Análise molecular do gene p53 em pacientes com esofagite, metaplasia intestinal da cárdia e esôfago de Barrett

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Micropartículas contendo pantoprazol sódico : preparação, caracterização físico-química e avaliação anti-ulcerativa in vivo e da absorção intestinal ex vivo

O pantoprazol (PAN) é um inibidor da bomba de prótons clinicamente empregado para o tratamento de úlcera gástrica e refluxo gastro-esofágico. Estudos relacionados à estabilidade físico-química mostraram que a degradação do PAN está diretamente relacionada com a acidez do meio, determinando a necessidade de administrá-lo em uma forma gastrorresistente. Desse modo, este trabalho propôs-se a desenvolver micropartículas à base de polímero gastrorresistente (Eudragit S100®), polímero de baixa permeabilidade (Eudragit RS30D®) ou de blenda polimérica (Eudragit S100®/ Eudragit RS30D®), contendo PAN pela técnica de spraydrying . O estudo de dissolução in vitro utilizando célula de fluxo demonstrou que o PAN foi liberado das micropartículas em 120 minutos, seguindo cinética de primeira ordem, de acordo com o modelo monoexponencial. A avaliação da gastrorresistência in vitro em célula de fluxo e em dissolutor evidenciou que as formulações de micropartículas à base de Eudragit S100® e da blenda (Eudragit S100®/ Eudragit RS30D®), garantiram adequada proteção ao fármaco em ambiente ácido. Estudos in vivo confirmaram esses resultados, pois possibilitaram a constatação da proteção do fármaco pelas micropartículas durante a passagem pelo estômago, o que possibilitou absorção entérica do PAN em quantidade adequada para exercer atividade farmacológica. Por fim, a investigação ex vivo da permeação do PAN carreado por micropartículas no epitélio intestinal mostrou que estes sistemas foram capazes de garantir a absorção da totalidade do fármaco carreado, constatando-se ainda que este processo ocorreu segundo o modelo monoexponencial.

Pré-condicionamento isquêmico em diferentes tempos e seu efeito na translocação bacteriana induzida por isquemia e reperfusão intestinal em ratos

Para avaliar os efeitos de diferentes tempos de pré-condicionamento isquêmico (IPC) em translocação bacteriana intestinal (BT). MÉTODOS: Trinta ratos Wistar pesando 280 ± 27g foram divididos em cinco grupos. No grupo IV (n = 6), a laparotomia foi realizada e a artéria mesentérica superior foi obstruído por um microclampe atraumática durante 30 minutos. Nos quatro grupos de pré-condicionamento (n = 6 cada) antes dos 30 minutos de isquemia-reperfusão (I / R), os ratos foram submetidos a IPC para duas, cinco, dez e 15 minutos, seguido pelo mesmo momento da reperfusão. A fim de avaliar se o tempo de pré-condicionamento influenciaram o surgimento de translocação bacteriana, as amostras de nódulos linfáticos mesentéricos, fígado e baço foram colhidas em condições estéreis, 24 horas após os procedimentos para a quantificação de unidades formadoras de colónias de bactérias por grama de tecido (CFU / g). O sangue foi recolhido para a medição de citoquinas. RESULTADOS: No grupo I / R, o total de CFU / g em gânglios linfáticos mesentéricos, baço, fígado, bem como o soro de TNF-a, IL-1A e IL-6 foram significativamente mais elevados do que nos outros grupos (p <0,05). Pré-condicionamento por 15 minutos significativamente atenuada BT e citocinas séricas quando comparado a outros períodos de pré-condicionamento (p <0,05). CONCLUSÃO: Nossos dados sugerem que o pré-condicionamento como um fator chave para reduzir a translocação bacteriana intestinal em I / R. Numa escala de dois a 15 minutos, o melhor tempo de pré-condicionamento isquémico pela atenuação da translocação bacteriana foi de 15 minutos

Translocation of 99mTc labelled bacteria after intestinal ischemia and reperfusion

Ischemia and reperfusion of the small intestine disrupts gut barrier, causes bacterial translocation and activates inflammatory responses. An experimental study was planned to evaluate if 99mTc labelled Escherichia coli translocates to mesenteric lymph nodes, liver, spleen, lung and serum of rats submitted to mesenteric ischemia/reperfusion. Additionally, it was observed if the time of reperfusion influences the level of translocation. METHODS: Forty male Wistar rats underwent 45 minutes of gut ischemia by occlusion of the superior mesenteric artery. The translocation of labelled bacteria to different organs and portal serum was determined in rats reperfused for 30 minutes, 24 hours, sham(S) and controls(C), using radioactivity count and colony forming units/g (CFU). RESULTS: All the organs from rats observed for 24 hours after reperfusion had higher levels of radioactivity and positive cultures (CFU) than did the organs of rats reperfused for 30 minutes, C and S, except in the spleen (p<0,01). CONCLUSION: The results of this study indicated that intestinal ischemia/reperfusion led to bacterial translocation, mostly after 24 hours of reperfusion

