmune erosive arthritis widely used to evaluate etiopathogenetic mechanisms in RA as well as for testing anti-inflammatory drugs. Pinosylvin (PIN), 3,5-dihydroxy-trans-stilbene, is an analogue of resveratrol mainly found in the heartwood of Pinus sylvestris. The aim of the present study was to examine the eventual antioxidant and anti-inflammatory effect of PIN on the progression of AA in rats in monotherapy and in combination with methotrexate (MTX).
AA was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund’s adjuvant. The experiments included healthy animals, arthritic animals not treated, arthritic animals treated with MTX, with PIN, and with a combination of PIN and MTX. The two latter groups received a daily oral dose of 50 mg/kg b.w. of PIN, either alone or with MTX in an oral dose of 0.4 mg/kg b.w. twice a week during 28 experimental days.
Our data demonstrated that PIN potentiated both the anti-arthritic (decrease of hind paw volume) and the antioxidant effect of MTX (TBARS in plasma). The level of inflammatory protein CRP in plasma and activity of GGT in spleen were not improved by addition of PIN to MTX due to the prominent effect of MTX alone on these parameters. Arthritic animals showed increased OS, also evaluated as plasma levels of isoprostanes. PIN alone or in combination with MTX strongly reduced isoprostane levels (about 50%). Anti-inflammatory and antioxidant functions have been attributed to heme oxygenase (HO-1). Our data show a significant decline in HO-1 (about 40%) in the lung from AA rats. In these animals, PIN alone increased the levels of HO-1 by about 30% more than MTX. Moreover, the combination therapy was the most effective in increasing the levels of HO-1 (3-fold in respect to AA values). Finally, activated NF-B plays an important role in the expression of pro-inflammatory genes. In our model, we observed a marked increase in NF-B in the lung and liver from AA animals. This increase was strongly reduced by PIN alone as well as in combination with MTX. These results suggest that the anti-inflammatory activity of PIN can be mediated by suppression of NF-B activation.
In conclusion, PIN is able to reduce OS in AA rat model. In fact, the combined administration of PIN and MTX suppressed arthritic progression more effectively than did MTX alone. This natural compound may then be useful in the treatment of rheumatoid arthritis.
Acknowledgement: VEGA 2/0045/11, APVV-052-10, CNR/SAV bilateral project 2010-2012: In vitro and in vivo models of arthritic processes for studying the mechanisms of inflammation and oxidative stress link-up. New perspectives for arthritis therapy. Pinosylvin used in this study was prepared by Prof. Jan Šmidrkal (Institute of Chemical Technology, Prague, Czech Republic) and Ing. Juraj Harmatha, PhD (Institute of Organic Chemistry and Biochemistry, Academy of Sciences of Czech Republic)
Roflumilast N-oxide, a PDE4 inhibitor, inhibits fibrotic changes induced by isoprostanes in human lung fibroblasts
No full textOxidative stress plays an critical role in the pathogenesis of pulmonary fibrosis. Isoprostanes, the most proximal products of lipid peroxidation, are known mediators of important biological effects and have been found to be increased in fibrosis. Roflumilast, a PDE4 inhibitor, has been demonstrated to mitigate the oxidative stress-induced lung fibrotic response in vivo.
In this study we evaluated in vitro the effect of roflumilast N-oxide (RNO), the active metabolite of roflumilast, on oxidative stress and some markers of fibrotic response induced by isoprostanes. Human lung fibroblasts (HLF) were incubated in the absence or presence of RNO (2nM-1M) for 30 min and then treated with 8-epi-PGE2the most represented isomer of the species).
8-epi-PGE2 (10nM) induced a 1.3-fold increase of radical oxygen species (ROS) generation that was abolished by RNO both at the low (2nM) and at the high (1M) concentration (p<0.05). RNO did not change baseline ROS levels. The time course for total glutathione (GSH) levels showed that 8-epi-PGE2 (10nM) induced an increase (by 19% vs respective control, p<0.05) in total GSH levels after 6 h of incubation. RNO did not add to this effect. On the other hand, RNO (1μM) alone increased total GSH levels by 16% (p<0.05). Based on the latter findings the notion was raised that PDE4 inhibition may enhance total glutathione production possibly by inducing an increased expression of glutamate cysteine ligase (GCLC). In fact, RNO 1μM but also 8-epi-PGE2 (10nM) increased GCLC mRNA expression by 1.3 (p<0.05) and 1.2 fold (p<0.05), respectively. Furthermore, 8-epi-PGE2alpha (10nM) stimulated cell proliferation (+17%; p<0.05) and collagen synthesis (+27%; p<0.05) and RNO (2nM) completely abolished such an increase. Taken together, inhibition of PDE4 (by roflumilast N-oxide) curbs ROS formation, collagen synthesis and proliferation of human lung fibroblasts triggered by the isoprostane 8-epi-PGE2alpha. In addition, the PDE4 inhibitor enhanced total GSH
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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