Poster presentations was to evaluate the effects of B-98, a newly synthesized benzoxazole derivat... more Poster presentations was to evaluate the effects of B-98, a newly synthesized benzoxazole derivative and a novel 5-lipoxygenase inhibitor, in mice model of IBD induced by dextran sulfate sodium (DSS). We also investigated the effect of B-98 on the Th (helper T) cell and Treg (regulatory T) cell profiles. Methods: Seven to eight week old C57BL/6 mice were randomly assigned to 3 groups: normal control, DSS colitis group (DSS + saline), B-98 group (DSS + B-98 20 mg/kg). For the induction of acute colitis, the mice were treated with 3% DSS for seven days. B-98 diluted in dimethyl sulfoxide was administered simultaneously with DSS from day 1 to 7 by intraperitoneal route. On day 8, the mice were sacrificed and proximal and distal colonic specimens were obtained. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic grading. The production of cytokines IL-6 and TNF-a was determined by RT-PCR. Th cells from the lamina propia were examined for the expression of IFN-g (Th1 cell), IL-4 (Th2 cell), IL-9 (Th9 cell), IL-17 (Th17 cell) and Foxp3 (Treg cell) using intracellular cytometry. Results: The mice in the DSS colitis group suffered hematochezia from day 4 and showed marked colonic shortening compared with the normal control group (82.5 vs 49.5 mm, p < 0.01). The B-98 group showed lower DAI, less shortening of the colon length and lower histopathologic grading (p < 0.01) compared with the DSS colitis group. The expression of inflammatory cytokine IL-6 in colonic tissue was significantly lower in the B-98 groups than in the DSS colitis group (p < 0.05). However, there were no significant differences in the TNF-a levels between the groups. The cellular profiles revealed that the Th1, Th9 and Th17 cells were elevated in the DSS colitis group and decreased in the B-98 group (p < 0.05). No significant differences were found in the Th2 or Treg cells between the groups. Conclusions: Our results suggest that the B-98 ameliorated intestinal inflammation and reduced the IL-6 levels. B-98 may be involved with Th1, Th9 and Th17 cellular immunity in acute colitis model. Further evaluations would be needed to elucidate the exact effects of B-98.
Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease. Cure of the inf... more Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease. Cure of the infection is essential in ulcer healing, but an additional PPI therapy after completing eradication treatment is widespread in clinical practice. In the present work clinical studies evaluating peptic ulcer healing followed or not by PPI treatment after eradication therapy were analyzed. The results of these trials are concordant that only a minority of patients with duodenal ulcer would benefit from prolonged acid suppressive treatment, a successful eradication therapy (that counts for a large proportion) is sufficient. There are less data available concerning gastric ulcer: successful eradication is also essential to ulcer healing and to avoid relapse, however it seems that post-eradication PPI therapy might be beneficial.
Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. ... more Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. Aminosalicylates, nitroimidazoles and azathioprine (AZA) reduce severity of recurrence. Endoscopic lesions predict the clinical course of CD. Goal: to examine if a combination of AZA + 3 months of metronidazole (MET) reduces postoperative CD recurrence. Methods: high risk CD pts undergoing ileocecal resection were started immediately after surgery on open label MET 250 mg TID for 3 months + AZA (100 mg/day if BW< 60 kg, 150 mg/day if BW>60 kg) or placebo (PLA) for 12 months and underwent ileocolonoscopy at 3 and 12 months. Primary endpoint was the proportion of pts with severe endoscopic recurrence (Rutgeerts i2-4). Results: Eighty-one pts were randomized; 73 pts reached month 3 and 61 month 12. Characteristics of both groups were comparable. At 3 months, 32/73 pts (60%) had severe recurrence (20/38 (52.6%) on PLA and 12/35 (34%) on AZA, p=0.11). At 12 months, 34/61 pts (55.7%) had severe recurrence (20/29 (69%) on PLA, 14/32 (44%) on AZA, p<0.05). Very severe recurrence (i3+i4) was rare (3/73 (4.1%) at month 3 and 14/61 (22.9%) at month 12) and occurred similarly in either group. Absence of lesions (i0) was more frequent with AZA than with PLA (at month 12: 7/32 vs 1/29, p=0.04). Reasons for discontinuation before week 12 included withdrawal of consent, liver toxicity and abscess in 8 pts. From week 12-52, 12 additional pts discontinued: 3 for severe CD relapse, 1 for pregnancy, 2 for arthralgia, 2 for liver toxicity and 4 because of non-compliance, evenly distributed in both groups. Other adverse events were mild and transient. Conclusions: In this cohort of pts, the incidence of severe endoscopic recurrence was significantly reduced 12 months after surgery with combination therapy of MET for 3 months and AZA for 12 months.
Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bo... more Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres. Clinical and safety data was registered at fixed appointments. Trough levels and anti-drug antibody (ADA) concentration were measured by ELISA. Association between demographic, clinical, laboratory parameters and infusion reaction rates were evaluated statistically. Three hundred and eighty-four IBD patients were included. Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction during the treatment, 64.3% of them was previously exposed to anti TNF therapy. No infusion reaction occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients who developed infusion reaction and was switched to adalimumab in 12 patients. However in 39.3% of patients developing infusion reaction CT-P13...
Adalimumab was approved for the treatment of ulcerative colitis refractory to conventional therap... more Adalimumab was approved for the treatment of ulcerative colitis refractory to conventional therapy several years later than infliximab in Europe. Due to the relatively low remission rate observed in Ultra trials, data on the efficacy of adalimumab in ulcerative colitis are really helpful in the daily practice. The aim of this study was to prospectively collect data on induction and maintenance adalimumab therapy in patients with ulcerative colitis treated in Hungarian centres. This prospective study collected data of all patients with ulcerative colitis treated with adalimumab in 10 Hungarian centres. The primary endpoints of the study were rates of remission, response and primary failure at week 12, and the rate of continuous clinical response, remission and loss of response at weeks 30, and 52. Secondary endpoints were endoscopic outcome at week 52 and comparison of the efficacy of adalimumab between treatment naive and infliximab-experienced patients. 73 patients with active ulce...
Background: Recent results show that plasma free DNA concentration (fDNA) is increased in autoimm... more Background: Recent results show that plasma free DNA concentration (fDNA) is increased in autoimmune and malignant diseases. Anti-nuclear antibody related to circulating fDNA plays a role in the disease pathogenesis in systemic lupus erythematosus. There is no data in regarding fDNA concentrations in inflammatory bowel disease (IBD). Our aim was to determine plasma fDNA in patients with clinically active and inactive IBD. Methods: We included 28 people into the study. 7 patients with active (aCD), 7 with inactive Crohn’s disease (iCD) and 7 inactive or mild ulcerative colitis (UC) and results were compared with 7 healthy controls. The CD was defined to be inactive by the Crohn’s disease activity index (CDAI <150), while it was considered to be active in case of the CDAI was more than 250 and CRP is more than 5mg/l. UC was considered inactive if the partial Mayo score was less than 3. Samples collected from patients were cooled after centrifugation. The fDNA was isolated with Roche Magna Pure Compact and measured with Qubit fluorometer. Results: The mean plasma fDNA concentration was 0.309±0.250 in the healthy control subjects. Concentrations of fDNA did not differed significantly in aCD, iCD and UC patients compared to healthy controls (0.331±0.318, p = 0.458; 0.158±0.061, p = 0.068; and 0.208±0176, p = 0.147; respectively). However, a strong correlation had been observed between plasma fDNA levels and C-reactive protein (r = 0.95) concentrations, and partial Mayo score (r = 0.78) also. Conclusions: Initial results indicate that the plasma concentration of fDNA does not help to diagnose inflammatory bowel disease. Further investigations are needed to determine the use of fDNA concentration as a surrogate marker of severity in UC patients.
