877 resultados para HDAC inhibition


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Snake venoms have been used as antineoplastic substances in several experimental models. We demonstrated in previous studies that Bothrops jararaca venom (BjV) induces inhibition of Ehrlich ascites tumor ( EAT) growth accompanied by an increase of mononuclear (MN) leukocytes in all groups inoculated with EAT and/or venom. The objective of the present study was to characterize the subpopulations of MN leukocytes involved in the inhibition of EAT growth by treatment with BjV. Swiss mice were inoculated with 1.0 x 10(3) EAT cells by the intraperitoneal route and treated with 0.4 mg/kg of BjV by the same route ( Group TV). Treatment was started 24 h after tumor cell inoculation and consisted of five intraperitoneal injections performed at 72 h intervals. After 2, 8 and 14 days, groups of animals were sacrificed and the number of B, TCD4 and TCD8 lymphocytes, macrophages and natural killer cells present in the peritoneal cavity was determined by flow cytometry. The control group consisted of animals inoculated with EAT and treated with 0.1 ml of saline under the same conditions as the experimental group ( Group T). Two additional control groups consisted of animals not inoculated with EAT and treated with saline or venom. Data were analyzed statistically by the Kruskal - Wallis nonparametric test for independent samples. on the 2nd and 8th day we observed a difference between groups T and TV ( group T > group TV) for all cell types, except natural killer cells, that only differed on the 2nd day. However, on the 14th day there was no difference in MN cells among groups. These data suggest that the inhibition of EAT is related to the toxic action of BjV on tumor cells and/or to the proteolytic effect of the venom on the mediators produced by the cells for growth modulation.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Levels of rabies virus neutralization antibody in sera from vaccinated dogs and cattle were either measured by mouse neutralization test (MNT) or by rapid fluorescent focus inhibition test (RFFIT), performed on CER monolayers. The two tests were compared for their ability to detect the 0.5 International Units/ml (I.U.) recommended by the World Health Organization (WHO) as the minimum response for proof of rabies immunization. A significant correlation was found between the two tests (n = 211; r = 0.9949 in dogs and 0.9307 in cows, p < 0.001), good sensitivity (87.5%), specificity (94.7%) and agreement (96.6%) as well. RFFIT method standardized on CER cell system for neutralizing antibodies detection turns the diagnosis easier and less expensive, specially when a great number of samples must be tested from endemic areas as commonly found in Brazil. (c) 2005 the International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

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Peripheral treatment with cholinergic or adrenergic agonists results in salivation and the possibility of synergy between cholinergic and adrenergic efferent mechanisms in the control of salivation has been proposed. Central injections of the cholinergic agonist pilocarpine also induce salivation, while the effects of central injections of noradrenaline (norepinephrine) are not known. Here (a) the effects of intracerebroventricular (icv) injection of noradrenaline on the salivation induced by icv or intraperitoneal (i.p.) injection of pilocarpine and (b) the receptors involved in the effects of central noradrenaline on pilocarpine-induced salivation were investigated. Male Holtzman rats with a stainless-steel guide cannula implanted into the lateral ventricle were used. Rats were anaesthetized with tribromoethanol (200 mg/kg body weight) and saliva was collected on small, preweighed cotton balls inserted into the animal's mouth. Noradrenaline (40, 80 and 160 nmol/l mul) injected icv reduced the salivary secretion induced by pilocarpine (0.5 mumol/l mul) injected icv. Noradrenaline (80 and 160 nmol/l mul) injected icv also reduced the salivation induced by pilocarpine (4 mumol/kg) injected i.p. Previous treatment with the alpha(2)-adrenergic receptor antagonists RX 821002 (40, 80 and 160 nmol/l mul) or yohimbine (160 and 320 nmol/l mul) abolished the inhibitory effect produced by icv injection of noradrenaline on pilocarpine-induced salivation in rats. Prazosin (alpha(1)-adrenergic receptor antagonist) injected icv did not change the effect of noradrenaline on pilocarpine-induced salivation. Prior icv injection of only RX 821002 (80 or 160 nmol/l mul) or yohimbine (320 nmol/l mul) increased pilocarpine-induced salivation. The results show that (1) contrary to its peripheral effects, noradrenaline acting centrally inhibits cholinergic-induced salivation in rats; (2) central mechanisms involving alpha(2)-adrenergic receptors inhibit pilocarpine-induced salivation. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

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Background: the purpose of this study was to evaluate the effect of a selective cyclooxygenase-2 inhibitor on the progression of alveolar bone loss in an experimental periodontitis model in rats.Methods: One hundred eighty (180) Wistar rats were separated into 3 experimental groups. Cotton ligatures were placed at the gingival margin level of lower right first molars. The rats were randomly assigned to one of the following groups that received: a daily oral dose of 10 mg/kg body weight of celecoxib (Ce1); 20 mg/kg body weight of celecoxib (Ce2); or 10 ml/kg of saline solution (C). Serum levels of celecoxib and white blood cell count were determined. Standardized digital radiographs were taken after sacrifice at 3, 5, 10, 18, and 30 days to measure the amount of bone loss around the mesial root surface of the first molar tooth in each rat.Results: Two-way analysis of variance (ANOVA) indicated that groups treated with celecoxib had significantly less bone loss compared to controls (P <0.0001) and that there was a significant interaction between treatment with celecoxib and time (P <0.03). Post-hoc comparisons showed that in both groups treated with celecoxib, the bone loss became significant only after 10 days of ligature placement, while in the control group it was already significant after 5 days. However, differences in mean bone loss between control and Ce1 were significant only at 18 days and, between control and Ce2, at 5 and 18 days. There was no significant difference in bone loss among experimental groups at the end of the experimental period.Conclusion: These data provide evidence that systemic therapy with celecoxib can modify the progression of experimentally induced periodontitis in rats.

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Calcium channels mediate the actions of many drugs. The present work investigated whether diltiazem, an L-type calcium channel blocker, alters the inhibition of sodium appetite induced by noradrenaline and the alpha(2)-adrenoceptor agonist clonidine. Adult male Holtzman rats (N=4-8) with cannula implanted into the third cerebral ventricle were submitted to sodium depletion {furosemide sc+24-h removal of ambiente sodium). Sodium depleted control animals that received 0.9% NaCl as vehicle injected intracerebroventricularly (i.c.v) ingested 13.0+/-1.5 ml/120 min of 1.8% NaCl. Intracerebroventricular injection of either noradrenaline (80 nmol) or clonidine (20 nmol) inhibited 1.8% NaCl intake from 70 to 90%. Prior i.c.v. injection of diltiazem (6-48 nmol) inhibited from 50 to 100% the effect of noradrenaline and clonidine in a dose-response manner. Diltiazem alone at 100 nmol inhibited, but at 50 nmol had no effect on, sodium appetite. The results suggest: (1) common ionic mechanisms involving calcium channels for the inhibition that noradrenaline and clonidine exert on sodium appetite and (2) a dual role for the benzothiazepine site of L-type calcium channels in the control of sodium appetite. (C) 2002 Elsevier B.V. B V. All rights reserved.