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Objective: The aim of the study was to evaluate the short and long-term effects of different surface treatments on the bond strengths of zirconia. Material and Methods: 225 blocks of sintered zirconia samples (4 x 4 x 3 mm) were divided into five groups and subjected to different surface treatments: control group (without surface treatment), alumina group (sandblasting [25-µm-aluminum-oxide]), alumina+Ambar Universal-APS (AU) group, CoJet group (silica-coated [30-µm silica-modified aluminum particles]), and CoJet+AU group. Subsequently, zirconia samples were cemented against resin samples (total dimensions: 8x8x6mm) and assigned to three storage conditions: dry, humid (artificial saliva at 37°C for 30-days) or thermocycling [100.000-cycles] (n=15 per group). The microtensile bond strength (µTBS) was determined using a universal testing machine. The failure modes were observed and analyzed using a stereomicroscope. Normality tests, descriptive statistics, and two-way ANOVA, followed by post-hoc comparisons, were performed to evaluate the effect of surface treatments and storage conditions on µTBS (α=0.05). Results: µTBS was influenced by surface treatment in the short and long-term (P<0.0001). The highest values were found in CoJet+AU in dry (33.51 ±2.48 MPa), humid (32.87 ±2.68 MPa) and thermocycling (21.37 ±1.68 MPa) storage conditions compared with others. Interestingly, no significant differences in µTBS were found among alum +AU and CoJet alone under any of the three storage conditions. Adhesive failure increased in all groups after thermocycling, but CoJet+AU had the lowest values of adhesive failure compared with others. Conclusion: The combination of CoJet and Ambar universal as a surface treatment for zirconia specimens provides significantly higher short and long-term bond strengths of adhesive cementation (AU)

Objetivo: O objetivo do estudo foi avaliar os efeitos de curto e longo prazo de diferentes tratamentos de superfície na resistência de adesão da zircônia. Material e Métodos: 225 blocos de amostras de zircônia sinterizada (4 x 4 x 3 mm) foram divididos em cinco grupos e submetidos a diferentes tratamentos de superfície: grupo controle (sem tratamento de superfície), grupo de alumina (jateamento de 25 µm de óxido de alumínio), grupo alumina+Ambar Universal-APS (AU), grupo CoJet (partículas de alumínio modificadas por sílica de 30 µm), e grupo CoJet+AU. Posteriormente, as amostras de zircônia foram cimentadas em amostras de resina (dimensões totais: 8x8x6mm) e designadas para três condições de armazenamento: seco, úmido (saliva artificial a 37°C por 30 dias) ou ciclagem térmica (100.000 ciclos) (n=15 por grupo). A resistência de adesão de microtensão (µTBS) foi determinada usando uma máquina de teste universal. Os modos de falha foram observados e analisados usando um estereomicroscópio. Testes de normalidade, estatísticas descritivas e ANOVA de duas vias, seguidas de comparações pos-hoc, foram realizados para avaliar o efeito dos tratamentos de superfície e das condições de armazenamento na µTBS (α=0.05). Resultados: A µTBS foi influenciada pelo tratamento de superfície a curto e longo prazo (P<0.0001). Os valores mais altos foram encontrados em CoJet+AU nas condições de armazenamento a seco (33.51 ±2.48 MPa), úmido (32.87 ±2.68 MPa) e ciclagem térmica (21.37 ±1.68 MPa) em comparação com os outros. Curiosamente, não foram encontradas diferenças significativas na µTBS entre alum +AU e CoJet sozinho em nenhuma das três condições de armazenamento. A falha adesiva aumentou em todos os grupos após a ciclagem térmica, mas CoJet+AU teve os valores mais baixos de falha adesiva em comparação com os outros. Conclusão: A combinação de CoJet e Ambar Universal como tratamento de superfície para espécimes de zircônia proporciona resistências de adesão significativamente mais altas a curto e longo prazo para cimentação adesiva. (AU)

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Mechanical Allodynia (MA), a frequent chronic pain symptom caused by innocuous stimuli, constitutes an unmet medical need, as treatments using analgesics available today are not always effective and can be associated with important side-effects. A series of 3,5-disubstituted pyridin-2(1H)-ones was designed, synthesized and evaluated in vivo toward a rat model of inflammatory MA. We found that the series rapidly and strongly prevented the development of MA. 3-(2-Bromophenyl)-5-(phenylamino)pyridin-2(1H)-one 69, the most active compound of the series, was also able to quickly reverse neuropathic MA in rats. Next, when 69 was evaluated toward a panel of 50 protein kinases (PK) in order to identify its potential biological target(s), we found that 69 is a p38α MAPK inhibitor, a PK known to contribute to pain hypersensitivity in animal models. 3,5-Disubstituted pyridin-2(1H)-ones thus could represent a novel class of analgesic for the treatment of MA.

