Increased group II phospholipase A2 in colonic mucosa of patients with Crohn's disease and ulcerative colitis.

The immunochemical protein content of group II phospholipase A2 (PLA2) and PLA2 enzymatic activity were measured for colonic mucosal biopsy samples obtained from patients with either Crohn's disease of the colon or ulcerative colitis, and control patients without inflammatory bowel disease. Immunoreactive group II PLA2 (IR-PLA2 II) content and PLA2 activity in actively inflamed colonic mucosa of Crohn's disease patients were significantly higher than those in inactively inflamed mucosa of Crohn's disease patients and the colonic mucosa of controls. IR-PLA2 II content and PLA2 activity in severely inflamed mucosa of ulcerative colitis patients were significantly higher than those in the colonic mucosa of the controls. Mucosal PLA2 enzymatic activity was closely correlated with mucosal IR-PLA2 II content in patients with Crohn's disease and ulcerative colitis. These results suggest that an increase in PLA2 enzymatic activity in inflamed colonic mucosa of Crohn's disease and ulcerative colitis was mainly attributed to increased protein content of group II PLA2, and that an increase in mucosal group II PLA2 may be involved in the pathogenesis of intestinal inflammation of Crohn's disease and ulcerative colitis.     

Bactericidal/permeability-increasing protein in colonic mucosa in ulcerative colitis.

BACKGROUND/AIMS: Increased mucosal concentration of bactericidal/permeability-increasing protein (BPI) has been shown in inflammatory bowel diseases. The purpose of the present study was to investigate the relationship between the mucosal concentration of BPI and the grade of mucosal inflammation in ulcerative colitis. METHODOLOGY: Samples of colonic mucosa from 12 patients with ulcerative colitis and from 8 control patients were studied. The concentration of BPI in tissue extracts was measured by a time-resolved fluoroimmunoassay. The concentration of BPI was compared between samples with histological inflammatory changes of different severity. BPI was localized in tissue sections by immunohistochemistry. RESULTS: The concentration of BPI was higher (p < 0.001) in samples of colonic mucosa from patients with ulcerative colitis (median: 3.2 micrograms/g, range: 0.3-22.6 micrograms/g) than in control samples (0.4 microgram/g, 0.1-0.6 microgram/g,). Moreover, the concentration of BPI was higher (p = 0.015) in samples with severe inflammation (2.5 mu/g, 0.3-22.6 micrograms/g) than in those with mild inflammation (0.5 mu/g, 0.3-2.5 micrograms/g). The concentration of BPI in mucosal samples correlated well with the degree of histological inflammation (Spearman R = 0.70, p = 0.01). BPI was localized in polymorphonuclear leukocytes in the mucosa and stroma of the colonic wall. CONCLUSIONS: The concentration of BPI is increased in the colonic mucosa of patients with ulcerative colitis. The increase in the concentration of BPI in colonic mucosa seems to be closely associated with the inflammatory activity of ulcerative colitis.     

In vitro anticolon antibody production by mucosal or peripheral blood lymphocytes from patients with ulcerative colitis.

Serum anticolon antibody and in vitro anti-colon antibody production by peripheral blood and mucosal lymphocytes was investigated in patients with ulcerative colitis. The frequency of serum anticolon antibody was 71% in 41 patients with ulcerative colitis, estimated by enzyme linked immunosorbent assay (ELISA) using isolated rat colon epithelial cells. This finding confirms our previous report on the frequency of serum anticolon antibody detected by flow cytometry analysis. The estimated frequencies of IgG anticolon antibody secreting cells were 1.5-12.5/10(6) cells in the colonic mucosa and 0.1-0.5/10(6) cells in peripheral blood, from patients with ulcerative colitis when Epstein-Barr virus (EBV) was used as a B cell polyclonal activator. Poisson analysis of limiting dilution culture showed that about one per 140 IgG cells in the colonic mucosa synthesised anticolon antibody. Two monoclonal IgG antibodies were obtained from EBV transformed anticolon antibody secreting cells by limiting dilution method. One reacted with goblet cells in the intestine, and the other reacted mainly with colonic epithelial cells. These results suggest that heterogeneous anticolon antibodies are present in patients with ulcerative colitis and that colonic mucosa may be the main source of anticolon antibody. Local autoimmune reaction might have an important role in causing the inflammation of colonic mucosa in this disease.     

