154 resultados para Hypotensive agents


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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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An acidic (pI similar to 4.5) phospholipase A(2) (BthA-I-PLA(2)) was isolated from Bothrops jararacussu snake venom by ion-exchange chromatography on a CM-Sepharose column followed by reverse phase chromatography on an RP-HPLC C-18 column. It is an similar to13.7 kDa single chain Asp49 PLA(2) with approximately 122 amino acid residues, 7 disulfide bridges, and the following N-terminal sequence: 'SLWQFGKMINYVMJGESGVLQYLSYGCYCGLGGQGQPTDATDRCCFVHDCC(51). Crystals of this acidic protein diffracted beyond 2.0 Angstrom resolution. These crystals are monoclinic and have unit cell dimensions of a = 33.9, b = 63.8, c = 49.1 Angstrom, and beta = 104.0degrees. Although not myotoxic, cytotoxic, or lethal, the protein was catalytically 3-4 tithes more active than BthTX-II, a basic D49 myotoxic PLA(2) from the same venom and other Bothrops venoms. Although it showed no toxic activity, it was able to induce time-independent edema, this activity being inhibited by EDTA. In addition, BthA-I-PLA(2) caused a hypotensive response in the rat and inhibited platelet aggregation, Catalytic, antiplatelet and other activities were abolished by chemical modification with 4-bromophenacyl bromide, which is known to covalently bind to His48 of the catalytic site. Antibodies raised against crude B. jararacussu venom recognized this acidic PLA(2), while anti-Asp49-BthTX-II recognized it weakly and anti-Lys49-BthTX-I showed the least cross-reaction. These data confirm that myotoxicity does not necessarily correlate with catalytic activity in native PLA(2) homologues and that either of these two activities may exist alone. BthA-I-PLA(2), in addition to representing a relevant molecular model of catalytic activity, is also a promising hypotensive agent and platelet aggregation inhibitor for further studies. (C) 2002 Elsevier B.V. All rights reserved.

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Phospholipases A(2) belong to the superfamily of proteins which hydrolyzes the sn-2 acyl groups of membrane phospholipids to release arachidonic acid and lysophospholipids. An acidic phospholipase A(2) isolated from Bothrops juraracussu snake venom presents a high catalytic, platelet aggregation inhibition and hypotensive activities. This protein was crystallized in two oligomeric states: monomeric and dimeric. The crystal structures were solved at 1.79 and 1.90 Angstrom resolution, respectively, for the two states. It was identified a Na+ ion at the center of Ca2+-binding site of the monomeric form. A novel dimeric conformation with the active sites exposed to the solvent was observed. Conformational states of the molecule may be due to the physicochemical conditions used in the crystallization experiments. We suggest dimeric state is one found in vivo. (C) 2004 Elsevier B.V. All rights reserved.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Antineoplastic chemotherapeutic agents may indirectly activate dendritic cells (DCs) by inducing the release of danger signals from dying tumor cells. Whereas the direct cytotoxic or inhibitory effect of conventional chemotherapy on DCs has been reported, modulation of DC function by chemotherapeutic agents in low noncytotoxic concentrations has not yet been investigated. We have tested the effects of different classes of antineoplastic chemotherapeutic agents used in low noncytotoxic concentrations on the Ag-presenting function of DCs. We revealed that paclitaxel, doxorubicin, mitomycin C, and methotrexate up-regulated the ability of DCs to present Ags to Ag-specific T cells. Stimulation of DC function was associated with the up-regulation of expression of Ag-processing machinery components and costimulatory molecules on DCs, as well as increased IL-12p70 expression. However, the ability of DCs treated with paclitaxel, methotrexate, doxorubicin, and vinblastine to increase Ag presentation to Ag-specific T cells was abolished in DCs generated from IL-12 knockout mice, indicating that up-regulation of Ag presentation by DCs is IL-12-dependent and mediated by the autocrine or paracrine mechanisms. At the same time, IL-12 knockout and wild-type DCs demonstrated similar capacity to up-regulate OVA presentation after their pretreatment with low concentrations of mitomycin C and vincristine, suggesting that these agents do not utilize IL-12-mediated pathways in DCs for stimulating Ag presentation. These findings reveal a new mechanism of immunopotentiating activity of chemotherapeutic agents-a direct immunostimulatory effect on DCs (chemomodulation)-and thus provide a strong rationale for further assessment of low-dose chemotherapy given with DC vaccines for cancer treatment. The Journal of Immunology, 2009, 183: 137-144.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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INTRODUÇÃO: A solução cardioplégica farmacológica busca eliminar as conseqüências do dano isquêmico, que é o resultado do desbalanço entre a oferta e o consumo de energia durante a parada dos batimentos cardíacos, nas cirurgias cardíacas com circulação extracorpórea. OBJETIVO: Este trabalho avalia experimentalmente as alterações estruturais e ultra-estruturais em coração isolado de coelhos submetidos à parada protegida pela Solução para Cardioplegia de Baixo Volume (SCBV). MÉTODO: O estudo compreendeu um grupo controle e dois grupos experimentais. No grupo I, a parada cardíaca foi obtida pela infusão da SCBV por 2 horas. No grupo II, o experimento foi conduzido da mesma forma até a parada protegida pela SCBV por duas horas, imediatamente procedeu-se à reperfusão com solução oxigenada de Ringer Locke (RL) por uma hora. No grupo controle os corações foram perfundidos com solução oxigenada de RL por duas horas. Após os experimentos, oito amostras de parede lateral do ventrículo esquerdo foram fixadas em formaldeído 10% e glutaraldeído 2,5% para análises histológica e ultra-estrutural. RESULTADOS: As células do miocárdio, fibroblastos e células endoteliais, observadas nos grupos experimentais I e II, apresentaram marginalização da heterocromatina, compactação do nucléolo, alteração na forma das mitocôndrias, compactação das cristas e aumento da densidade da matriz mitocondrial, indicando que tanto a estrutura nuclear quanto a das organelas citoplasmáticas foram alteradas em relação às células do grupo controle. CONCLUSÃO: As modificações estruturais foram decorrentes de uma adaptação fisiológica da célula, não sendo indicativas de oncose ou apoptose, sugerindo, portanto, que a solução cardioplégica utilizada foi eficiente para a preservação das células.

