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| 1 | The role of gut microbiota(commensal bacteria)and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer:contribution of germ-free and gnotobiotic animal models of human diseases显示文摘Metagenomic approaches are currently being used to decipher the genome of the microbiota(microbiome),and,in parallel,functional studies are being performed to analyze the effects of the microbiota on the host.Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization.Animals used as models of human diseases can be maintained in sterile conditions(isolators used for germ-free rearing)and specifically colonized with defined microbes(including non-cultivable commensal bacteria).The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models.Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia(i.e.,using models of human inflammatory bowel disease and colorectal carcinoma).In contrast,a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic(NOD)mice.Interestingly,the development of atherosclerosis in germ-free apolipoprotein E(ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals.Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota.Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial,disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components(e.g.,probiotics and prebiotics)whose administration may aid in disease prevention and treatment. | Helena Tlaskalova-Hogenova Renata Stepankova Hana Kozakova Tomas Hudcovic Luca Vannucci Ludmila Tuckova Pavel Rossmann TomasHrncır Miloslav Kverka Zuzana Zakostelska Klara Klimesova Jaroslava Pribylova Jirina Bartova Daniel Sanchez Petra Fundova Dana Borovska Dagmar Sru˚tkova Zdenek Zıdek Martin Schwarzer Pavel Drastich David P Funda | 2011 | Cellular & Molecular Immunology2011，8，2： | 47 |
| 2 | Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis显示文摘AIM To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis(PSC) and ulcerative colitis(UC).METHODS Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with(n = 32) or without(n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16 S ribosomal RNA gene were sequenced on Illumina Mi Seq platform to cover low taxonomic levels. Data were further processed in QIIME employing Ma As Lin and LEf Se tools for analysis of the output data.RESULTS Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease(IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales.CONCLUSION PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes(PSC-IBD and UC). | Lukas Bajer Miloslav Kverka Martin Kostovcik Peter Macinga Jiri Dvorak Zuzana Stehlikova Jan Brezina Pavel Wohl Julius Spicak Pavel Drastich | 2017 | World Journal of Gastroenterology2017，23，25： | 22 |
| 3 | Risk of recurrence of primary sclerosing cholangitis after liver transplantation is associated with de novo inflammatory bowel disease显示文摘AIM To evaluate risk factors for primary sclerosing cholangitis(PSC) recurrence(rPSC) after orthotopic liver transplantation(OLT) in patients with well-preserved colons. METHODS We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with followup of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen(HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods.RESULTS Altogether, 31 men and 16 women with a median(range) age of 36(15-68) years at the time of OLT and a median follow-up of 122(60-249) mo were included. rPSC was confirmed in 21/47(44.7%) of patients, a median 63(12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio(HR): 4.02, 95% confidence interval(CI): 1.58-10.98] and history of acute cellular rejection(rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis(r PSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor(r PSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04(rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03(rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07(rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles.CONCLUSION De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation. | Lukas Bajer Antonij Slavcev Peter Macinga Eva Sticova Jan Brezina Matej Roder Radim Janousek Pavel Trunecka Julius Spicak Pavel Drastich | 2018 | World Journal of Gastroenterology2018，24，43： | 4 |
| 4 | Epithelial markers of colorectal carcinogenesis in ulcerative colitis and primary sclerosing cholangitis显示文摘AIM:To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis(UC) and primary sclerosing cholangitis(PSC) before and after transplantation.METHODS:Eight patients with UC and PSC prior to liver transplantation(PSC-UC),22 patients with UC after liver transplantation for PSC(OLT),9 patients with active ulcerative colitis without PSC(UCA),7 patients withUC in remission(UCR) and 10 controls(N) underwent colonoscopy with multiple biopsies.Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53,Bcl-2 and cyclooxygenase-2(COX-2) markers.Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests.RESULTS:PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT,UCA,UCR and N(P < 0.05).We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53(P < 0.001).UCA had a higher p53 expression as compared to UCR.OLT had a significantly lower expression of p53 as compared with PSC-UC(P < 0.001).Bcl-2 had a significant higher bcl-2 expression as compared with controls.No difference in COX-2 expression between PSC-UC,UCR and UCA was found.UCA had higher COX-2 expression as compared to UCR.We also found a statistically significant positive correlation between the expression of COX-2 and p53.Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSCUC(P < 0.001).PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score.CONCLUSION:Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53,suggesting a higher susceptibility of cancer.This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC. | Pavel Wohl Tomas Hucl Pavel Drastich David Kamenar Julius Spicak Eva Honsova Eva Sticova Alena Lodererova Jan Matous Martin Hill Petr Wohl Milos Kucera | 2013 | World Journal of Gastroenterology2013，19，14： | 2 |
