AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesi...AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.展开更多
The risk of colorectal cancer for any patient with ulcer-ative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer in...The risk of colorectal cancer for any patient with ulcer-ative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer in-clude extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflam-mation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epide-miological trends and causes for the observed chang-es. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.展开更多
AIM： To investigate the anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium （DSS）-induced colitis of rats. METHODS： Acute colitis was induced by giving 2% DSS orally in drinking water for 8 d. Twen...AIM： To investigate the anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium （DSS）-induced colitis of rats. METHODS： Acute colitis was induced by giving 2% DSS orally in drinking water for 8 d. Twenty-six male rats were randomized into oxymatrine-treated group （group A, 10 rats）, DSS control （group B, 10 rats） and normal control （group C, 6 rats）. The rats in group A were injected muscularly with oxymatrine at the dosage of 63 mg/（kg·d） from d 1 to 11 and drank 2% DSS solution from d 4 to 11. The rats in group B were treated with 0.9% saline in an equal volume as group A and drank 2% DSS solution from d 4 to 11. The rats in group C were treated with 0.9% saline as group B from d 1 to 11 and drank water normally. Diarrhea and bloody stool as well as colonic histology were observed. The levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were determined by ELISA, and nuclear factor-κB （NF-κB） activity and the expression of inter-cellular adhesion molecule-1 （ICAM-1） in colonic mucosa were detected by immunohistochemistry method. RESULTS： Compared with DSS control group, the inflammatory symptoms and histological damages of colonic mucosa in oxymatrine-treated group were significantly improved, the serum levels of TNF-α, IL-6, and the expression of NF-κB, ICAM-1 in colonic mucosa were significantly reduced. CONCLUSION： The fact that oxymatrine can reduce the serum levels of TNF-α, IL-6, and the expression of NF-κB and ICAM-1 in colonic mucosa in DSS-induced colitis of rats indicates that oxymatrine may ameliorate the colonic inflammation and thus alleviate diarrhea and bloody stool.展开更多
AIM: To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the...AIM: To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms. METHODS: Peripheral blood mononuclear cells (PBMNC) from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted. RESULTS: Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY. Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-α, whereas no such effect was observed with heat- killed bacteria. The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY. DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8. CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IκB-ζ mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM.CONCLUSION: Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.展开更多
AIM: To investigate the ameliorative effects of sodium ferulate (SF) on acetic acid-induced colitis and their mechanisms in rats.METHODS: The colitis model of Sprague-Dawley rats was induced by intracolon enema with 8...AIM: To investigate the ameliorative effects of sodium ferulate (SF) on acetic acid-induced colitis and their mechanisms in rats.METHODS: The colitis model of Sprague-Dawley rats was induced by intracolon enema with 8 % (WV) of acetic acid.The experimental animals were randomly divided into model control, 5-aminosalicylic acid therapy group and three dose of SF therapy groups. The 5 groups were treated intracolonically and daily (8:00 am) for 7 days 24 h following the induction of colitis. A normal control group of rats clystered with normal saline instead of acetic acid was also included in the study.Pathological changes of the colonic mucosa were evaluated by the colon mucosa damage index (CMDI) and the histopathological score (HS). The insulted colonic mucosa was sampled for a variety of determinations at the end of experiment when the animals were sacrificed by decapitation.Colonic activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), and levels of malondialdehyde (MDA)and nitric oxide (NO) were assayed with ultraviolet spectrophotometry. Colonic contents of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2)were determined by radioimmunoassay. The expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry.RESULTS: Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels,PGE2 and TXB2 contents, as well as the expressions of iNOS,COX-2 and NF-κB p65 proteins in the colonic mucosa,although the colonic SOD activity was significantly decreased compared with the normal control (CMDI: 2.9±0.6 vs0.0±0.0;HS: 4.3±0.9 vs0.7±1.1; MPO: 98.1±26.9 vs24.8±11.5; MDA:57.53±12.36 vs9.21±3.85; NO: 0.331±0.092 vs0.176±0.045;PGE2: 186.2±96.2 vs 42.8±32.8; TXB2: 34.26±13.51 vs 8.83±3.75; iNOS: 0.365±0.026 vs展开更多
