1,720,976 research outputs found
Exploring prospects of β3-adrenoceptor agonists and inverse agonists for colon motility control
No full textInverse agonists are useful active ingredient of drugs clinically used to treat diseases mainly involving receptors endowed with nonendogenous
agonist induced activity (constitutive
or basal activity). SP-1e and SP-1g are the first two potent and highly selective β3-adrenoceptor
inverse agonists [EC50=181 nM (IA=-
64%) and 136 nM (IA=-73%), respectively], which their peculiar activity seems due to the absolute configurations of the two stereogenic
centres present in each molecule. Rat proximal colon motility measurements allowed their further pharmacological characterization and pA2 values determination by Schild analysis (7.89
and 8.16, respectively). The purpose of our work is a further characterization of our novel β3-adrenoceptor agonists (SP-1a-d, SP-1f,1h) and inverse agonists (SP-1e and SP1g) on rat
proximal colon motility and a confirmation of their inverse agonist nature in a more complex
system like the functional test on rat proximal colon. Male Wistar rats segment of the proximal colon were placed in organ baths containing
Krebs solution. Muscle tension was recorded isotonically. Cumulative β3-AR agonists doses experiments were performed for each test compound: isoprenaline, BRL37344, SP-1a-d, SP-1f and SP-1h were dissolved in Krebs. The EC50 values of each agonists and
pA2 of inverse agonists were determined. SP-1a-d, SP-1f and SP-1h in rat colon have a muscle
relaxing effect thus confirming their partial agonist activity found in CHO-K1 cell line. SP-1e and SP-1g behaved as antagonists with pA2 values of 7.89 and 8.16, espectively. In conclusion, experiments carried out by using
isolated rat proximal colon allowed us to determine the pA2 values of the two β3-AR inverse agonists and add knowledge on the behavior of a novel set of compounds and their possible value as agents useful whenever is necessary to also control the colon motility
Effects of mechanical ventilation on radiographic images of patients with acute respiratory failure: a computer analysis
No full text
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
β 3 -Adrenoceptor agonists and (Antagonists as) inverse agonists. History, perspective, constitutive activity, and stereospecific binding
No full textβ 3 -Adrenergic receptor (β 3 -AR) is expressed in several tissues and is considered a drug target for the treatment of several pathologies such as obesity, type 2 diabetes, cachexia, metabolic syndrome, heart failure, anxiety and depressive disorders, preterm labor, overactive bladder, control colon motility, and of coadjuvants in colon cancer therapy. It is a seven-transmembrane domain (7TD) G-protein coupled receptor and is usually coupled to a Gs-protein (Gi-protein in very few cases), and its stimulation increases the production of cAMP. A lot of β 3 -AR agonists have been uncovered and extensively characterized. Conversely, very little is known about β 3 -AR inverse agonists that would suppress the agonist-independent activity (constitutive activity) of the receptor by stabilizing it in its inactive state. This chapter attempts to outline (a) the importance of the β 3 -AR as a therapeutic target through the disquisition of its role in human health (physiology) and disease (pathology); (b) the description of β 3 -AR structure [amino acid sequence and 7TD organization]; (c) the medicinal chemistry of β 3 -AR: 7TD amino acid-ligand specific interactions, β-adrenoreceptor subtype selectivity, stereospecific interactions and biological activity relationships, inverse agonism and blockage of β 3 -adrenoceptor constitutive activity; and (d) β 3 -AR inverse agonists. The detailed procedure to prepare and assess the biological activity/selectivity of the more potent and selective β 3 -AR inverse agonists (SP-1e and SP-1g) up to now known is also described. © 2010 Elsevier Inc
Baker's yeast-mediated reduction of ethyl 2-(4-chlorophenoxy)-3-oxoalkanoates intermediates for potential PPAR alpha ligands
No full textSeveral 2-(4-chlorophenoxy)-3-oxoesters were prepared in fair to good yields and then reduced in the presence of baker's yeast to the corresponding alcohols having de's up to 92% and ee's > 99%. The absolute configuration of nearly enantiomerically pure ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate was assigned by both comparison of the sign of the specific rotation and HPLC retention times of authentic samples prepared from threonines. Reduction of ethyl 2-(4-chlorophenoxy)-3-oxo-4-phenylbutanoate afforded only enantiomerically pure ethyl (2R,3S)-2-(4-chlorophenoxy)-3-hydroxy-4-phenylbutanoate (out of the four possible stereoisomers), whose absolute configuration was established by single crystal X-ray analysis. Furthermore, reduction of ethyl 2-methyl-2-(4-chlorophenoxy)-3-hydroxybutanoate with a quaternary stereogenic carbon (C-2) gave both of the two expected diastereoisomers with ee = 95% and 96%. Insight into the mechanism of baker's yeast-mediated reduction of prochiral ketoesters is also reported
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
Reaction of caesium 4-chlorophenate and chlorohydrins from threonines: synthesis of clotibrate analogues
No full textClofibrate is a well-known peroxisome prolifierator-activated receptor-alpha (PPARalpha) agonist, used in the treatment of hyperlipaemias and atherosclerosis and to prevent heart failure. Herein, the preparation of the four enantiomerically pure stereoisomers of ethyl 2-(4-chlorophenoxy)-3-hydroxybutanoate as clofibrate analogues is described. Biological evaluation of these new compounds was performed by a transactivation assay in a transiently transfected monkey kidney fibroblast cell line. All four diastereomers were inactive even at 300 muM, where clofibrate showed an evident activity, suggesting that the designed clofibrate molecular structural modifications in the analogues caused the loss of peroxisome proliferator-activated receptor-alpha (PPARalpha) activity
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