1,721,850 research outputs found
The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys
No full textThe adenosine A2A receptor agonist CGS 21680 has shown effects similar to dopamine antagonists in behavioural assays in rats predictive for antipsychotic activity, without induction of extrapyramidal side-effects (EPS). In the present study, we examined whether this functional dopamine antagonism and lack of EPS in rodents could also be observed in non-human primates. We investigated the effects of CGS 21680 on behaviours induced by D-amphetamine and (-)-apomorphine in EPS-sensitized Cebus apella monkeys. CGS 21680 was administered s.c. in doses of 0.01, 0.025 and 0.05 mg/kg, alone and in combination with D-amphetamine and (-)-apomorphine. The monkeys were videotaped after drug administration and the tapes were rated for EPS and psychosis-like symptoms. CGS 21680 decreased apomorphine-induced behavioural unrest, arousal (0.01-0.05 mg/kg) and stereotypies (0.05 mg/kg) while amphetamine-induced behaviours (unrest, stereotypies, arousal) were unaffected. EPS were not observed at any dose. At 0.05 mg/kg CGS 21680 produced vomiting. The two lower doses did not produce observable side-effects. Though the differential effect on amphetamine- and apomorphine-induced behaviours is intriguing, CGS 21680 showed a functional anti-dopaminergic effect in Cebus apella monkeys without production of EPS. This further substantiates that adenosine A2A receptor agonists may have potential as antipsychotics with atypical profiles
Beneficial effects of adenosine A<sub>2a</sub>agonist CGS-21680 in infarcted and stunned porcine myocardium
No full textAlthough there are conflicting results on whether adenosine infusion during reperfusion alters infarct size, there are several reports that indicate adenosine A2aagonists reduce infarct size. There are also reports that the A2aagonist CGS-21680 increases cAMP and contractility in ventricular myocytes. The purpose of this study was to determine whether low-dose intracoronary infusions of CGS-21680 during reperfusion exert any beneficial effects in irreversibly and reversibly injured myocardium. Open-chest pigs were submitted to 60 min of coronary artery occlusion and 3 h of reperfusion. Treated pigs were administered intracoronary CGS-21680 (0.2 μg · kg−1· min−1) for the first 60 min of reperfusion. Pigs submitted to regional stunning (15 min ischemia) were treated with intracoronary CGS-21680 (0.15 μg · kg−1· min−1) after 2 h of reperfusion. In the infarct protocol, CGS-21680 reduced infarct size from 62 ± 2% of the region at risk to 36 ± 2%. In stunned myocardium, CGS increased load-independent regional preload recruitable stroke work and area by ≥70%, but the same infusion in normal myocardium was associated with no inotropic effect. Both beneficial effects were associated with little systemic hemodynamic effects. These findings suggest that reperfusion infusions of low doses of the A2aagonist CGS-21680 exert beneficial effects in reversibly and irreversibly injured myocardium.</jats:p
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
Binding characteristics of the adenosine A2 receptor ligand [3H]CGS 21680 to human platelet membranes
No full textThe binding characteristics of the selective adenosine A2 agonist [3H]CGS 21680 ([3H]2-[p-(2-carboxyethyl)-phenethyl-amino]-5'-N- ethylcarboxamidoadenosine) were determined in human platelet membranes. Specific binding was saturable, reversible and dependent upon protein concentration. Saturation experiments revealed a single class of binding sites with Kd and Bmax values of 1.4 microM and 5.9 pmol/mg of protein, respectively. Adenosine receptor agonists and antagonists competed for the binding of [3H]CGS 21680 (50 or 200 nM) to human platelet membranes showing a rank order of potency consistent with that typically found for interactions at the adenosine A2 receptor. Adenylate cyclase stimulation and platelet aggregation inhibition induced by adenosine agonists exhibited a rank order of potency close to that observed in binding experiments. However, the adenosine A1 receptor agonists, R- and S-N6-(2-phenylisopropyl)adenosine, (R-PIA) and (S-PIA), N6-cyclohexyladenosine (CHA) and 2-chloro-N6-cyclopentyladenosine (CCPA), which stimulate adenylate cyclase and inhibit platelet aggregation in the low microM range, displaced [3H]CGS 21680 only in the high microM range. In conclusion, we have found that [3H]CGS 21680, which is widely used as a specific A2 agonist in binding studies on brain tissues, is not appropriate for the characterization of the human platelet adenosine A2 receptor
