Orientador: Claudio Saddy Rodrigues Coy / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Medicas / Made available in DSpace on 2018-08-14T01:57:13Z (GMT). No. of bitstreams: 1 Moreira_AnaPaulaPaiva_M.pdf: 1853908 bytes, checksum: e3ffa2637de54d6f4e2d71efbafe382d (MD5) Previous issue date: 2009 / Resumo: A doença de Crohn apresenta aspectos controversos e pouco compreendidos em relação a sua etiopatogenia e à sua evolução; o que torna difícil o manejo terapêutico desta doença. Nos últimos anos os avanços da biologia molecular têm possibilitado novas descobertas, no entanto, ainda existem muitas dúvidas em relação à sua etiopatogenia e à ação de diversos mediadores inflamatórios. Objetivo: Avaliar a expressão das citocinas pró-inflamatórias TNF-a, IL-1ß e IL-8 em fragmentos de íleo terminal de pacientes portadores de doença de Crohn em uso de mesalazina e azatioprina e compará-los aos indivíduos normais. Casuística e Métodos: Foram selecionados 25 pacientes acompanhados no Ambulatório de Doença Inflamatória Intestinal do HC-UNICAMP, portadores de doença de Crohn com acometimento de íleo terminal, e que foram, de acordo com protocolos vigentes, submetidos à colonoscopia de controle para avaliação da doença ou procedimento cirúrgico para ressecção ou plastia do segmento doente. Foi obtida amostra de íleo terminal para avaliação dos mediadores inflamatórios acima citados, por meio de técnica de imunoblot. Foram estudados sete pacientes que estavam em uso de mesalazina, nove que estavam em uso de azatioprina, sendo comparados com 9 controles que não portadores de doença inflamatória intestinal. Resultados: Não foi encontrada diferença na expressão do TNF-a entre os três grupos. Foi encontrada diferença estatisticamente significativa quando avaliadas as expressões da IL1- ß e da IL-8. Os níveis de expressão de IL-8 e de IL1- ß foram maiores no grupo que estava em uso de azatioprina quando comparados aos grupos Mesalazina e Controle (p < 0,05). Conclusão: Os pacientes em uso de azatioprina apresentam maior expressão de IL-8 e IL1- ß que aqueles em uso de mesalazina e que os controles. Isto poderia estar associado à ação da mesalazina que diminui, especificamente a ativação destas interleucinas. / Abstract: Crohn's disease is an inflammatory bowel disease that is not currently understood. Much research is being carried out in order to comprehend its mechanisms of lesion and the inflammatory mediators involved in this disease. New advances in molecular biology have opened up new possibilities for further understanding this intricate pathology, yet, some doubts remain. Objective: To evaluate the expressions of TNF-a, IL-1ß and IL-8 in terminal ileum biopsies from patients with Crohn's disease in treatment with mesalazine and azathioprine, and compare these expressions. Patients and Methods: 25 patients from the Inflammatory Bowel Disease Ambulatory from the Clinic Hospital of the University of Campinas, who were submitted to colonoscopy or ileal resection and plastic surgery, were randomly selected. Biopsies from the terminal ileum were obtained and sent for imunoblotting analysis in order to determine the expressions of the proteins studied. Seven of the patients were taking mesalazine, while nine were on azathioprine and expressions were all compared to those of nine healthy controls. Results: No statistical difference was found between the expressions of TNF-a amongst the three groups. In contrast, IL1- ß and IL-8 were found in different levels of expression in the group taking azathioprine when compared to the mesalazine group and control (p<0, 05). Conclusion: Patients chronically taking azathioprine demonstrate higher levels of expression of the inflammatory mediators, IL1- ß and IL-8, in terminal ileum biopsies, when compared to mesalazine treated and healthy counterparts. This effect could be due the inhibition of these proteins' expression induced by mesalazine, cooling down bowel's inflammatory activity back to normal. / Mestrado / Cirurgia / Mestre em Cirurgia

Ulm, Univ. Diss., 2006.

Regensburg, Univ., Diss., 2008.

Regensburg, Universiẗat, Diss., 2008.

Zugl.: Giessen, Univ., Diss., 2008

Th.--Biol. hum.--Tours, 1983. N°: 1.