Greatly increased mucosal nitric oxide in ulcerative colitis determined in situ by a novel nitric oxide-selective microelectrode

Although current nitric oxide (NO) electrodes are simple, selective and sensitive, they are fragile and hard to use in clinical studies of patients. By preparing an improved NO electroneedle that overcomes these defects, we directly measured mucosal NO concentrations in 11 patients (six male, five female; mean 26.0 years old) with ulcerative colitis (UC) and five normal volunteers (three male, two female; mean 28.3 years old) in situ . An electroneedle was inserted into colonic mucosa through a biopsy channel during colonoscopy. The information concerning the concentration of NO generated and the appearances of the colonic mucosa at the same site were obtained simultaneously. In the ulcerative colitis patients, NO concentrations were significantly increased at all 24 mucosal sites tested. These included sites where: there was an absence of visible inflammation (five sites); the mucosa was mildly inflamed (eight sites); the mucosa was moderately inflamed (five sites); or severely inflamed (six sites). The NO concentrations in ulcerative colitis patients were 12–72 times higher than the NO levels in normal controls (10 sites). At the same 10 sites in four ulcerative colitis patients, the high NO concentrations were decreased by 53% after glucocorticoid treatment. These data are consistent with those of previous studies utilizing different NO electrodes. Excess mucosal NO is generated from inducible NO synthase in the inflamed mucosa itself and the invading inflammatory cells. Our results suggested that mucosal NO could be a marker for the extent of inflammation and its various actions correlated with the pathogenesis, natural history and prognosis of UC. Using the NO microelectrode system reported here, the concentration of NO generated can be monitored in real-time while observing the mucosal condition at the same site during endoscopy. This novel NO electrode may contribute to understanding the role of NO in colonic mucosal inflammation.     

丹参对大鼠乙酸性溃疡性结肠炎粘膜保护作用的研究

目的研究丹参(SM)对大鼠乙酸性溃疡性结肠炎(UC)粘膜保护作用.方法预防性静脉给予丹参注射液后评价大鼠乙酸性UC肠粘膜损伤指数,检测肠组织中的超氧化物歧化酶(SOD)、丙二醛(MDA)含量,并与生理盐水(NS)组对照.结果SM组和NS组肠粘膜损伤指数分别为5.75士1.04,14.70士3.15;肠组织中SOD含量分别为(80.8士2.4)U/g、(57.3士3.6)U/g;MDA含量分别为(19.7士1.2)nmol/g、(40.2士2.1)nmol/g.结论丹参对大鼠乙酸性UC肠粘膜具有保护作用,其机制可能与丹参清除氧自由基有关.     

Colonic mucosal hemodynamics and tissue oxygenation in patients with ulcerative colitis: Investigation by organ reflectance spectrophotometry

Colonic mucosal hemodynamics were investigated at the rectosigmoidal region of the colon in 46 patients with ulcerative colitis and in 18 normal subjects by organ reflectance spectrophotometry under colonoscopy. The value for the index of mucosal hemoglobin concentration (IHb) was significantly higher, and value for the index of mucosal hemoglobin oxygen saturation (ISO₂) was significantly lower in patients with active ulcerative colitis than values in the normal controls or in patients with inactive ulcerative colitis. The results indicate mucosal congestion and hypoxemia in patients with active ulcerative colitis. The changes in IHb and ISO₂ correlated well with the severity of ulcerative colitis scored by endoscopic findings and with the number of infiltrating inflammatory cells in the mucosa analyzed histologically in biopsy samples. In conclusion, the colonic mucosal microcirculation in patients with active ulcerative colitis was disturbed and showed congestion and hypoxemia. The analysis of hemodynamic changes may be helpful for assessing the activity of ulcerative colitis.     

Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel

BACKGROUND: Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients with ulcerative colitis, 10 patients with collagenous colitis and 20 controls with uninflamed mucosa. METHODS: The tip of a Teflon tube was placed in the caecum during colonoscopy. Subsequently, argon was infused at a constant rate for 70-180 min. Argon and NO in gas sampled from the rectum were measured by neutron activation analysis and the chemiluminescence technique, respectively. RESULTS: The use of argon as a marker of colonic NO output was justified by complete recovery (96%+/-2; mean +/- s(x); n = 5) of argon in gas collected from the rectum and a constant output of NO at varying perfusion rates (25, 50 and 75 ml/min coefficient of variation 21%; n = 6). In patients with ulcerative colitis, colonic output of NO was 10-fold higher (P < 0.001) than in controls and positively correlated (P < 0.01) to indices of disease activity. In patients with collagenous colitis, colonic output of NO was 50-fold higher (P < 0.01) than in controls during periods with watery diarrhoea (n = 6), but within the range observed in ulcerative colitis in the absence of diarrhoea (n = 4). CONCLUSIONS: Argon gas perfusion of whole colon using chemiluminescence technique for measurement of NO is a reliable method for quantification of colonic mucosal NO production. Increased colonic production of NO in collagenous colitis, which exceeds the output observed even in extensive ulcerative colitis, militates against the theory that NO per se is a cause of mucosal injury.     

Effect of gender on the manifestations of celiac disease: Evidence for greater malabsorption in men

Background: Nitric oxide (NO) produced in excess by the inflamed human colon is generally considered a pathway of mucosal damage. In an attempt to quantify colonic mucosal production of NO in various forms of colitis we performed 'steady-state' gas perfusion of whole colon in 11 patients with ulcerative colitis, 10 patients with collagenous colitis and 20 controls with uninflamed mucosa. Methods: The tip of a Teflon tube was placed in the caecum during colonoscopy. Subsequently, argon was infused at a constant rate for 70-180 min. Argon and NO in gas sampled from the rectum were measured by neutron activation analysis and the chemiluminescence technique, respectively. Results: The use of argon as a marker of colonic NO output was justified by complete recovery (96% ± 2; mean ± s- x ; n = 5) of argon in gas collected from the rectum and a constant output of NO at varying perfusion rates (25, 50 and 75 ml/min; coefficient of variation 21%; n = 6). In patients with ulcerative colitis, colonic output of NO was 10-fold higher ( P < 0.001) than in controls and positively correlated ( P < 0.01) to indices of disease activity. In patients with collagenous colitis, colonic output of NO was 50-fold higher ( P < 0.01) than in controls during periods with watery diarrhoea ( n = 6), but within the range observed in ulcerative colitis in the absence of diarrhoea ( n = 4). Conclusions: Argon gas perfusion of whole colon using chemiluminescence technique for measurement of NO is a reliable method for quantification of colonic mucosal NO production. Increased colonic production of NO in collagenous colitis, which exceeds the output observed even in extensive ulcerative colitis, militates against the theory that NO per se is a cause of mucosal injury.     

Lymphocytic infiltration and expression of inducible nitric oxide synthase in human duodenal and colonic mucosa is a characteristic feature of ankylosing spondylitis

OBJECTIVE: In patients with ankylosing spondylitis (AS), inflammatory processes have been detected in the ileal and colonic mucosa. The inducible isoform of nitric oxide synthase (iNOS) may be expressed early in the inflammatory process. We investigated iNOS activity and lymphocytic infiltration in the duodenum and colon in patients with AS and ulcerative colitis compared with controls. METHODS: Gastroscopy with duodenal biopsies and/or colonoscopy with biopsies were conducted in 42 patients with AS treated or not treated with nonsteroidal antiinflammatory drugs (NSAID), in 15 with ulcerative colitis, and in 46 controls. Lymphocytic infiltration in the lamina propria and intraepithelial infiltration were quantified by histological score. iNOS expression was assessed by immunohistochemistry with monoclonal antibodies, and iNOS activity was determined by radiochemical assay. RESULTS: Endoscopic examination of the gastroduodenal or colonic mucosa did not reveal macroscopic lesions in the AS patients. In the duodenum, mucosal lymphocytic infiltration was found in 83.3% of the AS group compared to 48.6% of controls (p = 0.02), and was independent of the NSAID intake. Intraepithelial lymphocyte infiltration was increased in both duodenum and colon in AS patients compared to controls. iNOS activity in duodenum and colon and expression of iNOS protein in lamina propria inflammatory cells was increased in AS patients compared to controls. CONCLUSION: Lymphocytic infiltration and iNOS expression and activity were detected in duodenal and colonic mucosa from patients with AS. Such findings may indicate an inflammatory process in the small intestine and colon of patients with AS.     