Adenosine A(2A) receptor agonist (CGS-21680) prevents endotoxin-induced effects on nucleotidase activities in mouse lymphocytes
No full textAdenosine 5'-triphosphate (ATP) released during inflammation presents proinflammatory properties. Adenosine, produced by catabolism of ATP, is an anti-inflammatory compound. Considering the role of ATP and adenosine in inflammation and the importance of ectonucleotidases in the maintenance of their extracellular levels, we investigated the effect of a selective agonist of the adenosine A(2A) receptor (CGS-21680) on ectonucleotidase activities and gene expression patterns in lymphocytes from mice submitted to an endotoxemia model. Animals were injected intraperitoneally with 12 mg/kg Lipopolyssacharide (LPS) and/or 0.5 mg/kg CGS-21680 or saline. Nucleotidase activities were determined in lymphocytes from mesenteric lymph nodes and analysis of ectonucleotidase expression was carried out by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Exposure to endotoxemia promoted an increase in nucleotide hydrolysis. When CGS-21680 was administered concomitantly with LPS, this increase was prevented for ATP, adenosine 5'-monophosphate (AMP), and p-Nitrophenyl thymidine 5'-monophosphate (p-Nph-5'-TMP) hydrolysis. However, when CGS-21680 was administered 24 h after LPS injection, the increase was not reversed. the expression pattern of ectonucleotidases was not altered between LPS and LPS plus CGS-21680 groups, indicating that the transcriptional control was not involved on the effect exerted for CGS-21680. These results showed an enhancement of extracellular nucleotide catabolism in lymphocytes after induction of endotoxemia, which was prevented, but not reversed by CGS-21680 administration. These findings suggest that the control of nucleotide and nucleoside levels exerted by CGS-21680 could contribute to the modulation of the inflammatory process promoted by adenosine A(2A) agonists. (C) 2010 Elsevier B.V. All rights reserved.Pontificia Univ Catolica Rio Grande do Sul, Programa Posgrad Biol Celular & Mol, Dept Biol Celular & Mol, Lab Neuroquim & Psicofarmacol,Fac Biociencias, BR-90619900 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, Programa Posgrad Ciencias Biol Bioquim, BR-90035003 Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, Programa Posgrad Farmacol, BR-04044020 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Farmacol, Programa Posgrad Farmacol, BR-04044020 São Paulo, BrazilWeb of ScienceCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul (FAPERGS
CGS 21680, an Agonist of the Adenosine (A2A) Receptor, Reduces Progression of Murine Type II Collagen-induced Arthritis
No full textObjective.The aim of our study was to investigate the effect of an adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenylethylamino]-50 ethylcarboxamidoadenosine (CGS 21680), on modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).Methods.CIA was induced by intradermal injection of 100 μl of emulsion containing 100 μg of bovine type II collagen (CII) and complete Freund’s adjuvant (CFA) at the base of the tail. On Day 21, a second injection of CII in CFA was administered. Immunized mice developed erosive hind paw arthritis. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by Day 27 in the CII challenged mice and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of cartilage at the joint margins.Results.Treatment of mice with CGS 21680 starting at the onset of arthritis (Day 25) ameliorated the clinical signs at Days 26–35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in CGS 21680-treated mice as indicated by elevated levels of malondialdehyde, formation of nitrotyrosine, and activation of poly(ADP-ribose) polymerase. Plasma levels of proinflammatory cytokines such as tumor necrosis factor, interleukin 1ß (IL-1ß) and IL-6 were also reduced by CGS 21680. Treatment with CGS 21680 also decreased the expression of inducible nitric oxide synthase and cyclooxygenase-2.Conclusion.We demonstrate that CGS 21680 exerts an antiinflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA.</jats:sec
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
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