1,720,973 research outputs found
New biological aspects of Chromogranin A-derived peptides: Focus on vasostatins
No full textChromogranin A (CgA), one component of the granin family, represents the major soluble protein co-stored and co-released with catecholamines, within chromaffin cells secretory granules. It is considered a diagnostic and prognostic marker of several diseases, including a variety of tumours and cardiac heart failure. It also represents a precursor of biologically active fragments, generated after proteolytic cleavage at the level of the multiple pairs of dibasic sites which enrich its sequence
Recombinant N-terminal fragments of chromogranin-A modulate cardiac function of the Langendorff-perfused rat heart
No full textIn this study we tested the hypothesis that vasostatins could act as myocardial modulators in the mammalian heart. Using the Langendorff-perfused rat heart, the cardiac effects of the two recombinant human CGA N-terminal fragments STA-CGA1-78 and STA-CGA1-115, containing the vasostatin-1 (CGA 1-76) and vasostatin-2 (CGA 1-113) sequences, respectively, were evaluated at concentrations of 11 divided by 165 nM. Cardiac performance was evaluated by analyzing left ventricular pressure (LVP) and the rate pressure product (RPP: HR x LVP), used as indexes of contractile activity and cardiac work, respectively. Under basal conditions, STA-CGA1-78 at all concentrations tested elicited a dose-dependent negative inotropism (LVP variations ranging from -9.6% +/- 2 to -23% +/- 2.9) without affecting coronary pressure (CP). In contrast, STA-CGA1-115 increased CP at 110 and 165 nM without affecting inotropism. Both STA-CGA1-78 and STA-CGA1-115 counteracted the cardio-stimulatory effects of isoproterenol (ISO). The ISO-dependent positive chronotropism was unaffected by STA-CGA1-78, while being reduced by STA-CGA1-115. Both peptides abolished the ISO-induced positive inotropism without modifying either the beta-adrenergic-dependent coronary dilation or the ouabain-induced positive inotropism. The analysis of the percentage of variations of RPP in terms of EC50 values of ISO alone (-8.5 +/- 0.3; r(2) = 0.88) and in presence of STA-CGA1-78 (11, or 33, or 65 nM: -7.7 +/- 0.15, r(2) = 0.97; -7.7 +/- 0.15, r(2) = 0.97; -7.8 +/- 0.78, r(2) = 0.55, respectively) revealed a non-competitive type of antagonism of STA-CGA1-78. Taken together, these data suggest vasostatins as novel cardioregulatory peptides in mammals
AngII-dependent morpho-functional remodelling of the zebrafish heart.
No full textProgramme and Abstracts of the 68th National Congress of the Italian Physiological Society
(Società Italiana di Fisiologia
A physiological approach to assess the impact of endocrine disruptors, from invertebrate to human models
No full textEndocrine Disruptors (EDs) are exogenous chemicals that interfere with the endocrine system and may cause adverse health effects. The difficulties encountered so far to identify EDs and define the risks to humans and wildlife strongly suggest that investigations must be performed with a new focus, based on main features of endocrine physiology: i) effects of hormones (Hs) are exerted at very low concentration through specific receptors and coupled pathways; ii) some Hs may act through more than one receptor; iii) Hs may act through different/multiple mechanisms in different physiological systems; iv) Hs produce different effects during animal life cycle. Same properties are shared by EDs and us such have to be investigated. Our laboratories demonstrated that natural and environmental estrogens affect embryo development in mussels and zebrafish, and impair cardiac activity leading to expression of cellular stress markers in seabass. BPA in particular is known to impair many steps of amphibians metamorphosis. We showed that it induces lipid accumulation in rat liver, and mimics the effect of E2 reducing ER intracellular levels and activating ER - dependent gene transcription in human cell lines; it also induces breast and trophoblast cell proliferation. Although the involvement of intracellular receptors was expected, the different models showed that membrane receptors, including Gprotein coupled receptors, are also targets, and MAPK, PI3K, calcium and cAMP – dependent pathways are involved. Data highlighted action mechanisms of EDs, suggested the taxonomic conservation of some routes, and provided the basis to establish key-events shared by Hs and EDs. Further work addressing comparative aspects from invertebrates to humans is needed to develop full understanding
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
Distinct signalling mechanisms are involved in the dissimilar myocardial and coronary effects elicited by quercetin and myricetin, two red wine flavonols
No full textAbstract Background and Aims: Moderate red wine consumption associates with lower incidence
of cardiovascular diseases. Attention to the source of this cardioprotection was focused
on flavonoids, the non-alcoholic component of the red wine, whose intake inversely correlates
with adverse cardiovascular events.
We analysed whether two red wine flavonoids, quercetin and myricetin, affect mammalian
basal myocardial and coronary function.
Methods and results: Quercetin and myricetin effects were evaluated on isolated and Langendorff
perfused rat hearts under both basal conditions and a- and b-adrenergic stimulation. The
intracellular signalling involved in the effects of these flavonoids was analysed on perfused
hearts and by western blotting on cardiac and HUVEC extracts. Quercetin induced biphasic
inotropic and lusitropic effects, positive at lower concentrations and negative at higher
concentrations. Contrarily, Myricetin elicits coronary dilation, without affecting contractility
and relaxation. Simultaneous administration of the two flavonoids only induced vasodilation.
Quercetin-elicited positive inotropism and lusitropism depend on b1/b2-adrenergic receptors
and associate with increased intracellular cAMP, while the negative inotropism and lusitropism
observed at higher concentrations were a-adrenergic-dependent. NOS inhibition abolished
Myricetin-elicited vasodilation, also inducing Akt, ERK1/2 and eNOS phosphorylation in both
ventricles and HUVEC. Myricetin-dependent vasodilation increases intracellular cGMP and is
abolished by triton X-100.Abstract
BACKGROUND AND AIMS: Moderate red wine consumption associates with lower incidence of cardiovascular diseases. Attention to the source of this cardioprotection was focused on flavonoids, the non-alcoholic component of the red wine, whose intake inversely correlates with adverse cardiovascular events. We analysed whether two red wine flavonoids, quercetin and myricetin, affect mammalian basal myocardial and coronary function.
METHODS AND RESULTS: Quercetin and myricetin effects were evaluated on isolated and Langendorff perfused rat hearts under both basal conditions and alpha- and beta-adrenergic stimulation. The intracellular signalling involved in the effects of these flavonoids was analysed on perfused hearts and by western blotting on cardiac and HUVEC extracts. Quercetin induced biphasic inotropic and lusitropic effects, positive at lower concentrations and negative at higher concentrations. Contrarily, Myricetin elicits coronary dilation, without affecting contractility and relaxation. Simultaneous administration of the two flavonoids only induced vasodilation. Quercetin-elicited positive inotropism and lusitropism depend on beta1/beta2-adrenergic receptors and associate with increased intracellular cAMP, while the negative inotropism and lusitropism observed at higher concentrations were alpha-adrenergic-dependent. NOS inhibition abolished Myricetin-elicited vasodilation, also inducing Akt, ERK1/2 and eNOS phosphorylation in both ventricles and HUVEC. Myricetin-dependent vasodilation increases intracellular cGMP and is abolished by triton X-100.
CONCLUSIONS: The cardiomodulation elicited on basal mechanical performance by quercetin and the selective vasodilation induced by myricetin point to these flavonoids as potent cardioactive principles, able to protect the heart in the presence of cardiovascular diseases
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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