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Colonic injury induced by trinitrobenzene sulfonic acid is attenuated by antioxidant therapy
A1120 AGA ABSTRACTS
GASTROENTEROLOGYVol. 114, No. 4
• G4582 AN EPIDEMIOLOGICAL STUDY OF ULCERATIVE COLITIS IN THE SONGPA DISTRICT, SEOUL, KOREA. S.-K. Yang I Y.I. Min, 1 H.Y. Kim2, J.Y. Yoo2, P.L. Rhee 3, J.C. Rhee 3, D.K. Chang 4, I.S. Song4, S.A. Jung5, E.B. Park6, H.W. Chung7, D.K. Lee7, Y.K. Kim8. Dept. of Medicine, Univ. of Ulsan l, Hallym Univ. 2, Sungkyunkwan Univ), Seoul National Univ.4, Depts. of Medicine 5 and Surgery 6, Ewha Womans Univ., Lee Dong Keun Surgical Clinic 7, Chamshil Seoul Surgical Clinic s, Seoul, Korea.
administration of TNBS in 50% ethanol into the distal 8 cm of the colon. Vehicle-treated rats (Veh) received ethanol and controls (C) received saline. All rats were decapitated on the 24th h (acute) or 6th day (chronic) after induction of colitis. Superoxide dismutase (SOD; 30 000U/kg; s.c.) or catalase (CAT; 400 000U/kg; s.c.) were administered twice with a 24 h interval before the rats were decapitated. Macroscopic score (0 to 10 points), microscopic score (0 to 13 points) and colonic wet weight were assessed in the colonic segments. Results: In both acute and chronic colitis groups, the macroscopic (7.37 -+ 0.56 and 6.56 -+0.41, respectively) and the microscopic scores (10.0-+ 1.19 and 9.22-+ 0.54, respectively) were significantly higher than those of C and corresponding Veh groups (p<0.001). Colonic wet weight showed an increase in the acute colitis group (2.63 -+0.24 g) as compared to Veh and C groups (p<0.001). In the chronic colitis group, colonic weight (2.05-+ 0.15g) was significantly higher than C (p<0.01), but not than Veh group. Pretreatment with SOD or CAT caused a significant decrease in the macroscopic scores of acute (4.66 -+0.47 and 3.55 -+ 0.37, respectively) and chronic colitis groups (1.44- 0.58 and 1.22-+ 0.43, respectively; p<0.001) compared to untreated colitis groups. The microscopic scores in SOD- or CAT-pretreated groups (8.44 _+ 1.16 and 7.55 --- 0.69, respectively) were not significantly different than untreated acute Colitis group, but there was a significant reduction in the SOD- or CAT-pretreated chronic groups (4.66-+ 0.76 and 4.44 -+ 0.94, respectively; p<0.001). Similarly, SOD- or CAT-pretreatment did not change the colonic weight in acute colitis group, but both treatments caused a significant decrease in the chronic groups (1.30-+ 0.13g and 1.07-+ 0.09g, respectively; p<0.05-0.001). Conclusion: These data suggest that the antioxidants, SOD and catalase may have beneficial effects on the chronic inflammatory responses in this model.
Background: Ulcerative colitis (UC) is regarded as a rare disease in Korea. However, there has been no epidemiological study of UC in Korea. We performed this study to evaluate the prevalence and incidence of UC in Korea. Methods: A retrospective study was performed in the Songpa district, Seoul, from 1986, in which the first patient was diagnosed, to 1996. The population in the study area has varied between 635,000 and 685,000 during the study period. The main source of patients was one referral center in the Songpa district. The remaining patients were recruited from four referral centers around the study area, and all 125 primary health care clinics and three local hospitals in the study area after the careful review of the medical records and, if necessary, telephone interview. For all patients diagnosed in the study area, demographic details and the extent of disease at the time of diagnosis were noted. Results: During the whole study period, 47 patients (24 males and 23 females) were diagnosed in the Songpa district and four patients diagnosed elsewhere have moved into the study area, while six incidence cases have left the area and one died. Consequently, there were 44 patients with UC in the Songpa district at the end of 1996, giving a point prevalence of 6.6/105 inhabitants. The mean annual incidence has increased from 0.2/105 during 1986-1989 to 0.8/105 during 1990-1996. Even in 1990s, there was steady increase in the annual incidence from 0.6/105 in 1990 to 1.2/105 in 1996. In 12 patients (25.5%), the diagnosis was made between 20-29 years of age. The family history of first-degree relatives with UC was observed in only one case (2.1%). In 17 patients (36.2%), the disease was limited to the rectum at the time of diagnosis. Conclusion: From the present study in the Songpa district, we assume that the prevalence of UC remains still low, but the annual incidence is increasing steadily in Korea.