NÓBREGA, Ana Carolina Mello. Sintomas dispépticos e retardo do esvaziamento gástrico de sólidos em pacientes com doença de Crohn em remissão. 2011. 118 f. Dissertação (Mestrado em Ciências Médicas) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2011. / Submitted by denise santos (denise.santos@ufc.br) on 2014-12-22T13:07:36Z No. of bitstreams: 1 2014_dis_acmnóbrega.pdf: 1956976 bytes, checksum: b15c50261cbe6e1908584941b5d70e23 (MD5) / Approved for entry into archive by denise santos(denise.santos@ufc.br) on 2014-12-22T13:08:40Z (GMT) No. of bitstreams: 1 2014_dis_acmnóbrega.pdf: 1956976 bytes, checksum: b15c50261cbe6e1908584941b5d70e23 (MD5) / Made available in DSpace on 2014-12-22T13:08:40Z (GMT). No. of bitstreams: 1 2014_dis_acmnóbrega.pdf: 1956976 bytes, checksum: b15c50261cbe6e1908584941b5d70e23 (MD5) Previous issue date: 2011 / Patients with Crohn’s disease have been shown to present dyspeptic symptoms more frequently than the general population. Some of these symptoms could be related to some degree of motility disorders. Our objectives were to investigate whether gastric emptying of solids in patients with inactive Crohn’s disease is delayed and to determine the relationships between gastric emptying and dyspeptic symptoms in inactive Crohn’s disease. Twenty-six patients with inactive Crohn’s disease, as defined by a Crohn’s Disease Activity Index (CDAI) < 150, underwent a gastric emptying test by breath test using 13C octanoic acid coupled to a solid meal and answered a validated questionnaire (The Porto Alegre Dyspeptic Symptoms Questionnaire) to assess dyspeptic symptoms. Patients were divided in two groups: without dyspepsia (total score < 6) and with dyspepsia (total score ≥ 6). The control group was composed by 14 healthy volunteers age and sex matched. Patients with Crohn’s disease had a significantly longer t 1/2 and t lag (p<0.05) than the controls. Crohn’s disease patients with dyspepsia had significantly (p<0.05) delayed gastric emptying when compared to patients without dyspeptic symptoms. When the individual symptom patterns were analyzed, only vomiting was significantly associated with delayed gastric emptying (p<0.05). There was no difference between the subgroups of patients with respect to gender, CDAI scores, disease location, clinical behavior (obstructive/obstructive) or previous gastrointestinal surgery. However, it was observed that patients in the group without dyspepsia were treated with immunosuppressants (azatioprina/6-MP) in a proportion significantly higher (p <0.05) than patients in the group with dyspepsia. In conclusion, delayed gastric emptying in inactive Crohn’s disease patients seems to be associated with dyspeptic symptoms, particularly vomiting, even without any evidence of gastrointestinal obstruction. / Estudos demonstraram que pacientes com doença de Crohn apresentam sintomas dispépticos com mais freqüência do que a população geral. Alguns desses sintomas podem estar relacionados a algum grau de distúrbio de motilidade. Nossos objetivos foram investigar se há retardo no esvaziamento gástrico de sólidos em pacientes com doença de Crohn em remissão e determinar se há correlações entre esvaziamento gástrico e sintomas dispépticos nesta patologia. Vinte e seis pacientes com doença de Crohn em remissão, ou seja, com índice de atividade de doença de Crohn (Crohn’s Disease Activity Index – CDAI)<150 foram submetidos a um teste de esvaziamento gástrico por teste respiratório usando o 13C-ácido octanóico ligado a uma refeição sólida e responderam a um questionário (Questionário Porto Alegre de Sintomas Dispépticos) que avalia quantitativamente os sintomas dispépticos. A partir daí os pacientes foram divididos em dois grupos: sem dispepsia (total de escores < 6) e com dispepsia (total de escores ≥ 6). O grupo controle foi composto por 14 voluntários saudáveis, que também realizaram teste de esvaziamento. Pacientes com doença de Crohn apresentaram t 1/2 e t lag significativamente mais prolongados (p<0,05) do que os controles. Além disso, pacientes com doença de Crohn e dispepsia tiveram significativo retardo esvaziamento gástrico (p<0,05), quando comparados aos pacientes sem sintomas dispépticos. Quando o padrão de sintomas individuais foi analisado, somente o sintoma vômito foi significativamente associado com o retardo no esvaziamento gástrico (p<0,05). Quanto à presença de retardo no esvaziamento gástrico de sólidos, não houve diferença entre os subgrupos de pacientes em relação ao gênero, ao escore CDAI, localização da doença, comportamento da doença (obstrutivo/não-obstrutivo) ou cirurgia gastrointestinal anterior. Porém, foi observado que os pacientes do grupo sem dispepsia fizeram uso de imunossupressores numa proporção significativamente maior (p <0,05) que os pacientes do grupo com dispepsia. Em conclusão, a presença de retardo no esvaziamento gástrico de sólidos em pacientes com doença de Crohn em remissão parece estar associada com sintomas dispépticos, particularmente com o sintoma vômito, mesmo sem evidência de obstrução gastrointestinal.

