1,721,047 research outputs found
Thiols enhance NO formation from nitrate photolysis
No full textNitrate is generally considered an inert oxidative breakdown product of nitric oxide (NO). Whereas it has been shown that limited amounts of NO are produced during the photolysis of nitrate in aqueous solution, the photochemistry of nitrate in biological matrices such as plasma is unknown. We hypothesized that thiols, which are ubiquitously present in biological systems, may significantly enhance NO-quantum yields from nitrate photolysis. Exposure of fresh human plasma to high-intensity UV-light resulted in NO-formation (19 +/- 3 nmol/l/min) as measured by gas phase chemiluminescence, and this signal was almost completely abolished by the removal of plasma N-oxides (2 +/- 1 nmol/l/min). Reconstitution of NOx-depleted plasma samples with a physiological concentration of nitrate, but not nitrite, restored photolytic NO-generation to values comparable to naïve plasma. Addition of the thiol-reducing agent, dithiothreitol or the sulfhydryl-bearing amino acid, L-cysteine increased NO-formation above control levels. Thiol-blockade by either N-ethylmaleimide (NEM) or mercuric chloride (HgCl2) reduced basal NO formation from 19 +/- 3 to 7 +/- 2 and 4 +/- 1 nmol/l/min, respectively. Exposure of plasma to UV-light increased NO-adduct concentrations from 18 +/- 5 to 1662 +/- 658 nmol/l. Collectively, our results show that thiols facilitate photolytic conversion of nitrate to NO and NO-adducts such as S-nitrosothiols. This may lead to substantial overestimation of the latter when photolysis-based methodologies are used for their determination. Whether this novel reaction channel also has in vivo relevance remains to be investigated
Direct biochemical evidence for eNOS stimulation by bradykinin in the human forearm vasculature
No full textObjective: Although it has been shown recently that acetylcholine (ACh)-induced vasodilation of forearm resistance vessels is predominantly mediated by nitric oxide, direct biochemical evidence for eNOS stimulation by bradykinin (BK) in the human arterial circulation is still lacking. Therefore, the present study was designed to test the hypothesis that in the human forearm vasculature eNOS stimulation significantly contributes to BK-induced vasodilation. Methods: BK was infused in the presence and absence of the NOS inhibitor L-NMMA (8 ?mol/min) into the brachial artery of 16 healthy volunteers and the effects compared to muscarinergic eNOS stimulation following acetylcholine infusion. Forearm blood flow (FBF) was measured by venous occlusion plethysmography, and plasma nitrite (NO2 ?), which represents a sensitive and specific marker of regional eNOS activity, was determined in the antecubital vein and brachial artery by flow injection analysis. Nitric oxide production was calculated as product of the veno-arterial difference of NO2 ? concentration times FBF.Results: Kininergic (BK: 20, 60, 200 ng/min) as well as muscarinergic (ACh: 1, 3, 10 ?g/min) stimulation resulted in a dose-dependent increase in FBF and NO2 ? in each individual. The relationship between FBF and NO production upon BK infusion was comparable to that obtained with ACh (r = 0.98; n = 64, p < 0.01). Moreover, NOS inhibition reduced both flow responses and NO production (BK: 54 and 75 %; ACh: 57 and 72 %) to a similar extent. Conclusions: These data provide direct biochemical evidence for the involvement of eNOS in bradykinin-induced vasodilation of forearm resistance vessels in humans
Plasma nitroso compounds are decreased in patients with endothelial dysfunction
No full textEndothelial dysfunction in patients with cardiovascular risk factors is associated with decreased levels of circulating RXNOs. Plasma RXNOs may be diagnostically useful markers of NO bioavailability and a surrogate index of endothelial function. Whether the observed decrease in concentration reflects impaired NO formation, accelerated decomposition, and/or consumption of RXNOs and whether these processes play a causal role in the pathophysiology of arteriosclerosis remain to be investigated
Funktionelle Auswirkungen von humanem koronarem Aspirat-Plasma: Untersuchungen im Rattenherz-Bioassay
Full text linkDie Implantation eines Stents in das Lumen eines atherosklerotisch stenosierten oder eines atherosklerotisch degenerierten aortokoronaren Venenbypasses verursacht eine Ruptur der atherosklerotischen Plaque. Hierbei werden neben partikulären Bestandteilen auch lösliche Mediatoren freigesetzt, die mit dem Blutstrom in die koronare Zirkulation embolisiert werden. Hier wurden die funktionellen Auswirkungen der löslichen Faktoren auf die koronare Perfusion und myokardiale Kontraktilität im Rattenherz Bio-Assay untersucht
Is There a Mitochondrial Protection via Remote Ischemic Conditioning in Settings of Anticancer Therapy Cardiotoxicity?
No full textPurpose of Review: To provide an overview of (a) protective effects on mitochondria induced by remote ischemic conditioning (RIC) and (b) mitochondrial damage caused by anticancer therapy. We then discuss the available results of studies on mitochondrial protection via RIC in anticancer therapy-induced cardiotoxicity. Recent Findings: In three experimental studies in healthy mice and pigs, there was a RIC-mediated protection against anthracycline-induced cardiotoxicity and there was some evidence of improved mitochondrial function with RIC. The RIC-mediated protection was not confirmed in the two available studies in cancer patients. In adult cancer patients, RIC was associated with an adverse outcome. There are no data on mitochondrial function in cancer patients. Summary: Studies in tumor-bearing animals are needed to determine whether RIC does not interfere with the anticancer properties of the drugs and whether RIC actually improves mitochondrial function, ultimately resulting in improved cardiac function. © The Author(s) 2024
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
Vascular (dys)function in the failing heart
No full textHeart failure (HF) is not confined to contractile failure of cardiomyocytes or myocardial fibrosis. Coronary and systemic vascular dysfunction contributes to the initiation and progression of HF with or without reduced ejection fraction. Furthermore, HF compromises vascular function, creating and sustaining a vicious cycle with deranging effects on coronary blood flow, cardiac metabolism and cardiac function. In HF, systemic arterial dysfunction, characterized by increased arterial stiffness and resistance, raises cardiac afterload and impedes myocardial contractile function. Reduced coronary blood flow impairs myocardial oxygen delivery and consequently cardiomyocyte metabolism and function. Coronary microvascular dysfunction is heterogeneous in its pathogenesis and manifestations, complicating the diagnosis and management across different HF phenotypes. Understanding the alterations in function in different segments of the vasculature, from the aorta to the capillary level, offers mechanistic insights into disease drivers and therapeutic interventions. Interventional approaches can improve vascular haemodynamics, whereas established and emerging pharmacotherapies target the neurohumoral axis and reduce extravascular compression, inflammation, and oxidative stress, thereby improving vascular function and HF-related outcomes. In this Review, we provide a mechanistic framework of vascular dysfunction in the pathogenesis of HF with or without reduced ejection fraction, pointing towards integrated therapies that consider the vascular implications of contemporary HF management across HF phenotypes
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
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