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Effetto dell'infusione di albumina in un modello sperimentale di cirrosi con ascite
Full text linkBackground: There isn't therapeutic option for systolic dysfunction in decompensated cirrhosis. Previous data showed that albumin infusion may improve cardiac contractility in a model of septic shock through an inhibitory action on reactive oxygen species (ROS) or on tumor necrosis factor (TNF)α-inducible nitric oxide synthase (iNOS) pathway.
Aim: To evaluate the effect of albumin infusion on cardiac contractility in experimental cirrhosis with ascites and its possible molecular mechanism.
Methods: 30 Wistar Kyoto rats with CCl4-induced cirrhosis and ascites and 30 control rats were studied. For each groups, 15 rats have been treated with 40% solution of albumin, 15 with the same volume of saline. Isoproterenol-stimulated cardiac contractility was recorded in isolated hearts. Cardiac gene and protein expression of ÃÂ22 adrenergic receptor, of an inhibitory G-protein (Gαi2),of adenylate cyclase 3 (Adcy3), of iNOS, and of NAD(P)H-oxidase activity, source of ROS, were obtained using real time PCR and Western Blot respectively. Serum level of TNF-α and NF-kB translocation into nucleus in cardiac tissue were analyzed with ELISA.
Results: Baseline cardiac contractility was significantly reduced in rats with cirrhosis as compared to control rats (p<0.01). This finding was associated with: a) an higher serum level of TNF-α (p<0.05), b) an increased gene and protein expression of ÃÂ22-AR (p<0.05), Gαi2 (p<0.05), iNOS (p<0.05), c)an increased NAD(P)H-oxidase activity (p<0.05), d) an increased nuclear translocation of NF-kB (p<0.05) and e) a lower expression of Adcy 3 (p<0.05) in cardiac tissue of rats with cirrhosis. After albumin infusion the cardiac contractility was completely recovered in rats with cirrhosis (p<0.01). Protein expression of Gαi2 (p<0.05), iNOS (p <0.05) and NAD(P)H-oxidase activity (p<0.05) in rats with cirrhosis were reversed to control levels. A significant decrease in serum level of TNF-α (p<0.05) and in nuclear translocation of NF-kB in cardiac tissue (p<0.05) of cirrhotic rats was also observed.
Conclusions: These results showed that albumin exerts a positive cardiac inotropic effect in rats with cirrhosis and ascites, involving its capacity to counteract the negative effects on cardiac contractility of ROS and TNF-α-induced NF-kB- iNOS pathwayBackground: La cirrosi epatica è associata ad alterazioni cardiovascolari che comprendono una circolazione iperdinamica, caratterizzata da una ridotta resistenza periferica e splancnica, bassa pressione media arteriosa e un'aumentata portata cardiaca. Studi sperimentali e clinici hanno dimostrato la presenza di un'insufficienza cardiaca latente chiamata "cardiomiopatia cirrotica", che è caratterizzata da una disfunzione diastolica, anomalie elettrofisiologiche, una compromessa contrattilità cardiaca in risposta a stress farmacologici o fisiologici, malgrado l'aumentata portata cardiaca di base. L'infusione di albumina viene usata nella gestione dei pazienti con cirrosi epatica avanzata allo scopo di migliorare il volume circolante efficace attraverso un incremento della pressione oncotica. Tuttavia studi recenti hanno dimostrato che l'azione dell'albumina è più complessa ed è legata alla sua azione antiossidante e alla sua capacità di legare citochine e ossido nitrico.
Scopo: Lo scopo di questo studio è stato quello di valutare in un modello animale di cirrosi avanzata il ruolo del sistema beta adrenergico, dello stress ossidativo e del TNF-α sulla patogenesi della miocardiopatia cirrotica.
Materiali e metodi: Sono stati utilizzati ratti maschi Wistar Kyoto 30 di controllo e 30 trattati con CCl4, per indurre la cirrosi. In ogni gruppo 15 ratti sono stati trattati con albumina (1.5 g/Kg tre giorni prima del sacrifico e 0.5g/Kg un giorno prima) e 15 con lo stesso volume di soluzione fisiologica (come intervento sham). Il cuore è stato prelevato e la contrattilità è stata misurata stimolando il cuore con concentrazioni crescenti di isoproterenolo (da 10-10 a 10-6 M). Sul tessuto cardiaco è stata analizzata l'espressione genica e proteica, mediante Real Time PCR e Western Blot rispettivamente, dei recettori beta adrenergici (beta 1 e beta2), della Adenilato ciclasi (Adcy3), della proteina G inibitoria α 2(Gαi2), dell'isoforma inducibile della ossido nitrico sintetasi (iNOS) e delle NAD(P)H ossidasi. Abbiamo poi analizzato la concentrazione plasmatica e nel liquido ascitico del Tumor necrosis factor-α (TNF-α) e la traslocazione nel nucleo del fattore nucleare NF-kB, attraverso kit ELISA.
Risultati: La contrattilità è cardiaca nei ratti ascitici era significativamente diminuita rispetto ai controlli (p<0.01). Questa scoperta è stata associata con: a) un'aumentata espressione genica e proteica di beta2-AR (p<0.05) e di Gαi2 (p<0.05), b) la diminuzione dell'espressione genica di Adcy3, c) un'aumentata attività delle NAD(P)H ossidasi, d) un'aumentata concentrazione plasmatica e nel liquido ascitico di TNF-α (p<0.05), e) un'aumentata traslocazione nucleare di NF-kB e f) un'aumentata espressione proteica di iNOS. Dopo il trattamento con albumina la contrattilità cardiaca dei ratti ascitici è ritornata ai valori dei controlli (p<0.01). L'espressione proteica nel tessuto cardiaco degli animali ascitici di Gαi2 (p<0.05), iNOS (p<0.05) e l'attività delle NAD(P)H-oxidase (p<0.05) è simile a quella dei ratti di controllo. Una significativa diminuzione dei livelli di TNF- nel plasma (p<0.05) e nell'ascite (p<0.05) e della traslocazione nucleare di NF-kB negli animali cirrotici è stata notata dopo il trattamento con l'albumina.
Conclusioni: I nostri risultati per la prima volta dimostrano che l'albumina esercita un effetto inotropo positivo sul cuore dei ratti cirrotici con ascite. Questo effetto coinvolge la sua capacità di contrastare gli effetti negativi sulla contrattilità cardiaca dei ROS e della pathway TNF-α-NF-kB- iNO
Positive cardiac inotropic effect of albumin infusion in rodents with cirrhosis and ascites: molecular mechanisms
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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
Positive cardiac inotropic effect of albumin infusion in rats with cirrhosis and ascites: molecular mechanisms
No full textDispelling 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
Bilirubin inhibits the TNFα-related induction of three endothelial adhesion molecules
No full textSince an increased serum unconjugated bilirubin (UCB) level has been proposed as an independent protective factor against atherosclerotic disease, we investigated the molecular events at the basis of this effect. HUVEC and H5V cells were treated with TNFalpha and UCB and the effects assessed on E-selectin, VCAM-1 and ICAM-1. In HUVEC cells, UCB blunted the TNFalpha-induced gene upregulation of E-selectin VCAM-1 and ICAM-1. The same pattern was observed in H5V cells except for ICAM-1. UCB also inhibited the PMN endothelial adhesion in HUVEC H5V cells. Western blot and FACS analysis confirmed that UCB prevented TNFalpha-induced over-expression of adhesion molecules proteins in H5V cells. These data contribute to further explain the protective effect of bilirubin against development of atherosclerosis
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