溃疡性结肠治的新思路

溃疡性结肠炎(ulcerative colitis)黏膜损伤无法修复的原因还没有阐明,至今无特异性治疗方法,造成该病病程迁延、无法治愈.通过研究结肠黏膜干细胞减少与病变黏膜损伤的关系以及骨髓干细胞随血液循环到达结肠黏膜并转分化为结肠黏膜干细胞和上皮细胞情况,有可能阐明溃疡性结肠炎黏膜损伤无法修复的原因及为从根本上治疗该病提供新思路.     

Evaluation of the Role of Neutrophils in the Pathogenesis of Acetic Acid-Induced Colitis in Mice

Background: Neutrophils are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease, since prominent neutrophil infiltration has been observed in the inflamed colonic mucosa of patients with IBD. However, the role of neutrophils in the pathogenesis of IBD and experimental colitis remains equivocal. The aim of the present study is to clarify the possible role of neutrophils in the progression of acetic acid-induced colitis in mice. Methods: Using neutropenic mice treated with cyclophosphamide or with an LTB₄ receptor antagonist, ONO-4057, the relationship between the severity of macroscopic colonic damage, the extent of myeloperoxidase (MPO) activities in the colonic tissues, and the number of neutrophils in the blood were examined after induction of colitis in mice. Results: Changes of MPO activity in the colonic tissues paralleled well with the severity of the mucosal damage. In spite of a significant reduction in the number of neutrophils in the blood in cyclophosphamide-treated mice, neither the severity of mucosal damage in the colon nor the increase in MPO activities in the colonic tissues was affected 24 h after induction of colitis. Treatment with ONO-4057 significantly suppressed both the severity of mucosal damage in the colon and MPO activities in the colonic tissues in acetic acid-induced colitis in mice. Conclusions: The present results, obtained using treatment with cyclophosphamide and ONO-4057, show that the severity or the progression of acetic acid-induced colitis in mice was not influenced by a reduction of circulating neutrophils to about 25% of base line.     

The Role of Short-Chain Fatty Acid Metabolism in Colonic Disorders

During the past decade it has become evident that colonic mucosal metabolism is more complex than previously suspected. Luminal short-chain fatty acids (SCFAs) are recognized as an essential fuel source for colonocytes, particularly in the distal colon. Their absence may explain the development of diversion colitis; however, this has not been confirmed by clinical trials. The histologic, endoscopic, and metabolic similarities between diversion colitis and ulcerative colitis suggest that a nutritional SCFA deficiency state may play a role in the pathogenesis of these disorders. Diversion colitis and continent urinary diversion, utilizing distal and proximal colon reservoirs, provide in vivo models to study normal colonic mucosa in circumstances of reduced intraluminal SCFA concentrations and altered luminal effluent. Further studies utilizing these models would enhance our understanding of the regional differences in mucosal cell metabolism and adaptability and, hopefully, provide therapeutic alternatives for the management of colonic disorders. The welfare of colonic mucosa, as it relates to SCFA metabolism, awaits another exciting decade of investigation.     

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.     

Immunohistochemical localization of vascular endothelial growth factor in colonic mucosa of patients with inflammatory bowel disease

