1,721,049 research outputs found

    DOES THE INHIBITION OF P2Y12 INHIBIT THE PRODUCTION OF THROMBOXANE A2 BY PLATELETS?

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    Patients with acute coronary syndromes (ACS) are treated with dual antiplatelet therapy (DAPT), which includes aspirin, an inhibitor of thromboxane A2 (TxA2) production, and an antagonist of the P2Y12 receptor for ADP. Based on the recent observation that P2Y12 antagonists also inhibit the platelet production of TxA2, it has been suggested that patients with ACS might be safely treated with P2Y12 antagonists only. However, the observation that platelets congenitally deficient of P2Y12 synthesize normal amounts of TxA2 contrasts the results obtained with P2Y12 antagonists. To test whether the reported inhibitory effect of P2Y12 antagonists on TxA2 production is due to off-target effects, or secondary to inhibition of platelet aggregation (PA). Serum TxB2 was measured in 2 patients with inherited P2Y12 deficiency and 7 healthy subjects in presence/absence of increasing concentrations of P2Y12 antagonists added in vitro, and in 20 patients treated with 10 mg/d prasugrel (P2Y12 antagonist) or placebo for 14 days in a randomized, double-blind, cross-over study. TxB2 levels were also measured after stimulation of citrate-PRP by collagen (0,5μg/mL) or arachidonic acid (1mM) in an aggregometer in presence/absence of P2Y12 antagonists, under stirring and non-stirring conditions (PA does not occur without stirring). P2Y12 antagonists did not decrease serum TxB2 levels both in vitro and ex vivo (prasugrel-treated patients). They partially inhibited TxB2 production under stirring, but not under non-stirring conditions. In conclusion, P2Y12 antagonists do not inhibit the platelet TxA2 production; therefore, there is no pharmacological evidence that aspirin should be withheld in patients with ACS

    Inhibition of the platelet P2Y12 receptor for adenosine diphosphate does not impair the capacity of platelet to synthesize thromboxane A2

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    Aims Patients with acute coronary syndromes (ACSs) are treated with acetylsalicylic acid (ASA) and antagonists of the P2Y12 receptor (P2Y12R) for adenosine diphosphate (ADP). Based on the demonstration that P2Y12R antagonists inhibit thromboxane A2 (TxA2) production (target of ASA), it was surmised that ACS patients might be treated with P2Y12R antagonists only. However, this demonstration contrasts with the results of previous studies. The aim of this study was to test whether P2Y12R antagonists have off-target/indirect inhibitory effects on platelet TxA2 production. Methods and results We studied 3 patients with inherited P2Y12R deficiency and 33 healthy subjects. Serum TxB2 (TxA2 metabolite) levels were similar in P2Y12R-deficient patients and healthy subjects and were not decreased by P2Y12R antagonists in vitro. Serum TxB2 levels did not decrease in 20 patients treated with prasugrel (10 mg q.i.d.) or placebo for 14 days. Arachidonic acid- and collagen-induced platelet aggregation (PA) and TxB2 production in platelet-rich plasma (PRP) of healthy subjects were inhibited in vitro by P2Y12R antagonists. However, P2Y12R antagonists did not inhibit TxB2 production when PA was prevented by avoiding the stirring of PRP in the aggregometer. The P2Y1 ADP-receptor antagonist MRS2500 had similar effects on PA and TxB2 production as P2Y12R antagonists. Acetylsalicylic acid inhibited TxB2 production more effectively than a P2Y12R antagonist; only the combination of ASA and a P2Y12R antagonist inhibited PA induced by high concentration of collagen. Conclusion Inherited deficiency or pharmacological inhibition of P2Y12R does not affect the platelet capacity to synthesize TxA2. There is no pharmacological evidence that ACS patients may be safely treated with P2Y12R antagonists without ASA

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Usefulness of the INNOVANCE® PFA P2Y test cartridge for the detection of patients with congenital defects of the platelet P2Y12 receptor for adenosine diphosphate

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    INTRODUCTION: The platelet function analyzer (PFA)-100® is used in clinical practice to screen patients with bleeding diathesis and suspected defects of primary hemostasis. A new cartridge, INNOVANCE® PFA P2Y, has been specifically developed to monitor patients' response to drugs inhibiting the platelet P2Y12 receptor for ADP. In this study, we compared the ability of INNOVANCE® PFA P2Y to detect congenital defects of the platelet P2Y12 receptor to that of standard cartridge formulations currently in clinical use. MATERIALS AND METHODS: We studied two patients with severe P2Y12 deficiency, one patient with heterozygous P2Y12 deficiency and one with dysfunctional P2Y12 receptor. Closure times were measured using 3 cartridges: collagen/ADP, collagen/epinephrine, and INNOVANCE® PFA P2Y. The results obtained in the four patients with P2Y12 defects were compared to those obtained for 20 healthy controls. RESULTS: In 2 patients with severe P2Y12 deficiency, closure times of INNOVANCE® PFA P2Y and collagen/ADP cartridges were >300s, while those of collagen/epinephrine cartridge were variable (186s and >300s). In the patient with dysfunctional P2Y12, closure time of INNOVANCE® PFA P2Y was >300s, while closure times of collagen/ADP and collagen/epinephrine were normal. Closure times of all cartridges were normal in the patient with heterozygous P2Y12 deficiency. CONCLUSION: Our study provides the first evidence that INNOVANCE® PFA P2Y cartridge is sensitive to congenital severe and moderate defects of the platelet P2Y12 receptors

    Effect of platelet count on platelet aggregation measured by impedance aggregometry (Multiplate(TM) analyser) and by light transmission aggregometry

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    The in vitro evaluation of platelet aggregation is useful to diagnose platelet function disorders [1, 2]; in some laboratories, the test is also used to monitor antiplatelet treatment [3]. Traditionally, platelet aggregation is measured by light transmission aggregometry (LTA), which measures the changes in transmission of a beam of light through a sample of platelet-rich plasma (PRP) or platelet suspensions in buffer, which occur when platelets change shape and aggregate upon stimulation. As this technique has some disadvantages [2], novel methods were introduced to measure platelet aggregation in vitro

    Variations on the Author

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    “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

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    We 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

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    We 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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