Made available in DSpace on 2014-06-11T19:23:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-05-18Bitstream added on 2014-06-13T18:51:17Z : No. of bitstreams: 1 agustoni_d_me_arafcf.pdf: 695369 bytes, checksum: 3c7f05f6fcf3e0cf6a8cc9b9e2f99aee (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Universidade Estadual Paulista (UNESP) / A variabilidade das regiões geográficas brasileiras favorece o desenvolvimento de diferentes espécies vegetais, o que estimula o estudo na busca de novos agentes bioativos. A quimioprevenção envolve o uso de substâncias naturais ou sintéticas a fim de prevenir, retardar ou reverter o desenvolvimento do câncer e a espécie escolhida para investigação de seu possível efeito quimiopreventivo é a Eugenia jambolana pertencente à família Myrtaceae, seu perfil químico revela a presença de antocianinas e substâncias fenólicas com potencial efeito antioxidante, antiinflamatório e analgésico. O presente estudo tem por objetivo realizar o rastreamento bioguiado para atividade de quimioprevenção em extratos e frações das folhas e dos frutos de Eugenia jambolana como parte da bioprospecção de produtos naturais. Até o momento não existem estudos sobre a capacidade de quimioprevenção dessa espécie vegetal. No presente estudo foi avaliada a indução da enzima quinona-redutase em células de hepatocarcinoma murino selvagem (Hepa 1c1c7) e mutantes (TAOr1BPrc1 e BPrc1), a citotoxicidade, genotoxicidade e antigenotoxicidade, mutagenicidade e antimutagenicidade em células de hepatocarcinoma humano (HepG2) competentes para metabolização de xenobióticos. Experimentos esses realizados através do ensaio da Quinona-redutase, coloração por sulforrodamina B, ensaio do cometa e teste do micronúcleo. Os resultados demonstraram que o extrato bruto e a fração n-butanólica das folhas, e o extrato bruto e a fração hidroalcoólica dos frutos de E. jambolana são capazes de promover significativamente a indução da enzima quinona-redutase em diferentes concentrações, de 1,25 a 40 μg/mL. Porém nessas condições esses extratos e frações foram potencialmente genotóxico. Em menores... / The variability of geographical regions favors the development of different plant species, which encourages the study in the search for new bioactive agents. The chemoprevention involves the use of natural or synthetic substances to prevent, retard or reverse the developing cancer and the species chosen for investigation of their possible chemopreventive effect was Eugenia jambolana belonging to the Myrtaceae family, chemical profile reveals the presence of anthocyanins and phenolic compounds with potential antioxidant, anti-inflammatory and analgesic effect. This study aims to perform a screning chemoprevention activity in extracts and fractions from leaves and fruits of Eugenia jambolana as part of bioprospecting of natural products. So far there are no studies on the ability of chemoprevention of plant species. The present study evaluated the induction of quinone-reductase in wild murine hepatoma cell line (Hepa 1c1c7) and mutant murine hepatoma cell line (TAOr1BPrc1 and BPrc1), cytotoxicity, genotoxicity, antigenotoxicity, mutagenicity and antimutagenicity in human hepatoma cell line (HepG2) responsible for metabolizing xenobiotics. The experiments were performed by quinone-reductase assay, staining sulforrodamina B, comet assay and micronucleus test. The results showed that the crude extract and the n-butanol fraction from the leaves, and the crude extract and hydroalcoholic fraction from the fruits of E. jambolana were able to significantly promote the induction of quinone-reductase in different concentrations from 1.25 to 40 μg/ mL. But under these conditions these compounds were potentially genotoxic. In lower concentrations these compounds were not genotoxic or mutagenic. The antigenotoxicity and antimutagenicity assays were performed from non-genotoxic concentrations... (Complete abstract click electronic access below)

Thesis (Ph. D.)--West Virginia University, 2003. / Title from document title page. Document formatted into pages; contains x, 158 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 133-145).

