<p>Currently, there is no effective cure for Inflammatory Bowel Disease (IBD), medications are aimed solely at alleviating symptoms and not curative. Great scientific efforts have been aimed at elucidating the mechanisms underlying the pathogenesis of IBD. Macrophages—antigen presenting cells—play a chief role in the pathophysiology of IBD. It has been proposed that CD36 receptor present on the surface of macrophages, may play a role in the inflamed intestine. CD36-expressing macrophages have been implicated in a variety of human diseases; however the role of CD36+ macrophages in the intestine has been limited. The aim of this study was to decipher whether or not CD36+ F4/80+ macrophages are inflammatory in the colonic intestine. Our study discovered the proportion of CD36+ F4/80+ macrophages were markedly upregulated in active IBD patients and TNBS-induced colitis mice. CD36+ macrophages isolated from the LPMC of the small and large intestine of Balb/c treatment groups(a) 12TNBS, (b) MHS+12TNBS, and (c) MHS+PA mice confirmed these macrophages expressed some level of proinflammatory cytokine TNF-α. Two macrophage ligands, LCFA: Palmitic Acid and PGN, in conjunction or separately, appeared to be two culprits which induced MHS macrophages to produce TNF-α both in vitro and in vivo. It is possible these two ligands may work in concert, however the mouse model has yet to be examined. The precise role(s) of these CD36+ F4/80+ macrophages requires further scientific inquiry and elucidation in the context of intestinal inflammation. It is quite possible understanding the mechanisms and roles of these macrophages will greatly advance our knowledge in the pathophysiology of IBD and potential therapeutic treatments or targets.</p> / Master of Science (MSc)

Orientador: José Murilo Robilotta Zeitune / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T02:57:17Z (GMT). No. of bitstreams: 1 Parente_JoseMiguelLuz_D.pdf: 3595737 bytes, checksum: a5229b134d3c146b3029f45e146e580e (MD5) Previous issue date: 2014 / Resumo: Introdução: Doença de Crohn (DC) e Retocolite Ulcerativa Idiopática (RCUI) são as duas principais doenças inflamatórias intestinais (DII), cuja prevalência é mais expressiva no norte da Europa, Estados Unidos da América e Canadá. Mais recentemente, elas passaram a ser detectadas em frequência crescente em todos os continentes. O objetivo desta pesquisa foi analisar as características demográficas e fenótipos clínicos dos pacientes com DII no Nordeste brasileiro, referentes à época da confirmação do diagnóstico. Casuística e Método: Este é um estudo descritivo e transversal, o qual foi aprovado pelo Comitê de Ética e Pesquisa da UFPI. Foram incluídos censitariamente os pacientes com DII que faziam seguimento clínico em serviços especializados de hospitais universitários em todas as capitais do Nordeste do Brasil. As variáveis analisadas foram: as características demográficas e socioeconômicas, e os dados clínicos de DC e RCUI de acordo com a classificação de Montreal. As análises estatísticas incluíram: média, mediana e desvio padrão para variáveis quantitativas; teste do qui-quadrado (c2) de Pearson para análise das variáveis qualitativas. O nível de significância adotado foi de 5%. Resultados: Foram incluídos 913 indivíduos com DII, sendo 486 (52,1%) com RCUI, 412 (44,2%) com DC e 35 (3,7%) com colite não classificada (CNC). A idade dos pacientes variou de 8 anos a 83 anos, média de 37,9 (DP = 14,4) anos, sendo 469 (50,3%) mulheres. Em todo o período estudado (1975 ¿ 2013), o atraso na confirmação diagnóstica foi de 31,0 meses. As características preponderantes dos pacientes com DC, segundo a classificação de Montreal foram: idade entre 17 e 40 anos (A2), localização com envolvimento de cólons (L2) e comportamento inflamatório (B1). Para os pacientes com RCUI, houve predomínio de pacientes com idade entre 17 e 40 anos e extensão da doença até ângulo esplênico (E2). Conclusão: Este estudo demonstrou que houve expressivo aumento na frequência de DC e RCUI na região Nordeste do Brasil nos últimos trinta anos / Abstract: Introduction: Usually, inflammatory bowel diseases (IBD), as Crohn's disease (CD) and ulcerative colitis (UC), have been described in northern Europe, United States of America and Canada. In the last decades, IBD frequency has been also increased in all continents. The aim of the study was to analyze the demographic characteristics and clinical phenotypes of IBD in the northeastern of Brazil, according to the time of the diagnosis. Casuistic and methods: This is a cross-sectional study, which was approved by the Institutional Ethics and Research Committee. We included patients who were undergoing medical treatment for IBD in specialized centers in the Federal University Hospitals from all Northeasthern areas in Brazil. Demographic and socioeconomic characteristics were analyzed, as well as clinical data of CD and UC according to the Montreal classification. Statistical analyses included mean, median and standard deviations for quantitative variables, and the Pearson chi-square (c2) test for qualitative variables. The level of significance adopted was 5%. Results: A total of 913 patients with IBD were included, 486 (52,1%) with UC, 412 (44,2%) with CD and 35 (3,7%) with unclassified colitis (UnC). The ages ranged from 8 years to 83 years, mean 37.9 (SD = 14.4) years. Of the total, 469 (50.3%) were women. Throughout the study period (1975 ¿ 2013), the delay in diagnosis confirmation was 31.0 months. The predominant characteristics of CD patients, according to the Montreal classification were: age between 17 and 40 years (A1); colon location (L2); and inflammatory behavior (B1). For patients with UC, there was a predominant age between 17 and 40 years, and left colitis (E2). Conclusion: This study showed that there was significant increase in the frequency of IBD (CD and UC) in northeastern of Brazil over the past thirty years / Doutorado / Medicina Interna / Doutor em Ciências Médicas

