Ulcerative Colitis: Ouyang Q

Anonymous00018, Anonymous00019, Ouyang Q, Hu PJ, Qian JM, Zheng JJ, Hu RW. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. · J Dig Dis. · Pubmed #18251795 No free full text.

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Ouyang Q, Tandon R, Goh KL, Pan GZ, Fock KM, Fiocchi C, Lam SK, Xiao SD. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. · J Gastroenterol Hepatol. · Pubmed #17074013 No free full text.

Abstract: At the present there are no large-scale epidemiologic data on inflammatory bowel disease (IBD) in the Asia-Pacific region, but several studies have shown an increased incidence and prevalence of IBD in this region. Compared to the West, there appears to exist a time lag phenomenon. With regard to the two main forms of IBD, ulcerative colitis (UC) is more prevalent than Crohn's disease (CD). In addition to geographic differences, ethnic differences have been observed in the multiracial Asian countries. Moreover, the genetic backgrounds are different in the Asian compared to Western patients. For instance, NOD2/CARD15 variants have not been found in Asian CD patients. In general, the clinical course of IBD seems to be less severe in the Asia-Pacific region than in Western countries. Diagnosis of IBD in this region poses special problems. The lack of a gold standard for the diagnosis of IBD, and the existence of a variety of infectious enterocolitis with similar manifestations to those of IBD make the differential diagnosis particularly difficult. So far, Western diagnostic criteria have been introduced for the diagnosis of IBD. A stepwise approach to exclude non-IBD enterocolitis also must be introduced, and a definite diagnosis must include typical histological features. In some patients, follow up and therapeutic trials might be necessary to obtain a definitive diagnosis. A better understanding of the pathogenesis of IBD will allow the development of better diagnostic markers. The management of IBD also poses some special problems in the Asia-Pacific Region. There is often a delay in using proper medications for IBD, and alternative local remedies are still widely used. With a combination of Western guidelines and regional experiences, similar principles can be used for induction and maintenance of remission. A stepwise selection of medications is advocated depending on the extent, activity and severity of the disease. Comprehensive and individualized approaches are suggested for different IBD patients. Deeper understanding of disease pathogenesis and the unique characteristics of IBD in the Asia-Pacific region, combined with reasonable and practical guidelines for drug management and the future use of biological agents would improve the therapeutic outlook of IBD in this region.

Ouyang Q, Tandon R, Goh KL, Ooi CJ, Ogata H, Fiocchi C. · Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. · Curr Opin Gastroenterol. · Pubmed #15930979 No free full text.

Abstract: PURPOSE OF REVIEW: Inflammatory bowel disease has been traditionally considered rare in the Asian Pacific region, but recent evidence indicates that both Crohn disease and ulcerative colitis are becoming increasingly common among local populations. This review will validate this significant epidemiological and clinical observation using data published in the current Asian literature and information presented at the 2004 Asian Pacific Digestive Week in Beijing, China. RECENT FINDINGS: A progressive rise in the incidence and prevalence of inflammatory bowel disease is discernible is most Asian Pacific countries, more so for ulcerative colitis than Crohn disease. Some ethnic differences are notably evident, as Indians suffer more inflammatory bowel disease than Chinese or Malays. Age of onset and gender are similar to those of Western patients, as are the distribution and extent of disease which, however, tends to be clinically less severe than in European and North American patients. A family history is occasionally elicited, whereas smoking and appendectomy appear to have the same impact on inflammatory bowel disease as seen in the West. A remarkable difference is the absence of any association of Asian Crohn disease with NOD2/CARD15 mutations, as repeatedly observed in white and Jewish populations. Intestinal tuberculosis is still common in the Asian Pacific region, and poses major diagnostic and therapeutic hurdles, often delaying the diagnosis of true Crohn disease. SUMMARY: Investigation of inflammatory bowel disease in the Asian Pacific region offers the unprecedented opportunity to study the 'early stages' of the disease, and may provide new clues to its pathophysiology by identifying key environmental factors and distinct genetic make-ups.

Li Z, Zhang de K, Yi WQ, Ouyang Q, Chen YQ, Gan HT. · Department of Gastroenterology and Geriatric Medicine West China Hospital, Sichuan University, Chengdu, China. · Arch Med Res. · Pubmed #18996285 No free full text.

Abstract: BACKGROUND: Activation of nuclear factor-kappa B (NF-kappaB), which controls transcription of various proinflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). The aim of this study was to investigate if NF-kappaB p65 antisense oligonucleotides may affect the expression of NF-kappaB p65 and cytokines in lamina propria mononuclear cells (LPMCs) from patients with UC. METHODS: LPMCs, which were isolated from intestinal mucosal biopsy specimens from patients with UC, were cultured with or without NF-kappaB p65 antisense oligonucleotides, missense oligonucleotides and dexamethasone. NF-kappaB p65 expression was determined by Western blot analysis. The expression of cytokine mRNA was studied by reverse transcription-polymerase chain reaction (RT-PCR). Cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: NF-kappaB p65 antisense oligonucleotides resulted in downregulation of NF-kappaB p65 expression, blocked the expression of IL-1beta mRNA and IL-8 mRNA, and strikingly reduced the production of IL-1beta and IL-8. These effects were greater than those of dexamethasone in cultured LPMCs from patients with UC (p <0.05). CONCLUSIONS: Application of NF-kappaB p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with UC.

