The duodenal epithelium is regularly exposed to HCl, digestive enzymes, bacteria and toxins, and sometimes also to ethanol and drugs. The imbalance of aggressive factors in the intestinal lumen and mucosal barrier function increases the risk of tissue injury and inflammation. The key components of the duodenal barrier function include mucosal permeability, bicarbonate transport and the secretion or absorption of fluids. This thesis aims to elucidate the role of melatonin, neuropeptide S (NPS) and short chain fatty acids (SCFAs) in the regulation of intestinal mucosal barrier function and motility in the anesthetized rat in vivo and in tissues of human origin in vitro. Melatonin was found to reduce ethanol-induced increases in paracellular permeability and motility by a neural pathway within the enteric nervous system involving nicotinic receptors. In response to luminal exposure of ethanol, signs of mild mucosal edema and beginning of desquamation were observed in a few villi only, an effect that was not influenced by melatonin. Melatonin did not modify increases in paracellular permeability in response to luminal acid. NPS decreased basal and ethanol-induced increases in duodenal motility as well as bethanechol stimulated colonic motility in a dose-dependent manner. Furthermore, NPS was shown to inhibit basal duodenal bicarbonate secretion, stimulate mucosal fluid absorption and increase mucosal paracellular permeability. In response to luminal exposure of acid, NPS increased bicarbonate secretion and mucosal paracellular permeability. All effects induced by the administration of NPS were dependent on nitrergic pathways. In rats, administration of NPS increased the tissue protein levels of the inflammatory biomarkers IL-1β and CXCL1. Immunohistochemistry showed that NPS was localized at myenteric nerve cell bodies and fibers, while NPSR1 and nNOS were only confined to the myenteric nerve cell bodies. Perfusing the duodenal segment with the SCFAs acetate or propionate reduced the duodenal mucosal paracellular permeability, decreased transepithelial net fluid secretion and increased bicarbonate secretion. An i.v. infusion of SCFAs reduces mucosal paracellular permeability without any effects on mucosal net fluid flux. However, it significantly decreased bicarbonate secretion. Luminal SCFAs changed the duodenal motility pattern from fasting to feeding motility while i.v. SCFAs was without effect on motility. The systemic administration of glucagon-like peptide-2 (GLP-2) induced increases in mucosal bicarbonate secretion and fluid absorption. An i.v. GLP-2 infusion during a luminal perfusion of SCFAs significantly reduced the duodenal motility. In conclusion, the results in the present thesis show that melatonin, NPS and SCFAs influence the neurohumoral regulation of intestinal mucosal barrier function and motility. Aberrant signaling in response to melatonin, NPS and to luminal fatty acids might be involved in the symptom or the onset of disease related to intestinal dysfunction in humans. / <p>Research funders and strategic development areas:</p><p>- Bengt Ihre Foundation (grant SLS-177521)</p><p>- Socialstyrelsen(grant SLS-176671)</p><p>- Erik, Karin, and Gösta Selanders Foundation</p><p>- Emil and Ragna Börjesson Foundation</p><p>- Uppsala University </p><p>- Ministry of Education of Malaysia</p><p>- Universiti Malaysia Sabah, Malaysia</p>

Made available in DSpace on 2014-06-11T19:23:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-25Bitstream added on 2014-06-13T19:30:19Z : No. of bitstreams: 1 ibrahim_inaf_me_jabo.pdf: 543269 bytes, checksum: 6d5f6bc9c43fb9bfc2c060443c59bb18 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O complexo enteropatia proliferativa dos suínos (EPS), causado pela bactéria Lawsonia intracellularis, é doença infecciosa de grande importância para suínos nas fases de crescimento e terminação e para adultos jovens. Caracteriza-se por determinar alterações proliferativas, hemorrágicas e necróticas da porção final do intestino delgado (íleo). É doença de ocorrência mundial e afeta especialmente animais de alto valor genético, oriundos de programas sanitários tipo SPF (Specific Pathogen Free), sendo responsabilizada por importantes perdas econômicas, seja devido à morte ou queda no desempenho produtivo dos animais. Com o objetivo de desenvolver metodologia rápida e barata para monitoramento padronizado das lesões na linha de abate foi realizado este estudo. Durante o processo de abate, em frigoríficos localizados em Ipuã-SP e Tupã-SP, foram colhidas ao acaso, amostras da porção final do íleo de 156 suínos, todos castrados, de linhagens comerciais, aproximadamente com 150 dias de idade e peso médio de 110 kg. Após padronizadas no comprimento, para exatos 10 centímetros, as amostras foram submetidas à paquimetria, para verificação da sua espessura e do seu diâmetro, e à pesagem, em balança de precisão. Foram, em seguida, cuidadosamente inspecionadas e palpadas, externa e internamente, com o intuito de identificar lesões macroscópicas de