| 5 | Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding显示文摘 | Drastich P Lata J Petrtyl J | 2011 | Ann Hepatol2011，10，2： | 1 |
| 6 | Expression of Toll-like receptor 2 (TLR2) , TLR4, and CDI4 in biopsy samples of patients with inflammatory bowel diseases: upregulated expression of TLR2 in terminal ileum of patients with ulcerative colitis显示文摘 | FROLOVA L DRASTICH P ROSSMANN P | 2008 | J Histochem Cytochem2008，56，3： | 1 |
| 7 | Expression of Toll-like receptor 2 ( TLR2 ), TLR4, and CD14 in bi- opsy samples of patients with inflammatory bowel diseases : upregulated expression of TLR2 in terminal ileum of patients with ulcerative colitis 显示文摘 | LENKA FROLOVA PAVEL DRASTICH PAVEL ROSSMANN et al | 2008 | Histochem Cytochem2008，56，3： | 1 |
| 8 | Endoscopic variceal band ligation compared with propranolol for prophylaxis of first varical bleeding显示文摘 | DRASTICH P LATA J PETRTYL J | 2011 | Ann Hepatol2011，10，6： | 1 |
| 9 | Endoscopic variceal band ]igation compared with propranolol for prophylaxis of first variceal bleeding 显示文摘 | Drastich P Lata J Petrtyl J | 2011 | Ann Hepatol2011，10，2： | 1 |
| 10 | Endoscopic treatment of malignant gastric and duodenal strictures: a prospective, multicenter study显示文摘 | Andrea Tringali Paul Didden Alessandro Repici Manon Spaander Michael J. Bourke Stephen J. Williams Julius Spicak Pavel Drastich Massimiliano Mutignani Vincenzo Perri André Roy Krystal Johnston Guido Costamagna | 2014 | Gastrointestinal Endoscopy2014，，1： | 1 |
| 11 | Spontaneous in vitro IL-6 production in various intestinal segments in patients with inflammatory bowel disease显示文摘 | Drastich P Frolova-Brizova L Zanvit P | 2011 | Folia Microbiol (Praha)2011，56，3： | 1 |
| 12 | Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding显示文摘 | Drastich P Lata J Petrtyl J | 2011 | Ann Hepatol2011，10，6： | 1 |
| 13 | Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding显示文摘 | Drastich P Lata J Petrtyl J | | 0，，： | 1 |
| 14 | Spontaneous in vitro IL-6 production in various intestinal segments in patients with inflammatory bowel disease显示文摘 | Drastich P Frolova-Brizova L Zanvit P | 2011 | Folia Microbiol (Praha)2011，56，： | 1 |
| 15 | Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding显示文摘 | DRASTICH P LATA J PETRTYL J BRUHA R PROCHAZKA V VANASEK T | 2011 | Ann Hepatol2011，10，： | 1 |
| 16 | Endoscopic varieeal band? ligation? compared with propranolol for prophylaxis of first variceal bleeding显示文摘 | Drastich P Lata J Petrtyl J | 2011 | Ann Hepatol2011，10，2： | 1 |
| 17 | Endoscopic variceal band ligation compared with propranolol for prophylaxis of first variceal bleeding显示文摘 | Drastich P Lata J Petrtyl J | | 0，，02： | 1 |
| 18 | Endoscopic Treatment of Malignant Gastric and Duodenal Strictures: A Prospective Multicenter Study显示文摘 | Andrea Tringali Paul Didden Alessandro Repici Manon Spaander Michael J. Bourke Stephen J. Williams Julius Spicak Pavel Drastich Massimiliano Mutignani Vincenzo Perri André Roy Krystal Johnston Guido Costamagna | 2013 | Gastrointestinal Endoscopy2013，，： | 1 |
| 19 | Expression of Toll-like receptor 2 (TLR2),TLR4 and CD14 in biopsy samples of patients with inflammatory bowel disease:up- regulated expression of TLR2 in terminal ileum of patients with ulcerative colitis 显示文摘 | Frolova L Drastich P Rossmann P | 2008 | J Histochem Cytochem2008，56，3： | 1 |
| 20 | Celiac disease markers in patients with liver diseases: A single center large scale screening study显示文摘AIM:To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases.METHODS:Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry, in patients with various liver diseases (n = 962) and patients who underwent liver transplantation (OLTx, n = 523) was performed. The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out. The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy. RESULTS:We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies. However, celiac disease was biopsy-diagnosed in 16 patients:4 with autoimmune hepatitis type Ⅰ, 3 with Wilson's disease, 3 with celiac hepatitis, 2 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, 1 with Budd-Chiari syndrome, 1 with toxic hepatitis, and 1 with non-alcoholic steatohepatitis. Unexpectedly, the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%), with which it is only rarely associated. On the other hand, no OLTx patients were diagnosed with celiac disease in our study. A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis, primary sclerosing cholangitis or autoimmune hepatitis type Ⅰ. CONCLUSION:We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases, but also in patients with Wilson's disease. | Pavel Drastich Eva Honsová Alena Lodererová Marcela Jaresová Aneta Pekáriková Iva Hoffmanová Ludmila Tuková Helena Tlaskalová-Hogenová Julius piák Daniel Sánchez | 2012 | World Journal of Gastroenterology2012，18，43： | 0 |
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