Chang YY, Ouyang Q. · Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu 610041, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #18346318 No free full text.

Abstract: OBJECTIVE: To investigate the expression and significance of human beta-defensin-2 (HBD2), TNFalpha and IL-1beta in ulcerative colitis (UC). METHODS: Thirty-five patients with active UC diagnosed by the department of gastroenterology in West China Hospital were included in this study. Ulcerative colitis disease activity index (UCAI) was assessed and the pathological grades of UC were classified. Immunohistochemistry assay and real-time quantitative PCR were used for the expression of HBD2, TNFalpha, IL-1beta in colonic mucosa of UC. RESULTS: Among the 35 patients with UC, 10 cases were mild, 13 moderate and 12 severe. Of the 35 cases, there were 11 with grade I, 13 grade II and 11 grade III lesion according to Truelove criteria. The score of UCAI had positive correlation with pathological grading (r = 0.890, P < 0.01). The expressions of HBD2, TNFalpha, IL-1beta in colonic mucosa of UC with immunohistochemistry and real-time quantitative PCR were significantly higher than those in healthy control (P < 0.05); the expressions increased gradually with the severity of pathological grade and there was a higher expression of them in inflamed area than in non-inflamed (P < 0.05). A good positive correlation was also found between HBD2 and other inflammatory cytokines. CONCLUSIONS: It is shown that there is a higher expression of HBD2 in colonic mucosa as compared with healthy control, a higher expression of it in inflamed area than in non-inflamed area and a positive correlation of expression between HBD2 and pro-inflammatory cytokines such as TNFalpha and IL-1beta, implying that HBD2 and pro-inflammatory cytokines are interdependent and interactive playing an important role in magnifying and aggravating inflammatory injury in UC.

Liang HL, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. · World J Gastroenterol. · Pubmed #18176972 links to  free full text

Abstract: AIM: To investigate the therapeutic effects of the combined use of rosiglitazone and aminosalicylate on mild or moderately active ulcerative colitis (UC). METHODS: According to the national guideline for diagnosis and treatment of inflammatory bowel disease (IBD) in China, patients with mild or moderately active UC in our hospital were selected from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure and those who had received corticosteroid or immunosuppressant treatment within the last month were excluded. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group (TG) with rosiglitazone 4 mg/d plus 5-ASA 2 g/d daily or the control group (CG) with 5-ASA 2 g/d alone, respectively, for 4 wk. Clinical changes were evaluated by Mayo scoring system and histological changes by Truelove-Richards' grading system at initial and final point of treatment. RESULTS: Forty-two patients completed the trial, 21 each in TG and CG. The Mayo scores in TG at initial and final points were 5.87 (range: 4.29-7.43) and 1.86 (range: 1.03-2.69) and those in CG were 6.05 (range: 4.97-7.13) and 2.57 (range: 1.92-3.22) respectively. The decrements of Mayo scores were 4.01 in TG and 3.48 in CG, with a remission rate of 71.4% in TG and 57.1% in CG, respectively. Along with the improvement of disease activity index (DAI), the histological grade improvement was more significant in TG than in CG (P < 0.05). CONCLUSION: Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. Rosiglitazone can alleviate colonic inflammation which hopefully becomes a novel agent for UC treatment.

Xiang JY, Ouyang Q, Li GD, Xiao NP. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. · World J Gastroenterol. · Pubmed #18176961 links to  free full text

Abstract: AIM: To investigate possibility and clinical application of fecal calprotectin in determining disease activity of ulcerative colitis (UC). METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of calprotectin in feces obtained from 66 patients with UC and 20 controls. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), acid glycoprotein (AGP) were also measured and were compared with calprotectin in determining disease activity of UC. The disease activity of UC was also determined by the Sutherland criteria. RESULTS: The fecal calprotectin concentration in the patients with active UC was significantly higher than that in the inactive UC and in the controls (402.16 +/- 48.0 microg/g vs 35.93 +/- 3.39 microg/g, 11.5 +/- 3.42 microg/g, P < 0.01). The fecal calprotectin concentration in the inactive UC group was significantly higher than that in the control group (P < 0.05). A significant difference was also found in the patients with active UC of mild, moderate and severe degrees. The area under the curve of the receiver operating characteristics (AUCROC) was 0.975, 0.740, 0.692 and 0.737 for fecal calprotectin, CRP, ESR and AGP, respectively. There was a strong correlation between the fecal calprotectin concentration and the endoscopic gradings for UC (r = 0.866, P < 0.001). CONCLUSION: Calprotectin in the patient's feces can reflect the disease activity of UC and can be used as a rational fecal marker for intestinal inflammation in clinical practice. This kind of marker is relatively precise, simple and noninvasive when compared with other commonly-used markers such as CRP, ESR and AGP.

Yi WQ, Gan HT, Huang XL, Zhang M, Ouyang Q. · Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu 610041, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #18028805 No free full text.

