Submitted by Eunice Novais (enovais@uepg.br) on 2018-03-12T18:21:00Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Luiza Stolz Cruz.pdf: 10331435 bytes, checksum: 9b1d4ec95714f86c9315354c7d388689 (MD5) / Made available in DSpace on 2018-03-12T18:21:00Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Luiza Stolz Cruz.pdf: 10331435 bytes, checksum: 9b1d4ec95714f86c9315354c7d388689 (MD5) Previous issue date: 2017-03-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Euphorbia umbellata (Pax) Bruyns tem seu látex utilizado, etnofarmacologicamente, para tratamento de câncer, incluindo leucemias. Uma doença maligna que atinge os leucócitos, com alta incidência, sendo o tipo de câncer mais comum na infância. O tratamento quimioterápico é, na maioria dos casos, o mais recomendado, mas apresenta-se como terapia muito agressiva e com diversos efeitos colaterais. Por conseguinte, o objetivo deste trabalho foi o de avaliar o potencial citotóxico da fração hexano do látex de Euphorbia umbellata suas subfrações e da substância isolada, eufol, frente a linhagens modelo de leucemia. Para tanto as células, Jurkat e HL-60, foram tratadas por 72 horas com a fração hexano (1,25-75 μg/mL), subfrações éter de petróleo, diclorometano, etanol e metanol (1,25-75 μg/mL) e com o eufol (10-50 μg/mL), sendo sua viabilidade celular avaliada pelo ensaio de redução do MTT ao final deste período. Para a subfração diclorometano (mais ativa) foi avaliada a viabilidade celular no período de 24 e 48 horas, além de ter sido determinado o índice de seletividade. Cabe ressaltar que a fração hexano e as subfrações foram obtidas por fracionamento em extrator de Soxhlet, enquanto o eufol, por precipitação ácida, seguida de cromatografia em coluna, e sendo identificado por ressonância magnética nuclear e espectrometria de massas. A fração hexano e as subfrações resultantes foram analisadas por cromatografia gasosa acoplada ao espectrômetro de massas. A avaliação cromatográfica das subfrações permitiu sugerir 10 substâncias, os triterpenos: eufol; lanosterol; cicloartenol; tirucalol; taraxasterol e lupeol, os diterpenos: forbol-12,13,20- triacetato; 4-β forbol e 3-desoxo-3- 16-dihidroxi-12-desoxiforbol-3-13-16-20- tetracetato, e o esteroide sitosterol. Como resultado do ensaio citotóxico obteve-se, para a fração hexano uma CI50 de 0,061 ± 1,226 μg/mL para as células HL-60 e 4,624 ± 1,088 μg/mL para células Jurkat; para o eufol uma CI50 de 21,031 ± 1,778 μg/mL (HL-60) e 35,925 ± 5,011 μg/mL (Jurkat). Dentre as subfrações a diclorometano apresentou o melhor perfil de resposta com valores de 0,005±0,098 μg/mL (HL-60) e 0,200±0,957 μg/mL (Jurkat), revelando que o tratamento é tempo dependente. Ademais a subfração diclorometano mostrouse seletiva para o tratamento de leucemia com índices de seletividade superior a 2. Portanto, conclui-se que a subfração diclorometano é a promissora para o tratamento de leucemia, possivelmente por ação sinérgica dos terpenos nela presente. / Euphorbia umbellata (Pax) Bruyns has its latex used, ethno-pharmacologically, for the treatment of cancer, including leukemias. A malignant disease that affects leukocytes, with high incidence, being the most common type of cancer in childhood. Chemotherapy treatment is, normally, the most recommended, but it presents as very aggressive therapy and with several side effects. Therefore, the objective of this work was to evaluate the cytotoxic potential of the hexane fraction of Euphorbia umbellata latex, the subfraction of that and the isolated substance, euphol, against leukemia model lines. For this, the cells, Jurkat and HL-60, were treated for 72 hours with the hexane fraction (1.25-75 μg/mL), subfractions petroleum ether, dichloromethane, ethanol and methanol (1.25-75 μg/mL), and euphol (10-50 μg/mL), and their cell viability was evaluated by the assay of MTT reduction at the end of this period. For the dichloromethane subfraction (the most active), the cell viability was evaluated in the period of 24 and 48 hours, in addition, the selectivity index was determined. It should be noted that the hexane fraction and subfractions were obtained by fractionation in Soxhlet extractor, while euphol