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

A dissertation submitted to the Faculty of Health Sciences, university of the witwatersrand, in fulfilment ofthe requirements for the degree of Master of Medicine (paediatrics) Johannesburg, 20 I 6 / Background: Though features of infants with congenital tubercuiosis (TB) are known including being low-birth-weight (LBw), features of in-utero TB-exposed infants including non-infected are not well reported. Infants bom to TB-infected women are at risk of contracting TB post-delivery, therefore chemoprophylaxis is recommended, and this includes use of isoniazid and rifampicin combination, but littie is known about its effectiveness. Objective: To determine features of in-utero TB-exposed infants and proportion with TB after chemoprophylaxis with isoniazid and rifampicin. Methods: Retrospective review of records of TB-infected women and their infants, from ZA07-20rc. Clinical features of mothers and infants at time of delivery; and follow-up of infants after completion of isoniazid and rifampicin are described. Results: Eighty-eight infants bom to 86 women with a diagnosis of TB were studied. TB diagnosis was made peripartum in24.4Yoof women, 23.3%had exka-pulmonary TB. Among those diagnosed antepa$um 46.2o/owere on treatment for >2 months. Human immunodeficiency virus (HIV) was positive in 97.7Yo;wi& CD4 count <200 cells/mm3 in 74'6yo' Eight mothers (9.3%) died before discharge. There were 56 {63.6%)LBW and 45 (51'2W preterun infants. Culture for acid-fast-bacilli was positive in 4 (4.5%)infants. At 3- months follow-up, 17 (20.2%)defaulted, and among 67 who returned, 7 OAoA)did not return for Mantoux test reading, 1160 (1.7%)had positive Manroux. Conclusion: Majority of TB-exposed infants are born to mothers with TB/ HIV co-infection. A high proportion of TB-exposed infants are born preterm and LBW. The high attrition rate made it difficult to assess effectiveness of chemoprophylaxis with isoniazid and rifampicin / MT2016

No description available.

The present study was carried out to examine the chemopreventive effects of curcumin and green tea polyphenols on the hamster cheek pouch carcinogenesis model. This model of oral carcinogenesis has been widely used in chemoprevention studies, however, these studies have been limited to the use of DMBA as the carcinogenic agent. We have developed a protocol of carcinogenesis in the hamster cheek pouch using B[a]P, a broadly distributed environmental carcinogen, formed as a by-product of the combustion of organic materials including cigarette smoke. B[a]P- induced tumors in the hamster cheek pouch are primarily endophytic squamous cell carcinomas that closely resemble squamous cell carcinomas of the human oral mucosa. The cheek pouch of male Syrian hamsters were treated topically for eight weeks with 0.6% curcumin, 6.0% curcumin, 2.5% green tea polyphenols, or 5.0% green tea polyphenols, 3 times per week 30 minutes prior to the application of 2.0% B[a]P. The animals were sacrificed 24 hours and 72 hours after the last treatments. Short-term mechanistic markers of malignant progression were used to determine effects of each compound. Cellular proliferation, assessed by bromodeoxyuridine (Brdu) incorporation, p53 protein accumulation, and apoptotic activity were evaluated. The results of the present study demonstrated that 0.6% curcumin and 2.5% green tea polyphenols had strong inhibitory effects on cellular proliferation and p53 protein accumulation. And 6.0% curcumin and 5.0% green tea polyphenols appeared to induce apoptosis. Our data suggest that curcumin and green tea polyphenols may have a plausible chemopreventive effect on oral carcinogenesis in the hamster cheek pouch model.

Orientador: Christiane Pienna Soares / Banca: Denise Crispim Tavares / Banca: Dulce Helena Siqueira Silva / Resumo: A variabilidade das regiões geográficas brasileiras favorece o desenvolvimento de diferentes espécies vegetais, o que estimula o estudo na busca de novos agentes bioativos. A quimioprevenção envolve o uso de substâncias naturais ou sintéticas a fim de prevenir, retardar ou reverter o desenvolvimento do câncer e a espécie escolhida para investigação de seu possível efeito quimiopreventivo é a Eugenia jambolana pertencente à família Myrtaceae, seu perfil químico revela a presença de antocianinas e substâncias fenólicas com potencial efeito antioxidante, antiinflamatório e analgésico. O presente estudo tem por objetivo realizar o rastreamento bioguiado para atividade de quimioprevenção em extratos e frações das folhas e dos frutos de Eugenia jambolana como parte da bioprospecção de produtos naturais. Até o momento não existem estudos sobre a capacidade de quimioprevenção dessa espécie vegetal. No presente estudo foi avaliada a indução da enzima quinona-redutase em células de hepatocarcinoma murino selvagem (Hepa 1c1c7) e mutantes (TAOr1BPrc1 e BPrc1), a citotoxicidade, genotoxicidade e antigenotoxicidade, mutagenicidade e antimutagenicidade em células de hepatocarcinoma humano (HepG2) competentes para metabolização de xenobióticos. Experimentos esses realizados através do ensaio da Quinona-redutase, coloração por sulforrodamina B, ensaio do cometa e teste do micronúcleo. Os resultados demonstraram que o extrato bruto e a fração n-butanólica das folhas, e o extrato bruto e a fração hidroalcoólica dos frutos de E. jambolana são capazes de promover significativamente a indução da enzima quinona-redutase em diferentes concentrações, de 1,25 a 40 μg/mL. Porém nessas condições esses extratos e frações foram potencialmente genotóxico. Em menores... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The variability of geographical regions favors the development of different plant species, which encourages the study in the search for new bioactive agents. The chemoprevention involves the use of natural or synthetic substances to prevent, retard or reverse the developing cancer and the species chosen for investigation of their possible chemopreventive effect was Eugenia jambolana belonging to the Myrtaceae family, chemical profile reveals the presence of anthocyanins and phenolic compounds with potential antioxidant, anti-inflammatory and analgesic effect. This study aims to perform a screning chemoprevention activity in extracts and fractions from leaves and fruits of Eugenia jambolana as part of bioprospecting of natural products. So far there are no studies on the ability of chemoprevention of plant species. The present study evaluated the induction of quinone-reductase in wild murine hepatoma cell line (Hepa 1c1c7) and mutant murine hepatoma cell line (TAOr1BPrc1 and BPrc1), cytotoxicity, genotoxicity, antigenotoxicity, mutagenicity and antimutagenicity in human hepatoma cell line (HepG2) responsible for metabolizing xenobiotics. The experiments were performed by quinone-reductase assay, staining sulforrodamina B, comet assay and micronucleus test. The results showed that the crude extract and the n-butanol fraction from the leaves, and the crude extract and hydroalcoholic fraction from the fruits of E. jambolana were able to significantly promote the induction of quinone-reductase in different concentrations from 1.25 to 40 μg/ mL. But under these conditions these compounds were potentially genotoxic. In lower concentrations these compounds were not genotoxic or mutagenic. The antigenotoxicity and antimutagenicity assays were performed from non-genotoxic concentrations... (Complete abstract click electronic access below) / Mestre