OLIVEIRA, Gisele Ramos de. Manifestações neurológicas em pacientes com doença de Crohn e retocolite ulcerativa. 2008. 144 f. Tese (Doutorado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2008. / Submitted by denise santos (denise.santos@ufc.br) on 2012-06-11T11:43:12Z No. of bitstreams: 1 2008_tese_groliveira.pdf: 861241 bytes, checksum: baaeada8f79d066b29241168aa7197fe (MD5) / Approved for entry into archive by Eliene Nascimento(elienegvn@hotmail.com) on 2012-06-11T15:32:18Z (GMT) No. of bitstreams: 1 2008_tese_groliveira.pdf: 861241 bytes, checksum: baaeada8f79d066b29241168aa7197fe (MD5) / Made available in DSpace on 2012-06-11T15:32:18Z (GMT). No. of bitstreams: 1 2008_tese_groliveira.pdf: 861241 bytes, checksum: baaeada8f79d066b29241168aa7197fe (MD5) Previous issue date: 2008 / Several neurological disorders have been described in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown. We prospectively studied the prevalence and incidence of neurological disorders in a cohort of 82 patients with IBD (protocol 1) and the presence and severity of tremor in patients with IBD or healthy volunteers (Protocol 2). Patients from protocol 1 were evaluated at the IBD Clinic from the Hospital Walter Cantídio for at least one year, with complete periodic neurological evaluations. The second protocol consisted in quantifying the amount of tremor in Archimedes spirals from patients with Crohn´s disease (CD, N=31), ulcerative colitis (UC, N=63) and healthy volunteers (N=41) by a neurologist specialized in movement disorders (Dr. Elan Louis, Columbia University, New York City). Sensory or sensorimotor large-fiber polyneuropathy was observed in 16.1% of the patients with CD and 19.6% of the patients with UC. Neuropathy was usually mild, predominantly distal, symmetric, and axonal. Carpal tunnel syndrome was more commonly observed in women with UC. Sensory complaints without electrodiagnostic (EMG) abnormalities suggestive of small fiber neuropathy or subclinical myelopathy were observed in 29% of the patients with CD and 11.8% of the patients with UC. After excluding other etiological or contributory factors for the development of neuropathy, still 13.4% of the IBD patients had large or small fiber neuropathy (7.3% had large-fiber polyneuropathy). Non-debilitating headache was the most common neurological complaint, 3 patients had strokes, 5 were diagnosed with epilepsy and one had transient chorea. Patients with IBD had lower scores of tremor in the Archimedes spiral assessment due to decreased caffeine intake. In patients with CD, there was a significant correlation between tremor grade, use of medications with effect on the central nervous system, use and amount of caffeine intake and presence of other neurological conditions. In patients with UC, there was only a significant correlation between tremor grade, age and use and the amount of caffeine intake prior to the evaluation. In summary, patients with CD and UC exhibit a wide range of neurological manifestations that are frequently neglected clinically. / Vários distúrbios neurológicos foram observados em pacientes com doença inflamatória intestinal (DII), porém sua prevalência exata é desconhecida. Estudamos prospectivamente a incidência e a prevalência das manifestações neurológicas em uma coorte de 82 pacientes com DII (protocolo 1) e a presença e gravidade de tremor em pacientes com DII e voluntários sadios (Protocolo 2). Os pacientes do protocolo 1 foram avaliados no ambulatório de DII do Hospital Walter Cantídio por um período de pelo menos 1 ano, realizando avaliações neurológicas completas periódicas. O segundo protocolo consistiu na quantificação de tremor em espirais de Arquimedes realizadas por pacientes com doença de Crohn (DC, N=31), retocolite ulcerativa (RCU, N=63) e voluntários sadios (N=41) por um neurologista especializado em distúrbios de movimento (Dr. Elan Louis, Columbia University, Nova Iorque). Polineuropatia de fibras grossas sensitivas ou sensitivo-motoras foi observada em 16,1% dos pacientes com DC e 19,6% dos pacientes com RCU, sendo usualmente leve, predominantemente simétrica, distal e axonal. Síndrome do túnel do carpo foi observada comumente em mulheres com RCU. Sintomas sensitivos sem anormalidades eletromiográficas, sugestivos de neuropatia de pequenas fibras ou mielopatia subclínica, foram observados em 29% dos pacientes com DC e 11,8% com RCU. Após excluir outros fatores etiológicos ou contributórios para polineuropatia, 13,4% dos pacientes com doença inflamatória intestinal apresentaram polineuropatia de fibras grossas ou fibras finas (7,3% com polineuropatia de fibras grossas sensitivo-motoras). Cefaléia não debilitante foi a queixa neurológica mais comum, 3 pacientes apresentaram acidente vascular cerebral isquêmico, 5 epilepsia e 1 coréia transitória. Pacientes com DII apresentaram menor quantidade de tremor que os voluntários sadios devido ao menor uso de cafeína. Nos pacientes com DC, houve correlação significativa entre a nota do tremor, uso de medicações com ação sobre o sistema nervoso central, uso e quantidade de cafeína e presença de doenças neurológicas. Em pacientes com RCU, só houve correlação significativa entre a nota do tremor e idade ou uso/quantidade de cafeína ingerida. Em resumo, pacientes com RCU e DC apresentam uma vasta gama de manifestações neurológicas que são com freqüência clinicamente negligenciadas.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