ileíte, sendo os resultados destas análises anotados em fichas apropriadas e individuais. Fragmentos de tecido foram colhidos e imersos em formalina neutra a 10%, para análises histopatológicas posteriores... / The complex of porcine proliferative enteropathy (PPE), caused by the bacteria Lawsonia intracellularis, is an infectious disease of great importance to pigs during the growing and ending and for the young adults. Characterized by determining proliferative disorders, hemorrhagic and necrosis of the small intestine (ileum)’s final portion. It is a worldwide occurrence disease and particularly affects animals of high genetic value, type of health programs from SPF (Specific Pathogen Free), being responsible for important economic losses, either due to death or failure in the of animals’ productive performance. With the main goal to develop rapid and inexpensive methodology for standardized monitoring of lesions on the slaughter line this study was accomplished. During the slaughter in slaughterhouses located in Ipuã-SP and Tupã-SP, samples were picked at random from final portions of the ileum from 156 pigs, all castrated, of commercial strains, with approximately 150 days old and weighing 110 kg. After standardized in length, to exactly 10 centimeters, the samples were submitted to the caliper to check the thickness and diameter, and weighing on a precision scale. They were, after all carefully inspected and palpated, externally and internally, in order to identify gross lesions of ileitis, and the results of these tests recorded on proper and individual forms. Fragments of tissue were harvested and immersed in 10% neutral formalin for subsequent histopathological analysis ... (Complete abstract click electronic access below)

Orientador: Luiz Fernando de Oliveira e Silva Carvalho / Banca: Geraldo Camilo Alberton / Banca: Samir Issa Samara / Resumo: O complexo enteropatia proliferativa dos suínos (EPS), causado pela bactéria Lawsonia intracellularis, é doença infecciosa de grande importância para suínos nas fases de crescimento e terminação e para adultos jovens. Caracteriza-se por determinar alterações proliferativas, hemorrágicas e necróticas da porção final do intestino delgado (íleo). É doença de ocorrência mundial e afeta especialmente animais de alto valor genético, oriundos de programas sanitários tipo SPF (Specific Pathogen Free), sendo responsabilizada por importantes perdas econômicas, seja devido à morte ou queda no desempenho produtivo dos animais. Com o objetivo de desenvolver metodologia rápida e barata para monitoramento padronizado das lesões na linha de abate foi realizado este estudo. Durante o processo de abate, em frigoríficos localizados em Ipuã-SP e Tupã-SP, foram colhidas ao acaso, amostras da porção final do íleo de 156 suínos, todos castrados, de linhagens comerciais, aproximadamente com 150 dias de idade e peso médio de 110 kg. Após padronizadas no comprimento, para exatos 10 centímetros, as amostras foram submetidas à paquimetria, para verificação da sua espessura e do seu diâmetro, e à pesagem, em balança de precisão. Foram, em seguida, cuidadosamente inspecionadas e palpadas, externa e internamente, com o intuito de identificar lesões macroscópicas de ileíte, sendo os resultados destas análises anotados em fichas apropriadas e individuais. Fragmentos de tecido foram colhidos e imersos em formalina neutra a 10%, para análises histopatológicas posteriores ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The complex of porcine proliferative enteropathy (PPE), caused by the bacteria Lawsonia intracellularis, is an infectious disease of great importance to pigs during the growing and ending and for the young adults. Characterized by determining proliferative disorders, hemorrhagic and necrosis of the small intestine (ileum)'s final portion. It is a worldwide occurrence disease and particularly affects animals of high genetic value, type of health programs from SPF (Specific Pathogen Free), being responsible for important economic losses, either due to death or failure in the of animals' productive performance. With the main goal to develop rapid and inexpensive methodology for standardized monitoring of lesions on the slaughter line this study was accomplished. During the slaughter in slaughterhouses located in Ipuã-SP and Tupã-SP, samples were picked at random from final portions of the ileum from 156 pigs, all castrated, of commercial strains, with approximately 150 days old and weighing 110 kg. After standardized in length, to exactly 10 centimeters, the samples were submitted to the caliper to check the thickness and diameter, and weighing on a precision scale. They were, after all carefully inspected and palpated, externally and internally, in order to identify gross lesions of ileitis, and the results of these tests recorded on proper and individual forms. Fragments of tissue were harvested and immersed in 10% neutral formalin for subsequent histopathological analysis ... (Complete abstract click electronic access below) / Mestre