1,720,988 research outputs found
Tumor necrosis factor in congestive heart failure: a mechanism of disease for the new millennium?
No full textTumor necrosis factor alpha (TNF-alpha), a protein belonging to the family of cytokines, is one of the leading mediators of the immune response to inflammation. Its widespread biological effects are modulated by two circulating binding proteins corresponding to the extracellular domain of the membrane receptors, namely soluble TNF receptors. TNF-alpha was first supposed to be linked with congestive heart failure (CHF) on a cachexia-inducing basis. In patients with advanced CHF, elevated levels of circulating TNF-alpha and soluble TNF receptors have been found. The pathophysiological implications of activation of the TNF system in CHF seem to rely mainly on its effects on the heart and the endothelium. TNF-alpha exerts a negative inotropic effect both directly and indirectly, this latter being mediated by enhancement of nitric oxide production. Moreover, TNF-alpha has been suggested to trigger the apoptotic process in cardiac myocytes. There is consensus on the detrimental role played by TNF-alpha in CHF further supported by the evidence of a temporal association between TNF activation and transition from asymptomatic to symptomatic CHF
High-dose heparin impairs nitric oxide pathway and vasomotion in rats.
No full textBACKGROUND: Platelet-activating effects have been reported with high-dose heparin in acute thrombotic disorders. Recent studies have shown that increased platelet aggregation is due to reduced nitric oxide (NO) production in endothelial cells cultured in the presence of high-dose heparin. The aim of this study was to determine whether heparin can affect the NO pathway and the regulation of the vascular tone in vivo. METHODS AND RESULTS: Anesthetized and mechanically ventilated Sprague-Dawley rats were treated with high-dose heparin. After 4 hours, the endothelial constitutive NO synthase (ecNOS) protein content in the aorta decreased (36\% reduction, P<0.05), as detected by immunoblotting, and NO-dependent vascular reactivity was impaired. In fact, the increase in mean arterial blood pressure after inhibition of ecNOS with NG-nitro-L-arginine methyl ester (30 mg/kg) was smaller in heparin-treated animals than in controls (+26. 9+/-4.8 versus +48.3+/-9.1 mm Hg, P<0.05), and further infusion of the biological ecNOS substrate L-arginine (0.5 g/kg) was ineffective in reversing systemic vasoconstriction (-1\% versus 28\% vasodilatation, P<0.001). CONCLUSIONS: High-dose heparin can significantly affect vascular reactivity in vivo by downregulation of ecNOS protein expression
High-dose heparin impairs nitric oxide pathway and vasomotion in rats
No full textBackground - Platelet-activating effects have been reported with high- dose heparin in acute thrombotic disorders. Recent studies have shown that increased platelet aggregation is due to reduced nitric oxide (NO) production in endothelial cells cultured in the presence of high-dose heparin. The aim of this study was to determine whether heparin can affect the NO pathway and the regulation of the vascular tone in vivo. Methods and Results - Anesthetized and mechanically ventilated Sprague-Dawley rats were treated with high-dose heparin. After 4 hours, the endothelial constitutive NO synthase (ecNOS) protein content in the aorta decreased (36% reduction, P < 0.05), as detected by immunoblotting, and NO-dependent vascular reactivity was impaired. In fact, the increase in mean arterial blood pressure after inhibition of ecNOS with N(G)-nitro-L-arginine methyl ester (30 mg/kg) was smaller in heparin-treated animals than in controls (+26.9 ± 4.8 versus +48.3 ± 29.1 mm Hg, P < 0.05), and further infusion of the biological ecNOS substrate L-arginine (0.5 g/kg) was ineffective in reversing systemic vasoconstriction (-1% versus 28% vasodilatation, P < 0.001). Conclusions - High-dose heparin can significantly affect vascular reactivity in vivo by downregulation of ecNOS protein expression
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
Right heart failure chronically stimulates heat shock protein 72 in heart and liver but not in other tissues.
No full textOBJECTIVES: During cardiac failure several ontogenically developed adaptional mechanisms are activated. Among these, heat-shock proteins (HSP) are expressed in response to stress. The aim of the present study was to investigate the HSP72 protein expression in lungs, liver, cardiac and skeletal muscles during congestive heart failure (CHF). METHODS: CHF was induced in Sprague-Dawley rats by a single intraperitoneal injection of monocrotaline (50 mg/kg). Two groups of animals emerged: a CHF group (n = 10) with right ventricular hypertrophy, pleural and peritoneal effusions, and an Hypertrophy group (n = 12) with right ventricular hypertrophy without CHF. The data for each group were compared with those of control (saline infused) age-matched rats. Lungs, liver, right and left ventricles, soleus, extensor digitorum longus and tibialis anterior muscles were excised and analyzed for HSP72 concentration by Western blot analysis using a specific monoclonal antibody. Noradrenaline levels in the heart were also measured using HPLC. RESULTS: The CHF group showed: (1) reduced right (0.460 +/- 0.090 vs 0.830 +/- 0.070 nmol/ventricle, P < 0.01) and left (1.10 +/- 0.09 vs 2.10 +/- 0.130 nmol/ventricle, P < 0.001) ventricular content of noradrenaline compared to the control; (2) significant activation of HSP72 concentration in right and left ventricles (39.4 +/- 1.6 vs 5 +/- 0.9\% and 13 +/- 1.2 vs 3.5 +/- 0.6\%, P < 0.001 both) and in the liver (39.8 +/- 11 vs 6 +/- 2\%, P < 0.001); (3) no modification in HSP72 concentration in lungs and all of the peripheral muscles considered. The Hypertrophy group showed: (1) unchanged total noradrenaline tissue content as compared to the control; and (2) unmodified HSP72 concentration in all tissues analyzed. CONCLUSIONS: The present study demonstrates that CHF, but not compensatory hypertrophy, is a specific stimulus for chronic HSP72 induction in the heart and liver. On the contrary, CHF does not affect HSP in lungs and peripheral muscles. HSP 72 induction represents an intracellular marker of stress reaction which can persist chronically
Transcriptional dysregulation and impairment of PHOX2B auto-regulatory mechanism in the pathogenesis of Congenital Central Hypoventilation Syndrome
No full textThe PHOX2B transcription factor plays a crucial role in autonomic nervous system development. In humans, heterozygous mutations of the PHOX2B gene lead to Congenital Central Hypoventilation Syndrome (CCHS), a rare disorder characterized by a broad variety of symptoms of autonomic nervous system dysfunction including inadequate control of breathing. The vast majority of patients with CCHS are heterozygous for a poly-alanine repeat expansion mutation of a twenty residues poly-alanine tract in the C-terminus of PHOX2B. Although several lines of evidence support a dominant-negative mechanism for PHOX2B mutations in CCHS, the molecular effects of PHOX2B mutant proteins on the transcriptional activity of the wild-type protein have not yet been elucidated. One of the targets of PHOX2B is the PHOX2B gene itself, and we have recently demonstrated that mutated PHOX2B variants can actually negatively interfere with the expression of the normal allele. Since in vitro the poly-alanine expanded proteins alter the regulation of other three PHOX2B target genes (PHOX2A, DBH, TLX2) in a promoter-specific manner and that, in CCHS patients, different PHOX2B mutations may affect different target genes, this highlights the importance of identifying PHOX2B target genes in order to get new insights into the molecular pathogenesis of the disease. To this purpose, we carried out Chromatin Immunoprecipitation experiments from IMR32 neuroblastoma cell line, followed by massively parallel sequencing of the co-immunoprecipitated genomic DNA fragments (ChIP-Seq). We are currently validating the most promising candidate target genes by biochemical and functional approaches
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
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