AIM: To investigate the protective effects of Astragalus membranaceus(Am) against hapten-induced colitis in male Sprague-Dawley rats as well as its underlying mechanism.METHODS: Experimental colitis was induced in rat...AIM: To investigate the protective effects of Astragalus membranaceus(Am) against hapten-induced colitis in male Sprague-Dawley rats as well as its underlying mechanism.METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Rats were either pretreated with Am extract (2 or 4 g/kg, p.o. once daily) starting from 10 d before DNBS enema, or received Am post-treatment (2 or 4 g/kg, p.o.twice daily) on the three consecutive days following DNBS administration. Colonic lesion area and histological damage were determined, while the activities of myeloperoxidase (MPO) and xanthine oxidase, as well as reduced glutathione (GSH) content were measured in the excised colonic tissues. Besides, protein expression of inducible nitrite oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and P-selectin was also detected by Western blot analysis.RESULTS: Our findings had shown that both macroscopic lesion area and histological colonic damage induced by DNBS were significantly reduced by both Am pre- and post-treatments. These were accompanied by attenuation of the elevated colonic MPO activity and downregulation of the iNOS, P-selectin, and ICAM-1 protein expression.Besides, deprivation of colonic GSH level under colitis condition was also preserved.CONCLUSION: These results demonstrate that Am possesses both preventive and therapeutic potential in experimental colitis. The anti-inflammatory actions involve anti-oxidation along with inhibition of adhesion molecule synthesis in the colonic tissues.展开更多
AIM: To ascertain the molecule mechanism of nuclear factor-KB (NF-κB) inhibitor curcumin preventive and therapeutic effects in rats' colitis induced by trinitrobenzene sulfonic acid (TNBS). METHODS: Sixty rats wi...AIM: To ascertain the molecule mechanism of nuclear factor-KB (NF-κB) inhibitor curcumin preventive and therapeutic effects in rats' colitis induced by trinitrobenzene sulfonic acid (TNBS). METHODS: Sixty rats with TNBS-induced colitis were treated with 2.0% curcumin in the diet. Thirty positive control rats were treated with 0.5% sulfasalazine (SASP). Thirty negative control rats and thirty model rats were treated with general diet. Changes of body weight together with histological scores were evaluated. Survival rates were also evaluated. Cell nuclear NF-κB activity in colonic mucosa was evaluated by using electrophoretic mobility shift assay. Cytoplasmic IκB protein in colonic mucosa was detected by using Western Blot analysis. Cytokine messenger expression in colonic tissue was assessed by using semiquantitative reverse-transcription polymerase chain reaction. RESULTS: Treatment with curcumin could prevent and treat both wasting and histopathologic signs of rats with TNBS-induced intestinal inflammation. In accordance with these findings, NF-κB activation in colonic mucosa was suppressed in the curcumin-treated groups. Degradations of cytoplasmic IκB protein in colonic mucosa were blocked by curcumin treatment. Proinflammatory cytokine messenger RNA expression in colonic mucosa was also suppressed. CONCLUSION: This study shows that NF-κB inhibitor curcumin could prevent and improve experimental colitis in murine model with inflammatory bowel disease (IBD). The findings suggest that NF-κB inhibitor curcumin could be a potential target for the patients with IBD.展开更多
AIM: To study the effects of Rheum tanguticum polysaccharide-1 (RTP-1) on ulcerative colitis in rats induced by 2, 4, 6-trinitrophene sulphonic acid (TNBS) and their possible mechanism.METHODS: RTP1 (200 mg@kg-1, ig) ...AIM: To study the effects of Rheum tanguticum polysaccharide-1 (RTP-1) on ulcerative colitis in rats induced by 2, 4, 6-trinitrophene sulphonic acid (TNBS) and their possible mechanism.METHODS: RTP1 (200 mg@kg-1, ig) extracted from Rheum tanguticum Maxim. Ex Regel was administrated to rats with colitis induced by TNBS for 5 d, 7 d, 10 d and 14 d,respectively. The effects of RTP1 and dexamethasone (DX,0.2 mg@kg-1, ig) were contrastively investigated. The MPO level and SOD activity were determined by chromatometry.The expansion and protein expression of CD4+T lymphocytes isolated from colon mucosae and mesenteric lymph nodes of colitis rats were performed by immunohistochemical analysis and Western-blot methods.RESULTS: Treatments of RTP1 (200 mg@kg-1, ig) significantly reduced diarrhea, mortality, colon mass, ulcer areas and MPO level in colon mucosae on days 5, 7, 10 and 14 (5.2±1.4,5.4±0.7, 5.2±1.8, P＜0.05.3.4±0.8, P＜0.01. 16.1±12.1,P＜0.01.31.8±8.6, 17.7±5.3, 12.7±4.1, P＜0.05). The effectsof RTP1 were similar to those noted above in DX group, but there were no immunosupressive effects of DX in RTP-1group, such as body mass loss, thymus and spleen atrophy.The decreased number and down-regulated protein levels of CD4+T cells isolated from the colon of colitis rats treated with RTP1 were found.CONCLUSION: RTP1 shows significantly protective effects but lower side effects on rats with colitis induced by TNBS.The mechanism may be due to the resistance to over expansion of CD4.展开更多
AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and muc...AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.展开更多
Both ulcerative colitis and Crohn’s disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at...Both ulcerative colitis and Crohn’s disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis, greater extent and duration of disease, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis. Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication. Nonetheless heightened vigilance and a careful, comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients. Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia- carcinoma sequence. A thorough understanding of the definition and natural history of dysplasia in IBD, as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention, and understanding the limitations of the current approach to prevention. This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD, as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia.展开更多
AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polym...AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.展开更多
