1,720,959 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)
Effect of nonanimal high- and low-molecular-mass chondroitin sulfates produced by a biotechnological process in an animal model of polyarthritis
No full textBACKGROUND/AIMS:
We planned to report on the effect of two nonanimal chondroitin sulfates (CSs) with different molecular masses produced using an innovative biotechnological process in an adjuvant arthritis animal model.
METHODS:
The experiments included healthy animals, untreated arthritic animals and arthritic animals having been administered 900 mg/kg of either of the two CS samples daily. Arthritic score, γ-glutamyltransferase (GGT) activity in hind paw joint tissue homogenates, plasmatic C-reactive protein (CRP) and pro-inflammatory cytokines IL-1β and IL-6 were assayed.
RESULTS AND CONCLUSIONS:
Low-molecular-mass (LMM) CS significantly reduced the arthritic score by up to about 30% from 14 to 28 days. In contrast, no significant differences were observed for high-molecular-mass (HMM) CS, even if a trend in its capacity to decrease the arthritic score by up to about 11% was observed. Additionally, LMM CS was able to significantly decrease GGT activity by approximately 31% and plasmatic CRP levels by about 9%. Both nonanimal CS samples were effective in reducing plasmatic levels of proinflammatory cytokines. A greater efficacy was also observed for LMM CS compared with a pharmaceutical-grade CS of extractive origin, while the efficacy of the HMM CS sample was found to be rather similar. The greater effect of LMM CS in reducing arthritic parameters may be related to its lower molecular mass with respect to HMM CS and natural CS
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
N-feruloylserotonin in preventive combination therapy with methotrexate reduced inflammation in adjuvant arthritis
No full textMany of disease-modifying anti-rheumatic drugs often have side effects at high doses and/or during long-term administration. Increased efficacy without increased toxicity is expected for combination therapy of rheumatoid arthritis (RA). The aim of the study was to examine the effect of N-feruloylserotonin (N-f-5HT) and methotrexate (MTX) in monotherapy and in combination therapy on disease progression and inflammation in arthritic rats. Adjuvant arthritis was induced by intradermal injection of Mycobacterium butyricum in incomplete Freund's adjuvant in Lewis rats. The experiment included healthy animals, arthritic animals without any drug administration, arthritic animals with administration of N-f-5HT in the oral daily
dose of 15 mg/kg b.w., arthritic animals with administration of MTX in the oral dose of 0.3 mg/kg b.w. twice a week and arthritic animals treated with the combination of N-f-5HT and MTX. N-f-5HT in monotherapy reduced only activation of NF-jB and did not have any significant effect on other parameters monitored. Low-dose treatment of MTX decreased the level of IL-1b and MCP-1 on day 14 and activation of NF-jB in liver without significant effect on other parameters. N-f-5HT and MTX combination showed both the anti-arthritic (hind paw volume and arthritic score) and anti-inflammatory effect (plasmatic levels of IL-1b, IL-17, MCP-1, CRP, and activation of NF-jB in liver). In combination with MTX, N-f-5HT markedly potentiated the therapeutic effect of MTX low dose, which resulted in significant improvement of all parameters measured. The findings showed that the combination therapy simultaneously decreased multiple markers of inflammation, a result crucial for future therapy of RA
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
Activity of pinosylvin administered in monotherapy and in combination with methotrexate on the development of rat adjuvant arthritis
No full textOxidative stress (OS) has been implicated in various pathological conditions involving several diseases and aging. Rheumatoid arthritis (RA) is a common severe joint disease that involves all age groups. The pathogenesis of RA is associated predominantly with the formation of free radicals at the site of inflammation. However, knowledge on the role of OS in the progression of RA is scarce and the link between OS and inflammation status in arthritis should be more precisely investigated. Pinosylvin (PIN), 3,5-dihydroxy-trans-stilbene, is mainly found in the heartwood of Pinus sylvestris. PIN used in this study was synthesized in the Institute of Organic Chemistry and Biochemistry, Academy of Sciences, Prague, Czech Republic by Ing. Juraj Harmatha, PhD. The aim of the present study was to examine the effect of PIN on the progression of adjuvant-induced arthritis (AA) in rats in monotherapy and in combination with methotrexate (MTX), which is a classical immunosuppressant drug.
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.
We found that PIN potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect of MTX (reduction of plasmatic levels of TBARS). Activity of GGT in spleen, level of MCP-1 and CRP in plasma 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, evaluated as plasma levels of isoprostanes. PIN alone or in combination with MTX strongly reduced isoprostane levels (about 50%). On the contrary, a significant decline in Nrf2-regulated antioxidant defences, such as hemeoxygenase-1 (HO-1), was observed in the lung (about 40%) but not in the liver from AA rats. In the AA lung, 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). OS can also activate NF-B, which plays a critical role in the transcription of proinflammatory genes. Our data showed 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. Our results suggest that the anti-inflammatory activity of PIN is mediated by suppression of NF-kB activation in the liver and lung of arthritic animals.
In summary, combined administration of PIN and MTX suppressed arthritic progression in rats more effectively than did MTX alone. This natural compound is able to reduce OS in vivo and may help improve the treatment of rheumatoid arthritis.
Acknowledgement: VEGA 2/0045/11, APVV-0315-07, 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
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
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