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O objetivo deste estudo foi avaliar os efeitos da concentração subletal de 0,3 ppm da FSA de petróleo em parâmetros do sistema imune inato e hepático de Rachycentron canadum após o período de 7 e 14 dias. Observou-se uma diminuição do fator de condição dos animais expostos por 14 dias, comparado ao grupo controle. A contagem diferencial de leucócitos mostrou um aumento do número de leucócitos após 7 dias, e uma diminuição destes após 14 dias. A atividade da enzima lisozima no grupo exposto por 14 dias foi maior em comparação ao grupo controle. Foram observadas, ainda, alterações nos tecidos branquiais, renais e hepáticos, após análises histológicas nos grupos expostos a FSA. Notou-se um aumento do índice hepatossomático e da atividade da enzima AST dos animais expostos a FSA. Não foi observada atividade da enzima ALT em todos os grupos. Conclui-se que a concentração de 0,3 ppm da FSA de petróleo altera parâmetros do sistema imune inato e hepáticos de R. canadum, podendo causar imunossupressão e comprometimento do sistema de biotransformação. / The objective of this study was to evaluate the effects of sublethal concentration of 0.3 ppm of the petroleum WSF in parameters of the innate immune system and hepatic of Rachycentron canadum, after the periods of 7 and 14 days. It was observed a decrease in condition factor of animals exposed for 14 days compared to control group. The differential leukocyte count showed an increased number of total leukocytes after 7 days and decreased after 14 days. The activity of the lysozyme enzyme in group exposed for 14 days was higher compared to the control group. There were, also, changes in gill, kidney and liver tissues in groups exposed to WSF of petroleum for 7 and 14 days. It was noted an increase of the hepatosomatic index and AST enzyme activity of animals exposed WSF. It was not observed activity of the enzyme ALT in all groups. It was concluded that the sublethal concentration of 0.3 ppm of the WSF of petroleum alters parameters of the innate immune system and hepatic of R. canadum that may cause immunosuppression and biotransformation system impairment.

Introduction: The incidence of gastro-oesophageal cancers has increased considerably over the last decade. As the disease is associated with a poor prognosis, there is a need to identify markers of treatment response which could be used in the future to improve the management of gastro-oesophageal tumours. Aims: 1) To compare the ability of published histological grading criteria (Becker, Mandard and Ninomiya) to assess response to neo-adjuvant chemotherapy (NCT) in gastro-oesophageal cancers. 2) To evaluate the expression of thymidylate synthase (TS) in pre-treatment diagnostic biopsy samples as a predictive marker of response to NCT. 3) To investigate whether measurements of hypoxia obtained using pimonidazole are prognostic for treatment outcome in patients with gastro oesophageal adenocarcinoma (ACC). 4) To study the prognostic significance and clinicopathological associations of epithelial mesenchymal transition (EMT) related proteins S100A4, Vimentin and Snail1 in gastro-oesophageal junction (GOJ) tumours. 5) To evaluate the ability of dynamic contrast enhanced (DCE) MRI to assess chemoradiotherapy (CRT) induced changes in oesophageal cancer. Methods: 1) Formalin fixed paraffin embedded (FFPE) tumour blocks and haematoxylin and eosin stained slides of samples from resected tumours (n=66) were obtained from patients who received NCT for gastric and GOJ tumours. The slides were scored independently by two observers and kappa scores calculated. 2) Pre-treatment diagnostic tissue biopsy samples were obtained from 45 patients with gastric and GOJ cancer who received NCT. TS expression was assessed using immunohistochemistry (IHC) and scored by two observers. The clinical and pathological data were analysed. 3) 57 patients were prospectively administered intravenous pimonidazole and the tumour specimens were collected both at staging laparoscopy and resection. IHC was performed to assess pimonidazole expression and determine its association with clinico-pathological factors. 4) Tissue microarrays were prepared from resection specimens from GOJ ACC. IHC was performed to investigate EMT related protein expression. 5) DCE-MRI was performed on five patients diagnosed with oesophageal cancer treated with CRT. Multiple pharmacokinetic parameters were evaluated. Findings: 1) Becker's histological grading criteria was the most reproducible and prognostic of outcome. The incidence of complete histological response (5%) was low in patients receiving NCT. 2) No prognostic benefit of TS expression was identified. 3) Results from only 34 patients were available for analysis. 77% pimonidazole positivity was observed. Preoperative anaemia was associated with significant tumour pimonidazole expression (p=0.04). Pimonidazole was not prognostic for outcome. 4) The overall positive expression was S100A4 (85%), Vimentin (14%) and Snail1 (89%). The increased expression of S100A4 at the tumour body (p=0.02) and luminal surface (p=0.01) was associated with a poor outcome. 5) Significant changes were measured in DCE-MRI pharmacokinetic parameters after CRT. Conclusion: 1) Becker's histological response grading criteria should be further studied in routine clinical practice for response assessment to NCT. 2) TS should be explored further as a marker of NCT response in gastro-oesophageal cancer. 3) Hypoxia is a characteristic feature of upper gastrointestinal ACC and is associated with anaemia. 4) S100A4 is the most useful marker of EMT in GOJ adenocarcinoma. 5) DCE-MRI tracer kinetic parameters should be explored in a larger study to assess their ability to monitor the efficacy of and predict response to neo-adjuvant treatment.