AIM: To explore the changes of nuclear factor-kappa B (NF-κB) DNA-binding activity, the expression of intercellular adhesion molecule-1(ICAM-1) regulated by IMF-κB at various times and to evaluate the effects of pyr...AIM: To explore the changes of nuclear factor-kappa B (NF-κB) DNA-binding activity, the expression of intercellular adhesion molecule-1(ICAM-1) regulated by IMF-κB at various times and to evaluate the effects of pyrrolidine dithiocarbamate (PDTC) on trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. METHODS: TNBS of 0.6 mL was mixed with ethanol of 0.3 mL solution and instilled into the lumen of the rat colon. The rat models were divided into 6 groups, which were killed at 24 h, 3, 7,14, and 21 d after enema. Colonic inflammation and damage were assessed by macroscopical and histological criteria. Activity of NF-κB DNA-binding was analyzed by electrophoresis mobility shift assays (EMSA). Expression of ICAM-1 was detected by in situ hybridization (ISH) and immunohistochemistry (IH). Then various doses of PDTC were injected into rat abdomen 30 min before enema with TNBS/ethanol as pretreatment. The rats were killed 4 h after enema and the colonic inflammation, myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and DNA-binding activity of NF-κB were assessed. Finally, PDTC was injected intraperitoneally after colitis was induced. Changes of morphology were assayed. RESULTS: During the first week, hyperemia, hemorrhage, edema and ulceration of the colonic mucosa appeared with predominant infiltration of leukocytes. Neutrophils, macrophages, lymphocytes infiltrated in mucosa and submucosa 14 d later. Fibroblasts and granuloma-like structures were also obviously seen. The binding activity of NF-κB began to increase at 24 h time point and reached a peak at 14 d, then decreased but still was higher than control group at 21 d (P<0.01). Levels of ICAM-1 mRNA and protein significantly elevated at 24 h and the peak was at 21 d. Pretreatment with PDTC could attenuate the development of inflammation but not by reducing NF-KB activity. This attenuation of inflammation had a positive relationship with the dose of PDTC. PDTC at the dose of 100 mg/kg had no therapeutic effect after colitis was induced. CONCLU展开更多
AIM： To evaluate the efficacy and mechanism of action of NCB-02, a standardized Curcumin preparation, against 2, 4-dinitrochlorobenzene （DNCB）-induced ulcerative colitis in rats. METHODS： Ulcerative colitis was in...AIM： To evaluate the efficacy and mechanism of action of NCB-02, a standardized Curcumin preparation, against 2, 4-dinitrochlorobenzene （DNCB）-induced ulcerative colitis in rats. METHODS： Ulcerative colitis was induced in male rats by sensitizing with topical application of DNCB in acetone for 14 d and intra-colonol challenge with DNCB on day 15. A separate group of animals with vehicle treatment in similar fashion served as control group. Colitis rats were divided into different groups and treated with NCB-02 at doses of 25, 50 and 100 mg/kg b.wt p.o. for 10 d. Sulfasalazine at a dose of 100 mg/kg b.wt for 10 d served as a reference group. On day 10 after respective assigned treatment, all the animals were euthanized and the length of the colon, weight of entire colon and distal 8 cm of the colon were recorded. The distal part of the colon was immediately observed under a stereomicroscope and the degree of damage was scored. Further distal 8 cm of the colon was subject to the determination of colonic myeloperoxidase （MPO）, lipid peroxidation （LPO） and alkaline phosphatase （ALP） activities. A small piece of the sample from distal colon of each animal was fixed in 10% neutral buffered formalin and embedded in paraffin wax and sectioned for immunohistochemical examination of NFK-B and iNOS expression. RESULTS： NCB-02 showed a dose dependent protection against DNCB-induced alteration in colon length and weight. NCB-02 treatment also showed a dose dependent protection against the elevated levels of MPO, LPO and ALP, induced by DNCB. NCB-02 demonstrated a significant effect at a dose of 100 mg/kg b.wt., which was almost equipotent to 100 mg/kg b.wt. of sulfasalazine. Treatment with sulfasalazine and curcuminat a dose of 100 mg/kg b.wt. inhibited the DNCB-induced overexpression of NFK-B and iNOS in the colon. CONCLUSION： Curcumin treatment ameliorates colonic damage in DNCB-induced colitic rats, an effect associated with an improvement in intestinal oxidative stress and downregulation of colonic展开更多
Despite the new and ever expanding array of medications for the treatment of inflammatory bowel disease (IBD), there are still clear indications for operative management of IBD and its complications. We present an ove...Despite the new and ever expanding array of medications for the treatment of inflammatory bowel disease (IBD), there are still clear indications for operative management of IBD and its complications. We present an overview of indications, procedures, considerations, and controversies in the surgical therapy of IBD.展开更多
To propose a new pathogenesis called Radical Induction to explain the genesis and progression of ulcerative colitis (UC). UC is an inflammatory bowel disease. Colonic inflammation in UC is mediated by a buildup of whi...To propose a new pathogenesis called Radical Induction to explain the genesis and progression of ulcerative colitis (UC). UC is an inflammatory bowel disease. Colonic inflammation in UC is mediated by a buildup of white blood cells (WBCs) within the colonic mucosal lining; however,to date there is no answer for why WBCs initially enter the colonic mucosa to begin with. A new pathogenesis termed 'Radical Induction Theory' is proposed to explain this and states that excess un-neutralized hydrogen peroxide, produced within colonic epithelial cells as a result of aberrant cellular metabolism, diffuses through cell membranes to the extracellular space where it is converted to the highly damaging hydroxyl radical resulting in oxidative damage to structures comprising the colonic epithelial barrier. Once damaged, the barrier is unable to exclude highly immunogenic fecal bacterial antigens from invading the normally sterile submucosa. This antigenic exposure provokes an initial immune response of WBC infiltration into the colonic mucosa. Once present in the mucosa,WBCs are stimulated to secrete toxins by direct exposure to fecal bacteria leading to mucosal ulceration and bloody diarrhea characteristic of this disease.展开更多
