Made available in DSpace on 2014-06-11T19:27:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-23Bitstream added on 2014-06-13T19:15:39Z : No. of bitstreams: 1 lopes_gad_me_botfm.pdf: 2094801 bytes, checksum: a391e976f0d943b5e9bbb19083fc6a30 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Clicar acesso eletrônico abaixo. / Click electronic access below.

Resumo: Clicar acesso eletrônico abaixo. / Abstract: Click electronic access below. / Orientador: Maria Aparecida Marchesan Rodrigues / Coorientador: Luís Fernando Barbisan / Banca: Patrícia Aline Boer / Banca: Fernando Silva Ramalho / Mestre

Submitted by Marco Antônio de Ramos Chagas (mchagas@ufv.br) on 2016-08-11T18:17:51Z No. of bitstreams: 1 texto completo.pdf: 1299816 bytes, checksum: d0ec9d52f7cd7c70f384aca27e1a1e8d (MD5) / Made available in DSpace on 2016-08-11T18:17:51Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1299816 bytes, checksum: d0ec9d52f7cd7c70f384aca27e1a1e8d (MD5) Previous issue date: 2015-07-16 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A bebida fermentada kefir é produzida a partir da atividade metabólica de bactérias e leveduras que vivem em associação simbiótica nos grãos de kefir. O consumo regular do kefir tem sido associado a uma série de atividades terapêuticas, dentre elas a inibição do desenvolvimento tumoral. Devido às altas taxas de incidência e de mortalidade do câncer colorretal, este estudo teve como principal objetivo avaliar o efeito do consumo regular do kefir de leite integral na redução do desenvolvimento de lesões pré-neoplásicas no cólon de ratos Wistar. Inicialmente, avaliamos a sobrevivência das bactérias do ácido láctico e das leveduras presentes no kefir de leite integral após a simulação in vitro das condições prevalecentes no trato gastrointestinal humano. Posteriormente, trinta ratos Wistar foram divididos em três grupos experimentais. Nas cinco primeiras semanas, fase de pré-indução, os animais do grupo controle foram tratados com 1 mL de água destilada, o grupo leite recebeu 1 mL de leite integral pasteurizado, e o grupo kefir foi tratado com 1 mL de kefir de leite integral, via gavagem diariamente. Ao término desta fase os animais foram submetidos ao protocolo de indução das lesões pré-neoplásicas com 1,2-dimetilhidrazina. Neste momento teve início à fase de pós-indução, a qual teve duração de quinze semanas, onde os animais continuaram recebendo seus respectivos tratamentos. Assim, o experimento teve duração total de vinte semanas. Dados da simulação in vitro demonstraram que as leveduras presentes no kefir de leite integral são mais resistentes às condições prevalecentes no trato gastrointestinal do que as bactérias do ácido láctico. Quanto à atividade anticarcinogênica do kefir, observou- se que o tratamento com o kefir foi capaz de reduzir em 36,7 % a incidência dos focos de cripta aberrante no cólon dos animais tratados em comparação ao controle (p < 0,001). Ainda, o kefir aumentou a atividade da enzima antioxidante catalase (p < 0,001 ) no cólon e a concentração dos ácidos graxos de cadeia curta nas fezes do ceco (p < 0,001), além de reduzir a razão lactulose/manitol (p = 0,020) ao final da fase de pós-indução. Com isto, conclui-se que a atividade anticarcinogênica do kefir de leite integral se deve à redução da permeabilidade intestinal, ao aumento da atividade antioxidante, e ao aumento da produção dos ácidos graxos de cadeia curta. / Kefir is a fermented beverage produced from the metabolic activity of bacteria and yeasts living in symbiotic association in kefir grains. Regular consumption of kefir has been associated with a variety of therapeutic activities among them, the inhibition of tumor development. Due to high rates of incidence and mortality of colorectal cancer, this study aimed to evaluate the effect of regular consumption of whole milk kefir in the risk reduction of the development of preneoplasic lesions in Wistar rats. Initially, we evaluated the survival of lactic acid bacteria and yeasts present in whole milk kefir after in vitro simulation of the conditions prevailing in the human gastrointestinal tract. Subsequently, thirty Wistar rats were divided into three experimental groups. In the first five weeks, the so-called pre-induction phase, the control group was treated with 1 mL of distilled water, the milk group received 1 mL of pasteurized milk and the kefir group was treated with 1 mL of whole milk kefir, administered daily through gavage. At the end of this phase the animals were subjected to the induction protocol of preneoplasic lesions with 1,2-dimethylhydrazine. At this time it began the post-induction phase, fifteen weeks, when the animals continued to receive their treatments. Thus, the experimental lasted twenty weeks. The in vitro simulation data showed that the yeasts present in whole milk kefir are more resistant to the conditions prevailing in the gastrointestinal tract than the lactic acid bacteria. Regarding the anticarcinogenic activity of kefir, it was observed that treatment with kefir was able to reduce by 36.7 % the incidence of aberrant crypt foci in the colon of the treated animals compared to the control (p < 0.001). Furthermore, kefir increased the antioxidant enzyme catalase activity (p < 0.001) in the colon and the concentration of short-chain fatty acids in the feces of the cecum (p = 0.046), while reducing the reason lactulose/mannitol (p = 0.020) at the end of the post-induction phase. Thus, it was concluded that the anticarcinogenic activity of whole milk kefir is due to reduction of intestinal permeability, increased antioxidant activity, and increased production of short chain fatty acids. / Liberação do sigilo autorizada pela Orientadora por e-mail, em 15-08-2016.