HINTERGRUND: Chronisch entzündliche Darmerkrankungen (CED) zeigen eine Fehlfunktion der Epithelbarriere. Antimikrobielle Peptide wie Cathelicidine sind Effektormoleküle des angeborenen Immunsystems auf Epitheloberflächen. Cathelicidine beeinflussen das Bakterienwachstum und die Entzündungsreaktion, und können eine Rolle in der Pathogenes der CED spielen. In dieser Studie wurde die Expression des einzigem humanen Cathelicidin LL37 in Schleimhautbiopsien von Patienten mit Colitis ulcerosa und Morbus Crohn untersucht. METHODEN: Biopsiematerial aus Colon- und Ileumschleimhaut von insgesamt 61 Patienten (21 Morbus Crohn, 15 Colitis ulcerosa und 25 Kontrollen) wurde mittels Real-Time reverse Transkriptase Polymerasekettenreaktion und Immunhistochemie untersucht. ERGEBNISSE: Die Cathelicidin-Expression ist in Biopsien von Colitis ulcerosa Patienten signifikant erhöht, sowohl aus entzündeten als auch aus nicht entzündeten Darmabschnitten, verglichen mit gesunden Kontrollpatienten. In Biposien von Morbus Crohn Patienten hingegen zeigten die Cathelicidin-Expressionslevel keinen Unterschied beim Vergleich von entzündeten oder nicht entzündeten Darmabschitten mit gesunden Kontrollpatienten. Diese Ergebnisse waren unabhängig vom NOD2-Satus der Patienten. Auch bei Vergleich von Ileumbiopsien konnte kein signifikanter Unterschied in der Cathelicidin-Expression festgestellt werden. Die Biopsien die mittels Immunhistochemie analysiert wurden zeigten Cathelicidin Expression in den oberen Krypten, die in Kontrollen diffus, in Biopsien von Patienten mit CED basal betont ist. DISKUSSION: Bei CED ist die Cathelicidin-Expression im Colon verändert. Bei Patienten mit Colitis ulcerosa ist die Expression erhöht, bei Patienten mit Morbus Crohn nicht. Dies kann die Barrierefunktion des Epithels bei Patienten mit Morbus Crohn beeinträchtigen. / BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by a breakdown of colon epithelial barrier function. Antimicrobial peptides like cathelicidins are molecules of the innate immune system located at epithelial surfaces. Cathelicidins influence microbial growth and inflammation and may play a role in IBD. In this study, the expression of human cathelicidin LL-37 was investigated in the intestinal mucosa from patients suffering from ulcerative colitis or Crohn's disease. METHODS: Biopsy material from colon and ileal mucosa of a total of 61 patients (21 with Crohn's disease, 15 with ulcerative colitis, 25 control patients) was evaluated for cathelicidin expression by real-time reverse-transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: Cathelicidin expression was significantly increased in inflamed and non-inflamed colon mucosa from ulcerative colitis patients compared to non-inflamed control mucosa. In patients with Crohn's disease cathelicidin expression was not changed in inflamed or non-inflamed colon or ileal mucosa independent of NOD2 status. Biopsies evaluated by immunohistochemistry showed epithelial cathelicidin expression in the upper crypt that was diffuse in controls and only basal in IBD patients. CONCLUSIONS: In IBD the colonic expression of human cathelicidin is altered: cathelicidin expression is increased in inflamed and non-inflamed mucosa in patients suffering from ulcerative colitis but not in Crohn's disease. This deficiency may further compromise the antimicrobial barrier in Crohn's disease.