Made available in DSpace on 2014-06-11T19:31:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2001Bitstream added on 2014-06-13T18:41:27Z : No. of bitstreams: 1 vailati_mcf_dr_botfm.pdf: 326485 bytes, checksum: 40ae6105076d1617c946e93f6158fd3d (MD5) / Um aspecto pouco explorado na literatura, é o caráter sistêmico das alterações vasculares induzidas pela angiotensina II (AII). Teoricamente, todos os tecidos podem ser afetados, visto que os receptores da AII já foram identificados em vários órgãos. Os trabalhos que avaliam o efeito da AII no miocárdio são concordantes no sentido de indicar lesões envolvendo vasos e tecido muscular. Não encontramos qualquer estudo que avaliasse o impacto dessas lesões na função ventricular, numa fase que precede a fibrose miocárdica. Foram utilizados 65 ratos Wistar, machos, com aproximadamente 250g de peso corpóreo, divididos em quatro grupos: controle (n=16), ratos tratados com AII (n= 17), ratos tratados com AII + carvedilol (90 mg/kg/dia; n = 15) e AII + losartan (30 mg/kg/dia; n = 17). A infusão contínua de AII foi realizada na dose de 150 hg/min, através de mini-bombas osmóticas colocadas no subcutâneo no dorso do animal. O registro das pressões arteriais caudais (PA) dos animais de cada grupo foi obtido, aproximadamente, 24h antes da implantação da minibomba e antes da realização da eutanásia. Foram realizados cortes histológicos de miocárdio, rim e fígado para coloração pela hematoxilina-eosina e observação das áreas de necrose. A intensidade das lesões foi definida por meio de escores. Uma parte dos animais foi destinada ao estudo histológico e a outra ao estudo do coração isolado. Também foi realizada a técnica de imunohistoquímica para identificação de macrófagos e a técnica vermelho-congo azul de toluidina para mastócitos e eosinófilos. A função ventricular foi avaliada no coração isolado (preparação de Langendorff). Os resultados foram comparados com os ratos do grupo controle, sem qualquer tratamento, por meio de ANOVA com nível de significância p<0,05... / The systemic aspect of vascular damage induced by angiotensin II (AII) is poorly explored in the literature. Considering the presence of AII in various organs, all these tissues might be affect by of AII. There is an agreement among the authors in relation to the effects of AII on the myocardium as involving vessels and myocytes. There is no published data regarding the impact of these lesions on ventricular function preceeding myocardial fibrosis. Sixty five male Wistar rats, (250 ± 20g) distributed in four groups were used: control (n=16), treated with AII (n=17), with AII + carvedilol (90 mg/kg/d, n=15) and AII+ losartan (30 mg/kg/d, n=17). AII was infused continuously at 150 hg/min (for 72 hs) by subcutaneous osmotic pumps. Tail cuff blood pressure was recorded 24 hours before the mini-pump implantation and before euthanasia. Histological sections of the myocardium, kidney and liver were stained by haematoxylin and eosin and observed for presence of necrosis. The injury intensity was scored. Immunohistochemistry was used for macrophages identification and congo red toluidine blue for identification of mast cells and eosinophils. The ventricular function was evaluated in the isolated heart (Langendorff preparation). The results were compared with untreated control rats, by ANOVA and the statistical significance was set at p<0,05. Blood pressure was higher in the groups AII and AII + carvedilol compared to control (165 ± 30 mmHg e 181± 35 mmHg vs 126 ± 13 mmHg, p<0,01). Losartan prevented hypertension. Histopathological analysis showed perivascular inflammation and necrosis of arteriolar wall in the myocardium, kidney, and liver. Carvedilol and losartan partially protected the organs. The intensity of tissular lesions was less than the vascular lesions, without statistical difference among the groups. There were macrophages and mast... (Complete abstract, click electronic address below)