Abstract: OBJECTIVE: To investigate the expression of phosphorylated p38 mitogen activated protein kinase (MAPK) in colonic mucosa of patients with ulcerative colitis (UC) and the effects of SB203580 which is a p38 MAPK inhibitor on the secretion of TNFalpha in colonic mucosa from patients with UC. METHODS: Samples of colonic mucosa were collected from 30 UC patients, 20 males and 10 females, aged (33.50 +/- 10.20) years, during enteroscopy. Samples of normal colonic mucosa 10 cm beyond the tumorous tissue were collected from 15 patients with colonic cancer, 10 males and 5 females, aged (46.64 +/- 10.49) years, as normal controls. The samples underwent pathological and immunohistochemical examination. The remaining samples of the colonic mucosa were cultured and divided into 3 groups: UC + SB203580 group (n = 10, SB203580, an inhibitor of p38 MAPK signal pathway, in a concentration of 20 micromol/L was added), UC control group (n = 10, without addition of SB203580), and peri-cancer normal colonic tissue group (n = 10). 5 hours after the culture, immunohistochemistry was used to detect the expression of phosphorylated p38 MAPK and the expression of phosphorylated transcription of activation factor-2 (ATF(2)), which is a downstream molecule of p38 MAPK. ELISA array was used to detect the content of tumor necrosis factor (TNFalpha) in the supernatant. RESULTS: (1) The A value of phosphorylated p38 MAPK in the colonic mucosa of the UC was 549.22 +/- 32.54, being significantly higher than that of the normal colonic mucosa (143.52 +/- 11.89, P < 0.01). The positive area of the UC group was (1680.61 +/- 115.30) x 10(-5) microm(2), being significantly higher than that of normal colonic mucosa (351.68 +/- 12.73) x 10(-5) microm(2), P < 0.01. (2) The level of TNFalpha in the supernatant of the UC + SB203580 group was (72.07 +/- 20.30) ng/L, being significantly lower than that of the UC control group (549.96 +/- 107.63) ng/L (P < 0.01), but still higher than that of the normal control group (19.44 +/- 3.81) ng/L (P < 0.01). (3) The A value of phosphorylated ATF(2) in the colonic mucosa biopsy specimens of the UC + SB203580 group was 265.82 +/- 40.25, being significantly lower than that of the UC control group (688.32 +/- 47.37, P < 0.01), but still higher than that of the normal control group (120.22 +/- 6.45, P < 0.01). The positive area of phosphorylated ATF(2) in the colonic mucosa biopsy specimens of the UC + SB203580 group was (1213.76 +/- 204.77) x 10(-5) microm(2), being significantly lower than that of the UC control group (2489.02 +/- 193.63) x 10(-5) microm(2), P < 0.01, but no difference in expression of phosphorylated p38 MAPK was found between UC + SB203580 group and UC control group [respectively, A value: 465.64 +/- 38.69 vs 480.34 +/- 38.87, positive area: (1486.26 +/- 165.49) x 10(-5) microm(2) vs (1536.68 +/- 182.16) x 10(-5) microm(2), both P > 0.05]. CONCLUSIONS: p38 MAPK signal transduction pathway plays an important role in the development of UC. Blockade of the signal transduction pathway could ameliorate inflammation, at least in part, by reducing secretion of proinflammatory cytokines, suggesting that p38 MAPK pathway might be a new target for treatment of UC, and SB203580 could be a hopeful novel drug for the treatment of UC.

Xiang JY, Ouyang Q, Li GD. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #18001547 No free full text.

Abstract: OBJECTIVES: To explore the possibility and clinical application value of fecal lactoferrin as a marker of the activity of ulcerative colitis (UC). METHODS: Specimens of feces were collected from 66 UC patients and 20 healthy persons or irritable bowel syndrome patients. ELISA was used to measure the concentration of lactoferrin in feces, and CRP and ESR were also measured. The disease activity of UC was determined by Mayo criteria. RESULTS: The fecal lactoferrin concentration of the patients with active UC was (61.6 +/- 4.8) microg/g, significantly higher than that of the patients with inactive UC and the controls [(7.9 +/- 1.1) microg/g and (3.0 +/- 0.5) microg/g, both P < 0.01], and the fecal lactoferrin concentration of the patients with inactive UC group was also significantly higher than that of the controls (P < 0.05). The higher the grade of activity of disease the higher the concentration of lactoferrin (P < 0.05 or P < 0.01). The area under curve of receiver operating characteristic (AUCROC) of fecal lactoferrin was 0.982, significantly larger than those of the CRP and ESR (0.740 and 0.692 respectively, both P < 0.01). However, there was no significant difference in AUCROC between CPR and ESR. The fecal lactoferrin concentration was positively correlated with the endoscopic grades of UC (r = 0.871, P < 0.01). CONCLUSION: Lactoferrin in feces reflects the disease activity of UC and is a rational fecal marker of intestinal inflammation for clinical application. A precise, simple, and noninvasive method, lactoferrin examination is better than common clinically used markers, such as CRP and ESR.

Bai AP, Ouyang Q, Hu RW. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. · J Dig Dis. · Pubmed #17970875 No free full text.

