1,721,029 research outputs found
The Adenylate Cyclase Activator Forskolin Potentiates the Positive Inotropic Effect of the Phosphodiesterase Inhibitor Milrinone But Not of the Calcium Sensitizer Levosimendan nor of Its Hemodynamically Active Metabolites: An Apparent Conundrum
Full text linkOR-1855 and OR-1896 are 2 hemodynamically active metabolites of the inodilator levosimendan, with calcium sensitizing activity, but their mechanism of action is still not fully understood. It has been previously reported that the positive inotropic effect of levosimendan is not potentiated by the adenylate cyclase activator forskolin, whereas forskolin does potentiate the effects of the phosphodiesterase (PDE) inhibitor milrinone. To ascertain whether the active metabolites follow the same pattern of levosimendan, the positive inotropic effects of OR- 1855 and OR-1896 were studied in guinea-pig-isolated papillary muscle in the presence and absence of forskolin. OR-1855 and OR-1896 were also tested as inhibitors of PDE-III and PDE-IV. Our results show that 0.1 µM forskolin did not potentiate the positive inotropic effect of OR-1855 or OR-1896, as in the case of the parent compound levosimendan. As in previous studies, the positive inotropic effect of milrinone was markedly potentiated in the presence of forskolin. From these data, we propose an explanation for the divergent behavior of the calcium sensitizing drugs and PDE inhibitors
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
Drug discovery and development for acute heart failure drugs: Are expectations too high?
No full textDispelling 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
Use of Levosimendan in Patients with Advanced Heart Failure: An Update
No full textLevosimendan is an inodilator drug that, given its unique pharmacological actions and safety profile, represents a viable therapeutic option in patients with heart failure with reduced ejection fraction in the advanced stage of the disease (advHFrEF). Pulsed levosimendan infusion in patients with advHFrEF improves symptoms and clinical and hemodynamic status, prevents recurrent hospitalizations, and enables optimization of guidelines-directed medical therapy. Furthermore, considering its proprieties on right ventricular function and pulmonary circulation, levosimendan could be helpful for the prevention and treatment of the right ventricular dysfunction post-implanting a left ventricular assist device. However, to date, evidence on this issue is scarce and has yielded mixed results. Finally, preliminary experiences indicate that treatment with levosimendan at scheduled intervals may serve as a “bridge to transplant” strategy in patients with advHFrEF. In this review, we summarized the clinical pharmacology of levosimendan, the available evidence in the treatment of patients with advHFrEF, as well as a hypothesis for its use in patients with advanced heart failure with preserved ejection fraction
Intracellular calcium, preconditioning and regulation of cellular respiration in heart
Full text linkAbstractHeart muscle has to work constantly throughout the life and its energy metabolism is heavily dependent on a continuous supply of oxygen. Energy metabolism must be effectively regulated to meet the demands of changing workloads in different circumstances. If the oxygen supply is interrupted, the function of the heart is easily disturbed and cells injured. Calcium metabolism is of great importance in these pathological conditions.In this thesis respiratory regulation was studied by non-destructive optical methods in mouse heart. The myoglobin-deficient mouse was used as an experimental model to avoid the artefact caused by intracellular myoglobin. Results show that increased consumption of energy and oxygen lead to concomitant reduction of cytochrome aa3 and oxidation of flavoproteins. This finding supports the view that cell respiration in intact myocardium is dominantly regulated at the level of the respiratory chain.The intracellular Ca2+ accumulation during ischemia is one of the major causes of irreversible ischemia-reperfusion injury. Ischemic preconditioning (IPC) has been shown to protect the heart muscle significantly from ischemic damage. In this thesis Ca2+ accumulation during ischemia and reperfusion was studied in perfused rat heart using Fura-2 as a fluorescent Ca2+ indicator. As there is a significant decrease in intracellular pH during prolonged ischemia, the pH-dependency of Fura-2 signal was taken into account. It was found that IPC attenuates Ca2+accumulation during ischemia and this was connected to a decrease in mitochondrial membrane potential. Both IPC and the pharmacologically induced preconditioning with the mitoKATP opener diaxozide were shown to be associated with increased production of superoxide monitored by means of lucigenin chemiluminescence. The superoxide production correlated with the oxidation-reduction state of flavoproteins. We also describe here a method for measuring of intracellular free Ca2+ in mouse heart during ischemia by simultaneous monitoring of Fura-2 and the pH probe BCECF fluorescence by means of dual wavelength excitation of both probes. The paradoxical decrease of Fura-2 fluorescence during ischemia indicating decreasing intracellular Ca2+ concentration was due to the pH effect on the dissociation constant of the Fura-2-Ca2+ complex. When the pH-dependency of Fura-2 was compensated, an extensive Ca2+ accumulation during ischemia was detected. Much of the previous literature on this subject must be re-evaluated because the pH-dependency of intracellular Ca2+ probes has been largely overlooked.Academic dissertation to be presented with the assent of the Faculty of Medicine of the University of Oulu for public defence in Auditorium F101 of the Department of Physiology (Aapistie 7), on 15 January 2010, at 12 noonAbstract
Heart muscle has to work constantly throughout the life and its energy metabolism is heavily dependent on a continuous supply of oxygen. Energy metabolism must be effectively regulated to meet the demands of changing workloads in different circumstances. If the oxygen supply is interrupted, the function of the heart is easily disturbed and cells injured. Calcium metabolism is of great importance in these pathological conditions.
In this thesis respiratory regulation was studied by non-destructive optical methods in mouse heart. The myoglobin-deficient mouse was used as an experimental model to avoid the artefact caused by intracellular myoglobin. Results show that increased consumption of energy and oxygen lead to concomitant reduction of cytochrome aa3 and oxidation of flavoproteins. This finding supports the view that cell respiration in intact myocardium is dominantly regulated at the level of the respiratory chain.
The intracellular Ca2+ accumulation during ischemia is one of the major causes of irreversible ischemia-reperfusion injury. Ischemic preconditioning (IPC) has been shown to protect the heart muscle significantly from ischemic damage. In this thesis Ca2+ accumulation during ischemia and reperfusion was studied in perfused rat heart using Fura-2 as a fluorescent Ca2+ indicator. As there is a significant decrease in intracellular pH during prolonged ischemia, the pH-dependency of Fura-2 signal was taken into account. It was found that IPC attenuates Ca2+accumulation during ischemia and this was connected to a decrease in mitochondrial membrane potential. Both IPC and the pharmacologically induced preconditioning with the mitoKATP opener diaxozide were shown to be associated with increased production of superoxide monitored by means of lucigenin chemiluminescence. The superoxide production correlated with the oxidation-reduction state of flavoproteins.
We also describe here a method for measuring of intracellular free Ca2+ in mouse heart during ischemia by simultaneous monitoring of Fura-2 and the pH probe BCECF fluorescence by means of dual wavelength excitation of both probes. The paradoxical decrease of Fura-2 fluorescence during ischemia indicating decreasing intracellular Ca2+ concentration was due to the pH effect on the dissociation constant of the Fura-2-Ca2+ complex. When the pH-dependency of Fura-2 was compensated, an extensive Ca2+ accumulation during ischemia was detected. Much of the previous literature on this subject must be re-evaluated because the pH-dependency of intracellular Ca2+ probes has been largely overlooked
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