AIM: To investigate the phenotype of inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD). METHODS: Data from 75 PSC-IBD patients evaluated in our tertiary center between 1963 and 2006 w...AIM: To investigate the phenotype of inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD). METHODS: Data from 75 PSC-IBD patients evaluated in our tertiary center between 1963 and 2006 were collected and compared to 150 IBD patients without PSC, matched for sex, birth date, IBD diagnosis date and initial disease location regarding ileal, different colonic segments, and rectum, respectively. RESULTS: While PSC-IBD patients received more 5-aminosalicylates (8.7 years/patient vs 2.9 years/ patient, P < 0.001), they required less immuno-suppressors (24% vs 46% at 10 years; P < 0.001) and less intestinal resection (10% vs 44% at 10 years, P < 0.001). The 25-year cumulative rate of colectomy was 25.1% in PSC-IBD and 37.3% in controls (P = 0.004). The 25-year cumulative rate of colorectal cancer was 23.4% in PSC-IBD vs 0% in controls (P = 0.002). PSC was the only independent risk factor for the development of colorectal cancer (OR = 10.8; 95% CI, 3.7-31.3). Overall survival rate without liver transplantation was reduced in PSC-IBD patients (67% vs 91% in controls at 25 years, P = 0.001).CONCLUSION: This study confirms that patients with PSC-IBD have a particular disease phenotype independent of the initial disease location. Although their disease is less active and they use more 5-aminosalicylates, they present a higher risk of colorectal cancer.展开更多
I schemic colitis is an uncommon complication in patients with systemic lupus erythematosus (SLE). In previously reported cases of colitis caused by SLE, intestinal vasculitis is implicated as the causative process, b...I schemic colitis is an uncommon complication in patients with systemic lupus erythematosus (SLE). In previously reported cases of colitis caused by SLE, intestinal vasculitis is implicated as the causative process, but is rarely confirmed histologically. We described a case of a 32-year-old man with increased activity of SLE, who presented with hematochezia and abdominal pain due to ischemic colitis with small vessel vasculitis which was proven by sigmoidoscopic biopsy. The clinical course of the patient was improved after steroid and conservative management.展开更多
Ulcerative colitis （UC） and Crohn＇s disease （CD） are the major forms of idiopathic inflammatory bowel disease （IBD）. Both UC and CD are debilitating chronic disorders that afflict millions of individuals throug...Ulcerative colitis （UC） and Crohn＇s disease （CD） are the major forms of idiopathic inflammatory bowel disease （IBD）. Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor （TNF）-α reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-α, interleukin （IL）-Iβ, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages （GH） are major sources. Further, in IBD, peripheral GHs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GH by receptor-mediated adsorption （GHA）. Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid nai＇ve patients （the best responders）, GHA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GHA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety a展开更多
Active ulcerative colitis （UC） is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential ...Active ulcerative colitis （UC） is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis （GMCAP） for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session （session time, 60 min） per week for five consecutive weeks （a total of five apheresis sessions） has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, doubleblind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ￥145 000 （$1 300）. However, if this treatment p展开更多
RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by ind...RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I^-/- mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I^-/- mice are viable and fertile. Histological analysis shows that Rig-I^-/ mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer＇s patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation ofT-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit （Gαi2） in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.展开更多
基金the Research Institute of Veterinary Science,College of Veterinary Medieine,Seoul National University
文摘AIM:Irritable bowel syndrome(IBS)is a functional bowel disorder characterized by visceral hypersensitivity and altered bowel motility.There is increasing evidence suggesting the role of inflammation in the pathogenesis of IBS,which addresses the possibility that formerly established rat model of colitis could be used as an IBS model after the inflammation subsided. METHODS:Colitis was induced by intracolonic instillation of 4% acetic acid in male Sprague-Dawley rats.The extent of inflammation was assessed by histological examination and myeloperoxidase(MPO)activity assay.After subsidence of colitis,the rats were subjected to rectal distension and restraint stress,then the abdominal withdrawal reflex and the number of stress-induced fecal output were measured, respectively. RESULTS:At 2 days post-induction of colitis,the colon showed characteristic inflammatory changes in histology and 8-fold increase in MPO activity.At 7 days post-induction of colitis,the histological features and MPO activity returned to normal.The rats at 7 days post-induction of colitis showed hypersensitive response to rectal distension without an accompaning change in rectal compliance,and defecated more stools than control animals when under stress.CONCLUSION: These results concur largely with the characteristic features of IBS, visceral hypersensitivity and altered defecation pattern in the absence of detectable disease, suggesting that this animal model is a methodologically convenient and useful model for studying a subset of IBS.