G4585 SIALIC ACID RESIDUES ON THE EPITHELIAL CELL MEMBRANE GLYCOPROTEIN, gp180, PLAY A ROLE IN THE INTERACTIONS BETWEEN INTESTINAL EPITHELIAL CELLS AND T CELLS. X.Y. Yio, X. T. Wang, L.S. Toy, N. Campbell and L. Mayer. Clinical Immunology, Mount Sinai Medical Center, NY, NY 10029. Previous studies have shown that the activation of CD8+suppressor T cells by intestinal epithelial cells appears to be mediated by a novel intestinal epithelial cell membrane glycoprotein, gpl80, together with the non classical class 1 molecule CDld. Biochemical and functional studies have demonstrated that gpl80 is capable of activating CD8 associated p561ck in T cells via binding to the CD8 molecule. This molecule is also heavily glycosylated and recent studies suggest that the carbohydrate component of gpl80 plays a significant role in the interactions between T cells and epithelial cells, gpl80 was treated with neuraminidase to determine the role of sialic acid residues. A molecular weight shift from 180 kDa to 160 kDa was demonstrated on SDS-PAGE suggesting that notable amount of sialic acid is present on gpl80. The removal of sialic acid from gpl80 resulted in a 35% enhancement in its ability to bind CD8, as demonstrated by ELISA using CD8-Fc fusion proteins. The neuramainidase treated gpl80 was also tested functionally for its capacity to activate 3G8 cells, murine T cell hybridomas transfected with human CD8a eDNA. Compared to the untreated gpl80 control, neuraminidase treated gp180 showed an increased capacity to activate CD8 associated p561ck phosphorylation. Thus, the presence of sialic acid on gpl80 may decrease the binding capacity of gpl80 for CD8 and lead to a weaker T cell activation response.
G4583 HLA-DRBI*1502 IS NEGATIVELY ASSOCIATED WITH THE RISK OF COLECTOMY IN PATIENTS WITH ULCERATIVE COLITIS : A KOREAN STUDY. S.-K. Yank, W.I. Oh, H.-Y. Jung, W.-S. Hong, Y.I. Min. Departments of Internal Medicine & Clinical Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. Background: Several studies on HLA class II alleles have documented the high incidence of HLA-DR2 in Japanese patients with ulcerative colitis (UC). It was also suggested that DRB 1* 1502 was found more frequently in Japanese patients with intractable UC (Am J Gastroenterol 1994;89:1957). Although the characteristics of HLA system in Koreans are quite similar to those in Japanese, it is not clear whether the HLA pattern in Korean UC is similar to that in Japanese UC. The present study was performed to investigate an association between HLA class II genes and UC patients and the clinical meaning of these genes in Korea. Methods: Unrelated Korean patients with UC (n=70) and ethnically matched unrelated controls (n=182) were genotyped for HLA-DRB1, -DRB3, -DRB4, and -DRB5 by PCR amplification of HLA-DR sequences followed by reverse hybridization using sequence-specific oligonucleotide probes. Clinical characteristics of the patients were analyzed with regard to ANCA status and total colectomy for intractability. Results: HLA-DR2 and DRBI*1502 were found more frequently in patients (42.9% and 21.4%, respectively) than controls (20.3% and 5.5%, respectively) (p<0.05). Total colectomy for intractability was performed more commonly in patients without DRBI*1502 (14/55) than in those with it (0/15) (p<0.05). ANCA positivity was not different between DRBl*1502-positive (73.3%) and -negative patients (72.7%). Conclusions: Our data are consistent with those of Japanese studies in that DRB 1" 1502 is positively associated with UC patients. In contrast to a Japanese study, however, our results demonstrate that DRB1*1502 is negatively associated with the risk of colectomy in Korean patients with UC. To draw a definite conclusion on the role of DRBI*1502 in the clinical course of UC, further studies are needed. G4584 COLONIC INJURY INDUCED BY TRINITROBENZENE SULFONIC ACID IS ATTENUATED BY ANTIOXIDANT THERAPY. Y. Yavuz, B. ~. Yemen, I. Alican. Depts. of Physiology and General Surgery, Marmara University School of Medicine, 81326, Istanbul, Turkey. Background: The inflammatory bowel diseases (IBD) are multifactorial disorders whose etiology remains unknown. Increasing numbers of studies indicate that reactive oxygen metabolites may play a role in the pathogenesis of IBD. Although the potential therapeutic effects of antioxidant agents were assessed in in vitro systems, no in vivo studies were performed in TNBSinduced colitis model. Aim: To investigate the protective effects of two antioxidants, superoxide dimutase (SOD) and catalase (CAT) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Methods: Colitis was induced in Sprague-Dawley rats of both sexes (200-300g) by intrarectal