Abstract: OBJECTIVE: Since the etiology and the pathogenesis of inflammatory bowel disease (IBD) are still not well known, research on IBD often focuses on these topics. Investigative science papers about IBD in Chinese medical journals from 1989 to 2003 were viewed to understand the progress of basic IBD research in China. MATERIALS AND METHODS: The basic science investigative papers about IBD from 1989 to 2003 in Chinese periodicals (VIP and CMCC) were reviewed and analyzed; the key words used were as follows: inflammatory bowel disease, ulcerative colitis, Crohn's disease, basic science investigation, and literature review. RESULTS: There were 3454 articles about IBD published in Chinese medical journals from 1989 to 2003, and during these 15 years, 508 papers focused on basic scientific investigations. There were 463 papers investigating the pathogenesis of IBD, 287 papers on immunological mechanisms, and 176 papers about other mechanisms. There were 142 papers investigating the mechanisms of Chinese traditional medicine on IBD from 1989 to 2003, which included 117 papers related to animal experiments and 25 papers related to clinical studies. CONCLUSIONS: There have been relatively few investigative scientific papers on IBD published in Chinese medical journals. However, the study of IBD has been emphasized in China. Research on the immunological mechanisms of IBD has been predominant. Furthermore, a large number of the research papers were about the mechanisms and effects of Chinese traditional medicine on IBD.

Wang Y, Ouyang Q, Anonymous00142. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. · J Gastroenterol Hepatol. · Pubmed #17716349 No free full text.

Abstract: BACKGROUND AND AIMS: This retrospective study analyzed the clinical characteristics of hospitalized patients with ulcerative colitis (UC) in China. METHODS: A total of 3100 hospitalized patients with UC admitted to 23 hospitals in China from 1990 to 2003 were retrospectively investigated and their clinical characteristics were analyzed. RESULTS: A male/female ratio of 1.34/1.00 was found in the 3100 patients, who had an average age of 44 +/- 15.1 years at diagnosis. Of the patients, 2972 (95.9%) had active UC. Active UC was mild in 35.4% of the 2972 patients, moderate in 42.9% and severe in 21.7%. Of the 2726 patients with a description of their lesion extent, 14.8% had proctitis, 26.4% had proctosigmoiditis, 25.0% had left-sided colitis, 6.3% had extensive colitis, 25.8% had pancolitis and 1.7% had regional colitis. The predominant complaints of the patients with UC were bloody diarrhea (48.2%), abdominal pain (67.3%) and mucus stools (58.4%). Among these patients, 13.6% had extraintestinal manifestations and 9.6% had related complications. A differential diagnosis was difficult to make, as there were 19 varieties of the disease; infectious enterocolitis had a misdiagnosis rate of 22.9% before admission. The main medications for UC in China were aminosalicylates (66.8%) and steroids (42.8%). Only 94 (3%) of the patients required colectomy and only 19 (0.6%) died of UC. CONCLUSIONS: Compared with UC in Western countries, ulcerative colitis in China has some differences in clinical characteristics. Therefore, a further population-based epidemiological study is required to determine the prevalence and incidence rates of UC in China.

Wang YF, Zhang H, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. · J Dig Dis. · Pubmed #17650222 No free full text.

Abstract: Inflammatory bowel disease (IBD) is very common in developed countries, while it is relatively uncommon in Asian countries. However, the incidence of IBD has been increasing in some Asian countries in recent years. Most cases of ulcerative colitis (UC) in Asia are of the chronic relapsing type, run a milder course, and the fulminant type is rarely seen. There is no difference in clinical manifestations between Asian and developed countries. The incidence of Crohn's Disease (CD) is mainly in males in Asia, while it is mainly in females in developed countries. The clinical manifestations of CD are similar between both sets of countries. In China there are less fistulae and perianal diseases, and extraintestinal manifestations of CD are uncommon. In China, 5.6% of patients with UC have a family history, which is lower than 10-20% in developed countries. NOD2/CARD15 variants in the locus of 16q112 (IBD1) are significantly associated with the susceptibility of CD in developed countries, but NOD2/CARD15 variants have not been found in Asian CD patients.

Huang XL, Yi WQ, Zhang M, Ouyang Q, Gan HT. · Department of Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China. · Zhonghua Yi Xue Za Zhi. · Pubmed #17456377 No free full text.

