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Effect of the ATP-sensitive potassium channel opener ZM226600 on cystometric parameters in rats with ligature-intact, partial urethral obstruction
No full textThe activity of a recent KATP channel opener, the N-(4-Phenylsulfonylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide (ZM226600) was investigated on a female rat model of overactive bladder with outlet obstruction. Both ZM226600 and pinacidil instilled into the bladder (10-7 M, 30 min) or following systemic administration (10, 100 nmol/kg e.v.) almost completely abolished bladder overactivity and improved residual volume and frequency of micturition. However, pinacidil affected arterial pressure. Oxybutynin instilled into the bladder (10 -7, 10-6, 10-5 M, 30 min) decreased detrusor overactivity by about 16%, 25% and 46% respectively, but also blocked micturition reflexes at highest doses tested. Oxybutynin reduced detrusor overactivity by about 50% and 80%, after systemic administration (10, 100 nmol/kg e.v.), but also blocked micturition reflexes at the highest dose tested. In conclusion, ZM226600 is more active than oxybutynin in reducing bladder overactivity, and it is devoid of vascular side effects observed with pinacidil. Its short duration of action (about 1 h) is probably the main problem to solve, in order to consider this compound a valid alternative to antimuscarinics in the therapy of bladder overactivity. (copyright) 2005 Elsevier B.V. All rights reserved
Safety considerations for statins
No full textThe hydroxymethyl glutaryl coenzyme A reductase inhibitors or statins offer important benefits for the large populations of individuals at high risk for coronary heart disease. These drugs have a good safety profile. Nevertheless, differences in physicochemical and pharmacokinetic properties between statins may translate into significant differences in long-term safety. This review focuses on long-term adverse effects related to statin use, namely hepatotoxicity and myopathy. Moreover, the most common drugs used in combination with statins in long-term therapies are analyzed in terms of possible drug/drug interactions affecting the safety of statins
PHARMACOLOGICAL CHARACTERIZATION OF P2X AND P2Y PURINOCEPTORS IN RAT BLADDER SMOOTH-MUSCLE AND EPITHELIUM
No full textSelective agonists of estrogen receptor isoforms : new perspectives for cardiovascular disease
Full text linkThe cloning of estrogen receptors (ERs) and generation of ER-deficient mice have increased our understanding of the molecular mechanisms underlying the cardiovascular effects of estrogen. It is conceivable that clinical trials of estrogens so far failed to improve cardiovascular health because of the poor ER isoform selectivity and tissue specificity of endogenous hormones as well as incorrect treatment timing and regimens. Tissue-selective ER modulators (SERMs) may be safer agents than endogenous estrogens for cardiovascular disease. Yet, designing isoform-selective ER ligands (I-SERMs) with agonist or antagonist activity is required to pursue improved pharmacological control of ERs, especially taking into account emerging evidence for the beneficial role of vascular ER alpha activation. Ideally, the quest for unique ER ligands targeted to the vascular wall should lead to compounds that merge the pharmacological profiles of SERM and I-SERM agents. This review highlights the current bases for and approaches to selective ER modulation in the cardiovascular system
Prolonged ovarian hormone deprivation impairs the protective vascular actions of estrogen receptor alpha Agonists
No full textThe vascular consequences of estrogen treatment may be driven by its initiation timing. We tested the hypothesis that the duration of ovarian hormone deprivation before estrogen reintroduction affects the role of estrogen as mediator of endothelial function and vascular relaxation in nondiseased vessels. Rats were ovariectomized and implanted with 17β-estradiol (E2) or oil capsules 1, 4, and 8 months after surgery. After the longest hypoestrogenicity period, acetylcholine-mediated aortic relaxation was attenuated and insensitive to E2 administration despite endothelial integrity. Whereas no rapid vasorelaxant responses were elicited by an estrogen receptor (ER) β-selective agonist, responses to E2 and an ERα selective agonist waned postovariectomy at any given time and were restored by E2 treatment after 1 and 4 months but not 8 months postovariectomy. Accordingly, endothelial ERα mRNA and protein expression declined ≈6-fold after prolonged hypoestrogenicity and was restored by estrogen replacement starting 1 month but not 8 months postovariectomy. Furthermore, the amount of active phosphorylated endothelial NO synthase rose significantly after E2 replacement after 1 and 4 months but not 8 months postovariectomy. The present findings document that the functional impairment of the ERα/endothelial NO synthase signaling network after an extended period of hypoestrogenicity was not restored by E2 administration, providing experimental support to early initiation of estrogen replacement with preferential ERα targeting to improve cardiovascular outcomes
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
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