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G4586 IS CYCLOSPORINE AS EFFECTIVE IN CHRONIC ULCERATIVE COLITIS AS IN SEVERE ULCERATIVE COLITIS? C. Ynon, A. Kornbluth, J. George, M. Sternthal, S. Lichtiger, J. Marion, D. Present. The Henry D. Janowitz Division of Gastroenterology, Mount Sinai Medical Center, New York, New York. Introduction: Cyclosporine is effective in the treatment of severe ulcerative colitis, failing to respond to intravenous steroids. In addition, we have also treated patients who are either refractory to, or dependent on, oral steroids. The objective of this study was to determine if the success rates are influenced by the different indications for cyclosporine usage. Methods: We retrospectively reviewed the records of 104 ulcerative colitis patients treated with IV cyclosporine at Mount Sinai Hospital. We determined success rates at the conclusion of the IV cyclosporine phase, at 6 months, and at time of last follow-up (mean of 3.6 years). We stratified patients into three groups, all of whom were treated with IV cyclosporine: Group 1 were hospitalized patients being treated with at least 6 days of IV steroids. Group 2 were originally outpatients with persistent symptoms refractory to high dose (_>40mg) oral prednisone. Group 3 were outpatients with controlled symptoms but steroid dependent. Results: Patients in groups 1,2,3 were comparable in gender, age, and disease duration. More patients in group 1 had extensive disease, with pancolitis in 68% of patients, as compared to groups 2 and 3, with pancolitis in 55% and 53% of patients, respectively (P<0.05). Success rates are shown for groups 1,2,3 for each time period.
GASTROENTEROLOGYVol. 114, No. 4
• G4582 AN EPIDEMIOLOGICAL STUDY OF ULCERATIVE COLITIS IN THE SONGPA DISTRICT, SEOUL, KOREA. S.-K. Yang I Y.I. Min, 1 H.Y. Kim2, J.Y. Yoo2, P.L. Rhee 3, J.C. Rhee 3, D.K. Chang 4, I.S. Song4, S.A. Jung5, E.B. Park6, H.W. Chung7, D.K. Lee7, Y.K. Kim8. Dept. of Medicine, Univ. of Ulsan l, Hallym Univ. 2, Sungkyunkwan Univ), Seoul National Univ.4, Depts. of Medicine 5 and Surgery 6, Ewha Womans Univ., Lee Dong Keun Surgical Clinic 7, Chamshil Seoul Surgical Clinic s, Seoul, Korea.
administration of TNBS in 50% ethanol into the distal 8 cm of the colon. Vehicle-treated rats (Veh) received ethanol and controls (C) received saline. All rats were decapitated on the 24th h (acute) or 6th day (chronic) after induction of colitis. Superoxide dismutase (SOD; 30 000U/kg; s.c.) or catalase (CAT; 400 000U/kg; s.c.) were administered twice with a 24 h interval before the rats were decapitated. Macroscopic score (0 to 10 points), microscopic score (0 to 13 points) and colonic wet weight were assessed in the colonic segments. Results: In both acute and chronic colitis groups, the macroscopic (7.37 -+ 0.56 and 6.56 -+0.41, respectively) and the microscopic scores (10.0-+ 1.19 and 9.22-+ 0.54, respectively) were significantly higher than those of C and corresponding Veh groups (p<0.001). Colonic wet weight showed an increase in the acute colitis group (2.63 -+0.24 g) as compared to Veh and C groups (p<0.001). In the chronic colitis group, colonic weight (2.05-+ 0.15g) was significantly higher than C (p<0.01), but not than Veh group. Pretreatment with SOD or CAT caused a significant decrease in the macroscopic scores of acute (4.66 -+0.47 and 3.55 -+ 0.37, respectively) and chronic colitis groups (1.44- 0.58 and 1.22-+ 0.43, respectively; p<0.001) compared to untreated colitis groups. The microscopic scores in SOD- or CAT-pretreated groups (8.44 _+ 1.16 and 7.55 --- 0.69, respectively) were not significantly different than untreated acute Colitis group, but there was a significant reduction in the SOD- or CAT-pretreated chronic groups (4.66-+ 0.76 and 4.44 -+ 0.94, respectively; p<0.001). Similarly, SOD- or CAT-pretreatment did not change the colonic weight in acute colitis group, but both treatments caused a significant decrease in the chronic groups (1.30-+ 0.13g and 1.07-+ 0.09g, respectively; p<0.05-0.001). Conclusion: These data suggest that the antioxidants, SOD and catalase may have beneficial effects on the chronic inflammatory responses in this model.
