1,720,975 research outputs found
Renal iron deposition and stroke : a longitudinal MRI study in SHRSP
No full textBackground and Purpose - Oxidative stress plays a pivotal role in the pathogenesis of renal and cerebrovascular injury in salt-loaded stroke-prone spontaneously hypertensive rat (SHRSP)1,2. Our preliminary data showed an iron accumulation in the kidney of SHRSP before stroke appearance. Thus, the aim of the study was to characterize by magnetic resonance imaging (MRI) the renal iron deposition in a longitudinally in vivo study and to determine the role of iron on the pathological events occurring in SHRSP.
Methods and Results - SHRSP fed a high-salt diet were treated subcutaneously with vehicle or 200 mg/kg/day of deferoxamina (DFO) an iron chelator. The vehicle-treated rats developed hypertension, stroke, proteinuria and kidney morphological alterations. Renal iron accumulation visualized by MRI using a gradient echo sequence was detected after established proteinuria and before stroke appearance. Iron histological staining (Perls’) correlated with the T2* MR signal intensity (MRSI) data, indicating that the signal reduction in the MR images was due to the presence of iron. Interestingly, MRSI of the renal cortex was found to decrease with the progression of kidney disease. Vehicle-treated SHRSP showed decreased haematocrit, serum haptoglobin depletion and haematological alterations, suggesting an involvement of hemolytic process in the renal iron accumulation. Control animals developed systemic oxidative stress and renal mitochondrial dysfunction. DFO treatment delayed stroke appearance, prevented renal iron accumulation and preserved renal physiology and morphology. These beneficial effects seems mainly to be related to the ability of DFO to reduce free-iron derived from hemolysis and to its anti-oxidant proprieties.
Conclusions - We found, in this longitudinally in vivo study, that kidney T2* could be considered as a biomarker for renal iron accumulation. Our data, for the first time, support the involvement of iron in the development of renal and brain damage in salt-loaded SHRS
Expression of alternatively spliced tissue factor in human endothelial cells : induction by inflammatory stimuli and modulation by heparins
No full textTissue factor induction by protease-activated receptor 1 requires intact caveolin-enriched membrane microdomains in human endothelial cells
No full textBackground: Protease-activated receptors (PARs) comprise a family of G-protein-coupled receptors with a unique mechanism of proteolytic activation. PARs regulate a broad range of cellular functions and are active in the pathogenesis of disorders characterized by chronic inflammation or activation of the coagulation cascade. Signaling through PAR1and PAR2 shifts the endothelium towards a prothrombotic phenotype, thereby exacerbating the initial pathophysiologic condition. Objectives: This study aimed to analyze the localization of PARs in the cell membrane and how their compartmentalization affects tissue factor (TF) in human endothelial cells. Methods: TF expression was determined by quantitative real-time polymerase chain reaction analysis and by activity assays. The interaction of PARs with caveolin was investigated through: (i) caveolin-1 gene knockdown performed by transfection with specific small interfering RNA (siRNA); (ii) caveolin-enriched membrane microdomain disruption; and (iii) coimmunoprecipitation assay. Results: We have shown that PAR1, but not PAR2, is present in endothelial caveolinenriched membrane microdomains, where it is bound to caveolin-1, and that these structures must be intact if PAR1- induced signaling is to increase TF activity. Cholesterol depletion of endothelial cells by cholesterol-sequestering agents caused the PAR1 to relocate to high-density membranes, and impaired the induction of TF (P < 0.01) without affecting the PAR2-mediated procoagulant effect. In addition, siRNA directed against caveolin-1 inhibited TF activation by PAR1 (P < 0.01 and P < 0.01, respectively). Conclusions: PAR1 localization in the caveolin-enriched membrane microdomain, bound to caveolin-1, represents a crucial requirement for TF induction in endothelial cells
Visualizzazione con USPIO di processi patologici in un modello animale di danno renale spontaneo
No full textL’infiammazione ha un ruolo centrale nelle patologie cardio- e cerebro-vascolari; la possibilità di marcare in vivo con sostanze paramagnetiche le cellule infiammatorie offre un nuovo strumento di analisi. Scopo del lavoro era quello di visualizzare longitudinalmente la dinamica di infiltrazione delle cellule infiammatorie nei reni dei ratti SHRSP che spontaneamente sviluppano un danno renale (Sironi L. et al., JPET; 311:989-95).
Nella prima parte dello studio i ratti SHRSP erano suddivisi in 3 gruppi, il primo (G1) sottoposto a dieta standard, i restanti (G2 e G3) ad una dieta permissiva per accelerare i processi patologici. G1 e G2 erano trattati e.v. con USPIO, un mezzo di contrasto a base di ferro captato selettivamente da cellule fagiche, mentre G3 con fisiologica. Settimanalmente veniva misurata la proteinuria e i ratti analizzati all'MRI (gradient-echo; GE).
A proteinuria ≥80 mg nelle immagini GE dei reni dei ratti del gruppo G2 si osservavano spot ipointensi la cui intensità au-
mentava con la proteinuria; questi spot erano assenti nei ratti G1 e comparivano nel gruppo G3 ma solo a livelli di proteinuria ≥150 mg. L’analisi istologica ha mostrato che il segnale ipointenso era correlato all'accumulo di ferro nei macrofagi e nei tubuli renali.
In una fase successiva dello studio, ratti SHRSP a dieta permissiva erano trattati con deferoxamina (DFO) un chelante del ferro. Il trattamento con DFO preveniva lo sviluppo della proteinuria e la comparsa degli spot ipointensi a livello renale, aumentava la sopravvivenza dei ratti e preveniva l’espressione a livello renale di geni pro-infiammatori valutati sui tessuti prelevati dagli animali.
Lo studio dimostra per la prima volta (i) il coinvolgimento di un’alterato metabolismo del ferro nello sviluppo di un danno
renale spontaneo; (ii) l’utilità dell’USPIO nel visualizzare, tramite scansioni MRI, l’accumulo renale di ferro endogeno anche in fasi molto precoci della patologia. I dati raccolti indicano che il segnale ipointenso nelle immagini GE indotto dall’USPIO non è però selettivo per le cellule infiammatorie. Ulteriori approfondimento sono necessari per l’applicazione clinica della tecnica sviluppata nel modello animale di danno renale
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
Vascular fibrosis in stroke-prone rats (SHRSP) is prevented by drugs active on inflammatory pathways
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