文摘The risk of colorectal cancer for any patient with ulcer-ative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer in-clude extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflam-mation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epide-miological trends and causes for the observed chang-es. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.
基金Supported by the University Science and Technology Development Foundation of Shanghai, No.00B07
文摘AIM： To investigate the anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium （DSS）-induced colitis of rats. METHODS： Acute colitis was induced by giving 2% DSS orally in drinking water for 8 d. Twenty-six male rats were randomized into oxymatrine-treated group （group A, 10 rats）, DSS control （group B, 10 rats） and normal control （group C, 6 rats）. The rats in group A were injected muscularly with oxymatrine at the dosage of 63 mg/（kg·d） from d 1 to 11 and drank 2% DSS solution from d 4 to 11. The rats in group B were treated with 0.9% saline in an equal volume as group A and drank 2% DSS solution from d 4 to 11. The rats in group C were treated with 0.9% saline as group B from d 1 to 11 and drank water normally. Diarrhea and bloody stool as well as colonic histology were observed. The levels of serum tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were determined by ELISA, and nuclear factor-κB （NF-κB） activity and the expression of inter-cellular adhesion molecule-1 （ICAM-1） in colonic mucosa were detected by immunohistochemistry method. RESULTS： Compared with DSS control group, the inflammatory symptoms and histological damages of colonic mucosa in oxymatrine-treated group were significantly improved, the serum levels of TNF-α, IL-6, and the expression of NF-κB, ICAM-1 in colonic mucosa were significantly reduced. CONCLUSION： The fact that oxymatrine can reduce the serum levels of TNF-α, IL-6, and the expression of NF-κB and ICAM-1 in colonic mucosa in DSS-induced colitis of rats indicates that oxymatrine may ameliorate the colonic inflammation and thus alleviate diarrhea and bloody stool.
文摘AIM: To determine the anti-inflammatory activity of probiotic Bifidobacteria in Bifidobacteria-fermented milk (BFM) which is effective against active ulcerative colitis (UC) and exacerbations of UC, and to explore the immunoregulatory mechanisms. METHODS: Peripheral blood mononuclear cells (PBMNC) from UC patients or HT-29 cells were co-cultured with heat-killed probiotic bacteria or culture supernatant of Bifidobacterium breve strain Yakult (BbrY) or Bifidobacterium bifidum strain Yakult (BbiY) to estimate the amount of IL-10 or IL-8 secreted. RESULTS: Both strains of probiotic Bifidobacteria contained in the BFM induced IL-10 production in PBMNC from UC patients, though BbrY was more effective than BbiY. Conditioned medium (CM) and DNA of both strains inhibited IL-8 secretion in HT-29 cells stimulated with TNF-α, whereas no such effect was observed with heat- killed bacteria. The inhibitory effect of CM derived from BbiY was greater than that of CM derived from BbrY. DNAs of the two strains had a comparable inhibitory activity against the secretion of IL-8. CM of BbiY induced a repression of IL-8 gene expression with a higher expression of IκB-ζ mRNA 4 h after culture of HT-29 cells compared to that in the absence of CM.CONCLUSION: Probiotic Bifidobacterium strains in BFM enhance IL-10 production in PBMNC and inhibit IL-8 secretion in intestinal epithelial cells, suggesting that BFM has anti-inflammatory effects against ulcerative colitis.