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The participation of reactive oxygen species (ROS) generated by NOX1 and NOX2/NADPH oxidase has been documented during inflammatory pain. However, the molecular mechanism involved in their activation is not fully understood. We reported earlier a key role of Cyclin-dependent kinase 5 (Cdk5) during inflammatory pain. In particular, we demonstrated that TNF-α increased p35 expression, a Cdk5 activator, causing Cdk5-mediated TRPV1 phosphorylation followed by an increment in Ca2+ influx in nociceptive neurons and increased pain sensation. Here we evaluated if Cdk5 activation mediated by p35 transfection in HEK293 cells or by TNF-α treatment in primary culture of nociceptive neurons could increase ROS production. By immunofluorescence we detected the expression of catalytic subunit (Nox1 and Nox2) and their cytosolic regulators (NOXO1 and p47phox) of NOX1 and NOX2/NADPH oxidase complexes, and their co-localization with Cdk5/p35 in HEK293 cells and in nociceptive neurons. By using a hydrogen peroxide sensor, we detected a significant increase of ROS production in p35 transfected HEK293 cells as compared with control cells. This effect was significantly blocked by VAS2870 (NADPH oxidase inhibitor) or by roscovitine (Cdk5 activity inhibitor). Also by using another ROS probe named DCFH-DA, we found a significant increase of ROS production in nociceptive neurons treated with TNF-α and this effect was also blocked by VAS2870 or by roscovitine treatment. Interestingly, TNF-α increased immunodetection of p35 protein and NOX1 and NOX2/NADPH oxidase complexes in primary culture of trigeminal ganglia neurons. Finally, the cytosolic regulator NOXO1 was significantly translocated to plasma membrane after TNF-α treatment and roscovitine blocked this effect. Altogether these results suggest that Cdk5 activation is implicated in the ROS production by NOX1 and NOX2/NADPH oxidase complexes during inflammatory pain.

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A diario el hombre se enfrenta a situaciones que debe poner en la balanza para definir qué decisión tomar. Estas encrucijadas definen un conflicto de interés en donde una situación, juicio o acción que debería estar determinado por un valor primario establecido por razones profesionales o éticas, puede ser influido o parecer sesgado para obtener un beneficio secundario. En investigación biomédica cada vez es más factible enfrentarse a conflictos de interés, producto de los avances científicos y tecnológicos. Es preponderante entender en qué consisten, qué tipos de conflictos se pueden generar y cómo pueden poner en tela de juicio la calidad y veracidad de los resultados obtenidos ante la opinión pública, sobre todo cuando intereses económicos o beneficios personales son expuestos por terceros. Es necesario establecer mecanismos de control de cualquier tipo de conflicto de interés antes de ejecutar un protocolo de investigación si es que existiese. Estos mecanismos pueden ser: declaración pública, formularios mejorados y adaptados para la comunidad, unidades de apoyo a los comités de ética de investigación o el reporte de ingresos. Como conclusión se puede afirmar que, aunque se generen nuevos mecanismos o formas de manejo de conflictos de interés para la investigación biomédica, siempre será la conciencia del investigador, la virtud fundamentada por su propia moral y los principios éticos los que deben regir su actuar durante todo el tiempo que realice su vocación, en pos de proporcionar un bien al prójimo y a la sociedad en la que participa.

Man is confronted daily with situations he needs to weigh on to determine what decisions to make. These crossroads define a conflict of interest where a situation, suit or action, which should be determined by a primary value established by professional or ethical reasons, can be influenced or appear biased to obtain a secondary benefit. In biomedical research it is becoming more and more feasible to deal with conflicts of interest that result from scientific and technological advances. It is preponderant to understand what they are, what types of conflicts can be generated, and how these can challenge the quality and accuracy of the results obtained in the eye of the public opinion, especially when economic or personal interest gained are being exposed by third parties. It is necessary to set up mechanisms to control any type of conflict of interest before executing a research protocol, should any exist. These mechanisms could include: public declarations, forms improved and adapted to the community, support units to research ethics committees, or the earnings report. In conclusion, we can say that although new mechanisms or ways of managing conflicts of interest for the biomedical research are being generated, the researcher's conscience will always be the virtue based on its own moral and ethical principles that should govern his /her actions throughout the time they live out their vocation, towards offering or providing a good service to other beings and the society in which they participate.

Todos os dias, o homem enfrenta situações que deve pôr na balança para definir qual decisão tomar. Essas encruzilhadas definem um conflito de interesses no qual uma situação, juízo ou ação, que deveria estar determinado por um valor primário estabelecido por razões profissionais ou éticas, pode ser influído ou conduzido de forma inepta para obter um benefício secundário. Em pesquisa biomédica, cada vez é mais factível enfrentar-se conflitos de interesses, produto dos avanços científicos e tecnológicos. É preponderante entender em que consistem, que tipos de conflitos se podem gerar e como podem pôr em causa a qualidade e veracidade dos resultados obtidos ante a opinião pública, principalmente quando interesses econômicos ou benefícios pessoais são expostos por terceiros. É necessário estabelecer mecanismos de controle de qualquer tipo de conflito de interesses antes de executar um protocolo de pesquisa, se é que exista. Esses mecanismos podem ser: declaração pública, formulários melhorados e adaptados para a comunidade, unidades de apoio aos comitês de ética de pesquisa ou o relatório de ingressos. Como conclusão, pode-se afirmar que, embora se gerem novos mecanismos ou formas de manejo de conflito de interesses para a pesquisa biomédica, sempre será a consciência do pesquisador, a virtude fundamentada por sua própria moral e os princípios éticos os quais devem guiar seu agir durante todo o tempo que realizar sua vocação, em prol de proporcionar um bem ao próximo e à sociedade da qual participa.

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