Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (doctoral)--University of Uppsala, 1980. / Includes bibliographical references (p. 41-50).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Thesis (doctoral)--University of Lund, 1982.

Orientadores: Raquel Franco Leal, Luciana Rodrigues de Meirelles / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T15:37:12Z (GMT). No. of bitstreams: 1 Dias_CileneBicca_D.pdf: 2833344 bytes, checksum: 59a00c2b42daf6d300e935a2d91f6368 (MD5) Previous issue date: 2014 / Resumo: A doença de Crohn (DC) está associada com as vias patogênicas complexas envolvendo alterações nos mecanismos de apoptose. Recentemente, o tecido adiposo mesenterial (TAM) tem sido associado com a etiopatogenia DC, uma vez que é verificado um aumento da espessura do tecido adiposo mesenterial e envolvimento circunferencial da alça intestinal próximo à área intestinal afetada. Entretanto, não há estudos do mecanismo de apoptose no TAM na DC. Desta forma, o objetivo desse estudo foi avaliar apoptose na mucosa intestinal e no TAM de pacientes com DC, além de correlacionar estes achados com o estudo morfométrico dos adipócitos neste tecido. Casuística e Métodos: Foram estudadas amostras de mucosa intestinal e TAM de 10 pacientes com DC ileocecal e de 8 pacientes sem doenças inflamatórias intestinais (controles). A apoptose foi avaliada pelo ensaio de TUNEL e correlacionada com a análise histológica e morfométrica dos adipócitos. Determinou-se a análise transcripcional e proteica de uma seleção de genes e proteínas relacionadas com o mecanismo de apoptose. Resultados: O ensaio de TUNEL mostrou menor número de células em apoptose na DC, quando comparado com os grupos controles, tanto na mucosa intestinal quanto no TAM. Além disso, o número de adipócitos em apoptose (TUNEL) correlacionou significativamente com a área e perímetro destas células. A análise transcripcional e proteica revelaram níveis de transcritos e de proteína Bax significativamente mais baixos na mucosa intestinal de DC, em comparação com os respectivos controles; sendo que os baixos níveis de Bax foram encontrados na lâmina própria e não no epitélio intestinal; não houve diferença na expressão de Bax no TAM. Além disso, maior nível de Bcl-2 e baixo nível de Caspase 3 foram vistos no TAM de pacientes com DC. Conclusão: A alteração da apoptose no TAM pode explicar as características morfológicas singulares deste tecido na DC, que podem estar implicadas na fisiopatologia da doença / Abstract: Crohn¿s disease (CD) is associated with complex pathogenic pathways involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue (MAT) has been associated with CD ethiopathology, since adipose thickening is detected close to the affected intestinal area. However, there are no studies concern apoptosis pathways in MAT of CD. Therefore, the aim of this study was to evaluate apoptosis in the intestinal mucosa and MAT of patients with CD, besides to correlate these findings with the morphometricstudy of the adipocytes from MAT.Patients and Methods: Samples of intestinal mucosa and MAT from 10 patients with ileocecal CD and from 8 non-inflammatory bowel diseases patients (controls) were studied. Apoptosis was assessed by TUNEL assay and correlated with the adipocytes histological morphometric analysis. The transcriptional and protein analysis of selected genes and proteins related to apoptosis were determined. Results: TUNEL assay showed fewer apoptotic cells in CD, when compared to the control groups, both in the intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL) correlated significantly with the area and perimeter of the adipose cells in MAT. Transcriptomic and proteomic analysis reveal a significantly lower transcript and protein levels of Bax in the intestinal mucosa of CD, compared to the controls; low protein levels of Bax were found localized in the lamina propria and not in the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level of Caspase 3 were seen in the MAT of CD patients. Conclusion: The defective apoptosis in MAT may explain the singular morphological characteristics of this tissue in CD, which may be implicated in the pathophysiology of the disease / Doutorado / Fisiopatologia Cirúrgica / Doutora em Ciências

An altered small intestinal permeability has been proposed as an important aetiological factor in the pathogenesis of inflammatory bowel disease. The relevant literature was reviewed. Intestinal permeability to Polyethylene glycol 400 in patients with Crohn' s disease, their relatives and healthy controls was examined and the data compared with studies of small bowel permeability to other similar sized probes. A new technique of analysis of urinary Polythylene Glycol 400 by High Performance Liquid Chromatography was described and compared with a previously established HPLC method. No evidence of an altered bowel permeability could be found using Polyethylene glycol 400, but the possibility that this may have been related to probe size and characteristics can not be excluded .