PURPOSE:Selective Estrogen Receptor Modulators (SERMs) reduce the risk of breast cancer for women at increased risk by 38%. However, uptake is extremely low and the reasons for this are not completely understood. The aims of this study were to utilize time trade-off methods to determine the degree of risk reduction required to make taking SERMs worthwhile to women, and the factors associated with requiring greater risk reduction to take SERMs.METHODS:Women at increased risk of breast cancer (N=107) were recruited from two familial cancer clinics in Australia. Participants completed a questionnaire either online or in pen and paper format. Hierarchical multiple linear regression analysis was used to analyze the data.RESULTS:Overall, there was considerable heterogeneity in the degree of risk reduction required to make taking SERMs worthwhile. Women with higher perceived breast cancer risk and those with stronger intentions to undergo (or who had undergone) an oophorectomy required a smaller degree of risk reduction to consider taking SERMs worthwhile.CONCLUSION:Women at increased familial risk appear motivated to consider SERMs for prevention. A tailored approach to communicating about medical prevention is essential. Health professionals could usefully highlight the absolute (rather than relative) probability of side effects and take into account an individual's perceived (rather than objective) risk of breast cancer.

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Bile acids have been studied for many years for their role in either promoting (Deoxycholic Acid) or suppressing (Ursodeoxycholic Acid) colon tumor development in animal models. However, the molecular mechanisms of both DCA's and UDCA's biological effects in colon tumorigenesis is still unclear. The cholesterol-like composition of bile acids and evidence of deregulating signal transduction pathways, such as the p42/44 MAP kinase cascade, led us to identify the plasma membrane as a target for bile acid-mediated effects. Specifically, plasma membrane microdomains such as lipid rafts and caveolae are particularly capable of altering mitogenic signaling due to have their role as platforms to concentrate receptors and assemble signal transduction machinery. In this study I tested the hypothesis that the growth suppressive effects of UDCA are mediated by stimulating membrane microdomains to activate protein degradation machinery to facilitate the down-regulation of receptor tyrosine kinase activity. We found that UDCA suppresses EGF-induced ERK activation, promotes interactions between EGFR and Caveolin-1 membrane fractions, whereas DCA causes redistribution. EGFR proteins that are localized to membrane fractions in the UDCA treated cells are extensively ubiquitinylated and we present evidence that this yields recruitment of the ubiquitin ligase c-Cbl to membrane fractions. UDCA increases the rate of EGFR degradation, whereas DCA sustains its' stability. I present evidence that UDCA's growth inhibitory effects on colon cancer cells may be mediated by recruitment of protein degradation machinery to membrane domains that are enriched with signaling receptors, a mechanism which has not been previously described. Importantly, I demonstrate for the first time a novel mechanism by which UDCA promotes growth inhibition, through increasing the rates of degradation of EGFR, thereby down-regulating mitogenic signaling in the cell. These experiments show exciting insights into the mechanism of bile acids and represent potential mechanisms for other chemopreventive agents.