There are several types of disorders that affect our colon’s ability to function properly such as colorectal cancer, ulcerative colitis, diverticulitis, irritable bowel syndrome and colonic polyps. Automatic detection of these diseases would inform the endoscopist of possible sub-optimal inspection during the colonoscopy procedure as well as save time during post-procedure evaluation. But existing systems only detects few of those disorders like colonic polyps. In this dissertation, we address the automatic detection of another important disorder called ulcerative colitis. We propose a novel texture feature extraction technique to detect the severity of ulcerative colitis in block, image, and video levels. We also enhance the current informative frame filtering methods by detecting water and bubble frames using our proposed technique. Our feature extraction algorithm based on accumulation of pixel value difference provides better accuracy at faster speed than the existing methods making it highly suitable for real-time systems. We also propose a hybrid approach in which our feature method is combined with existing feature method(s) to provide even better accuracy. We extend the block and image level detection method to video level severity score calculation and shot segmentation. Also, the proposed novel feature extraction method can detect water and bubble frames in colonoscopy videos with very high accuracy in significantly less processing time even when clustering is used to reduce the training size by 10 times.

Este estudo tem como objetivo, descrever a microbiota intestinal de pacientes com retocolite ulcerativa grave, em tratamento clínico, antes e após retocolectomia com anastomose de bolsa ileal ao canal anal. Comparou-se a flora bacteriana do íleo terminal e do reto no pré-operatório com a flora encontrada na bolsa ileal após dois e oito meses do fechamento da ileostomia e com a flora do íleo terminal e do reto de um grupo controle. Observou-se que a Veillonella sp foi a bactéria mais freqüentemente encontrada em todos os grupos. Não houve diferenças significativas entre a flora intestinal do grupo controle e dos pacientes com retocolite ulcerativa / The aim of this study is to describe the intestinal microbiota of patients with severe ulcerative colitis, under clinical treatment, before and after proctocolectomy and ileal pouch-anal anastomosis. Intestinal flora of distal ileum and rectum before surgery was compared with the flora found in ileal pouch after two and eight months after ileostomy closure and with the flora of distal ileum and rectum of controls. Veillonella sp was the most frequent microorganism found in all groups. There were no significant differences between the intestinal microbiota found in controls and in patients with ulcerative colitis

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

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Este estudo tem como objetivo, descrever a microbiota intestinal de pacientes com retocolite ulcerativa grave, em tratamento clínico, antes e após retocolectomia com anastomose de bolsa ileal ao canal anal. Comparou-se a flora bacteriana do íleo terminal e do reto no pré-operatório com a flora encontrada na bolsa ileal após dois e oito meses do fechamento da ileostomia e com a flora do íleo terminal e do reto de um grupo controle. Observou-se que a Veillonella sp foi a bactéria mais freqüentemente encontrada em todos os grupos. Não houve diferenças significativas entre a flora intestinal do grupo controle e dos pacientes com retocolite ulcerativa / The aim of this study is to describe the intestinal microbiota of patients with severe ulcerative colitis, under clinical treatment, before and after proctocolectomy and ileal pouch-anal anastomosis. Intestinal flora of distal ileum and rectum before surgery was compared with the flora found in ileal pouch after two and eight months after ileostomy closure and with the flora of distal ileum and rectum of controls. Veillonella sp was the most frequent microorganism found in all groups. There were no significant differences between the intestinal microbiota found in controls and in patients with ulcerative colitis

No description available.

Immune-mediated inflammatory diseases (IMID) represent a group of ostensibly unrelated, chronic and highly disabling diseases that preferentially affect different organ systems. IMID are assumed to manifest as a result of the accumulation of genetic, environmental and immunological factors. A fundamental commonality between IMID is the idiopathic nature of disease, and moreover, substantial similarities are apparent in disease etiopathogenesis. The complex assemblage of microbes and their genes that exists within and on the human body, collectively known as the microbiome has emerged as a critical factor in human health and, altered microbial populations within the gastrointestinal tract lumen and mucosa have been linked to several IMID. Accordingly, we conducted several studies investigating the association of the gut microbiome with IMID. Our main study investigated differences in the microbial profile and functional potential of multiple IMID utilizing 16S rDNA amplicon sequencing and analysis of stool. We also investigated the mucosal-associated microbiome in IBD to characterize the microbial populations and their functions residing in distinct gastrointestinal compartments from inflamed and noninflamed mucosa. We also explored a potential environmental factor; specifically assessing whether microbes present in drinking water in low or high incidence areas of IBD might contribute to disease etiology. The findings of these studies are manifold. First, we show important differences of the stool microbial profile in IMID. In doing so, we were able to identify distinct states of gut dysbiosis and have revealed numerous microbes that are consistently or uniquely disproportionate between IMID. Second, we have shown the microbial profile associated with inflamed and noninflamed mucosa and have reported that a localized dysbiosis is not observed in the presence of inflammation. Third, we have revealed that distinct gastrointestinal compartments are comprised of similar microbial communities. Lastly, we have reported the drinking water microbiome to differ between low and high incidence areas of IBD, thus suggesting a potential role in IBD etiology. Understanding the role of the gut microbiome in human disease will enable the development and application of more appropriate therapeutic strategies that specifically target microbes within the gut. / May 2017