1,721,096 research outputs found
Latest advances in the discovery of fatty acid amide hydrolase inhibitors
No full textIntroduction: Fatty acid amide hydrolase (FAAH) is the major catabolic enzyme of the endocannabinoid N-arachidonoylethanolamine (anandamide) that, with different degrees of efficiency, also hydrolyzes other endogenous fatty acid ethanolamides. FAAH is increasingly being considered a relevant therapeutic target, especially in models of inflammatory pain. The opportunity to selectively increase the endocannabinoid tone only in those tissues where such an enhancement can be beneficial might result in a therapeutic benefit with more limited side effects, compared to the use of direct agonists of anandamide-binding receptors. Thus the research for selective FAAH inhibitors has become a hot topic in current drug discovery. Areas covered: This review highlights the advances in the development of different compounds belonging to different chemical families that have been proposed as FAAH inhibitors. Several classes of inhibitors have been reported so far, and they may be classified into two major classes: reversible and irreversible compounds. These inhibitors are reviewed herein with an emphasis on their potency and selectivity. Expert opinion: In recent years, tremendous efforts have been made to develop the FAAH inhibitors, and consequently many novel chemical templates have been discovered. It is still a major challenge to identify the first inhibitor of FAAH suitable for clinical exploitation that satisfies the requirements of potency, selectivity versus proteins related to anandamide activity as well as other potential off-targets, reversibility versus irreversibility, and efficacy toward rat versus human FAAH
2-arachidonoylglycerol levels are increased in leukocytospermia and correlate with seminal macrophages.
No full textEvidence has been produced that macrophages can actively generate endocannabinoids (eCBs) in response to inflammatory stimuli. As eCBs are involved in the control of several physiological processes, including reproduction, here, we explored whether seminal levels of the eCBs, N-arachidonoylethanolamine (AEA), and 2-arachidonoylglycerol (2-AG), were higher in the presence of leukocytospermia, and were correlated with semen concentration of macrophages. The content of AEA and 2-AG was measured by high-performance liquid chromatography/mass spectrometry in seminal plasma of ejaculates from 18 leukocytospermic patients (>1 × 106 leukocytes/mL) and 21 normozoospermic controls. In the same ejaculates, round cells were phenotyped by flow-cytometry as leukocytes (CD45+), macrophages (CD14+), and activated macrophages (CD14+, HLA-DR+). The levels of 2-AG, but not of AEA, were significantly higher in ejaculates from leukocytospermic patients than in controls and exhibited a significant correlation with semen concentration of macrophages and activated macrophages. Significant associations of 2-AG with macrophages and activated macrophages persisted after adjustment for semen volume and sperm concentration. In conclusion, here we provide evidence that seminal plasma levels of 2-AG are higher in the presence of leukocytospermia, as a marker of macrophages activation. Further studies are warranted to elucidate possible clinical implications
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
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