The exact pathological background of inflammatory bowel disease has not been clarified yet. Many ... more The exact pathological background of inflammatory bowel disease has not been clarified yet. Many aspects of genetical and environmental factors, as well as certain alterations of the functions of epithelial cells and immunoregulation which may attenuate chronic inflammation in the gastrointestinal tract are known. These three components have many connecting points. Among the inflammatory bowel disease genes we know only the function of the NOD2/CARD gene, and we have some idea about the OCTN and DRG genes. The function of the intestinal epithelial cells is changed in inflammatory bowel disease. The latter two genes may have a role in the increased permeability, so as the tumor necrosis factor alpha, interferon gamma may play affect it. The interleukin-10 helps the mucosal integrity. The interleukin-6 production is elevated in these diseases, and the interleukin-8 level can be elevated in case of mutation of toll like receptor 5. The tumor necrosis factor alpha, interferon gamma and ...
The exact pathological background of inflammatory bowel disease has not been clarified yet. Many ... more The exact pathological background of inflammatory bowel disease has not been clarified yet. Many aspects of genetical and environmental factors, as well as certain alterations of the functions of epithelial cells and immunoregulation which may attenuate chronic inflammation in the gastrointestinal tract are known. These three components have many connecting points. Among the inflammatory bowel disease genes we know only the function of the NOD2/CARD gene, and we have some idea about the OCTN and DRG genes. The function of the intestinal epithelial cells is changed in inflammatory bowel disease. The latter two genes may have a role in the increased permeability, so as the tumor necrosis factor alpha, interferon gamma may play affect it. The interleukin-10 helps the mucosal integrity. The interleukin-6 production is elevated in these diseases, and the interleukin-8 level can be elevated in case of mutation of toll like receptor 5. The tumor necrosis factor alpha, interferon gamma and ...
Abstract Intestinal stenosis is a frequent and oftentimes recurring problem in patients with Croh... more Abstract Intestinal stenosis is a frequent and oftentimes recurring problem in patients with Crohn's disease, accompanied by a high-risk for bowel resection and subsequent short bowel syndrome. Medical therapy has not proven successful, and even the most conservative surgical options are hampered by a definite mortality rate (and high recurrence rates) without doubt. Technical improvements in endoscopic devices over recent years have created an operative subspecialty (therapeutic endoscopy) that can be applied to several gastrointestinal diseases. Endoscopic balloon dilatation (EBD) for Crohn's disease has been developed to prevent or delay the need for surgical resection. The endoscopy-assisted dilatation is a safe and effective treatment modality for uncomplicated, short Crohn's strictures, and therefore should be offered to Crohn's disease patients. Here, we briefly review the current knowledge on hydrostatic balloon dilatation and present a relevant case from our clinical practice.
The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative coli... more The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative colitis. The changes of such regenerative and immortalizing pathways caused by the inflammatory process that are proved to be carcinogenic in other human tissues have not been fully and uniformly described. Aim of the study was to describe the expression alterations of regenerative signal receptors and cell aging inhibitory systems within colonic crypts considering the histological activity of the disease. I-type insulin-like growth factor receptor (IGF1R), hepatocyte derived growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on formalin fixed paraffin embedded biopsy specimen from 10 mild, 10 moderate, and 10 severe active inflammation of ulcerative colitis and from 10 normal colonic tissue. In mild inflammation all observed parameter showed significantly elevated protein expression ...
Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. ... more Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. Aminosalicylates, nitroimidazoles and azathioprine (AZA) reduce severity of recurrence. Endoscopic lesions predict the clinical course of CD. Goal: to examine if a combination of AZA + 3 months of metronidazole (MET) reduces postoperative CD recurrence. Methods: high risk CD pts undergoing ileocecal resection were started immediately after surgery on open label MET 250 mg TID for 3 months + AZA (100 mg/day if BW< 60 kg, 150 mg/day if BW>60 kg) or placebo (PLA) for 12 months and underwent ileocolonoscopy at 3 and 12 months. Primary endpoint was the proportion of pts with severe endoscopic recurrence (Rutgeerts i2-4). Results: Eighty-one pts were randomized; 73 pts reached month 3 and 61 month 12. Characteristics of both groups were comparable. At 3 months, 32/73 pts (60%) had severe recurrence (20/38 (52.6%) on PLA and 12/35 (34%) on AZA, p=0.11). At 12 months, 34/61 pts (55.7%) had severe recurrence (20/29 (69%) on PLA, 14/32 (44%) on AZA, p<0.05). Very severe recurrence (i3+i4) was rare (3/73 (4.1%) at month 3 and 14/61 (22.9%) at month 12) and occurred similarly in either group. Absence of lesions (i0) was more frequent with AZA than with PLA (at month 12: 7/32 vs 1/29, p=0.04). Reasons for discontinuation before week 12 included withdrawal of consent, liver toxicity and abscess in 8 pts. From week 12-52, 12 additional pts discontinued: 3 for severe CD relapse, 1 for pregnancy, 2 for arthralgia, 2 for liver toxicity and 4 because of non-compliance, evenly distributed in both groups. Other adverse events were mild and transient. Conclusions: In this cohort of pts, the incidence of severe endoscopic recurrence was significantly reduced 12 months after surgery with combination therapy of MET for 3 months and AZA for 12 months.
Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been... more Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been proposed that matrix metalloproteinase-9 (MMP-9) is involved in epithelial damage in ulcerative colitis (UC). However, to our knowledge, no data are available in terms of MMP-9 expression in microscopic colitis. Determination of mucosal protein expression levels of MMP-9 in lymphocytic colitis (LC), collagenous colitis (CC) and UC. MMP-9 immunohistochemical expressions were analyzed in paraffin-embedded tissue samples by immunohistochemistry including patients with LC, CC, UC, active diverticulitis, inactive diverticular disease and healthy control subjects. UC was also subgrouped according to the severity of inflammation. Immunostaining was determined semiquantitatively. Independent colonic biopsies from healthy and severe UC cases were used for gene expression analyses. For further comparison MMP-9 serum antigen levels were also determined in patients with UC and control patients without macroscopic or microscopic changes during colonoscopy. MMP-9 mucosal expression was significantly higher in UC (26.7 ± 19.5%) compared to LC (6.6 ± 9.3%), CC (6.4 ± 7.6%), active diverticulitis (5.33 ± 2.4%), inactive diverticular disease (5.0 ± 2.2%) and controls (6.3 ± 2.6%) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The immunohistochemical expression of MMP-9 in LC and CC was similar as compared to controls. MMP-9 expression was significantly higher in each inflammatory group of UC compared to controls (mild: 11.0 ± 2.8%, moderate: 23.9 ± 3.7%, severe UC: 52.6 ± 3.9% and 6.3 ± 2.6%, respectively, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.005). The gene expression microarray data and RT-PCR results demonstrated a significantly higher expression of MMP-9 in severely active UC compared to healthy controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Significantly higher MMP-9 serum antigen concentrations were observed in UC patients compared with the control group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). MMP-9 seems to play no role in the inflammatory process of LC and CC. In contrast, the mucosal up-regulation of MMP-9 correlated with the severity of inflammation in UC. The increased MMP-9 expression could contribute to the severity of mucosal damage in active UC.