Background: Ulcerative colitis (UC) is regarded as a rare disease in Korea. However, there has been no epidemiological study of UC in Korea. We performed this study to evaluate the prevalence and incidence of UC in Korea. Methods: A retrospective study was performed in the Songpa district, Seoul, from 1986, in which the first patient was diagnosed, to 1996. The population in the study area has varied between 635,000 and 685,000 during the study period. The main source of patients was one referral center in the Songpa district. The remaining patients were recruited from four referral centers around the study area, and all 125 primary health care clinics and three local hospitals in the study area after the careful review of the medical records and, if necessary, telephone interview. For all patients diagnosed in the study area, demographic details and the extent of disease at the time of diagnosis were noted. Results: During the whole study period, 47 patients (24 males and 23 females) were diagnosed in the Songpa district and four patients diagnosed elsewhere have moved into the study area, while six incidence cases have left the area and one died. Consequently, there were 44 patients with UC in the Songpa district at the end of 1996, giving a point prevalence of 6.6/105 inhabitants. The mean annual incidence has increased from 0.2/105 during 1986-1989 to 0.8/105 during 1990-1996. Even in 1990s, there was steady increase in the annual incidence from 0.6/105 in 1990 to 1.2/105 in 1996. In 12 patients (25.5%), the diagnosis was made between 20-29 years of age. The family history of first-degree relatives with UC was observed in only one case (2.1%). In 17 patients (36.2%), the disease was limited to the rectum at the time of diagnosis. Conclusion: From the present study in the Songpa district, we assume that the prevalence of UC remains still low, but the annual incidence is increasing steadily in Korea.
G4585 SIALIC ACID RESIDUES ON THE EPITHELIAL CELL MEMBRANE GLYCOPROTEIN, gp180, PLAY A ROLE IN THE INTERACTIONS BETWEEN INTESTINAL EPITHELIAL CELLS AND T CELLS. X.Y. Yio, X. T. Wang, L.S. Toy, N. Campbell and L. Mayer. Clinical Immunology, Mount Sinai Medical Center, NY, NY 10029. Previous studies have shown that the activation of CD8+suppressor T cells by intestinal epithelial cells appears to be mediated by a novel intestinal epithelial cell membrane glycoprotein, gpl80, together with the non classical class 1 molecule CDld. Biochemical and functional studies have demonstrated that gpl80 is capable of activating CD8 associated p561ck in T cells via binding to the CD8 molecule. This molecule is also heavily glycosylated and recent studies suggest that the carbohydrate component of gpl80 plays a significant role in the interactions between T cells and epithelial cells, gpl80 was treated with neuraminidase to determine the role of sialic acid residues. A molecular weight shift from 180 kDa to 160 kDa was demonstrated on SDS-PAGE suggesting that notable amount of sialic acid is present on gpl80. The removal of sialic acid from gpl80 resulted in a 35% enhancement in its ability to bind CD8, as demonstrated by ELISA using CD8-Fc fusion proteins. The neuramainidase treated gpl80 was also tested functionally for its capacity to activate 3G8 cells, murine T cell hybridomas transfected with human CD8a eDNA. Compared to the untreated gpl80 control, neuraminidase treated gp180 showed an increased capacity to activate CD8 associated p561ck phosphorylation. Thus, the presence of sialic acid on gpl80 may decrease the binding capacity of gpl80 for CD8 and lead to a weaker T cell activation response.
