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Diabetes mellitus and impairment of intestinal barier function
Hoffmanová, Iva ; Anděl, Michal (advisor) ; Haluzík, Martin (referee) ; Keil, Radan (referee)
Introduction: Impairment of intestinal barrier function is involved in pathogenesis of immune mediated diseases (such as type 1 diabetes mellitus or celiac disease) and metabolic diseases (such as type 2 diabetes mellitus). Aims of study: The first aim was to analyze impairment of mucosal part of intestinal barrier in both type of diabetes and to describe differences when compared to celiac disease, which is a typical condition associated with impairment of intestinal barrier function. The second aim was to find a correlation between duration or compensation of diabetes and intestinal barrier desintegration in patients with both type of diabetes, and to find a correlation between body mass index and intestinal barrier desintegration in patients with type 2 diabetes. The third aim was to assess influence of gluten-free diet on improvement of small intestinal mucosal integrity in patient with celiac disease. Methods: The study was performed on 166 individuals including healthy controls and five group of patients with: type 1 diabetes mellitus with fading insulitis (T1D), type 1 diabetes mellitus with ongoing insulitus (T1D/INS), type 2 diabetes mellitus (T2D), untreated celiac disease (CLD), and celiac disease on gluten-free diet (CLD-GFD). We tested the marker of epithelial apoptosis - cytokeratin 18...
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Clinical and genetic predictors of drug dependency in inflammatory bowel disease
Ďuricová, Dana ; Lukáš, Milan (advisor) ; Keil, Radan (referee) ; Špičák, Julius (referee)
IN ENGLISH Drug dependency in inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC), is a specific disease phenotype which determines disease prognosis and hence may be used as a prognostic marker for treatment management. Drug dependency in IBD has been well described in corticosteroid treatment and recently also in infliximab (IFX) therapy. The aims of this thesis were: 1) to assess the occurrence of IFX dependency in paediatric and adult patients with CD; further to search for clinical and genetic predictors of IFX outcome and to evaluate the impact of IFX dependency on surgical rate; 2) to assess in CD patients the outcome of the first course of 5-ASA monotherapy with emphasis on 5-ASA dependency and to define clinical predictors of 5-ASA treatment outcome. We found that 66% of children and 29% of adults with CD became IFX dependent. The high frequency in paediatrics is in agreement with previously published studies, while the finding in adult patients indicates a lower rate of IFX dependency in the only study to date. Perianal disease and no bowel surgery prior to IFX start were predicative of IFX dependency in paediatric patients. In adult cohort, 2 genetic variants LTA c.207 A>G and CASP9 c.93 C>T were associated with IFX outcome, whereas no relevant clinical...
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Resistance to antimicrobial therapy of Helicobacter pylori strains
Moravcová, Monika ; Keil, Radan (advisor) ; Nyč, Otakar (referee)
Helicobacter pylori (hereinafter referred to as H. pylori) is a gram-negative bacteria which colonises the human stomach mucosa. Its role in the aethiopathogenesis of chronic gastritis, ulcer disorders of the gastroduodenum and MALT-lymphoma has been clearly demonstrated, and in connection with the occurrence of stomach cancer it has been indicated by the World Health Organisation (WHO) as a class I carcinogen. H. pylori infection can be detected from samples of stomach mucosa taken in an endoscopic examination (rapid urease test, microscopic examination, culture), or the non-invasive method can be used (13 C-Urea Breath Test or H. Pylori stool antigen test - HpSA). Effective therapy of H. pylori infection resides in the administration of a combination of antibiotics and a proton pump inhibitor. In recent years the resistance of bacterial strains to used antibiotics has been increasing on a worldwide scale, and we can also observe this trend in the case of H. pylori. If the level of resistance exceeds 20 % for clarithromycin and 40 % for metronidazole, these antibiotics are not recommended for the treatment of an infection caused by this bacteria. In a group of 61 patients at the Department of Internal Medicine at the University Hospital Motol who had undergone an endoscopic examination of the...