Made available in DSpace on 2014-06-11T19:27:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-29Bitstream added on 2014-06-13T18:56:50Z : No. of bitstreams: 1 silva_frm_me_botfm.pdf: 2481576 bytes, checksum: 0cc379f4b864c599808f845e21be54a1 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente estudo foi delineado para investigar a possível ação quimioprotetora do quelato de zinco (ZnGly), na etapa de iniciação da carcinogênese do cólon, induzida pela 1,2- dimetilhidrazina (DMH) em ratos Wistar machos. Os animais foram distribuídos em quatro grupos experimentais e receberam três doses de 40mg/Kg, via subcutânea (sc) de DMH ou EDTA (veiculo da DMH) e 15mg/Kg de quelato de zinco (ZnGly) por gavagem durante quatro semanas. Após a narcose foram coletadas amostras de sangue e, em seguida fragmentos do cólon para dosagens de zinco. O cólon foi removido inteiro, fixado em formalina tamponada a 10%, corado com azul de metileno para análise de incidência de focos de criptas aberrantes (FCAs) e processado histologicamente para análise dos índices de proliferação celular e apoptose. A exposição à DMH aumentou significativamente os índices de proliferação celular e apoptose na mucosa do cólon. A administração do quelato de zinco (ZnGly) não alterou o número e multiplicidade de FCAs e não modificou as taxas de proliferação celular e de apoptose da mucosa do cólon, tanto no grupo tratado com DMH como no respectivo grupo controle. Os resultados deste estudo indicam o zinco não mostrou ação protetora na etapa de iniciação da carcinogênese do cólon induzida pela DMH em ratos Wistar machos / The present study was designed to investigate the possible chemopreventive action of zinc gluconate (ZnGly) on the initiation step of colon carcinogenesis induced by 1,2- dimethylhydrazine (DMH) in male Wistar rats. The animals were divided into four groups and received three doses of DMH (40 mg/Kg, s.c) or EDTA (DMH vehicle) and 15 mg/Kg of zinc glycine (ZnGly) administered by gavage for four weeks. After the narcosis, blood and colon fragments samples were collected for zinc dosage. The entire colon was removed, fixed in buffered formalin 10%, stained with methylene blue for the analysis of ACF formation. The rates of cell proliferation and apoptosis were also analyzed in epithelial crypt cells. The exposure to DMH significantly increased the rates of cell proliferation and apoptosis in epithelial cript cells. Treatment with zinc glycine (ZnGly) did not alter the number and multiplicity of ACFs, as well as apoptosis and cell proliferation indices in both DMH-treated and control group. The present findings indicate that zinc did not present chemopreventive effects on the initiation step of DMH-induced colon carcinogenesis in male Wistar rats