G4583 HLA-DRBI*1502 IS NEGATIVELY ASSOCIATED WITH THE RISK OF COLECTOMY IN PATIENTS WITH ULCERATIVE COLITIS : A KOREAN STUDY. S.-K. Yank, W.I. Oh, H.-Y. Jung, W.-S. Hong, Y.I. Min. Departments of Internal Medicine & Clinical Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. Background: Several studies on HLA class II alleles have documented the high incidence of HLA-DR2 in Japanese patients with ulcerative colitis (UC). It was also suggested that DRB 1* 1502 was found more frequently in Japanese patients with intractable UC (Am J Gastroenterol 1994;89:1957). Although the characteristics of HLA system in Koreans are quite similar to those in Japanese, it is not clear whether the HLA pattern in Korean UC is similar to that in Japanese UC. The present study was performed to investigate an association between HLA class II genes and UC patients and the clinical meaning of these genes in Korea. Methods: Unrelated Korean patients with UC (n=70) and ethnically matched unrelated controls (n=182) were genotyped for HLA-DRB1, -DRB3, -DRB4, and -DRB5 by PCR amplification of HLA-DR sequences followed by reverse hybridization using sequence-specific oligonucleotide probes. Clinical characteristics of the patients were analyzed with regard to ANCA status and total colectomy for intractability. Results: HLA-DR2 and DRBI*1502 were found more frequently in patients (42.9% and 21.4%, respectively) than controls (20.3% and 5.5%, respectively) (p<0.05). Total colectomy for intractability was performed more commonly in patients without DRBI*1502 (14/55) than in those with it (0/15) (p<0.05). ANCA positivity was not different between DRBl*1502-positive (73.3%) and -negative patients (72.7%). Conclusions: Our data are consistent with those of Japanese studies in that DRB 1" 1502 is positively associated with UC patients. In contrast to a Japanese study, however, our results demonstrate that DRB1*1502 is negatively associated with the risk of colectomy in Korean patients with UC. To draw a definite conclusion on the role of DRBI*1502 in the clinical course of UC, further studies are needed. G4584 COLONIC INJURY INDUCED BY TRINITROBENZENE SULFONIC ACID IS ATTENUATED BY ANTIOXIDANT THERAPY. Y. Yavuz, B. ~. Yemen, I. Alican. Depts. of Physiology and General Surgery, Marmara University School of Medicine, 81326, Istanbul, Turkey. Background: The inflammatory bowel diseases (IBD) are multifactorial disorders whose etiology remains unknown. Increasing numbers of studies indicate that reactive oxygen metabolites may play a role in the pathogenesis of IBD. Although the potential therapeutic effects of antioxidant agents were assessed in in vitro systems, no in vivo studies were performed in TNBSinduced colitis model. Aim: To investigate the protective effects of two antioxidants, superoxide dimutase (SOD) and catalase (CAT) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. Methods: Colitis was induced in Sprague-Dawley rats of both sexes (200-300g) by intrarectal
•
G4586 IS CYCLOSPORINE AS EFFECTIVE IN CHRONIC ULCERATIVE COLITIS AS IN SEVERE ULCERATIVE COLITIS? C. Ynon, A. Kornbluth, J. George, M. Sternthal, S. Lichtiger, J. Marion, D. Present. The Henry D. Janowitz Division of Gastroenterology, Mount Sinai Medical Center, New York, New York. Introduction: Cyclosporine is effective in the treatment of severe ulcerative colitis, failing to respond to intravenous steroids. In addition, we have also treated patients who are either refractory to, or dependent on, oral steroids. The objective of this study was to determine if the success rates are influenced by the different indications for cyclosporine usage. Methods: We retrospectively reviewed the records of 104 ulcerative colitis patients treated with IV cyclosporine at Mount Sinai Hospital. We determined success rates at the conclusion of the IV cyclosporine phase, at 6 months, and at time of last follow-up (mean of 3.6 years). We stratified patients into three groups, all of whom were treated with IV cyclosporine: Group 1 were hospitalized patients being treated with at least 6 days of IV steroids. Group 2 were originally outpatients with persistent symptoms refractory to high dose (_>40mg) oral prednisone. Group 3 were outpatients with controlled symptoms but steroid dependent. Results: Patients in groups 1,2,3 were comparable in gender, age, and disease duration. More patients in group 1 had extensive disease, with pancolitis in 68% of patients, as compared to groups 2 and 3, with pancolitis in 55% and 53% of patients, respectively (P<0.05). Success rates are shown for groups 1,2,3 for each time period.