43 research outputs found

    Myoepithelioma of minor salivary gland on the base of the tongue: a case report

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    This study reports a case of myoepithelioma of minor salivary gland on the base of the tongue of a 58 year-old patient. This theme is discussed because it is a rare tumor, and in this case, it was located in an uncommon position. The diagnosis was given by the pathologic and immunohistochemical study of the excised tumor. The course is usually benign, and the cure is possible if it is completely excised.Os autores apresentam um caso de mioepitelioma de glândula salivar menor, localizado na base da língua de uma paciente de 58 anos. O mioepitelioma é um tumor pouco freqüente, de evolução benigna, sendo possível obter-se a cura através da excisão cirúrgica completa da lesão. Neste caso, apresentou-se numa posição bastante incomum, a base da língua. Foi realizada a exérese da lesão, com margens de segurança, e a paciente está assintomática e sem recidiva local depois de 6 meses de acompanhamento pós-operatório. O diagnóstico foi obtido através do estudo anatomopatológico e imuno-histoquímico da peça.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Departamento de Otorrinolaringologia e Distúrbios da Comunicação HumanaUNIFESP, EPM, Depto. de Otorrinolaringologia e Distúrbios da Comunicação HumanaSciEL

    SAR Study of Niclosamide Derivatives for Neuroprotective Function in SH-SY5Y Neuroblastoma

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    Background: Neurodegenerative disease is a debilitating and incurable condition that affects millions of people around the world. The loss of functions or malfunctions of neural cells causes mortality. A proteasome inhibitor, MG132, is well known to cause neurodegeneration in vitro when model neuronal-derived cell lines are exposed to it. Niclosamide, an anthelmintic drug, which has been used for more than 50 years, has recently attracted renewed attention in drug repurposing because it has been found as a good candidate against various diseases in screenings. We recently found that all markers of MG132-induced neuronal cell toxicity, including the accumulation of ubiquitinated proteins, were prevented by niclosamide. In addition, niclosamide was shown to enhance autophagy induced by MG132. Therefore, our results suggest that niclosamide could be a potential neuroprotective agent. In the present study, niclosamide derivatives were synthesized by changing substituents, and their structure-activity relationship (SAR) of the protein ubiquitination induced by MG132 and cell survival signaling pathways for neuroprotective function were studied. Methods: The 12 niclosamide derivatives were synthesized; mostly, they were prepared from the corresponding benzoic acid and aniline derivatives in the presence of PCl3 in dry xylene under reflux conditions. Niclosamide and the 12 derivatives were dissolved in DMSO. The SH-SY5Y cells were cultured at 5% CO2 at 37 °C in EMEM: Ham’s F-12K medium (1:1), 5% horse serum with penicillin (100 units/mL), and streptomycin (100 μg/mL). The cells were sub-cultured weekly in 60 mm or 100 mm cell culture dishes and used for experiments at 85-90% confluence of the cell monolayer. SH-SY5Y cells were treated with niclosamide or derivatives and 5 μM MG132 for 24 h. The cell lysates were prepared for Western blot assays using anti-ubiquitin antibodies, including ubiquitin, PARP, p-JNK, CHOP, cyclin D, and p53. Results: Our results indicate that when phenol OH was present, the compounds demonstrated neuroprotective activity, while the presence or absence of Cl (5- or 2’-Cl) showed almost the same neuroprotective effect. 4’-NO2 can be replaced by N3 or CF3 to have neuroprotective activity, whereas NH2 significantly decreased activity. Yet, when there is no substituent at the 4’- position, there is no significant activity. All the bioassays showed that niclosamide and certain derivatives showed a neuroprotective function. While there is no evidence for the direct bindings of niclosamide and their derivatives to any specific proteins, the results indicate that the phenol OH plays an important role, and chloride at 2’-Cl or 5-Cl, does not affect the neuroprotective activity. 4’-NO2 can be replaced with N3 or CF3. However, 4’-NH2 and 4’-H significantly decreased the neuroprotective function. This suggested the substituent at 4’ position plays some role in bindings. The inhibition of p53 expression by these compounds may have a different mechanism of action, and further investigation will be required in the future. Conclusions: Based on the results of the present study, niclosamide, and its derivatives can be new target molecules for the prevention of Parkinson’s disease (PD) and other neurodegenerative diseases. Also, these findings provide valuable information for the development of the next generation of niclosamide analogs

    Resource-based view as a perspective for public tourism management research: evidence from two brazilian tourism destinations

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    This study adopted the Resource-Based View approach to analyse two public organizations located in Curitiba and Foz do Iguaçu, Brazil. The focus was to verify how organizational and tourist resources are being used for planning and public management in these cities. Data collection was made by adopting semi-structured interviews with two groups: public and private sector managers. The insights of these two groups and the use of documentary secondary data made it possible to infer that the main resource for the implementation of public policies was organizational architecture. However, the most influential resource in public tourism management is the existence of tourist resources and organizational resources related to internal and external relationships and organizational culture. The analysis demonstrated that the researched cities do not use or do not know how to use the available resources in value-creating activities for local tourist management. Both cities present imperfections that do not earmark the full exploitation of organizational resources, compromising the exploration of available tourist resources

    A quantitative genome-wide RNAi screen in C. elegans for antifungal innate immunity genes

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