基金key Project in Scientific and Technological Researches of Hubei Province,No.2001AA308B
文摘AIM: To investigate the ameliorative effects of sodium ferulate (SF) on acetic acid-induced colitis and their mechanisms in rats.METHODS: The colitis model of Sprague-Dawley rats was induced by intracolon enema with 8 % (WV) of acetic acid.The experimental animals were randomly divided into model control, 5-aminosalicylic acid therapy group and three dose of SF therapy groups. The 5 groups were treated intracolonically and daily (8:00 am) for 7 days 24 h following the induction of colitis. A normal control group of rats clystered with normal saline instead of acetic acid was also included in the study.Pathological changes of the colonic mucosa were evaluated by the colon mucosa damage index (CMDI) and the histopathological score (HS). The insulted colonic mucosa was sampled for a variety of determinations at the end of experiment when the animals were sacrificed by decapitation.Colonic activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), and levels of malondialdehyde (MDA)and nitric oxide (NO) were assayed with ultraviolet spectrophotometry. Colonic contents of prostaglandin E2 (PGE2) and thromboxane B2 (TXB2)were determined by radioimmunoassay. The expressions of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) p65 proteins in the colonic tissue were detected with immunohistochemistry.RESULTS: Enhanced colonic mucosal injury, inflammatory response and oxidative stress were observed in the animals clystered with acetic acid, which manifested as the significant increase of CMDI, HS, MPO activities, MDA and NO levels,PGE2 and TXB2 contents, as well as the expressions of iNOS,COX-2 and NF-κB p65 proteins in the colonic mucosa,although the colonic SOD activity was significantly decreased compared with the normal control (CMDI: 2.9±0.6 vs0.0±0.0;HS: 4.3±0.9 vs0.7±1.1; MPO: 98.1±26.9 vs24.8±11.5; MDA:57.53±12.36 vs9.21±3.85; NO: 0.331±0.092 vs0.176±0.045;PGE2: 186.2±96.2 vs 42.8±32.8; TXB2: 34.26±13.51 vs 8.83±3.75; iNOS: 0.365±0.026 vs
基金Supported by the HKBU Faculty Research Grant FRG/02-03/Ⅱ-64
文摘AIM: To investigate the protective effects of Astragalus membranaceus(Am) against hapten-induced colitis in male Sprague-Dawley rats as well as its underlying mechanism.METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Rats were either pretreated with Am extract (2 or 4 g/kg, p.o. once daily) starting from 10 d before DNBS enema, or received Am post-treatment (2 or 4 g/kg, p.o.twice daily) on the three consecutive days following DNBS administration. Colonic lesion area and histological damage were determined, while the activities of myeloperoxidase (MPO) and xanthine oxidase, as well as reduced glutathione (GSH) content were measured in the excised colonic tissues. Besides, protein expression of inducible nitrite oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and P-selectin was also detected by Western blot analysis.RESULTS: Our findings had shown that both macroscopic lesion area and histological colonic damage induced by DNBS were significantly reduced by both Am pre- and post-treatments. These were accompanied by attenuation of the elevated colonic MPO activity and downregulation of the iNOS, P-selectin, and ICAM-1 protein expression.Besides, deprivation of colonic GSH level under colitis condition was also preserved.CONCLUSION: These results demonstrate that Am possesses both preventive and therapeutic potential in experimental colitis. The anti-inflammatory actions involve anti-oxidation along with inhibition of adhesion molecule synthesis in the colonic tissues.
基金Supported by the National Natural Science Foundation of China, No. 30270078 the Guangdong Traditional Chinese and Medicine Bureau Foundation of China, No. 1040191
文摘AIM: To ascertain the molecule mechanism of nuclear factor-KB (NF-κB) inhibitor curcumin preventive and therapeutic effects in rats' colitis induced by trinitrobenzene sulfonic acid (TNBS). METHODS: Sixty rats with TNBS-induced colitis were treated with 2.0% curcumin in the diet. Thirty positive control rats were treated with 0.5% sulfasalazine (SASP). Thirty negative control rats and thirty model rats were treated with general diet. Changes of body weight together with histological scores were evaluated. Survival rates were also evaluated. Cell nuclear NF-κB activity in colonic mucosa was evaluated by using electrophoretic mobility shift assay. Cytoplasmic IκB protein in colonic mucosa was detected by using Western Blot analysis. Cytokine messenger expression in colonic tissue was assessed by using semiquantitative reverse-transcription polymerase chain reaction. RESULTS: Treatment with curcumin could prevent and treat both wasting and histopathologic signs of rats with TNBS-induced intestinal inflammation. In accordance with these findings, NF-κB activation in colonic mucosa was suppressed in the curcumin-treated groups. Degradations of cytoplasmic IκB protein in colonic mucosa were blocked by curcumin treatment. Proinflammatory cytokine messenger RNA expression in colonic mucosa was also suppressed. CONCLUSION: This study shows that NF-κB inhibitor curcumin could prevent and improve experimental colitis in murine model with inflammatory bowel disease (IBD). The findings suggest that NF-κB inhibitor curcumin could be a potential target for the patients with IBD.
基金the National Natural Science Foundation of China,No 30100239
文摘AIM: To study the effects of Rheum tanguticum polysaccharide-1 (RTP-1) on ulcerative colitis in rats induced by 2, 4, 6-trinitrophene sulphonic acid (TNBS) and their possible mechanism.METHODS: RTP1 (200 mg@kg-1, ig) extracted from Rheum tanguticum Maxim. Ex Regel was administrated to rats with colitis induced by TNBS for 5 d, 7 d, 10 d and 14 d,respectively. The effects of RTP1 and dexamethasone (DX,0.2 mg@kg-1, ig) were contrastively investigated. The MPO level and SOD activity were determined by chromatometry.The expansion and protein expression of CD4+T lymphocytes isolated from colon mucosae and mesenteric lymph nodes of colitis rats were performed by immunohistochemical analysis and Western-blot methods.RESULTS: Treatments of RTP1 (200 mg@kg-1, ig) significantly reduced diarrhea, mortality, colon mass, ulcer areas and MPO level in colon mucosae on days 5, 7, 10 and 14 (5.2±1.4,5.4±0.7, 5.2±1.8, P＜0.05.3.4±0.8, P＜0.01. 16.1±12.1,P＜0.01.31.8±8.6, 17.7±5.3, 12.7±4.1, P＜0.05). The effectsof RTP1 were similar to those noted above in DX group, but there were no immunosupressive effects of DX in RTP-1group, such as body mass loss, thymus and spleen atrophy.The decreased number and down-regulated protein levels of CD4+T cells isolated from the colon of colitis rats treated with RTP1 were found.CONCLUSION: RTP1 shows significantly protective effects but lower side effects on rats with colitis induced by TNBS.The mechanism may be due to the resistance to over expansion of CD4.
