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Characterization of ORG 20241, a combined phosphodiesterase IV/III cyclic nucleotide phosphodiesterase inhibitor for asthma
No full textThe pharmacological profile of a novel cyclic nucleotide phosphodiesterase (PDE) inhibitor, Org 20241, has been characterized. The compound selectively inhibits PDE IV (plC(50), 5.2-6.1) and PDE III (plC(50), 4.4-4.6) from animal and human tissues. Org 20241 relaxed preparations of bovine trachea (pD(2), 5.9 and 5.4), guinea pig trachea (pD(2), 6.2 and 4.9) and human bronchi (pD(2), 5.3 and 4.7) for histamine and methacholine-induced contractions, respectively. Rolipram and Org 20241 inhibited leukotriene B-4-induced thromboxaneB(2) (IC50 0.3 and 1.4 mu M, respectively) and H2O2 (IC50, 2.1 and 0.4 mu M, respectively) production in guinea pig eosinophils. In phenylephrine (0.3 mu M) precontracted rabbit aorta preparations, the PDE III inhibitor Org 9935 (pD(2), 6.3 and 6.1 in the presence and absence of endothelium, respectively) was the most effective relaxant, whereas Org 20241 (pD,, 5.3 and 5.4 in the presence and absence of endothelium, respectively) was more effective than rolipram (pD(2), 4.6 and 4.1 in the presence and absence of endothelium, respectively). Org 20241 relaxed rabbit aorta preparations and airway preparations at similar concentrations. In electrically stimulated rabbit cardiac papillary muscles, Org 20241 had little effect on contractility at concentrations up to 30 mu M. Lower concentrations (10 mu M) potentiated the inotropic effect of Org 9935. Whereas the PDE III inhibitor milrinone (1-100 mu M) enhanced the rate of repolarization of guinea pig papillary muscles and shortened the effective refractory period; Org 20241 and rolipram (1-100 mu M) did not reduce the action potential duration. In the presence of Org 20241 or rolipram, isoproterenol did not produce a greater increase in the rate of repolarization or reduction in the effective refractory period than in the absence of these PDE inhibitors. Org 20241 is a dual PDE IV/III inhibitor with some PDE IV selectivity. This compound relaxes airways smooth muscle and inhibits eosinophil activation. The data indicate that such PDE IV/III inhibitors may be effective for the long-term therapy of asthma
Characterization of ORG 20241, a combined phosphodiesterase IV/III cyclic nucleotide phosphodiesterase inhibitor for asthma
No full textThe pharmacological profile of a novel cyclic nucleotide phosphodiesterase (PDE) inhibitor, Org 20241, has been characterized. The compound selectively inhibits PDE IV (plC(50), 5.2-6.1) and PDE III (plC(50), 4.4-4.6) from animal and human tissues. Org 20241 relaxed preparations of bovine trachea (pD(2), 5.9 and 5.4), guinea pig trachea (pD(2), 6.2 and 4.9) and human bronchi (pD(2), 5.3 and 4.7) for histamine and methacholine-induced contractions, respectively. Rolipram and Org 20241 inhibited leukotriene B-4-induced thromboxaneB(2) (IC50 0.3 and 1.4 mu M, respectively) and H2O2 (IC50, 2.1 and 0.4 mu M, respectively) production in guinea pig eosinophils. In phenylephrine (0.3 mu M) precontracted rabbit aorta preparations, the PDE III inhibitor Org 9935 (pD(2), 6.3 and 6.1 in the presence and absence of endothelium, respectively) was the most effective relaxant, whereas Org 20241 (pD,, 5.3 and 5.4 in the presence and absence of endothelium, respectively) was more effective than rolipram (pD(2), 4.6 and 4.1 in the presence and absence of endothelium, respectively). Org 20241 relaxed rabbit aorta preparations and airway preparations at similar concentrations. In electrically stimulated rabbit cardiac papillary muscles, Org 20241 had little effect on contractility at concentrations up to 30 mu M. Lower concentrations (10 mu M) potentiated the inotropic effect of Org 9935. Whereas the PDE III inhibitor milrinone (1-100 mu M) enhanced the rate of repolarization of guinea pig papillary muscles and shortened the effective refractory period; Org 20241 and rolipram (1-100 mu M) did not reduce the action potential duration. In the presence of Org 20241 or rolipram, isoproterenol did not produce a greater increase in the rate of repolarization or reduction in the effective refractory period than in the absence of these PDE inhibitors. Org 20241 is a dual PDE IV/III inhibitor with some PDE IV selectivity. This compound relaxes airways smooth muscle and inhibits eosinophil activation. The data indicate that such PDE IV/III inhibitors may be effective for the long-term therapy of asthma.</p
Predicting wave-induced ripple equilibrium geometry
Get PDFAuthor Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 118 (2013): 3202–3220, doi:10.1002/jgrc.20241.A comprehensive database of existing (since 1954) field and laboratory measurements of ripple geometry is compiled and combined with newly collected field data to examine the performance of ripple equilibrium predictors. Reanalysis of this enlarged ripple geometry data set reveals that ripples formed from monochromatic waves scale differently than ripples formed from random waves for many existing ripple predictors. Our analysis indicates that ripple wavelengths from the two data sets collapse into a single scaling when the semiorbital excursion and sediment grain diameter are used as normalizing factors. Ripple steepness remains relatively constant for both regular and irregular wave conditions, and it only slightly increases for shorter ripple wavelengths. These findings allowed for the development of a new equilibrium ripple predictor suitable for application in a wide range of wave and sediment conditions.Financial support for this work was provided
by the National Science Foundation (NSF awards OCE-0451989 and
OCE-0535893) and by the South Carolina Coastal Erosion Project, a cooperative
study supported by the U.S. Geological Survey and the South Carolina
Sea Grant Consortium (Sea Grant Project R/CP-11).2013-12-2
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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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