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New markers of colon cancer evolution in ulcerative colitis
Švec, Jiří ; Kment, Milan (advisor) ; Keil, Radan (referee) ; Hampl, Aleš (referee)
Background: Long-standing ulcerative colitis (UC) has an increased risk of evolving into colorectal cancer (CRC) and upregulated expression of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), survivin, telomerase catalytic subunit (TERT), integrin-linked kinase (ILK) and transcription factors c- MYB and TCF-4, has been implicated in the development and progression of sporadic colorectal cancer. Nevertheless much less is known about their role in the process of UC-associated colon carcinogenesis. Methods: We analyzed the gene expression of these markers during the transition of colonic mucosa from chronic inflammation to epithelial neoplasia in biopsies of UC patients using quantitative real-time polymerase chain reaction and immunohistochemistry, and compared the expression profiles of this gene panel in samples of patients with CRC and in human tumor xenografts of SW620 malignant colonic cells. Additionally, we determined the expression of these genes in mouse models of sporadic and colitis-associated CRC in A/J and ICR mouse strains using quantitative RT-PCR and laser microdissection. Results: The transcript levels of survivin, c-MYB, COX-2, iNOS, and TCF-4 showed statistically significant increase during neoplastic transformation of UC-patient colonic mucosa, whereas TERT and ILK...
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The importance of tumor markers and markers of angiogenesis for colorectal cancer prognosis
Levý, Miroslav ; Lipská, Ludmila (advisor) ; Třeška, Vladislav (referee) ; Šafarčík, Kristian (referee) ; Keil, Radan (referee)
Despite extensive progress in understanding of the molecular pattern of the tumor, growing possibilities of chemotherapy and surgical treatment, colorectal cancer remains the significant cause of death worldwide. Surgical treatment alone has already reached in oncologic radicality its limits, and therefore the surgeons turned to the molecular base of tumor growth in an effort to find markers that allow to operate patients at lower stages of the disease and thus improve the results and prognosis of the disease. And also to find markers, which, after currative operation will find a possible relapse in early stage to enable the surgeon to perform second curative intervention. Tumor markers are substances that often arise in connection with the changed metabolism transformed tumor cells, and therefore their levels increased in the presence of malignancy. Serum tumor markers are important parameters that may facilitate the prediction of the disease, its progression or regression (remission). Tumor markers are clinically used for screening, primary diagnosis, staging, prognosis, but particularly for predicting recurrence of disease, monitoring therapy. This work aims to summarize the current knowledge about the colorectal cancer markers, outline the possible development and present results of relationship...
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The use of physiological and pathophysiological pressure ratios in the area of the biliary ductal system and pancreas for diagnosis and treatment by endoscopic retrograde cholangiopancreatography
Keil, Radan ; Kvapil, Milan (advisor) ; Frič, Přemysl (referee) ; Hep, Aleš (referee) ; Mareš, Jan (referee)
:.In our work we wanted to confirm our clinical experience with therapy of biliary and pancreatic duct injuries from the endoscopic retrograde cholangiopancreatography (ERCP) which was done in 267. Children and infants with a variety of biliary tract disorders and traumatic injuries in the area of biliary and pancreatic duct.. Pressure of the bile plays the key role in the therapy of biliary tract injuries Therefore we have measured the pressure in biliary tract and duodenum before and after the sphincterotomy of Oddi sphincter. Thea aim of our study was to confirm the insertion of drainage into the biliary and pancreatic duct in children with injury in this area. Our results showed significant differences between biliary duct pressure and duodenal pressure in the patients before and after sphincterotomy of Oddi sphincter. This results on theoretical basis confirmed, that it is necessary in children after traumatic rupture of biliary duct to provide ERCP and insert a biliary drainage after sphincterotomy. With this procedure the biliary tract injury is healed ad integrum without surgical liver resection. To provide only papilosphincterotomy without biliary drainage is not sufficient. This new miniinvasive procedure plays a fundamental role in the therapy of blunt abdominal injuries in a children and infants...
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