Resumo: O presente estudo foi delineado para investigar a possível ação quimioprotetora do quelato de zinco (ZnGly), na etapa de iniciação da carcinogênese do cólon, induzida pela 1,2- dimetilhidrazina (DMH) em ratos Wistar machos. Os animais foram distribuídos em quatro grupos experimentais e receberam três doses de 40mg/Kg, via subcutânea (sc) de DMH ou EDTA (veiculo da DMH) e 15mg/Kg de quelato de zinco (ZnGly) por gavagem durante quatro semanas. Após a narcose foram coletadas amostras de sangue e, em seguida fragmentos do cólon para dosagens de zinco. O cólon foi removido inteiro, fixado em formalina tamponada a 10%, corado com azul de metileno para análise de incidência de focos de criptas aberrantes (FCAs) e processado histologicamente para análise dos índices de proliferação celular e apoptose. A exposição à DMH aumentou significativamente os índices de proliferação celular e apoptose na mucosa do cólon. A administração do quelato de zinco (ZnGly) não alterou o número e multiplicidade de FCAs e não modificou as taxas de proliferação celular e de apoptose da mucosa do cólon, tanto no grupo tratado com DMH como no respectivo grupo controle. Os resultados deste estudo indicam o zinco não mostrou ação protetora na etapa de iniciação da carcinogênese do cólon induzida pela DMH em ratos Wistar machos / Abstract: The present study was designed to investigate the possible chemopreventive action of zinc gluconate (ZnGly) on the initiation step of colon carcinogenesis induced by 1,2- dimethylhydrazine (DMH) in male Wistar rats. The animals were divided into four groups and received three doses of DMH (40 mg/Kg, s.c) or EDTA (DMH vehicle) and 15 mg/Kg of zinc glycine (ZnGly) administered by gavage for four weeks. After the narcosis, blood and colon fragments samples were collected for zinc dosage. The entire colon was removed, fixed in buffered formalin 10%, stained with methylene blue for the analysis of ACF formation. The rates of cell proliferation and apoptosis were also analyzed in epithelial crypt cells. The exposure to DMH significantly increased the rates of cell proliferation and apoptosis in epithelial cript cells. Treatment with zinc glycine (ZnGly) did not alter the number and multiplicity of ACFs, as well as apoptosis and cell proliferation indices in both DMH-treated and control group. The present findings indicate that zinc did not present chemopreventive effects on the initiation step of DMH-induced colon carcinogenesis in male Wistar rats / Orientador: Maria Aparecida Marchesan Rodrigues / Coorientador: Luis Fernando Barbisan / Banca: Daniel Araki Ribeiro / Banca: Alaor Aparecido Almeida / Mestre

Made available in DSpace on 2015-06-17T19:34:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-27. Added 1 bitstream(s) on 2015-06-18T12:47:25Z : No. of bitstreams: 1 000829940.pdf: 916653 bytes, checksum: 09926f007a66538b3dedd4cb298c6c6a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / We have recently observed that treatment of colon tumor cells with low concentration of paclitaxel increased the expression of several genes associated with antigen-presenting machinery. Since 5-fluoruracil (5-FU) is the main antineoplastic agent for colon cancer, in this study we aimed to evaluate immunomodulatory properties analyzing: a) if the DC transfection with drug-treated tumor cells RNA, enhances the effectiveness of DC-based vaccine; b) if the modulatory effects of vaccine can be observed in vivo, and c) if the combination of DC with low dose chemotherapy schedule improves the antitumor responsiveness. To achieve these goals s.c. MC-38 bearing C57/Bl-6 mice were treated with DC sensitized with RNA from tumor cells pre-treated with the minimum effective concentration (MEC) of 5-fluorouracil. Our results of studies show that vaccination with tumor RNA-transfected DC delays the tumor growth, increases the percentage of CD86+ (35%) CD40+ (63%) and MHC class II+ (47%) DC and significantly increases the in vitro production of IFN-ɣ. These results suggest that treatment of tumor cells with 5-FU induces transcriptional changes that can be transfered to DC by RNA transfection, enhancing their ability to stimulate the antitumor response / CNPq: 555857/2010-07 / FAPESP: 2009/18331-8

Orientador: Ramon Kaneno / Banca: Denise Fecchio / Banca: Priscila R. Martins / Banca: Orlando Ribeiro Filho / Resumo: Não disponível / Abstract: We have recently observed that treatment of colon tumor cells with low concentration of paclitaxel increased the expression of several genes associated with antigen-presenting machinery. Since 5-fluoruracil (5-FU) is the main antineoplastic agent for colon cancer, in this study we aimed to evaluate immunomodulatory properties analyzing: a) if the DC transfection with drug-treated tumor cells RNA, enhances the effectiveness of DC-based vaccine; b) if the modulatory effects of vaccine can be observed in vivo, and c) if the combination of DC with low dose chemotherapy schedule improves the antitumor responsiveness. To achieve these goals s.c. MC-38 bearing C57/Bl-6 mice were treated with DC sensitized with RNA from tumor cells pre-treated with the minimum effective concentration (MEC) of 5-fluorouracil. Our results of studies show that vaccination with tumor RNA-transfected DC delays the tumor growth, increases the percentage of CD86+ (35%) CD40+ (63%) and MHC class II+ (47%) DC and significantly increases the in vitro production of IFN-ɣ. These results suggest that treatment of tumor cells with 5-FU induces transcriptional changes that can be transfered to DC by RNA transfection, enhancing their ability to stimulate the antitumor response / Doutor