Poster presentations was to evaluate the effects of B-98, a newly synthesized benzoxazole derivat... more Poster presentations was to evaluate the effects of B-98, a newly synthesized benzoxazole derivative and a novel 5-lipoxygenase inhibitor, in mice model of IBD induced by dextran sulfate sodium (DSS). We also investigated the effect of B-98 on the Th (helper T) cell and Treg (regulatory T) cell profiles. Methods: Seven to eight week old C57BL/6 mice were randomly assigned to 3 groups: normal control, DSS colitis group (DSS + saline), B-98 group (DSS + B-98 20 mg/kg). For the induction of acute colitis, the mice were treated with 3% DSS for seven days. B-98 diluted in dimethyl sulfoxide was administered simultaneously with DSS from day 1 to 7 by intraperitoneal route. On day 8, the mice were sacrificed and proximal and distal colonic specimens were obtained. The severity of the colitis was assessed via the disease activity index (DAI), colon length, and histopathologic grading. The production of cytokines IL-6 and TNF-a was determined by RT-PCR. Th cells from the lamina propia were examined for the expression of IFN-g (Th1 cell), IL-4 (Th2 cell), IL-9 (Th9 cell), IL-17 (Th17 cell) and Foxp3 (Treg cell) using intracellular cytometry. Results: The mice in the DSS colitis group suffered hematochezia from day 4 and showed marked colonic shortening compared with the normal control group (82.5 vs 49.5 mm, p < 0.01). The B-98 group showed lower DAI, less shortening of the colon length and lower histopathologic grading (p < 0.01) compared with the DSS colitis group. The expression of inflammatory cytokine IL-6 in colonic tissue was significantly lower in the B-98 groups than in the DSS colitis group (p < 0.05). However, there were no significant differences in the TNF-a levels between the groups. The cellular profiles revealed that the Th1, Th9 and Th17 cells were elevated in the DSS colitis group and decreased in the B-98 group (p < 0.05). No significant differences were found in the Th2 or Treg cells between the groups. Conclusions: Our results suggest that the B-98 ameliorated intestinal inflammation and reduced the IL-6 levels. B-98 may be involved with Th1, Th9 and Th17 cellular immunity in acute colitis model. Further evaluations would be needed to elucidate the exact effects of B-98.
Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease. Cure of the inf... more Helicobacter pylori has a major role in the pathogenesis of peptic ulcer disease. Cure of the infection is essential in ulcer healing, but an additional PPI therapy after completing eradication treatment is widespread in clinical practice. In the present work clinical studies evaluating peptic ulcer healing followed or not by PPI treatment after eradication therapy were analyzed. The results of these trials are concordant that only a minority of patients with duodenal ulcer would benefit from prolonged acid suppressive treatment, a successful eradication therapy (that counts for a large proportion) is sufficient. There are less data available concerning gastric ulcer: successful eradication is also essential to ulcer healing and to avoid relapse, however it seems that post-eradication PPI therapy might be beneficial.
Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. ... more Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. Aminosalicylates, nitroimidazoles and azathioprine (AZA) reduce severity of recurrence. Endoscopic lesions predict the clinical course of CD. Goal: to examine if a combination of AZA + 3 months of metronidazole (MET) reduces postoperative CD recurrence. Methods: high risk CD pts undergoing ileocecal resection were started immediately after surgery on open label MET 250 mg TID for 3 months + AZA (100 mg/day if BW< 60 kg, 150 mg/day if BW>60 kg) or placebo (PLA) for 12 months and underwent ileocolonoscopy at 3 and 12 months. Primary endpoint was the proportion of pts with severe endoscopic recurrence (Rutgeerts i2-4). Results: Eighty-one pts were randomized; 73 pts reached month 3 and 61 month 12. Characteristics of both groups were comparable. At 3 months, 32/73 pts (60%) had severe recurrence (20/38 (52.6%) on PLA and 12/35 (34%) on AZA, p=0.11). At 12 months, 34/61 pts (55.7%) had severe recurrence (20/29 (69%) on PLA, 14/32 (44%) on AZA, p<0.05). Very severe recurrence (i3+i4) was rare (3/73 (4.1%) at month 3 and 14/61 (22.9%) at month 12) and occurred similarly in either group. Absence of lesions (i0) was more frequent with AZA than with PLA (at month 12: 7/32 vs 1/29, p=0.04). Reasons for discontinuation before week 12 included withdrawal of consent, liver toxicity and abscess in 8 pts. From week 12-52, 12 additional pts discontinued: 3 for severe CD relapse, 1 for pregnancy, 2 for arthralgia, 2 for liver toxicity and 4 because of non-compliance, evenly distributed in both groups. Other adverse events were mild and transient. Conclusions: In this cohort of pts, the incidence of severe endoscopic recurrence was significantly reduced 12 months after surgery with combination therapy of MET for 3 months and AZA for 12 months.
Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bo... more Safety data of the 'real life' use of an infliximab biosimilar, CT-P13 in inflammatory bowel disease (IBD) are still lacking. Our aim was to assess the frequency and characteristics of infusion reactions during CT-P13 therapy in 13 Hungarian and 1 Czech IBD centres. Clinical and safety data was registered at fixed appointments. Trough levels and anti-drug antibody (ADA) concentration were measured by ELISA. Association between demographic, clinical, laboratory parameters and infusion reaction rates were evaluated statistically. Three hundred and eighty-four IBD patients were included. Twenty-eight Hungarian IBD patients (9.6%) developed infusion reaction during the treatment, 64.3% of them was previously exposed to anti TNF therapy. No infusion reaction occurred in the Czech population. CT-P13 therapy had to be stopped in 17 patients who developed infusion reaction and was switched to adalimumab in 12 patients. However in 39.3% of patients developing infusion reaction CT-P13...
Adalimumab was approved for the treatment of ulcerative colitis refractory to conventional therap... more Adalimumab was approved for the treatment of ulcerative colitis refractory to conventional therapy several years later than infliximab in Europe. Due to the relatively low remission rate observed in Ultra trials, data on the efficacy of adalimumab in ulcerative colitis are really helpful in the daily practice. The aim of this study was to prospectively collect data on induction and maintenance adalimumab therapy in patients with ulcerative colitis treated in Hungarian centres. This prospective study collected data of all patients with ulcerative colitis treated with adalimumab in 10 Hungarian centres. The primary endpoints of the study were rates of remission, response and primary failure at week 12, and the rate of continuous clinical response, remission and loss of response at weeks 30, and 52. Secondary endpoints were endoscopic outcome at week 52 and comparison of the efficacy of adalimumab between treatment naive and infliximab-experienced patients. 73 patients with active ulce...
Background: Recent results show that plasma free DNA concentration (fDNA) is increased in autoimm... more Background: Recent results show that plasma free DNA concentration (fDNA) is increased in autoimmune and malignant diseases. Anti-nuclear antibody related to circulating fDNA plays a role in the disease pathogenesis in systemic lupus erythematosus. There is no data in regarding fDNA concentrations in inflammatory bowel disease (IBD). Our aim was to determine plasma fDNA in patients with clinically active and inactive IBD. Methods: We included 28 people into the study. 7 patients with active (aCD), 7 with inactive Crohn’s disease (iCD) and 7 inactive or mild ulcerative colitis (UC) and results were compared with 7 healthy controls. The CD was defined to be inactive by the Crohn’s disease activity index (CDAI <150), while it was considered to be active in case of the CDAI was more than 250 and CRP is more than 5mg/l. UC was considered inactive if the partial Mayo score was less than 3. Samples collected from patients were cooled after centrifugation. The fDNA was isolated with Roche Magna Pure Compact and measured with Qubit fluorometer. Results: The mean plasma fDNA concentration was 0.309±0.250 in the healthy control subjects. Concentrations of fDNA did not differed significantly in aCD, iCD and UC patients compared to healthy controls (0.331±0.318, p = 0.458; 0.158±0.061, p = 0.068; and 0.208±0176, p = 0.147; respectively). However, a strong correlation had been observed between plasma fDNA levels and C-reactive protein (r = 0.95) concentrations, and partial Mayo score (r = 0.78) also. Conclusions: Initial results indicate that the plasma concentration of fDNA does not help to diagnose inflammatory bowel disease. Further investigations are needed to determine the use of fDNA concentration as a surrogate marker of severity in UC patients.