Orientador: Beatriz Bojikian Matsubara / Resumo: Um aspecto pouco explorado na literatura, é o caráter sistêmico das alterações vasculares induzidas pela angiotensina II (AII). Teoricamente, todos os tecidos podem ser afetados, visto que os receptores da AII já foram identificados em vários órgãos. Os trabalhos que avaliam o efeito da AII no miocárdio são concordantes no sentido de indicar lesões envolvendo vasos e tecido muscular. Não encontramos qualquer estudo que avaliasse o impacto dessas lesões na função ventricular, numa fase que precede a fibrose miocárdica. Foram utilizados 65 ratos Wistar, machos, com aproximadamente 250g de peso corpóreo, divididos em quatro grupos: controle (n=16), ratos tratados com AII (n= 17), ratos tratados com AII + carvedilol (90 mg/kg/dia; n = 15) e AII + losartan (30 mg/kg/dia; n = 17). A infusão contínua de AII foi realizada na dose de 150 hg/min, através de mini-bombas osmóticas colocadas no subcutâneo no dorso do animal. O registro das pressões arteriais caudais (PA) dos animais de cada grupo foi obtido, aproximadamente, 24h antes da implantação da minibomba e antes da realização da eutanásia. Foram realizados cortes histológicos de miocárdio, rim e fígado para coloração pela hematoxilina-eosina e observação das áreas de necrose. A intensidade das lesões foi definida por meio de escores. Uma parte dos animais foi destinada ao estudo histológico e a outra ao estudo do coração isolado. Também foi realizada a técnica de imunohistoquímica para identificação de macrófagos e a técnica vermelho-congo azul de toluidina para mastócitos e eosinófilos. A função ventricular foi avaliada no coração isolado (preparação de Langendorff). Os resultados foram comparados com os ratos do grupo controle, sem qualquer tratamento, por meio de ANOVA com nível de significância p<0,05... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The systemic aspect of vascular damage induced by angiotensin II (AII) is poorly explored in the literature. Considering the presence of AII in various organs, all these tissues might be affect by of AII. There is an agreement among the authors in relation to the effects of AII on the myocardium as involving vessels and myocytes. There is no published data regarding the impact of these lesions on ventricular function preceeding myocardial fibrosis. Sixty five male Wistar rats, (250 ± 20g) distributed in four groups were used: control (n=16), treated with AII (n=17), with AII + carvedilol (90 mg/kg/d, n=15) and AII+ losartan (30 mg/kg/d, n=17). AII was infused continuously at 150 hg/min (for 72 hs) by subcutaneous osmotic pumps. Tail cuff blood pressure was recorded 24 hours before the mini-pump implantation and before euthanasia. Histological sections of the myocardium, kidney and liver were stained by haematoxylin and eosin and observed for presence of necrosis. The injury intensity was scored. Immunohistochemistry was used for macrophages identification and congo red toluidine blue for identification of mast cells and eosinophils. The ventricular function was evaluated in the isolated heart (Langendorff preparation). The results were compared with untreated control rats, by ANOVA and the statistical significance was set at p<0,05. Blood pressure was higher in the groups AII and AII + carvedilol compared to control (165 ± 30 mmHg e 181± 35 mmHg vs 126 ± 13 mmHg, p<0,01). Losartan prevented hypertension. Histopathological analysis showed perivascular inflammation and necrosis of arteriolar wall in the myocardium, kidney, and liver. Carvedilol and losartan partially protected the organs. The intensity of tissular lesions was less than the vascular lesions, without statistical difference among the groups. There were macrophages and mast... (Complete abstract, click electronic address below) / Doutor

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Made available in DSpace on 2014-06-11T19:29:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-26Bitstream added on 2014-06-13T20:38:46Z : No. of bitstreams: 1 martins_fsc_me_botfm.pdf: 203779 bytes, checksum: ffa2d7231e5b5a3d8f579954a343ca88 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Na prática clínica, muitas vezes observam-se situações de hemorragia aguda em pacientes submetidos a cirurgias que normalmente não apresentariam grandes perdas sangüíneas, fazendo com que a reposição dessa perda não seja imediata, tanto com solução cristalóide, como com colóide, ou mesmo com sangue. Quais as reais conseqüências para o rim trazidas por essa situação? O objetivo desta pesquisa foi avaliar a histologia do rim de rato normotérmico e anestesiado com sevoflurano, em situação de hemorragia aguda e reposição com solução de Ringer sem lactato e hidroxietilamido 130/0,4. Quatro grupos de ratos Wistar (n=10) anestesiados com sevoflurano, recebendo solução de Ringer sem lactato, 7 mL/kg/h, três