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

Efeito antiinflamatório de fucana extraída da alga Parda spatoglossum schroederii em modelos experimentais de Peritonite, choque não séptico e colite

Fucans is a name used for sulfated polysaccharides, which is most characteristic structure of the presence of sulfated L-fucose, are found in brown seaweed (Phaeophyceae) and echinoderms (sea urchins and sea cucumbers). These polysaccharides have been reported to possess anticoagulant, antitumor, anti-viral, anti-proliferative and anti-inflammatory activities. Therefore, in the present study was evaluate the effect of the fucan from the brown seaweed Spatoglossum schroederii in models of peritonitis and non-septic shock induced by zymosan, as well as in a murine model of colitis induces by DSS. So, the mice treatment by intravenous route with the fucan was able to reduce the exudate formation and the cell migration in the model of acute peritonitis induced by zymosan during the kinetic of 6, 24 and 48 hours. Similarly, in the model of non-septic shock induced by zymosan the fucan demonstrated a protector effect to inhibited the cellular migration to the peritoneo, to decrease the levels of IL-6 in the serum and in the peritoneal exudate, to attenuate the lose of weight in the mice; beside to reduce the serum levels of hepatic transaminases and as well as the liver injury. In the model of murine colitis, the treatment with the fucan reduced the lose of weight of the animals, decreased the levels of IL-17 and IFN- produced in the gut and decrease the intestinal lesion induced by DSS. In conclusion, the fucan used in this study presented a significant protector effect in the murine models of inflammation

Efeitos do potencial probiótico Enterococcus faecium 32 e de sua associação com o extrato da alga marinha Caulerpa mexicana no tratamento de colite experimental murina

Ulcerative colitis comprising an inflammatory bowel disease, whose most severe consequence is the development of intestinal neoplasia. The drugs currently used to treat the disease trigger a variety of serious adverse effects and are not effective in many cases. Recent studies demonstrated the effectiveness of natural products for the treatment of inflammatory processes. Seaweed extracts and their purified products have shown protective effects in models of inflammation and the association of traditional therapies with probiotics has significantly improved the clinical symptoms of ulcerative colitis. Therefore, the aims of this study include evaluating the potential effects of the use of probiotic strain Enterococcus faecium 32 (Ef32), the methanolic extract of the green seaweed Caulerpa mexicana (M.E.) and their concomitant administration in a murine model of colitis induced by dextran sodium sulfate (DSS). Accordingly, C57BL /6 mice were pretreated orally with Ef32 (109 CFU/ml) for seven days. In the seven days following, the colitis was induced by administration of 3% DSS (w/v) diluted in the animals drinking water. During this period, animals were treated daily with Ef32 and the M.E. (2.0 mg/kg) every other day by intravenous route. The development of colitis was monitored by the disease activity index (DAI), which takes into account the loss of body weight, consistency and presence of blood in stools. After euthanasia, the colon was removed, its length measured and tissue samples were destined for histological analysis and culture for cytokine quantification. The levels of cytokines in the culture supernatant of the colon were measured by ELISA. The treatments with the probiotic Ef32 or the M.E. alone or the combination of these two substances provoked significant improvement as to weight loss and DAI, and prevented the shortening of the colon in response to DSS. The isolated treatments triggered a slight improvement in intestinal mucosal tissue damage. However, their combination was able to completely repair the injury triggered by DSS. The association was also able to reduce the levels of all the cytokines analyzed (IFN-γ, IL-4, IL-6, IL-12, IL-17A and TNF-α). On the other hand, the treatment with Ef32 did not interfere with the levels of TNF-α, whereas treatment with M.E. did not alter the levels of IL-6. Moreover, the treatment with Ef32 not interferes in TNF-α levels, whereas treatment with M.E. did not alter the levels of IL-6. Therefore, the potential probiotic Ef32 and M.E. and especially when these samples were associated proved promising alternatives in the treatment of ulcerative colitis as demonstrated in an experimental model because of its beneficial effects on morphological and clinical parameters, and by reducing the production of proinflammatory cytokines of Th1, Th2 and Th17

Effects of 15d-PGJ(2)-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Emprego dos ácidos graxos de cadeia curta na colite de derivação fecal : estudo em ratos Wistar

Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, after a colostomy. It is postulated that nutritional deficiency of the colonic epithelium by the absence of short-chain fatty acids (SCFA) is one of the factors responsible for the appearance of DC and that their employment could reverse the morphological changes of the mucosa. The treatment of choice for fecal diversion colitis (DC) is the reconstruction of the intestinal tract, although they suggested therapeutic options using enemas. This study evaluates the effect of SCFA in atrophy and inflammation in excluded colonic segments before and after the installation DC. Forty Wistar rats were divided into four groups (n = 10 for each group), submitted colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after postoperative day 40), for 07 days. Histological sections stained with HE were used for histological analysis of the thickness of the colonic mucosa excluded (t- Student p ≤0.05). Inflammatory reaction of the lamina propria and mucosa were measured with scores previously established (Mann Whitney p ≤ 0.05). There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 did not prevent the mucosal atrophy and significant increases in the numbers of lymphocytes (p=0.0006) and 50 eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy

Effects of Tityus serrulatus scorpion venom on lung mechanics and inflammation in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of phospholipase A(2) and tyrosine kinase in Clostridium difficile toxin A-induced disruption of epithelial integrity, histologic inflammatory damage and intestinal secretion

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito de extratos da alga marinha caulerpa mexicana em modelos de inflamação em murinos

The regulation of the inflammatory response is essential to maintain homeostasis. Several studies have been performed to search new drugs that can contribute to avoiding or minimizing an excessive inflammatory process. The aim of this study was to evaluate the effect of extracts of green algae Caulerpa mexican in models of inflammation. In mice, the model of peritonitis induced inflammatory zymosan pretreatment of mice with aqueous and methanol extracts of C. mexican was able to reduce cell migration to the peritoneal cavity. Treatment of mice with extracts of C. mexican also reduced the ear edema induced by xylene and exerted inhibitory action on the migration of leukocytes in inflammation-induced zymosan the air pouch, and timedependent for the extracts tested in the model of ulcerative colitis induced by DSS 3%, the extract methanol, but not the aqueous C. mexican, significantly reduced the clinical symptoms of colitis, as well as the production of proinflammatory cytokines in the culture of mouse colon, in the histological analysis there was a slight reduction of inflammation in the intestinal mucosa. We concluded that the administration of the extracts resulted in the reduction of cell migration to different sites as well as reducing the edema formation induced by chemical irritant. This study demonstrates for the first time the antiinflammatory effect of aqueous and methanolic extracts from green marine algae Caulerpa mexican

Morphological abnormalities and apoptosis in lamellar tissue of equines after intestinal obstruction and treatment with hydrocortisone

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dermatose responsiva à biotina em cão

Os transtornos da pele e dos pelos são parte importante na prática clínica de pequenos animais. Numerosos fatores nutricionais afetam a homeostase, a qualidade e o aspecto da pelagem. As vitaminas do complexo B incluem compostos hidrossolúveis necessários como coenzimas em diversas funções celulares envolvidas no metabolismo energético e na síntese tecidual. A biotina, em especial, é necessária nas reações de carboxilação, participando da síntese de ácidos graxos, aminoácidos e purinas pelo tecido epitelial. Uma cadela com quadro de cistite recorrente e tumor venéreo transmissível foi tratada com antibioticoterapia prolongada e quimioterapia. Após alguns meses de tratamento, foram observadas lesões no plano nasal e nos coxins plantar e palmar, caracterizadas por hiperceratose, espessamento, fissuras, sangramento e inflamação. O paciente recebeu suplementação de 15mg de biotina por via oral (equivalente a 1,4mg kg-1 de peso corporal), uma vez por dia, durante 60 dias, havendo importante regressão das lesões. Sugere-se que, sob antibioticoterapia e doença, a síntese intestinal de biotina possa não ter sido suficiente, sendo necessária sua suplementação.

Morfometria da cicatrização do cólon descendente de eqüinos submetidos a enterorrafias aposicional e invaginante

A pesquisa foi conduzida com o objetivo de comparar duas técnicas de enterorrafias no cólon descendente de eqüinos, uma aposicional e outra invaginante, utilizando-se de avaliações morfométricas. As intervenções cirúrgicas foram executadas em 15 eqüinos adultos sadios, pelo flanco esquerdo, sob anestesia geral inalatória. As enterotomias foram realizadas na tênia antimesentérica do cólon descendente e as enterorrafias foram feitas com fio de poliglactina 910 n° 0. Os eqüinos foram distribuídos aleatoriamente em cinco grupos de três animais cada e submetidos à eutanásia aos três, sete, 14, 21 e 35 dias de pós-operatório para colheita de segmentos intestinais dos locais das enterorrafias para análise morfométrica. Com o auxílio de analisador de imagens, foram contados os números de neutrófilos, células mononucleares e eosinófilos ao redor do fio de sutura. Na contagem de neutrófilos, houve diferença (P = 0,05) entre as enterorrafias, com maior número na aposicional. Quanto aos mononucleares, observou-se diferença (P = 0,01) na interação entre os dias de pós-operatório e as enterorrafias. Não foram observadas diferenças (P > 0,05) na contagem de eosinófilos. Concluiu-se que a enterorrafia invaginante causou reação inflamatória de menor intensidade que a aposicional, sendo a opção preferencial para uso neste órgão.