1,723,215 research outputs found
A soluble guanylate cyclase stimulator, BAY 41-8543, preserves pulmonary artery endothelial function in experimental pulmonary embolism
No full textBackground: BAY 41-8543 reduces pulmonary vascular resistance and right ventricle injury in experimental PE. Objective: Test if BAY 41-8543 protects pulmonary artery (PA) endothelial function in PE. Methods: PE was induced (anesthetized, Sprague-Dawley rats, 25 µm polystyrene microspheres, 1.95 million/100g, IV) with BAY 41-8543 (50 ug/kg, IV) or solvent treatment. Controls had vehicle for microspheres. Rings isolated from primary PA branches (5hr. PE) were contracted (phenylephrine, 10-6M) and dilation was endothelium-dependent (acetylcholine, 10-7M – 10-5M) or with BAY 41-8543 (10-8M – 10-6M). Oxidant stress was assessed: PA tissue 4-hydroxynoneal (4-HNE) immunohistochemistry; plasma malondialdehyde (MDA). Other Control rings received red blood cell (RBC) lysate. Results: PE inhibited dilation to acetylcholine vs. Control (dose x group interaction p=0.001), while dilation to BAY 41-8543 was minimally changed. PE raised plasma hemoglobin (30-fold, p=0.003), 4-HNE stain and plasma MDA (2.2-fold, p=0.009). Treating PE rats with BAY 41-8543 reduced plasma hemoglobin, 4-HNE and MDA to levels not different from Control. Dilation to acetylcholine significantly improved in PE + BAY 41-8543 rats vs. PE (dose x group interaction p=0.04). Addition of RBC lysate to Control rings reduced dilation to acetylcholine, while BAY 41-8543 responses remained strong. Conclusion: PE caused PA endothelial dysfunction, elevated plasma hemoglobin and oxidant stress. Treating rats with BAY 41-8543 lowered plasma hemoglobin, oxidant stress and endothelial dysfunction in PE. Treating isolated rings with BAY 41-8543 bypassed endothelial dysfunction with PE or RBC lysate
Chronic intratracheal application of the soluble guanylyl cyclase stimulator BAY 41-8543 ameliorates experimental pulmonary hypertension
No full textDysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.
Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats. Four weeks after a single injection of monocrotaline (MCT, 60 mg/kg s.c.), rats were randomized to a two-week treatment with either placebo, BAY 41-8543 (10 mg/kg per os (PO)) or intra-tracheal (IT) instillation (3 mg/kg or 1 mg/kg).
Circulating concentrations of the drug 10 mg/kg PO and 3 mg/kg IT were comparable. BAY 41-8543 was detected in the lung tissue and broncho-alveolar fluid after IT delivery at higher concentrations than after PO administration. Systemic arterial pressure transiently decreased after oral BAY 41-8543 and was unaffected by intratracheal instillation of the drug. PO 10 mg/kg and IT 3 mg/kg regimens partially reversed pulmonary hypertension and improved heart function in MCT-injected rats. Minor efficacy was noted in rats treated IT with 1 mg/kg. The degree of pulmonary vascular remodeling was largely reversed in all treatment groups.
Intratracheal administration of BAY 41-8543 reverses PAH and vascular structural remodeling in MCT-treated rats. Local lung delivery is not associated with systemic blood pressure lowering and represents thus a further development of PH treatment with sGC stimulators
Pulmonary and systemic vasodilator responses to the soluble guanylyl cyclase stimulator, BAY 41-8543, are modulated by nitric oxide
No full textBAY 41-8543 is a nitric oxide (NO)-independent stimulator of soluble guanylyl cyclase (sGC). Responses to intravenous injections of BAY 41-8543 were investigated under baseline and elevated tone conditions and when NO synthase (NOS) was inhibited with Nω-nitro-l-arginine methyl ester (l-NAME). Under baseline conditions, intravenous injections of BAY 41-8543 caused small decreases in pulmonary arterial pressure, larger decreases in systemic arterial pressure, and increases in cardiac output. When pulmonary arterial pressure was increased to ∼30 mmHg with an intravenous infusion of U-46619, intravenous injections of BAY 41-8543 produced larger dose-dependent decreases in pulmonary arterial pressure, and the relative decreases in pulmonary and systemic arterial pressure in response to the sGC stimulator were similar. Treatment with l-NAME markedly decreased responses to BAY 41-8543 when pulmonary arterial pressure was increased to similar values (∼30 mmHg) in U-46619-infused and in U-46619-infused plus l-NAME-treated animals. The intravenous injection of a small dose of sodium nitroprusside (SNP) when combined with BAY 41-8543 enhanced pulmonary and systemic vasodilator responses to the sGC stimulator in l-NAME-treated animals. The present results indicate that BAY 41-8543 has similar vasodilator activity in the systemic and pulmonary vascular beds when pulmonary vasoconstrictor tone is increased with U-46619. These results demonstrate that pulmonary and systemic vasodilator responses to BAY 41-8543 are significantly attenuated when NOS is inhibited by l-NAME and show that vasodilator responses to BAY 41-8543 are enhanced when combined with a small dose of SNP in l-NAME-treated animals. The present results are consistent with the concept that pulmonary and systemic vasodilator responses to the sGC stimulator are NO-independent; however, the vasodilator activity of the compound is greatly diminished when endogenous NO production is inhibited with l-NAME. These data show that BAY 41-8543 has similar vasodilator activity in the pulmonary and systemic vascular beds in the rat.</jats:p
Lifetime of the 8543 keV (6<sup>+</sup>) State of <sup>28</sup>Si
No full text The 25Mg(α,nγ)28Si reaction has been used to populate the 8543 keV, 6+ state of 28Si and the mean lifetime has been determined from the attenuated Doppler shift of the 8543 → 4617, 6+ → 4+ transition. The result is 19 ± 8 fs, in good agreement with results from the (p,γ) reaction but not with an earlier measurement using the (α,nγ) reaction. </jats:p
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
Archeologisch Bureauonderzoek en Inventariserend Veldonderzoek door middel van grondboringen 'Uitbreiding Albert Heijn, Filiaal 8543', Lindenburghlaan 1, Steenbergen, Gemeente Steenbergen
No full textIn het kader van de vergunningverlening ten behoeve van de uitbreiding van Filiaal 8543 van Albert Heijn, ter plaatse van de Lindenburghlaan 1 te Steenbergen (Gemeente Steenbergen) werd een Archeologisch Bureauonderzoek en een Inventariserend Veldonderzoek door middel van grondboringen uitgevoerd
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
First-line cART regimens started during follow-up, N = 8543.
No full text<p>Data are counts (proportions).</p><p><sup>a</sup> Mainly PI/r + II or PI/r + NNRTI or 2 PIs/r.</p><p><sup>b</sup> Mainly PI/r monotherapy or 1 II + 1 PI/r or 1 PI/r + 1 NNRTI.</p><p>Abbreviations: FRA, French natives; SSA, sub-Saharan Africa; NFW, non-French West Indies; OTH, Other regions of the world; MSM, Men who have sex with men; cART, combination antiretroviral therapy; NRTI, Nucleoside Reverse Transcriptase Inhibitor; PI/r, ritonavir-boosted protease inhibitor; NNRTI, Non-nucleoside Reverse Transcriptase Inhibitor; II, Integrase inhibitor; PI, Protease Inhibitor.</p><p>First-line cART regimens started during follow-up, N = 8543.</p
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