by acid precipitation, followed by column chromatography, and being identified by nuclear magnetic resonance and mass spectrometry. The hexane fraction was partitioned and the resulting subfractions were analyzed by gas chromatography coupled to the mass spectrometer. The chromatographic evaluation of the subfractions allowed to suggest 10 substances, the triterpenes: euphol; lanosterol; cycloartenol; tirucallol; taraxasterol and lupeol, the diterpenes: phorbol-12,13,20-triacetate; 4- β-phorbol and 3-deoxo-3-16-dihydroxy-12-deoxyphorbol-3-13-16-20-tetracetate, and the steroid sitosterol. As a result of the cytotoxic assay, an IC50 of 0.061 ± 1.226 μg/mL was obtained for HL-60 cells and 4.624 ± 1.088 μg/mL for Jurkat cells; and for euphol an IC50 of 21.031 ± 1.778 μg/ml (HL-60) and 35.925 ± 5.011 μg/ml (Jurkat). Among the subfractions, the dichloromethane presented the best response profile with values of 0,005±0,098 μg/mL (HL-60) and 0,200±0,957 μg/mL (Jurkat), revealing that the treatment is time dependent. In addition, the dichloromethane subfraction was selective for the treatment of leukemia with indexes of selectivity superior to 2.Therefore, it is concluded that the subfraction dichloromethane is promising for the treatment of leukemia, possibly by synergistic action of the terpenes in it.

Human parainfluenza virus type-2 (HPIV-2) is a highly contagious respiratory pathogen that can cause severe respiratory disease known as laryngotracheobronchitis or croup-like disease in children. No specific vaccine or an antiviral drug is currently approved for treatment of HPIV-2 infections. In this project, a library of 14400 diverse compounds had been screened for anti-HPIV-2 activities in cultures of African green monkey kidney cells. All compounds that inhibited the virus induced syncytium-forming activity in these cells were considered as hit compounds. Three hit compounds showed moderate anti-HPIV-2 activity characterized by the IC50 values of 20 µM and selectivity indices of approximately 5. This suggests that the antiviral activity of these compounds was due to targeting activities of cellular rather than viral components. Another hit compound, referred to as compound 5, showed anti-HPIV-2 activity that was manifested as a reduction of area of the virus-induced plaques in cells at not cytotoxic concentrations. Interestingly, this compound did not inhibit initial infection nor the virus production in infected cells as revealed by the time-of-addition assay. Moreover, it showed no direct the virus-inactivating (virucidal activity) against HPIV-2 particles. However, relatively short pre-treatment (4 hours) of the cells with compound 5 prior to the virus infection was sufficient for its plaque size-reducing activity suggesting that anti-HPIV-2 activity of compound 5 was due to targeting activities of cellular rather than viral components. Further studies are needed to elucidate the anti-HPIV-2 mechanism of activity of hit compounds identified in the present study.

This article analyzes and compares an overview of the structure and evolution of the international and domestic mutual fund industry for the 2005–2014 period. The aim of this analysis is to identify opportunities for growth and development of the domestic mutual fund industry, in particular, passive management used by index equity funds. / Este artículo analiza y compara, de manera general, la estructura y evolución anual de la industria de fondos mutuos internacional y doméstica durante el período 2005-2014. El objetivo de este análisis es identificar las oportunidades de crecimiento y desarrollo del segmento de renta variable de la industria de fondos mutuos doméstica tomando como referencia el estilo de administración pasiva de las inversiones utilizado por los fondos mutuos indexados de renta variable. / Este artigo analisa e compara, em geral, a estrutura e a evolução da indústria internacional e nacional de fundos mútuos anuais ao longo do período 2005-2014. O objetivo desta análise é identificar oportunidades de crescimento e desenvolvimento dos fundos mútuos de ações na indústria nacional em função dos fundos de índice com gestão passiva de investimentos.