1,720,987 research outputs found
Prostacyclin in liver disease: a potential therapeutic option. Expert Opin Biol Ther. 2007; 7(6):1-6
No full textExpert Opin Biol The
How Can Interleukin-1 Receptor Antagonist Modulate Distinct Cell Death Pathways?
No full textMultiple mechanisms of cell death exist (apoptosis, necroptosis, pyroptosis) and the subtle balance of several distinct proteins and inhibitors tightly regulates the cell fate toward one or the other pathway. Here, by combining coimmunoprecipitation, enzyme assays, and molecular simulations, we ascribe a new role, within this entangled regulatory network, to the interleukin-1 receptor antagonist (IL-1Ra). Our study enlightens that IL-1Ra, which usually inhibits the inflammatory effects of IL-1α/β by binding to IL-1 receptor, under advanced pathological states prevents apoptosis and/or necroptosis by noncompetitively inhibiting the activity of caspase-8 and -9. Consensus docking, followed by cumulative 10 μs of molecular dynamics simulations unprecedentedly reveal that IL-1Ra binds both caspases at their dimeric interface, preventing, in this manner, the formation of their catalytically/signaling active form. The resulting IL-1Ra/caspase-8(9) adducts are stabilized by hydrophobic and by few key hydrogen bonding interactions, formed by residues fully conserved across distinct caspases (-3, -6, -7, -8, and -9), and closely resemble the binding mode of the caspases inhibitors XIAP (X-linked inhibitor of apoptosis) and c-FLIP (cellular FLICE-like inhibitory protein). Tight regulation of the different forms of cell death has a major impact on distinct human illnesses (i.e., cancer, neurodegeneration, ischemic injury, atherosclerosis, viral/bacterial infections, and immune reaction). Hence, our study, pinpointing IL-1Ra as new actor of the intricate cell death regulatory network and gaining an atomic-scale understanding of its mechanism may open new avenues toward innovative therapeutic strategies to tackle major human diseases
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
Interleukin-1 receptor antagonist myocardial synthesis in ischemic cardiomyopathy
No full textPlasma levels of systemic markers of inflammation have been used to monitor the risk of coronary artery disease (CAD). Interleukin-1 receptor antagonist (IL-1Ra) modulates the production and the activity of IL-1, a cytokine associated with inflammatory response. In order to ascertain whether detection of increased levels of IL-1Ra may be useful in the characterization of ischemic syndromes, we investigated IL-1ra levels in a first series of 117 consecutive patients undergoing coronary angiography with a clinical diagnosis of Braunwald's unstable or chronic stable angina, or atypical chest pain (lesion-free coronary arteries at coronary angiography). Characteristics of the patients were similar in the three groups. Clinical and laboratory assessment excluded active immune diseases. A statistically significant (p<0.001) increase of IL-1ra was found in unstable angina, compared to stable chronic angina and normal control group patients. In contrast, there were not significant differences between normal controls and chronic stable angina patients. On the other hand, C-reactive protein (CRP) levels were significantly higher in pts with stable and unstable angina as compared to subjects without corornary disease (P=0.034), but they did not discriminate between stable and unstable pts (P=0.7). IL-1Ra plasma levels were then measured upon Emergency Department (ED) admission in 44 consecutive pts with ST-segment elevation acute myocardial infarction (aMI). A comparison between IL-1Ra and common indicators of myocardial necrosis [creatin-kinase (CK), CK-MB, Troponin I and Myoglobin] or systemic inflammation [CRP] was also performed. On admission to ED, 82% of pts had elevated IL-1Ra levels vs 41% of pts with raised CK (P=0.001), CK-MB (45%, P=0.002), Troponin I ( 57%, P=0.027), Myoglobin (48%, P=0.004) and CRP (57%, P= 0.019) levels. Sensitivity of IL-1Ra determination to identify in the Emergency Department pts with aMI raised to 86% if pre-coronary time was <3 hours and to 91% if heralded infarction occurred. We then investigated the actual source of IL-1Ra in subjects with myocardial ischemic disease. Myocardial samples were taken in the peri-infarct and remote regions at time of explant for heart transplant in 4 subjects with ischemic cardiomyopathy and previous AMI. IL-1Ra production was evaluated using in situ hybridization for IL-1Ra mRNA and immunostaining with anti-IL-1Ra-protein specific antibodies. Myocardial IL-1Ra expression was found in all cases, particularly in the peri-infarct regions, with cardiomyocytes being the prevalent source for IL-1Ra. Conclusions. IL-1Ra, a cytokine with potential anti-inflammatory properties, is produced by the ischemic myocardium. Elevation of serum IL-1ra may identify pts with unstable angina with greater sensitivity than CRP and precedes the release of markers of necrosis in pts with aMI
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
Enhanced portal flow velocity and volume following Iloprots treatment.
No full textBACKGROUND:
Iloprost, a prostacyclin analog, reduces hepatic microcirculatory damage after ischemia-reperfusion injury in animal liver models. The objective of this study was to evaluate whether the portal flow velocity changes after Iloprost infusion in patients with systemic sclerosis and Raynaud's phenomenon, who usually have increased risk of microvascular thrombosis and transient liver disturbances.
PATIENTS AND METHODS:
Fifteen patients (3 males and 12 females, median age 58 years, range 47-66 years), with systemic sclerosis and Raynaud's phenomenon, were exclusively treated with an infusion of Iloprost (2 ng/kg/min, 6 h/day) for 5 days. In each subject, the portal flow velocity (PV, cm/sec) and portal flow volume (PFV, mL/min) were obtained by using portal color Doppler ultrasonography equipment.
RESULTS:
Iloprost administration significantly (p<0.001) increased both the PV (23.6+/-3.4 cmlsec vs. 29.1+/-3.9 cm/sec) and PFV (1748.8+/-310. 7 mL/min vs. 2254.9+/-404.1 mL/min) values.
CONCLUSION:
Hepatic perfusion significantly improved after Iloprost administration, suggesting that such treatment might be useful in preventing vascular complications in patients with systemic sclerosis. Iloprost improves the portal hemodynamics, favoring local microvascular patency, and its effectiveness may be safely monitored by using portal color Doppler ultrasonography
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