dos quais foram submetidos à hemorragia de 30% da volemia (três etapas de retirada de 10% com 10 min de intervalo): G1 - ratos sem reposição do sangue retirado; G2 - reposição com solução de Ringer sem lactato, em proporção de reposição de 3:1 de sangue retirado; G3 - reposição com solução de hidroxietilamido (HEA) 130/0,4, em proporção de 1:1 de sangue retirado; G4 - (sham) - ratos que não foram submetidos à hemorragia. Estudaram-se a pressão arterial média, a temperatura retal e o hematócrito, nos seguintes momentos: M1 – momento que correspondeu ao tempo em que ocorreu a 1a sangria; M2 - 40 min após a 1a sangria e 20 min após a 3a sangria; M3 – 50 min após a 3a sangria, quando os ratos foram sacrificados e foi realizada nefrectomia bilateral para análise histológica dos rins. A temperatura manteve-se estável durante todo o experimento em todos os grupos. Quanto ao hematócrito, em M1 e M2 os grupos foram iguais e, em M3, (G1=G4)>G3>G2. Quanto à pressão arterial média, em M1os grupos foram iguais, em M2, G4 > (G1 = G2 = G3) e, em M3, (G3 = G4) > G2 > G1. Na análise histológica... / In clinical practice, situations of acute hemorrhage are many times observed in patients submitted to surgeries that would normally not present great blood loss, and the replacement for such loss is not immediate, even when using crystalloid solutions, such as colloid, or blood. What are the real consequences to the kidney resulting from this situation? This study aimed at evaluating the histology of the kidney in normothermic rats anesthetized with sevoflurane, in a situation of acute hemorrhage and replacement with Ringer solution without lactate and hydroxyethylamide 130/0.4. Four groups of Wistar rats (n=10) anesthetized with sevoflurane and receiving Ringer solution without lactate, 7 mL/kg/h, were used. Three of these were submitted to hemorrhage of 30% of volemia (three phases for removal of 10% with a 10-min interval): G1 – rats without replacement of the removed blood; G2 – replacement with Ringer solution without lactate, following a replacement proportion of 3:1 of removed blood; G3 – replacement with hydroxyethylamide (HEA) 130/0.4, in a proportion of 1:1 of the removed blood; G4 - (sham) – rats that were not submitted to hemorrhage. Mean arterial pressure, rectal temperature and hematocrits were studied at the following moments: M1 - moment that corresponded to the time when the 1st bleeding occurred; M2 - 40 min after the 1st bleeding and 20 min after the 3rd bleeding; M3 - 50 min after the 3rd bleeding, when the rats were euthanized and bilateral nephrectomy was performed for histological analysis of the kidneys. Temperature was kept stable during the whole experiment in all groups. Concerning hematocrits, in M1 and M2, the groups were similar, and in M3, (G1 = G4) > G3 > G2. As regards mean arterial pressure... (Complete abstract click electronic access below)

Orientador: Yara Marcondes Machado Castiglia / Banca: Rosa Beatriz Amorim / Banca: Marco Aurélio Marangoni / Resumo: Na prática clínica, muitas vezes observam-se situações de hemorragia aguda em pacientes submetidos a cirurgias que normalmente não apresentariam grandes perdas sangüíneas, fazendo com que a reposição dessa perda não seja imediata, tanto com solução cristalóide, como com colóide, ou mesmo com sangue. Quais as reais conseqüências para o rim trazidas por essa situação? O objetivo desta pesquisa foi avaliar a histologia do rim de rato normotérmico e anestesiado com sevoflurano, em situação de hemorragia aguda e reposição com solução de Ringer sem lactato e hidroxietilamido 130/0,4. Quatro grupos de ratos Wistar (n=10) anestesiados com sevoflurano, recebendo solução de Ringer sem lactato, 7 mL/kg/h, três dos quais foram submetidos à hemorragia de 30% da volemia (três etapas de retirada de 10% com 10 min de intervalo): G1 - ratos sem reposição do sangue retirado; G2 - reposição com solução de Ringer sem lactato, em proporção de reposição de 3:1 de sangue retirado; G3 - reposição com solução de hidroxietilamido (HEA) 130/0,4, em proporção de 1:1 de sangue retirado; G4 - (sham) - ratos que não foram submetidos à hemorragia. Estudaram-se a pressão arterial média, a temperatura retal e o hematócrito, nos seguintes momentos: M1 - momento que correspondeu ao tempo em que ocorreu a 1a sangria; M2 - 40 min após a 1a sangria e 20 min após a 3a sangria; M3 - 50 min após a 3a sangria, quando os ratos foram sacrificados e foi realizada nefrectomia bilateral para análise histológica dos rins. A temperatura manteve-se estável durante todo o experimento em todos os grupos. Quanto ao hematócrito, em M1 e M2 os grupos foram iguais e, em M3, (G1=G4)>G3>G2. Quanto à pressão arterial média, em M1os grupos foram iguais, em M2, G4 > (G1 = G2 = G3) e, em M3, (G3 = G4) > G2 > G1. Na análise histológica... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: In clinical practice, situations of acute hemorrhage are many times observed in patients submitted to surgeries that would normally not present great blood loss, and the replacement for such loss is not immediate, even when using crystalloid solutions, such as colloid, or blood. What are the real consequences to the kidney resulting from this situation? This study aimed at evaluating the histology of the kidney in normothermic rats anesthetized with sevoflurane, in a situation of acute hemorrhage and replacement with Ringer solution without lactate and hydroxyethylamide 130/0.4. Four groups of Wistar rats (n=10) anesthetized with sevoflurane and receiving Ringer solution without lactate, 7 mL/kg/h, were used. Three of these were submitted to hemorrhage of 30% of volemia (three phases for removal of 10% with a 10-min interval): G1 - rats without replacement of the removed blood; G2 - replacement with Ringer solution without lactate, following a replacement proportion of 3:1 of removed blood; G3 - replacement with hydroxyethylamide (HEA) 130/0.4, in a proportion of 1:1 of the removed blood; G4 - (sham) - rats that were not submitted to hemorrhage. Mean arterial pressure, rectal temperature and hematocrits were studied at the following moments: M1 - moment that corresponded to the time when the 1st bleeding occurred; M2 - 40 min after the 1st bleeding and 20 min after the 3rd bleeding; M3 - 50 min after the 3rd bleeding, when the rats were euthanized and bilateral nephrectomy was performed for histological analysis of the kidneys. Temperature was kept stable during the whole experiment in all groups. Concerning hematocrits, in M1 and M2, the groups were similar, and in M3, (G1 = G4) > G3 > G2. As regards mean arterial pressure... (Complete abstract click electronic access below) / Mestre

O objetivo deste estudo foi avaliar os efeitos da concentração subletal de 0,3 ppm da FSA de petróleo em parâmetros do sistema imune inato e hepático de Rachycentron canadum após o período de 7 e 14 dias. Observou-se uma diminuição do fator de condição dos animais expostos por 14 dias, comparado ao grupo controle. A contagem diferencial de leucócitos mostrou um aumento do número de leucócitos após 7 dias, e uma diminuição destes após 14 dias. A atividade da enzima lisozima no grupo exposto por 14 dias foi maior em comparação ao grupo controle. Foram observadas, ainda, alterações nos tecidos branquiais, renais e hepáticos, após análises histológicas nos grupos expostos a FSA. Notou-se um aumento do índice hepatossomático e da atividade da enzima AST dos animais expostos a FSA. Não foi observada atividade da enzima ALT em todos os grupos. Conclui-se que a concentração de 0,3 ppm da FSA de petróleo altera parâmetros do sistema imune inato e hepáticos de R. canadum, podendo causar imunossupressão e comprometimento do sistema de biotransformação. / The objective of this study was to evaluate the effects of sublethal concentration of 0.3 ppm of the petroleum WSF in parameters of the innate immune system and hepatic of Rachycentron canadum, after the periods of 7 and 14 days. It was observed a decrease in condition factor of animals exposed for 14 days compared to control group. The differential leukocyte count showed an increased number of total leukocytes after 7 days and decreased after 14 days. The activity of the lysozyme enzyme in group exposed for 14 days was higher compared to the control group. There were, also, changes in gill, kidney and liver tissues in groups exposed to WSF of petroleum for 7 and 14 days. It was noted an increase of the hepatosomatic index and AST enzyme activity of animals exposed WSF. It was not observed activity of the enzyme ALT in all groups. It was concluded that the sublethal concentration of 0.3 ppm of the WSF of petroleum alters parameters of the innate immune system and hepatic of R. canadum that may cause immunosuppression and biotransformation system impairment.