Abstract: OBJECTIVE: To elucidate the role of phosphatidylinositol 3-kinase (PI3K)/Akt in the pathogenesis of ulcerative colitis (UC) and provide experimental evidence that PI3K inhibitor wortmannin can be used as a possible novel approach for treatment of UC. METHODS: Samples of intestinal mucosa were collected from 30 UC patients, 22 males and 8 females, aged 35 +/- 11, during enteroscopy. Samples of normal intestinal mucosa 10 cm beyond the cancerous tissues were collected from 15 patients with intestinal cancer, 9 males and 6 females, aged 40 +/- 9, as normal controls. The samples underwent pathological examination and immunohistochemistry. Another tissues of intestinal mucosa were cultured and divided into 3 groups: UC + wortmannin group, (n = 10, wortmannin, an inhibitor of PI3K/Akt pathway, of the concentration of 0.002 nmol/microl was added), UC control group (n = 10, without addition of wortmannin), and peri-cancer normal intestinal tissue group (n = 10). 4.5 hours after the culture, immunohistochemistry was used to detect the expression of phosphorylated Akt (p-Akt) in the intestinal mucosa and ELISA was used to detect the content of tumor necrosis factor (TNF-alpha) in intestinal mucosa. RESULTS: (1) The A value of p-Akt in the intestinal mucosa of the UC control group was 73.6 +/- 5.2, significantly higher than that of the normal control group (18.0 +/- 2.6, P < 0.05), the positive area of the UC control group was 720 +/- 58, significantly larger than that of the normal control group (133 +/- 29, P < 0.05). (2) The level of TNF-alpha in intestinal mucosa of the UC + wortmannin group was 135 +/- 11, significantly lower than that of the UC control group (296 +/- 39, P < 0.05), however, still significantly higher than that of the normal control group (26 +/- 5, P < 0.05). (3) The A value of p-Akt in the intestinal mucosa biopsy specimens of the UC + wortmannin group was 35.3 +/- 5.6, significantly lower than that of the UC control group (72.3 +/- 6.2, P < 0.05), however, still significantly higher than that of the normal control group (18.0 +/- 2.2, P < 0.05); and the positive area of the UC + wortmannin group was 351 +/- 50, significantly lower than that of the UC control group (716 +/- 94, P < 0.05), however, still significantly higher than that of the normal control group (129 +/- 30, P < 0.05). CONCLUSIONS: (1) PI3K/Akt signal transduction pathway is a critical factor in regulating the expression of pro-inflammatory cytokine, and plays a role in the pathogenesis of UC. (2) Decreasing the levels of relevant cytokines in UC by inhibiting PI3K/Akt signal transduction pathway, wortmannin may be a novel approach for the treatment of UC.

He G, Ouyang Q, Chen D, Li F, Zhou J. · Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China. · Dig Dis Sci. · Pubmed #17429731 No free full text.

Abstract: Mucosal microvascular thrombi in rectal biopsies were observed in some ulcerative colitis (UC). Heparin may be effective in steroid resistant UC in some studies, however, the new results of meta-analysis demonstrated a non-significant effect of heparin in controlled clinical trials, differing markedly from observational studies. The objective of this study was to identify colonic microvascular thrombi in larger cases with UC, and analyse its possible risk factors: age, gender, histologic score, extent of lesions and operation or biopsy specimens, and assess the significance of microvascular thrombosis in patients with UC. The microvascular thrombi were identified by immunohistochemical staining with anti-CD61 monoclonal antibody and Martius scarlet blue (MSB) staining in 40 colonic tissue samples of UC (31 biopsy specimens and nine operated cases) and 12 cases of normal colon tissue from operated colonic carcinoma. Logistic regression analysis was used to assess the relationship of age, gender, degree of histology, origin of the specimens, extent of lesions and microvascular thrombi examined. Microvascular thrombi were positive in 14 of 40 UC cases, and none in the controls. The presence of microvascular thrombi was related to operation specimens with odds ratio 11.667, P=0.0179, it might be also related to histologic score (OR=1.350) and extent of lesions (OR=1.619). These results suggest that microvascular thrombosis may be one of the important pathogenesis in some UC, and that the effect of anticoagulant treatment still needs to be assessed.

Liang HL, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China. · Zhonghua Nei Ke Za Zhi. · Pubmed #17074107 No free full text.

Abstract: OBJECTIVE: To investigate the therapeutic effects of the combination of rosiglitazone, which is peroxisome proliferators-activated receptor gamma (PPARgamma) ligands used to treat type 2 diabetes mellitus, and aminosalicylate on mildly or moderately active ulcerative colitis and on relevant cytokine expressions. METHODS: According to the national guideline of China for diagnosis and treatment of the inflammatory bowel disease (IBD), 42 patients with mild, moderately active ulcerative colitis were selected from the outpatient clinic of West China Hospital from July to November, 2004. Patients with infectious colitis, amoebiasis, or cardiac, renal or hepatic failure were excluded, as well as those who had received corticosteroid or immunosuppressant treatment within the last month. Following a quasi-randomization principle, patients were allocated alternatively into the treatment group with rosiglitazone 4 mg/d plus 5-aminosalicylic acid (5-ASA) 2 g/d or sulfasalazine 3 g/d and the control group with 5-ASA or sulfasalazine alone for 4 weeks. Clinical and histological changes were evaluated weekly by the Mayo scoring system for assessment of the activity of ulcerative colitis and the Truelove-Richards' grading system, respectively. PPARgamma and nuclear factor (NF)-kappaB p65 expressions in colonic mucosa were investigated before and after the treatment. RESULTS: Mayo scores decreased 4.01 in treatment group and 3.48 in control group respectively, with a remission rate 71.4% in treatment group and 57.1% in control group respectively. Along with the improvement of the Mayo score, the histological grade improvement was more significant in treatment group than in control group (P < 0.05). PPARgamma expression was higher, and NF-kappaB p65 positive rate was lower in treatment group than in control group after the treatment, and there was a good negative correlation between PPARgamma and NF-kappaB. CONCLUSIONS: Combined treatment with rosiglitazone and 5-ASA achieved better therapeutic effect than 5-ASA alone without any side effects. The PPARgamma expression was lower in active ulcerative colitis. Rosiglitazone alleviate colonic inflammation probably the through blockade of NF-kappaB, which can be a novel approach to the ulcerative colitis treatment.

