1,720,958 research outputs found
Polimorfismos genéticos asociados a la respuesta farmacológica de ciclosporina en pacientes trasplantados
Memoria para optar al título de Químico FarmacéuticoCiclosporina (CsA) es un fármaco inmunosupresor utilizado para prevenir el rechazo de
órganos en pacientes trasplantados. Sin embargo, esta droga se caracteriza por poseer un
rango terapéutico estrecho y una alta variación farmacocinética inter- e intra-individual por lo
cual se recomienda monitorear este medicamento constantemente para prevenir efectos
adversos. Por lo tanto, entender la variabilidad farmacocinética de CsA es de crucial
importancia para maximizar los resultados clínicos de los pacientes trasplantados de órganos.
En este estudio se investigaron variantes genéticas involucradas en la metabolización y
transporte de CsA que pueden afectar la farmacocinética de este fármaco. Para esto, pacientes
trasplantados renales fueron genotipificados para CYP3A4*1B, CYP3A5*3, MDR1 3435 C>T y
MDR1 2677 G>T/A mediante PCR-RFLP. Los genotipos obtenidos fueron relacionados con
efectos adversos, episodios de rechazo y concentraciones C2 ajustadas de CsA. También se
estudió la influencia de estos genotipos en la dosis administrada diaria de CsA y los niveles de
creatinina.
Los resultados mostraron una asociación entre el polimorfismo CYP3A5*3 y las
concentraciones C2 ajustadas en los primeros días del tratamiento. Sin embargo, con el resto de
los polimorfismos no se observaron asociaciones estadísticas significativas. Similarmente, al
evaluar la influencia de los genotipos en la dosis diaria de CsA, sólo CYP3A5*3 demostró
asociación. En cuanto a los episodios de rechazo se encontraron asociaciones en el gen MDR1,
en el cual la variante alélica corresponde a un factor de riesgo ante estos episodios. Para los
análisis de los efectos adversos y creatinina, no se encontraron asociaciones para ningún
polimorfismo.
En conclusión, en este estudio se encontró que posiblemente el polimorfismo
CYP3A5*3 estaría relacionado a la respuesta farmacocinética de CsA, y el gen MDR1 estaría
ligado al rechazo del órgano. Mientras tanto, como proyección se propone investigar
polimorfismos adicionales que puedan clarificar el aporte de los otros genes. Además, aumentar
el número de pacientes e incluir factores no genéticos y/o epigenéticos nos entregaría una
respuesta más completa a la variabilidad farmacocinética de este inmunosupresorCyclosporine (CsA) is an immunosuppressive drug used to prevent allograft rejection.
However, it is characterized by a narrow therapeutic index and high inter and intra individual
pharmacokinetics variations. Thus, monitoring of this drug is highly recommended in order to
prevent adverse effects. Therefore, understanding the pharmacokinetic variations of CsA is a
crucial to maximize clinical outcomes in transplanted patients.
In this study we investigated genetics variants involved in the metabolism and transport
of CsA which could affect the pharmacokinetics of the drug. For this purpose, renal transplanted
patients were genotyped for CYP3A4*1B, CYP3A5*3, MDR1 3435 C>T and MDR1 2677 G>T/A
genes through PCR-RFLP. Afterwards, genotypes were correlated with adverse effects,
rejection episodes and dose-adjusted C2 CsA levels in order to establish potential associations.
Also, was studied the influence of this genotypes on the daily dose of CsA and creatinine levels.
The results showed statistical association between CYP3A5*3 polymorphism and doseadjusted
C2 CsA levels at the first post-transplant days, whereas no association were observed
for CYP3A4*1B, MDR1 3435 C>T and MDR1 2677 G>T/A. Similarly, only CYP3A5*3 showed
association with daily dose of CsA. Regarding to rejection episodes, the allelic variant of MDR1
gen was observed as a risk factor. On the other hand, when adverse effects and creatinine
levels were analyzed no correlations were observed for any polymorphisms.
In conclusion, in this study was found that CYP3A5*3 is possibly associated to CsA
pharmacokinetics variation and MDR1 gen is related to rejection episodes. However, it is
proposed to investigate additional polymorphisms which could clarify the contribution of other
genes besides CYP3A5. Additionally, the number of patients needs to be increased to have
higher statistical power. Finally, non- genetic and/or epigenetic factors must be incorporated to
the study in order to have a more complete response on the variability of Cs
The effect of hydroxyurea treatment on DNA methylation and gene expression in essential thrombocythaemia and polycythaemia vera: a cross-species study
Going Beyond Counting First Authors in Author Co-citation Analysis
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
Variations on the Author
“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
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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.
Author-wise bibliometric analysis based on entropy.</p
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