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Aim To evaluate ex vivo effectiveness of the three formulations of bleaching materials for intracoronal bleaching of root filled teeth using the walking bleach technique.Methodology Extracted premolar teeth were stained artificially with human blood. After biomechanical preparation, the root canals were filled and a 3-mm thick intermediate base of zinc phosphate cement was placed at the level of the cementoenamel junction. The teeth were divided into four groups (n = 12): C (control, without bleaching material), A1 (sodium perborate + distilled water), A2 (sodium perborate + 10% carbamide peroxide) and A3 (sodium perborate + 35% carbamide peroxide). The bleaching materials were changed at 7 and 14 days. Evaluation of shade was undertaken with aid of the VITA Easyshade (TM) (Delta E*ab) and was performed after tooth staining and at 7, 14 and 21 days after bleaching, based on the CIELAB system. Data were analysed by ANOVA for repeated measurements, Tukey and Dunnett tests (alpha = 0.05).Results The Tukey test revealed that group A1 (10.58 +/- 4.83 Delta E*ab) was statistically different from the others (A2, 19.57 +/- 4.72 Delta E*ab and A3, 17.58 +/- 3.33 Delta E*ab), which were not different from each other. At 7 days: A1 was significantly different from A2; at 14 and 21 days: A2 and A3 were significantly better than A1; the Dunnett test revealed that the control group was different from A1, A2 and A3 at all periods (P < 0.05).Conclusion Sodium perborate associated with both 10% and 35% carbamide peroxide was more effective than when associated with distilled water.

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

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O objetivo deste estudo foi avaliar o selamento de ápices radiculares tratados com diferentes agentes desmineralizantes e retrobturados com agregado de trióxido mineral (MTA), mediante infiltração marginal por corante. Cinqüenta e seis dentes unirradiculares humanos extraídos foram instrumentados, obturados e seccionados apicalmente. Os preparos cavitários apicais foram confeccionados com pontas ultra-sônicas e os agentes desmineralizantes foram aplicados previamente à retrobturação com Pro Root MTA. Os espécimes foram divididos aleatoriamente em 4 grupos (n=14): grupo 1 (sem agente desmineralizante); grupo 2 (ácido fosfórico 35% durante 15 s); grupo 3 (solução de EDTA 17%, pH 7, durante 3 min); grupo 4 (gel de EDTA 24%, pH 7, durante 4 min). A extensão da infiltração de corante (rodamina B 2% a 37°C, por 24 h) foi avaliada em milímetros utilizando-se um estereomicroscópio. Os resultados foram analisados estatisticamente por meio de análise de variância a um critério e do teste Tukey com nível de significância de 5%. Dentre os grupos experimentais, a menor extensão de infiltração do corante foi verificada no grupo 1 (1,89 mm), seguido pelos grupos 2 (2,18 mm), 4 (2,54 mm) e 3 (2,64 mm). Não houve diferenças estatisticamente significante (p>0.05) na infiltração marginal pelo corante entre os grupos 1, 2 e 4 e os grupos 2, 3 e 4. Com base nos resultados obtidos, pode-se concluir que a aplicação de agentes desmineralizantes não pode ser recomendada quando da utilização do MTA em cirurgias parendodônticas.

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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)