文摘AIM: The aim of this study was to evaluate the association between ulcerative colitis activity and plasma or mucosal concentrations of interleukin (IL)-18. METHODS: 11-18 concentrations were measured in plasma and mucosal samples from 15 patients with active ulcerative colitis (UC). RESULTS: The mean plasma concentration of IL-18 measured in all patients (422±88 pg/mL) doubled the mean value in healthy controls (206±32 pg/mL); however, the difference was not statistically significant. Plasma IL-18 levels revealed a significant positive correlation with scored endoscopic degree of mucosal injury, disease activity index, clinical activity index and C-reactive protein concentration. The mean concentration of plasma IL-18 was significantly higher in patients with severe ulcerative colitis (535±115 pg/mL) than in patients with mild ulcerative colitis (195±41 pg/mL), and in healthy controls. Although the mucosal mean IL-18 concentration in severe ulcerative colitis (2 523±618 pg/mg protein) doubled values observed in mild one (1347±308 pg/mg protein), there was no statistically significant difference. CONCLUSION: Plasma IL-18 can be considered as a surrogate marker helpful in evaluation of ulcerative colitis activity.
文摘Both ulcerative colitis and Crohn’s disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis, greater extent and duration of disease, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis. Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication. Nonetheless heightened vigilance and a careful, comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients. Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia- carcinoma sequence. A thorough understanding of the definition and natural history of dysplasia in IBD, as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention, and understanding the limitations of the current approach to prevention. This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD, as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia.
文摘AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.
基金Supported by a Grant From Health Department Foundation of Guangdong Province, No. A2003554
文摘AIM: To explore the changes of nuclear factor-kappa B (NF-κB) DNA-binding activity, the expression of intercellular adhesion molecule-1(ICAM-1) regulated by IMF-κB at various times and to evaluate the effects of pyrrolidine dithiocarbamate (PDTC) on trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. METHODS: TNBS of 0.6 mL was mixed with ethanol of 0.3 mL solution and instilled into the lumen of the rat colon. The rat models were divided into 6 groups, which were killed at 24 h, 3, 7,14, and 21 d after enema. Colonic inflammation and damage were assessed by macroscopical and histological criteria. Activity of NF-κB DNA-binding was analyzed by electrophoresis mobility shift assays (EMSA). Expression of ICAM-1 was detected by in situ hybridization (ISH) and immunohistochemistry (IH). Then various doses of PDTC were injected into rat abdomen 30 min before enema with TNBS/ethanol as pretreatment. The rats were killed 4 h after enema and the colonic inflammation, myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and DNA-binding activity of NF-κB were assessed. Finally, PDTC was injected intraperitoneally after colitis was induced. Changes of morphology were assayed. RESULTS: During the first week, hyperemia, hemorrhage, edema and ulceration of the colonic mucosa appeared with predominant infiltration of leukocytes. Neutrophils, macrophages, lymphocytes infiltrated in mucosa and submucosa 14 d later. Fibroblasts and granuloma-like structures were also obviously seen. The binding activity of NF-κB began to increase at 24 h time point and reached a peak at 14 d, then decreased but still was higher than control group at 21 d (P<0.01). Levels of ICAM-1 mRNA and protein significantly elevated at 24 h and the peak was at 21 d. Pretreatment with PDTC could attenuate the development of inflammation but not by reducing NF-KB activity. This attenuation of inflammation had a positive relationship with the dose of PDTC. PDTC at the dose of 100 mg/kg had no therapeutic effect after colitis was induced. CONCLU
文摘AIM： To evaluate the efficacy and mechanism of action of NCB-02, a standardized Curcumin preparation, against 2, 4-dinitrochlorobenzene （DNCB）-induced ulcerative colitis in rats. METHODS： Ulcerative colitis was induced in male rats by sensitizing with topical application of DNCB in acetone for 14 d and intra-colonol challenge with DNCB on day 15. A separate group of animals with vehicle treatment in similar fashion served as control group. Colitis rats were divided into different groups and treated with NCB-02 at doses of 25, 50 and 100 mg/kg b.wt p.o. for 10 d. Sulfasalazine at a dose of 100 mg/kg b.wt for 10 d served as a reference group. On day 10 after respective assigned treatment, all the animals were euthanized and the length of the colon, weight of entire colon and distal 8 cm of the colon were recorded. The distal part of the colon was immediately observed under a stereomicroscope and the degree of damage was scored. Further distal 8 cm of the colon was subject to the determination of colonic myeloperoxidase （MPO）, lipid peroxidation （LPO） and alkaline phosphatase （ALP） activities. A small piece of the sample from distal colon of each animal was fixed in 10% neutral buffered formalin and embedded in paraffin wax and sectioned for immunohistochemical examination of NFK-B and iNOS expression. RESULTS： NCB-02 showed a dose dependent protection against DNCB-induced alteration in colon length and weight. NCB-02 treatment also showed a dose dependent protection against the elevated levels of MPO, LPO and ALP, induced by DNCB. NCB-02 demonstrated a significant effect at a dose of 100 mg/kg b.wt., which was almost equipotent to 100 mg/kg b.wt. of sulfasalazine. Treatment with sulfasalazine and curcuminat a dose of 100 mg/kg b.wt. inhibited the DNCB-induced overexpression of NFK-B and iNOS in the colon. CONCLUSION： Curcumin treatment ameliorates colonic damage in DNCB-induced colitic rats, an effect associated with an improvement in intestinal oxidative stress and downregulation of colonic
文摘Despite the new and ever expanding array of medications for the treatment of inflammatory bowel disease (IBD), there are still clear indications for operative management of IBD and its complications. We present an overview of indications, procedures, considerations, and controversies in the surgical therapy of IBD.