Bai AP, Ouyang Q, Xiao XR, Li SF. · Department of Gastroenterology,Westchina Hospital, Sichuan University, Chengdu, China. · Int J Clin Pract. · Pubmed #16494642 No free full text.

Abstract: Enteric microflora of ulcerative colitis patients becomes aberrant. The abnormal interaction between microflora and intestinal mucosal immune system leads the mucosal inflammation. Probiotic administration may recover the commensal microflora and normalise the host-microbial interaction. In this experiment, we cocultured colonic biopsies from active ulcerative colitis patients with bifidobacterium to investigate the modulation effect of probiotics on inflamed colonic tissues and its possible mechanism. Colonic biopsies from active ulcerative colitis were cocultured for 24 h with Bifidobacterium longum. Tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 in supernatants were measured using enzyme-linked immunosorbent assays, the biopsies were fixed using paraffin and the expression of NF-kappaB P65 of tissues was studied using immunohistochemical staining. The concentrations of TNF-alpha and IL-8 in supernatants of tissues cocultured with probiotics were lower than those cultured alone. The number of lamina propria mononuclear cells (LPMC) with nuclear factor-kappa B (NF-kappaB) P65 positive in cocultured tissues was also decreased. When cocultured with inflamed tissues of active ulcerative colitis, probiotics could inhibit NF-kappaB activation in LPMC and down-regulate inflammatory cytokine secretion from inflamed tissues of active ulcerative colitis.

Bai AP, Ouyang Q, Hu RW. · Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou City 510080, China. · Dig Dis Sci. · Pubmed #16110831 No free full text.

Abstract: The present study aimed to investigate the effect of diallyl trisulfide (DATS) on tumor necrosis factor (TNF)-alpha expression in inflammed mucosa of ulcerative colitis and its possible mechanism. Colonic biopsies from ulcerative colitis were treated with 0, 1, 5, and 10 microM DATS for 24 hr. Lactate dehydrogenase (LDH) activities and concentrations of TNF-alpha in supernatants were measured. mRNA expressions of TNF-alpha in biopsies were analyzed by RT-PCR. The expression of NF-kappaB P65 in tissues was studied by immunohistochemistry. Concentrations of TNF-alpha in supernatants of biopsies treated with 5 and 10 microM DATS were lower than those of untreated biopsies. There were fewer lamina propria mononuclear cells whose NF-kappaB P65 expression in nuclei was positive, and less mRNA expression of TNF-alpha in biopsies treated with 10 microM DATS than in untreated biopsies. There were no differences in LDH activities in supernatants between tissues treated with DATS and untreated tissues. DATS could downregulate TNF-alpha production and inhibit NF-kappaB activation in lamina propria mononuclear cells of inflammed mucosa, without any effect on the viability of colonic tissue cells.

Wang X, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China. · Sichuan Da Xue Xue Bao Yi Xue Ban. · Pubmed #16078585 No free full text.

Abstract: OBJECTIVE: To assess the effect of thalidomide on Trinitrobenzensulphonic acid (TNBS)-induced or oxazolone-induced colitis and discuss the possible mechanism of its action. METHODS: Transmural colitis was induced by TNBS in three groups of rats (n=6 each), and distal colitis was induced by oxazolone in three groups of rats (n=6 each). Then the rats of the groups were treated with thalidomide [200 mg/(kg x d)], prednisone [5 mg/(kg x d)] or vehicle (olive oil) respectively by oral gavage. The colitis was allowed to run its course for 7 d after gavage and at that time the following endpoints were assessed. Colitis was evaluated by macroscopic and microscopic score; the expression of NF-kappaB P65 was examined by immunohistchemical (IHC); the expression of TNF-alpha mRNA was assayed by hybridization in situ (ISH); the cytokine TNF-alpha, IL-4, IFN-gamma were estimated by enzyme-linked immunoadsordent assay (ELISA). RESULTS: With respect to TNBS model, in the control, prednisone-treatment and thalidomide-treatment groups, the macroscopic and microscopic scores were 6.33 +/- 1.03, 1.67 +/- 0.82, 2.00 +/- 0.89 and 7.33 +/- 1.03, 2.67s +/- 0.82, 3.17 +/- 0.75 respectively; the expression levels of NF-kappaB P65 and TNF-alpha mRNA in the three groups were 62.45 +/- 12.38, 23.62 +/- 8.54, 34.18 +/- 9.65 and 12.42 +/- 4.63, 9.86 +/- 3.29, 4.35 +/- 1.74 respectively; the levels of TNF-alpha, IL-4, IFN-gamma were 540.32 +/- 80.76, 94.58 +/- 14.45, 486.18 +/- 68.47; 396.53 +/- 92.42, 78.45 +/- 12.69, 347.56 +/- 82.94; and 385.68 +/- 88.57, 123.68 +/- 38.15, 378.27 +/- 90.65 respectively. The results indicated that thalidomide treatment significantly reduced colonic inflammation, suppressed NF-kappaB activation,enhanced TNF-alpha mRNA degradation, inhibited the synthesis of the TNF-alpha, IEN-gamma and increased the production of IL-4. However, with respect to oxazolone model, the macroscopic score and microscopic score were 2.00 +/- 0.89, 0.33 +/- 0.52, 1.83 +/- 0.75 and 7.83 +/- 1.47, 3.33 +/- 0.82, 6.50 +/- 1.22 respectively. Thalidomide appeared not to be effective in reducing the oxazolone-induced chronic colitis. CONCLUSION: Thalidomide may be proposed as a useful drug for Crohn's disease, but further work is needed to clarify whether it is an efficacious agent for ulcerative colitis.

