1,720,989 research outputs found
DUAL ACTING ANTI-INFLAMATORY DRUGS
No full textDrugs able to inhibit both cyclooxygenases (COX-1 and COX-2) and 5-lipoxygenase (5-LOX) (dual acting
anti-inflammatory drugs) have been designed in order to obtain compounds that retain the activity of classical nonsteroidal
anti-inflammatory drugs (NSAIDs) while avoiding their main drawbacks. The classical NSAIDs display their anti-
inflammatory action mainly through inhibition of COX and one of their main drawbacks is the curtailed production of
gastroprotective prostaglandins (PGs) being associated with the concurrent increased production of the gastro-damaging
and bronchoconstrictive leukotrienes (LTs). Leukotrienes and cysteinyl-leukotrienes are moreover pro-inflammatory and
increase microvascular permeability. One of the leukotrienes (LTB4) is the most potent chemotactic agent and it induces
chemotaxis of eosinophils, neutrophils and monocytes in the inflamed tissue, increases superoxide generation and
proinflammatory cytokines production. It is further advantageous for a drug to have both COX and 5-LOX inhibiting
activities because prostaglandins enhance leukotriene-mediated inflammation. Various structural families of dual
inhibitors have been designed and several compounds are currently undergoing clinical development. In the post-COX-2
selective inhibitors era, these dual acting inhibitors may turn out to be promising new drugs to treat inflammatory diseases
and possibly other diseases. Indeed, both COX-2 and 5-LOX are also involved in the development and progression of
several types of cancer; in these conditions, selective inhibition of COX-2 alone may lead to a shunt of arachidonic acid
metabolism towards the leukotriene pathway, and therefore the blockade of both COX-2 and 5-LOX may produce a better
anticancer response. In addition, the dual inhibition of both COX and 5-LOX is neuroprotective by suppressing toxic
actions of reactive microglia and macrophages, that are increased in aging brain and in age-related degenerative
conditions, particularly Alzheimer’s and Parkinson’s diseases. Finally, the blockade of 5-LOX does not impair the
synthesis of lipoxins (LXs), which are mainly produced by further lipoxygenation of 15-HPETE, and which have potent
anti-inflammatory properties and can be considered as stop-signal mediators. Leukocyte 15-LOX and platelet 12-LOX by
intercellular mechanism via leukocyte/platelet cell-cell interaction convert 15-HPETE into lipoxins
Naloxone-reverisble antinociception by paracetamol in the rat.
No full textParacetamol at the dose of 400 mg/kg i.p. displayed antinociceptive activity in the hot-plate test and the formalin test. Moreover, it induced a significant increase in brain serotonin (5-HT) concentration and a reduction in the number of 5-HT2 receptors in cortical membranes. Pretreatment with naloxone abolished this antinociceptive activity both in the hot-plate test and in the first phase of the formalin test without affecting the serum concentration of paracetamol. At the same time, naloxone prevented the increase in 5-HT concentration in the central nervous system and the reduction in 5-HT2 receptors in cortical membranes. Competition experiments demonstrated that paracetamol possesses affinity for [3H]naloxone binding sites. The action of morphine on nociception and on the serotonergic system was similar to that of paracetamol; all morphine-induced effects were blocked by naloxone. These data provide further evidence for a central antinociceptive effect of paracetamol and support the hypothesis that paracetamol exerts its antinociceptive activity through the serotonergic system. Moreover, our results point to the relationship between serotonergic and opiatergic systems in the antinociceptive activity of paracetamol
THE ANALGESIC ACTIVITY OF PARACETAMOL IS PREVENTED BY THE BLOCKADE OF CANNABINOID CB1 RECEPTORS
No full textThe mechanism of the analgesic activity of paracetamol (acetaminophen), one of the most widely used drugs for the treatment of pain, is still
not clear. Here we show that in rats, using the hot plate test, the analgesic effect of paracetamol is prevented by two antagonists at cannabinoid CB1
receptors (AM281 and SR141716A) at doses that prevent the analgesic activity of the cannabinoid CB1 agonist HU210. Our present results
suggest that paracetamol-induced antinociception involves the cannabinoid system
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
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