文摘To propose a new pathogenesis called Radical Induction to explain the genesis and progression of ulcerative colitis (UC). UC is an inflammatory bowel disease. Colonic inflammation in UC is mediated by a buildup of white blood cells (WBCs) within the colonic mucosal lining; however,to date there is no answer for why WBCs initially enter the colonic mucosa to begin with. A new pathogenesis termed 'Radical Induction Theory' is proposed to explain this and states that excess un-neutralized hydrogen peroxide, produced within colonic epithelial cells as a result of aberrant cellular metabolism, diffuses through cell membranes to the extracellular space where it is converted to the highly damaging hydroxyl radical resulting in oxidative damage to structures comprising the colonic epithelial barrier. Once damaged, the barrier is unable to exclude highly immunogenic fecal bacterial antigens from invading the normally sterile submucosa. This antigenic exposure provokes an initial immune response of WBC infiltration into the colonic mucosa. Once present in the mucosa,WBCs are stimulated to secrete toxins by direct exposure to fecal bacteria leading to mucosal ulceration and bloody diarrhea characteristic of this disease.
文摘AIM: To investigate the phenotype of inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD). METHODS: Data from 75 PSC-IBD patients evaluated in our tertiary center between 1963 and 2006 were collected and compared to 150 IBD patients without PSC, matched for sex, birth date, IBD diagnosis date and initial disease location regarding ileal, different colonic segments, and rectum, respectively. RESULTS: While PSC-IBD patients received more 5-aminosalicylates (8.7 years/patient vs 2.9 years/ patient, P < 0.001), they required less immuno-suppressors (24% vs 46% at 10 years; P < 0.001) and less intestinal resection (10% vs 44% at 10 years, P < 0.001). The 25-year cumulative rate of colectomy was 25.1% in PSC-IBD and 37.3% in controls (P = 0.004). The 25-year cumulative rate of colorectal cancer was 23.4% in PSC-IBD vs 0% in controls (P = 0.002). PSC was the only independent risk factor for the development of colorectal cancer (OR = 10.8; 95% CI, 3.7-31.3). Overall survival rate without liver transplantation was reduced in PSC-IBD patients (67% vs 91% in controls at 25 years, P = 0.001).CONCLUSION: This study confirms that patients with PSC-IBD have a particular disease phenotype independent of the initial disease location. Although their disease is less active and they use more 5-aminosalicylates, they present a higher risk of colorectal cancer.
文摘I schemic colitis is an uncommon complication in patients with systemic lupus erythematosus (SLE). In previously reported cases of colitis caused by SLE, intestinal vasculitis is implicated as the causative process, but is rarely confirmed histologically. We described a case of a 32-year-old man with increased activity of SLE, who presented with hematochezia and abdominal pain due to ischemic colitis with small vessel vasculitis which was proven by sigmoidoscopic biopsy. The clinical course of the patient was improved after steroid and conservative management.
文摘Ulcerative colitis （UC） and Crohn＇s disease （CD） are the major forms of idiopathic inflammatory bowel disease （IBD）. Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor （TNF）-α reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-α, interleukin （IL）-Iβ, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages （GH） are major sources. Further, in IBD, peripheral GHs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GH by receptor-mediated adsorption （GHA）. Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid nai＇ve patients （the best responders）, GHA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GHA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety a
文摘Active ulcerative colitis （UC） is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis （GMCAP） for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session （session time, 60 min） per week for five consecutive weeks （a total of five apheresis sessions） has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, doubleblind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ￥145 000 （$1 300）. However, if this treatment p
文摘RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I^-/- mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I^-/- mice are viable and fertile. Histological analysis shows that Rig-I^-/ mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer＇s patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation ofT-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit （Gαi2） in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.