Gan HT, Chen YQ, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. · J Gastroenterol Hepatol. · Pubmed #15955209 No free full text.

Abstract: BACKGROUND: Although sulfasalazine is widely used to treat inflammatory bowel disease, its mechanisms of action remain unclear. Activation of transcription factor nuclear factor (NF)-kappaB, which controls transcription of various pro-inflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of inflammatory bowel disease. The purpose of the present study was to determine whether sulfasalazine therapy affected NF-kappaB activation and the expression of pro-inflammatory cytokines in patients with ulcerative colitis. METHODS: A total of 38 patients with moderate ulcerative colitis were investigated. Twenty-one patients received sulfasalazine. Seventeen patients did not receive any medication. Biopsy specimens were obtained from inflamed mucosa and analyzed for NF-kappaB DNA binding activity, NF-kappaBp65/IkappaBalpha protein expression and the levels of pro-inflammatory cytokine mRNA using electrophoretic mobility shift assay, western blot analysis, immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively. RESULTS: Increased activation of NF-kappaB and high levels of the expression of interleukin (IL)-1beta mRNA and IL-8 mRNA were detected in biopsy specimens from patients with ulcerative colitis. Therapeutic administration of sulfasalazine effectively downregulated the activation of NF-kappaB and the expression of IL-1beta mRNA and IL-8 mRNA while IkappaBalpha levels were stable. CONCLUSION: The therapeutic benefits for ulcerative colitis of sulfasalazine might at least in part be attributed to its ability to inhibit NF-kappaB activation, resulting in the downregulation of pro-inflammatory cytokine mRNA expression.

Wang YF, Wei B, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China. · Sichuan Da Xue Xue Bao Yi Xue Ban. · Pubmed #15807267 No free full text.

Abstract: OBJECTIVE: To elucidate the differences in expression of TGFbeta1 and TGFbeta1 mRNA between ulcerative colitis (UC), infectious colitis (IC) and normal control. METHODS: TGFbeta1 in colonic mucosa was detected by immunohistochemistry (IHC). TGFbeta1 mRNA was detected by hybridization in situ. RESULTS: There was no difference in detecting TGFbeta1 expression and TGFbeta1 mRNA expression in colonic mucosa between UC group and IC group (P>0.05), but the expression rates for the two groups were significantly higher than those for normal control (P<0.001). The expression of TGFbeta1 in colonic mucosa of UC group was noted to have a positive correlation with UC histological grade (r=0.462, P=0.002). CONCLUSION: Enhanced TGFbeta1 production in the colonic mucosa of UC patients can not inhibit proinflammatory cytokine production and hence can not get control of inflammation; this finding suggests the possible presence of TGFbeta1 signaling defects in the cases of UC. TGFbeta1 may serve as a disease activity marker of ulcerative colitis.

Zhang H, Ouyang Q, Wen ZH, Fiocchi C, Liu WP, Chen DY, Li FY. · Department of Gastroenterology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China. · World J Gastroenterol. · Pubmed #15793862 links to  free full text

Abstract: AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRalpha and GRbeta) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n = 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRalpha and GRbeta expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRalpha and GRbeta expression. Both positive association between GRalpha expression and the response of UC to GC and strong negative association between GRbeta expression and the response of UC to GC were identified. There was no significant association between GRalpha/GRbeta expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRalpha and GRbeta may play an important role in the action of GC, and that GRbeta functions as a dominant negative inhibitor of GRalpha. Expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.

Wang X, Ouyang Q, Luo WJ. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China. · Chin J Dig Dis. · Pubmed #15612886 No free full text.

Abstract: OBJECTIVE: Animal models are useful for studying disease, but there is a shortage of suitable models of ulcerative colitis. The aim of the present study was to set up an oxazolone-induced murine colitis model and use it to research the pathogenesis of inflammatory bowel disease. METHODS: BALB/c mice were presensitized by painting the skin with 0.2 mL 3% oxazolone in 100% ethanol on days 0 and 1 followed by intrarectal administration of 0.15 mL 1% oxazolone in 50% ethanol on day 7. The disease activity index (DAI), histological changes of the colon, myeloperoxidase (MPO) activity and production of cytokines (TNF-alpha, IL-4, IFN-gamma) by the mucosa were evaluated. RESULTS: There were obvious changes in the DAI, histology and MPO activity, and the production of interleukin-4 was markedly increased compared with the concentrations of TNF-alpha and IFN-gamma, which remained normal, in the lesions. CONCLUSION: Oxazolone colitis is Th2-mediated and has similar histologic features and distribution of inflammation to ulcerative colitis (UC), which has important implications for the use of this model in the study of the pathogenesis and treatment of UC.