The gastro-intestinal (GI) tract represents the largest surface of the body and is continuously exposed to the microbial environment. In such anatomy, the survival of the host requires that the intestinal microbial flora be contained without excessive immune-reactivity to commensal bacteria while retaining the ability to respond to episodic pathogens. The discriminative recognition between beneficial commensal bacteria and potentially harmful pathogens demands an accurate interpretation by the GI mucosal immune system. Any defects in the processes of innate immune recognition and killing may lead to the development and perpetuation of chronic intestinal inflammation, namely inflammatory bowel disease (i.e. Crohn's disease (CD) and ulcerative colitis (UC)) and post-infectious irritable bowel syndrome (PI-IBS). The aim of ours studies was to evaluate the contribution of candidate genes, involved in the homeostasis and regulation of the intestinal innate immune response, to the susceptibility to CD, DC, and PI-IBS. In the first phase, we describe functional and genetic association results supporting NLRP3, encoding NALP3/cryopyrin, as a novel CD susceptibility gene. We subsequently report that the MEFV gene, encoding pyrin, known to interact with and be involved in the same pathway as NALP3/cryopyrin, does not contribute to CD and DC susceptibility. No CD or DC additional associations were observed upon NLRP3-MEFV gene-gene interaction analyses. In the third phase, we report the first association study evaluating genetic determinants for PI-IBS, using the well-characterized Walkerton population cohort. We uncovered variants in the TLR9, CDH1, and IL6 regions associated with PI-IBS susceptibility. These results are in keeping with the pathophysiologic changes observed in patients with PI-IBS, which include increased intestinal permeability and intestinal immune activation. / Overall, these results contribute to a better understanding of the genetic susceptibility to CD, DC and PI-IBS and shed light on new pathogenic signaling pathways in the development of these diseases.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Thesis (M.Sc.)--Memorial University of Newfoundland, 2004. / Bibliography: leaves 126-133.

nÃo hà / Muitas pesquisas evidenciaram o comprometimento do sistema nervoso perifÃrico na doenÃa inflamatÃria intestinal (DII). AtravÃs do teste de quantificaÃÃo sensitiva (QST) para pesquisa de limiares de sensibilidade a vibraÃÃo ( fibras nervosas grossas) e frio (fibras nervosas finas), (protocolo I) avaliamos 29 pacientes portadores de retocolite ulcerativa (RCU), 30 pacientes portadores de doenÃa de Crohn (DC) e 28 pacientes-controle. Foram aplicados questionÃrios de queixas sensitivas (protocolo II) em 27 pacientes portadores de RCU, 24 pacientes portadores de DC e 25 pacientes-controle. Esses mesmos pacientes realizaram o teste de enrugamento cutÃneo a Ãgua (TEC) (protocolo III), o qual avalia fibras finas do sistema nervoso autÃnomo. O teste de Fisher e teste de hipÃtese qui-quadrado comparando os 3 grupos (RCU, DC e Controle), utilizado na anÃlise do QST revelou maior propensÃo a neuropatia perifÃrica ou alteraÃÃo sensitiva em pacientes RCU e portadores de DII (RCU e DC) quando avaliados respectivamente sensibilidade vibratÃria e tÃrmica ao frio. Resultado de eletroneuromiografia (ENMG) foi anormal em 39,1% dos pacientes RCU e 38,4% pacientes DC. O questionÃrio de queixas sensitivas (protocolo II) revelou prevalÃncia de 51,8 % de queixas sensitivas em pacientes RCU e 50% em pacientes DC. Houve vÃrios tipos de queixas, sendo a mais comum, dormÃncia em mÃos e pÃs. TrÃs pacientes (2 RCU e 1 DC) apresentaram sintomas sugestivos da âsÃndrome das pernas inquietasâ e seis pacientes tinham relatos de tonturas (disfunÃÃo autonÃmica). Dos 14 pacientes RCU e 12 pacientes DC com queixas sensitivas, 57,1% e 25% respectivamente tinham alteraÃÃo em TEC. Dos pacientes RCU e DC que realizaram TEC (protocolo III), 48,1% e 41,7% respectivamente tinham resultado anormal, enquanto a ENMG foi anormal em 30% e 41,2% respectivamente. Podemos enfatizar que o QST e TEC parecem melhores que ENMG para diagnÃstico de alteraÃÃes sensitivas em pacientes com DII, visto que muitas destas alteraÃÃes podem corresponder a neuropatia de fibras finas. / Many studies have demonstrated the involvement of the peripheral nervous system in inflammatory bowel disease (IBD). By quantitative sensation testing (QST) to search for the vibration and cold sensitive thresholds (evaluates thick and small fibres respectively) (protocol I) we assessed 29 patients with ulcerative colitis (UC), 30 patients with Crohnâs disease (CD) and 28 control patients. Questionnaires were applied to sensory complaints (protocol II) in 27 patients with CD, 24 patients with UC and 25 control patients. The same patients underwent stimulated skin wrinkling induced by water (SSW) (protocol III), which evaluates small fibre of the autonomic nervous system. The Fisher test and hypothesis test chi-square comparing the three groups (UC, CD and control) used in analysis of QST revealed more prone to peripheral neuropathy or sensory changes in patients suffering from UC and IBD (UC and CD) when evaluated respectively vibration and cold thermal sensitivity. Results of electromyography (EMG) was abnormal in 39,1% of UC and 38,4% CD patients. The questionnaire of sensory complaints (protocol II) showed prevalence of sensory complaints in 51,8% UC and 50% CD patients. There were several types of complaints, the most common, numbness in hands and feet. Three patients (two UC and one CD) presented with symptoms suggestive of ârestless leg syndromeâ and six patients had reported dizziness (autonomic dysfunction). Of the 14 UC and 12 CD patients with sensory complaints, 57,1% and 25% respectively had change in SSW. Of UC and CD patients who underwent SSW (protoco III), 48,1% and 41,7% had abnormal results, while the EMG was abnormal in 30% and 41,2 % respectively. We emphasize that TEC and QST seem better than EMG for diagnosis of sensory changes in patients with IBD, as many of these changes may correspond to small fibre neuropathy.