1,720,956 research outputs found
SVILUPPO DI POSSIBILI NUOVI ANTAGONISTI DEL RECETTORE P2Y12
No full textThere is growing evidence that adenosine receptors could be the promising therapeutic targets in
a wide range of conditions. In fact, purines and pyrimidines nucleosides and nucleotides are
molecules involved in several physiological and pathophysiological processes through the
activation of cell membrane receptors called purinergic receptors. These receptors are classified
in P1 receptors (G-protein-coupled receptors whose natural ligand is adenosine), and P2
receptors (whose agonist and antagonist respectively are ADP and ATP)1. The P2 receptors are
classified in two main groups: P2Y receptors that are G-protein linked, and P2X receptors,
ligand-gated ion channels2. Among the different human P2Y subtypes, our attention was focused
on the P2Y12 or P2T receptor, with a tissue distribution restricted to platelets, and subregions of
the brain and vascular smooth muscle cells3. The P2Y12 receptor is a well-established target of
antithrombotic drugs like ticlopidine, clopidogrel4, prasugrel and cangrelor which have proved
efficacy in many clinical trials and experimental models of thrombosis. Beside the important
activity as antiaggregant therapeutic candidates, P2Y12 receptors seem to be involved in the
neuroprotection. They are present in high concentration in the astrocytes where they preserve the
integrity of the nervous tissues5. Consequently, it’s reasonable to hypothesize an important role
as therapeutic candidates in pathologies which involve a degeneration of the tissues in the some
areas of the brain, such as the Huntington’s disease and the Parkinson’s disease.
In order to find possible new antagonists for this receptor subtypes, we explored some 6-amino-
2-mercapto-3H-pyrimidine-4-one derivatives as extremely simplified analogs of the known
ATP-congeners antagonists. In this series, the compound 1 showed a weak activity in inhibiting
platelet aggregation, becoming our lead compound. Several substituents on hydroxy and thiol
functions were introduced with the purpose to improve the activity (2). Some of the newly
synthesized compounds showed only a slight improvement in the inhibition of platelet
aggregation.
The poor activity of this series of compounds could be explained with the lack of interaction
with the receptor considering the very simplified utilized structure. For this reason we focused
our attention on some bicyclic derivatives (3) in order to increase hydrophobic interactions into
the binding site.
Unfortunately and in contrast of our expectations all the derivatives of general formula 3 showed
an activity comparable with the more simplified compounds (2). A possible explanation of this
effect could be done considering the absence of negative charge on the core, which seems to be
essential for the activity at the P2Y12 receptors as recently reported in literature6.
References:
1. G. Kauffentein et al. “Adenine Triphosphate nucleotides are antagonists at P2y12 receptor” J. Thromb.
Haemost. 2004, 2, 1980-1988.
2. G. Burnstock et al. “P2 purinergic receptors: modulation of cell function and therapeutic potential” J.
Pharmacol. Exp. Ther. 2000, 295, 862-869.
3. I. von Kügelgen. “Pharmacological profiles of cloned-mammalian P2Y-receptors subtypes” Pharmacol. &
Therapeutics. 2006, 110, 415-432.
4. P. Savi et al. “identification and biological activity of the active metabolite of clopidogrel” Thromb. Haemost.
2000, 84, 891-896.
5. L. K. Mamedova et al. “Regulation of death and survival in astrocytes by ADP activating P2Y1 and P2Y12
receptors” Biochem. Pharmacol. 2006, 72, 1031-1041.
6. Y. Baqi et al. “High- affinity, non nucleotide-derived competitive antagonists of platelet P2Y12 receptors” J.
Med. Chem. 2009, 52(12), 3784-3793
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
Bioencapsulation methods for cell inclusion in polysaccharidic matrices for clinical applications
No full textIn this work the effect of including different human cells, i.e., hepatocytes and fibroblasts, within polysaccharidic matrices (beads, films) on cell viability, proliferation adn metabolic activity was studied
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