The exact pathological background of inflammatory bowel disease has not been clarified yet. Many ... more The exact pathological background of inflammatory bowel disease has not been clarified yet. Many aspects of genetical and environmental factors, as well as certain alterations of the functions of epithelial cells and immunoregulation which may attenuate chronic inflammation in the gastrointestinal tract are known. These three components have many connecting points. Among the inflammatory bowel disease genes we know only the function of the NOD2/CARD gene, and we have some idea about the OCTN and DRG genes. The function of the intestinal epithelial cells is changed in inflammatory bowel disease. The latter two genes may have a role in the increased permeability, so as the tumor necrosis factor alpha, interferon gamma may play affect it. The interleukin-10 helps the mucosal integrity. The interleukin-6 production is elevated in these diseases, and the interleukin-8 level can be elevated in case of mutation of toll like receptor 5. The tumor necrosis factor alpha, interferon gamma and ...
The exact pathological background of inflammatory bowel disease has not been clarified yet. Many ... more The exact pathological background of inflammatory bowel disease has not been clarified yet. Many aspects of genetical and environmental factors, as well as certain alterations of the functions of epithelial cells and immunoregulation which may attenuate chronic inflammation in the gastrointestinal tract are known. These three components have many connecting points. Among the inflammatory bowel disease genes we know only the function of the NOD2/CARD gene, and we have some idea about the OCTN and DRG genes. The function of the intestinal epithelial cells is changed in inflammatory bowel disease. The latter two genes may have a role in the increased permeability, so as the tumor necrosis factor alpha, interferon gamma may play affect it. The interleukin-10 helps the mucosal integrity. The interleukin-6 production is elevated in these diseases, and the interleukin-8 level can be elevated in case of mutation of toll like receptor 5. The tumor necrosis factor alpha, interferon gamma and ...
Abstract Intestinal stenosis is a frequent and oftentimes recurring problem in patients with Croh... more Abstract Intestinal stenosis is a frequent and oftentimes recurring problem in patients with Crohn's disease, accompanied by a high-risk for bowel resection and subsequent short bowel syndrome. Medical therapy has not proven successful, and even the most conservative surgical options are hampered by a definite mortality rate (and high recurrence rates) without doubt. Technical improvements in endoscopic devices over recent years have created an operative subspecialty (therapeutic endoscopy) that can be applied to several gastrointestinal diseases. Endoscopic balloon dilatation (EBD) for Crohn's disease has been developed to prevent or delay the need for surgical resection. The endoscopy-assisted dilatation is a safe and effective treatment modality for uncomplicated, short Crohn's strictures, and therefore should be offered to Crohn's disease patients. Here, we briefly review the current knowledge on hydrostatic balloon dilatation and present a relevant case from our clinical practice.
The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative coli... more The risk of colorectal carcinoma development is elevated in chronic, longstanding ulcerative colitis. The changes of such regenerative and immortalizing pathways caused by the inflammatory process that are proved to be carcinogenic in other human tissues have not been fully and uniformly described. Aim of the study was to describe the expression alterations of regenerative signal receptors and cell aging inhibitory systems within colonic crypts considering the histological activity of the disease. I-type insulin-like growth factor receptor (IGF1R), hepatocyte derived growth factor receptor (HGFR), telomerase reverse transcriptase (TERT) and telomerase associated protein (TP-1) expression were evaluated immunohistochemically on formalin fixed paraffin embedded biopsy specimen from 10 mild, 10 moderate, and 10 severe active inflammation of ulcerative colitis and from 10 normal colonic tissue. In mild inflammation all observed parameter showed significantly elevated protein expression ...
Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. ... more Over 80% of CD patients undergoing resection of terminal ileum +/-right colon suffer recurrence. Aminosalicylates, nitroimidazoles and azathioprine (AZA) reduce severity of recurrence. Endoscopic lesions predict the clinical course of CD. Goal: to examine if a combination of AZA + 3 months of metronidazole (MET) reduces postoperative CD recurrence. Methods: high risk CD pts undergoing ileocecal resection were started immediately after surgery on open label MET 250 mg TID for 3 months + AZA (100 mg/day if BW< 60 kg, 150 mg/day if BW>60 kg) or placebo (PLA) for 12 months and underwent ileocolonoscopy at 3 and 12 months. Primary endpoint was the proportion of pts with severe endoscopic recurrence (Rutgeerts i2-4). Results: Eighty-one pts were randomized; 73 pts reached month 3 and 61 month 12. Characteristics of both groups were comparable. At 3 months, 32/73 pts (60%) had severe recurrence (20/38 (52.6%) on PLA and 12/35 (34%) on AZA, p=0.11). At 12 months, 34/61 pts (55.7%) had severe recurrence (20/29 (69%) on PLA, 14/32 (44%) on AZA, p<0.05). Very severe recurrence (i3+i4) was rare (3/73 (4.1%) at month 3 and 14/61 (22.9%) at month 12) and occurred similarly in either group. Absence of lesions (i0) was more frequent with AZA than with PLA (at month 12: 7/32 vs 1/29, p=0.04). Reasons for discontinuation before week 12 included withdrawal of consent, liver toxicity and abscess in 8 pts. From week 12-52, 12 additional pts discontinued: 3 for severe CD relapse, 1 for pregnancy, 2 for arthralgia, 2 for liver toxicity and 4 because of non-compliance, evenly distributed in both groups. Other adverse events were mild and transient. Conclusions: In this cohort of pts, the incidence of severe endoscopic recurrence was significantly reduced 12 months after surgery with combination therapy of MET for 3 months and AZA for 12 months.
Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been... more Matrix metalloproteinases play an important role in extracellular matrix remodelling. It has been proposed that matrix metalloproteinase-9 (MMP-9) is involved in epithelial damage in ulcerative colitis (UC). However, to our knowledge, no data are available in terms of MMP-9 expression in microscopic colitis. Determination of mucosal protein expression levels of MMP-9 in lymphocytic colitis (LC), collagenous colitis (CC) and UC. MMP-9 immunohistochemical expressions were analyzed in paraffin-embedded tissue samples by immunohistochemistry including patients with LC, CC, UC, active diverticulitis, inactive diverticular disease and healthy control subjects. UC was also subgrouped according to the severity of inflammation. Immunostaining was determined semiquantitatively. Independent colonic biopsies from healthy and severe UC cases were used for gene expression analyses. For further comparison MMP-9 serum antigen levels were also determined in patients with UC and control patients without macroscopic or microscopic changes during colonoscopy. MMP-9 mucosal expression was significantly higher in UC (26.7 ± 19.5%) compared to LC (6.6 ± 9.3%), CC (6.4 ± 7.6%), active diverticulitis (5.33 ± 2.4%), inactive diverticular disease (5.0 ± 2.2%) and controls (6.3 ± 2.6%) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The immunohistochemical expression of MMP-9 in LC and CC was similar as compared to controls. MMP-9 expression was significantly higher in each inflammatory group of UC compared to controls (mild: 11.0 ± 2.8%, moderate: 23.9 ± 3.7%, severe UC: 52.6 ± 3.9% and 6.3 ± 2.6%, respectively, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.005). The gene expression microarray data and RT-PCR results demonstrated a significantly higher expression of MMP-9 in severely active UC compared to healthy controls (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Significantly higher MMP-9 serum antigen concentrations were observed in UC patients compared with the control group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). MMP-9 seems to play no role in the inflammatory process of LC and CC. In contrast, the mucosal up-regulation of MMP-9 correlated with the severity of inflammation in UC. The increased MMP-9 expression could contribute to the severity of mucosal damage in active UC.
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