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- ItemAcesso aberto (Open Access)Ação modulatória da proteína Anexina A1 sobre os efeitos do tratamento com Anti-TNF-α em modelo murino de colite experimental(Universidade Federal de São Paulo (UNIFESP), 2016-07-26) Silva, Marina de Paula [UNIFESP]; Oliani, Sonia Maria [UNIFESP]; http://lattes.cnpq.br/5102737730539655; http://lattes.cnpq.br/6729268883239928; Universidade Federal de São Paulo (UNIFESP)The tumor necrosis factor-alpha (TNF-α) is a key cytokine in the triggering of the inflammatory bowel diseases (IBDs), constituting an interesting target to therapeutic strategies. However, anti-TNF-α drugs, such as the infliximab (IFX) can still promote side effects and non-responsiveness in some patients, bringing the need to investigate other mediators potentially related to the efficacy of this therapy. In the IBDs, the anti-inflammatory protein annexin A1 (AnxA1) has been associated to the protection of gastrointestinal mucosa. Here, we evaluated the role of the endogenous AnxA1 on the TNF-α blockage efficacy, in rodent model of colitis. To this end, we assessed the colitis induced by dextran sulphate sodium (DSS) in Balb/c mice. Mice deficient in AnxA1 (AnxA1-/-) were employed as an interesting tool to evaluate the relevance of this protein on the intestinal inflammatory condition, comparing with the wide type strain (WT). Mice were also treated with IFX after colitis induction. We consistently observed that the endogenous AnxA1 is related to the prevention of clinical and physiological manifestations on the experimental colitis treated with IFX, since no improvement was found in AnxA1-/- mice. On WT mice, the epithelial damages promoted by the DSS administration were prevented after treatment, which reduced the rectal bleeding and diarrhea, consequently. AnxA1 also preserves the colonic morphology after IFX by decreasing the histological score and protecting against collagen degradation. The interleukin-6 (IL-6) was increased during the colitis in WT and AnxA1-/- mice. The IFX treatment reduced this cytokine only in hte presence of AnxA1. The influx of neutrophils and TNF-? secretion were largely higher compared to WT. Phagocytes, which plays important pro-inflammatory roles, were more susceptible to apoptosis after IFX in the presence of AnxA1. The expression of endogenous AnxA1, was increased in the experimental colitis and decreased on treatment, showing that the inflammatory response is attenuated in this condition. We indicated, for the first time to our knowledge, that AnxA1 plays a critical role to the return of the intestinal homeostasis and constitute a potential biomarker of therapeutic efficacy.
- ItemSomente MetadadadosAvaliação da musculatura longitudinal do segmento de colon distal interposto após ressecção extensa de jejuns-íleo de rato(Universidade Federal de São Paulo (UNIFESP), 1996) Taha, Murched Omar [UNIFESP]; Plapler, Hélio [UNIFESP]
- ItemAcesso aberto (Open Access)Estudo comparativo do tratamento de ferimento de colon de coelho com reparo seroso da parede de jejunum e sutura primária(Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia, 2000-03-01) Fontes, Carlos Edmundo [UNIFESP]; Bandeira, César Orlando Peralta; Ferreira, Marcos Victor; Nigro, Amaury José Teixeira [UNIFESP]; Campos, Leandro Ferracini; Senhorini Júnior, Sidney; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de MaringáThe present research aimed to compare the repair of colon wound using both the jejunal wall and the primary suture . Thirty young rabbits white New Zeland were used, weighing about 3,2 Kg. and were born and raised at the University of Maringá's Experimental farm. The animals were deeply anaesthetized and then submited to a surgery during wich two similar wounds were made in unprepared colon . An instrument created for this purpose was used. The first wound was made 2 cm away from the ceco , and the second one was made 20 cm from the first wound in the caudal location. The wounds were repaired using either the jejunal serosal wall or the primary suture. In both techniques were used separated stitches , made by monofilament poliglecaprone 4-0. The animal was used to control itself. The animals were submited to euthanasia either in the 7th or in 30th day after surgery, at random.Then a macroscopic and microscopic study was made. This research has come to prove that the use of jejunal's serosal wall is available. This techinique has shown better results than the primary suture : neither were there oclusion nor fistula. Besaid , the histologic studies have proved the existence of neomucous epithelium on the 7th day after surgery.
- ItemAcesso aberto (Open Access)Imunoexpressão das proteínas COX-2, p53 e caspase-3 em adenoma colorretal e mucosa não neoplásica(Instituto Israelita de Ensino e Pesquisa Albert Einstein, 2013-12-01) Nogueira, Renan Brito [UNIFESP]; Pires, Andréa Rodrigues Cordovil; Soares, Thélia Maria Santos; Rodrigues, Simone Rabello De Souza; Campos, Mariane Antonieta Menino; Toloi, Giovanna Canato; Waisberg, Jaques; Universidade Federal de São Paulo (UNIFESP); Universidade Federal Fluminense; Hospital Irmandade São João Batista; Fonte Medicina Diagnóstica; Faculdade de Medicina do ABCOBJECTIVE: To analyze the immunoexpression of the COX-2, p53, and caspase-3 proteins in colorectal adenomas and non-neoplastic mucosa. METHODS: 72 individuals were subjected to colonoscopy, which provided 50 samples of adenomas and 45 samples of non-neoplastic colorectal mucosa. The tissue samples were obtained via the tissue microarray technique and subjected to immunohistochemical analysis using primary anti-p53, anti-COX-2, and anti-caspase-3 antibodies. The positivity and intensity of the immunoreaction were classified. The analyzed variables were as follows: site of the adenomas in the colon, degree of dysplasia, size, and score of positivity and intensity of immunoexpression of the p-53, caspase-3, and COX-2 proteins. RESULTS: The immunoexpression of mutated protein p53 was positive in 30 (60%) adenoma samples and negative in 20 (40%) adenoma samples. The immunoexpression of mutated protein p53 was negative in 39 (86.6%) samples and positive in 6 (13.3%) samples of the non-neoplastic colorectal mucosa (p<0.0001). Significant differences were seen between both the largest size (p=0.006) and the highest degree of dysplasia (p<0.0001) of the adenomas and the intensity of immunoexpression of mutated protein p53. The positivity and intensity of immunoexpression of COX-2 (p=0.14) and caspase-3 (p=0.23) showed no significant differences between the adenomas and the non-neoplastic colorectal mucosa. CONCLUSION: Mutated protein p53 was hyperexpressed in the adenomas compared with the non-neoplastic mucosa. Greater size and greater degree of dysplasia in the adenomas were associated with higher expression of mutated protein p53. The immunoexpression of COX-2 and caspase-3 in the adenomas did not exhibit a correlation with the anatomical-pathological features of the tumors and did not differ from the corresponding expression levels in the non-neoplastic mucosa.