Chen Y, Gan H, Ouyang Q, Xu D, Pan Y, A Z. · Department of Life Sciences, Dali College, Dali 671000, China. · Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. · Pubmed #15553846 No free full text.

Abstract: The purpose of this study is to assess the effects of anti-inflammatory on activation of nuclear factor-kappaB and mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in intestinal mucosal biopsy specimens from patients with ulcerative colitis (UC). A total of 27 cases with UC were investigated. 15 cases received sulfasalazine (SASP) treatment or SASP and glucocorticoid treatment, 12 cases did not receive any medication related with UC. Normal mucosa from 9 colon cancer cases served as control. Ten pieces of intestinal mucosal biopsy specimens were obtained from each patient. The mRNA expression of ICAM-1 and VCAM-1 were determined by reversal transcription-polymerase chain reaction (RT-PCR). The protein levels of ICAM-1 and VCAM-1 were measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB DNA binding activity was evaluated by electrophoretic mobility shift assay (EMSA). The results showed that NF-kappaB DNA binding activity, mRNA and protein expression of ICAM-1 and VCAM-1 were increased significantly in patients with UC, compared with normal control (P<0.05). Glucocorticoids and SASP markedly inhibited NF-kappaB activation and significantly decreased mRNA and protein expression of ICAM-1 and VCAM-1 (P<0.05). Adhesion molecules (ICAM-1 and VCAM-1) gene activation had significant positive correlation with the NF-kappaB DNA binding activity (r=0.8652 P<0.05, r=0.7902, P<0.05, respectively). We concluded that NF-kappaB is a major and essential factor in regulating the expression of adhesion molecules, it plays an important role in the pathogenesis of UC. SASP and glucocorticoids ameliorate UC via inhibition of NF-kappaB activation and reduction of adhesion molecules expression.

Zhang H, Ouyang Q, Wen ZH, Liu WP, Chen DY, Li FY. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China. · Sichuan Da Xue Xue Bao Yi Xue Ban. · Pubmed #15460404 No free full text.

Abstract: OBJECTIVE: To investigate the relationship of the expression of GRalpha and GRbeta in the colonic mucosal cell of patients with ulcerative colitis to the efficacy of glucocorticoid (GC) therapy and the intensity of inflammation. METHODS: GRalpha expression and GRbeta expression in the colonic mucosal specimens were assessed by means of immunohistochemistry. Then comparative analyses were made on the GRalpha and GRbeta expression between the GC resistant group and GC sensitive group at various levels of inflammation. A normal response group was observed for comparison. RESULTS: The staining intensities of both GRalpha and GRbeta in colonic mucosal specimens showed significant differences between the GC resistant group, GC sensitive group and normal response group. No association between the expression of GRalpha and GRbeta and the degree of inflammation was found. CONCLUSION: These findings suggest that both GRalpha and GRbeta play an important role in the mechanism of the action of GC, and GRbeta functions as a dominant negative inhibitor of GRalpha in there. The expression of GRalpha and GRbeta in the colonic mucosal cell of patients with ulcerative colitis may serve as predictors of glucocorticoid response, but cannot be used as the markers of the severity of inflammation.

He G, Ouyang Q. · Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China. · Sichuan Da Xue Xue Bao Yi Xue Ban. · Pubmed #14619586 No free full text.

Abstract: OBJECTIVE: To evaluate the preventive and therapeutic effects of low molecular weight heparin (LMWH) on dextran sulphate sodium (DSS)-induced colitis in mice. METHODS: Twenty normal mice were randomized into two groups: 10 mice of the prevention group received DSS per os and LMWH by sub-cutaneous injection for 7 days; 10 mice as controls received DSS per os and sub-cutaneous normal saline for 7 days. Another 20 mice with DSS-induced colitis were randomized into two groups: the treatment group received sub-cutaneous injection of LMWH and the control group received subcutaneous injection of normal saline for 7 days. The preventive and therapeutic effects of LMWH were assessed by disease activity index (DAI), histologic score and MSB fibrin staining to identify microvascular thrombus. RESULTS: The DAI, rectal and transverse histological scores of the prevention group compared with those of the control group were 2.40 vs 2.52 (P > 0.05), 1.65 vs 1.85 (P > 0.05), 1.55 vs 1.72 (P > 0.05), respectively. Microvascular thrombi in the prevention group decrease significantly as compared with the control; microvascular thrombi were positive in 6 of 10 controls, but only one was positive in the prevention group, P = 0.029. The DAI, rectal and transverse histological scores in the treatment group compared with those of the control were 0.42 vs 0.44 (P > 0.05), 1.36 vs 1.75(P < 0.05), 1.30 vs 1.65(P < 0.05), respectively. Microvascular thrombi were positive in 3 of 10 controls, and one microvascular thromous was positive in the treatment group, P = 0.291. CONCLUSION: LMWH could effectively prevent microvascular thrombosis and inhibit colonic and rectal inflammation in the mice with DSS-induced colitis. These animal experimental results suggested that LMWH might also be used effectively in ulcerative colitis.