BACKGROUND/AIMS: Significantly enhanced serum levels of VEGF (vascular endothelial growth factor) were found in patients with inflammatory bowel disease. Peripheral blood mononuclear cells have been identified as one of the origins of the circulating VEGF. The present investigation examines the localization of VEGF at the site of inflammation in colonic mucosa of patients with Crohn's disease and ulcerative colitis. METHODOLOGY: Immunohistochemical localization of VEGF and immunostaining for leukocytes were performed in colonic mucosal biopsies of 41 patients with Crohn's disease, 26 patients with ulcerative colitis and normal mucosal specimens of 5 patients with irritable bowel syndrome. Measurement of immunohistochemical staining for VEGF and for leukocytes within the epithelium and the lamina propria was performed separately by area morphometry using a computerized cell analysis system. RESULTS: In both patients with Crohn's disease and ulcerative colitis immunohistochemical staining for VEGF within the lamina propria of inflamed colonic mucosa was significantly higher compared with noninflamed mucosa (Crohn's disease: 4.26% vs. 0.07%, P < 0.001; ulcerative colitis: 3.68% vs. 0.32%, P = 0.001). There was a significant correlation between immunostaining for leukocytes and VEGF within the lamina propria in both patients with Crohn's disease (r = 0.73, P < 0.05)) and ulcerative colitis (r = 0.67, P < 0.05). In Crohn's disease immunostaining for VEGF within the epithelium was significantly higher in inflamed mucosa compared with noninflamed mucosa (9.85% vs. 0.63%, P < 0.001). In contrast, strong immunostaining for VEGF has been observed in the epithelium of noninflamed mucosa (7.60%, P < 0.003), as well as in inflamed mucosa of patients with active ulcerative colitis (9.68%, P < 0.002) compared with noninflamed mucosa of patients with inactive ulcerative colitis (1.39%). CONCLUSIONS: The present data indicate, that the increased VEGF expression within the epithelium and the interstitial accumulation of VEGF-producing leukocytes in inflamed mucosa may play an important role in the inflammatory mechanisms of Crohn's disease and ulcerative colitis.     

ILEITIS AS A MAIN RECURRENT LESION IN A PATIENT WITH ULCERATIVE COLITIS: REPORT OF A CASE

We report a case of ulcerative colitis complicating ileitis that endoscopically and histologically resembled a colonic lesion. Eight years prior to the time of writing, the patient had undergone proctosigmoidectomy and ileocecal resection because of severe hemorrhagic lesions of ulcerative colitis. A month prior to the time of writing, bleeding from the stoma occurred. Endoscopy revealed erosions on easy‐bleeding mucosa in the ileum but no active inflammatory lesions in colonic mucosa except for small erosions in the descending colon beneath the stoma. Histologic findings of biopsy specimens from the ileal mucosa showed marked inflammation including neutrophile infiltration and crypt abscesses. This is a rare case of ulcerative colitis showing ileitis as a main recurrent lesion, suggesting that careful observation of the small intestine will be required after ileocecal resection in ulcerative colitis patients.     

Mobilization of tissue kallikrein in inflammatory disease of the colon

Colonic tissue was taken at operation from 10 patients with active ulcerative colitis and three patients with uncomplicated diverticular disease but with severe symptoms. Levels of kininogen, kallikrein, and kallikrein precursor were measured in blood-free tissue samples. In normal colon tissue a kininogen occurred in the muscle and none was detected in the mucosa. Kallikrein and its precursor were found in mucosa but not in muscle. In acutely inflamed tissue from ulcerative colitis patients relatively high levels of active kallikrein were detected in the underlying colonic muscle. There was little change in the level of kallikrein in inflamed mucosa or of kininogen in the muscle of these patients. No kallikrein was found in colonic muscle from patients with diverticular disease and the mucosal kallikrein level in these patients was unchanged. The findings suggest a mechanism for the formation of kinins in the wall of the colon which is present in ulcerative colitis but not in diverticular disease.     

Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful for estimating its therapeutic efficacy in distal ulcerative colitis: comparison of orally administered mesalamine and sulfasalazine

OBJECTIVES: Oral 5-aminosalicylic acid (5-ASA) preparations have been used frequently in the treatment of ulcerative colitis. However, there have been few reports investigating the relationship between colonic mucosal concentrations of 5-ASA and its clinical efficacy when oral sulfasalazine or 5-ASA compounds were administered. The aim of this study is to compare the mucosal concentrations of 5-ASA ensured by sulfasalazine or mesalamine, and to define the clinical significance of the measurement of 5-ASA concentrations in the treatment of distal ulcerative colitis. MATERIALS AND METHODS: Biopsies were taken from the rectum and sigmoid colon of the oral sulfasalazine group (n = 13) and the slow-release 5-ASA (mesalamine) group with (n = 5) or without (n = 11) rectal administration of 5-ASA. High-pressure liquid chromatography was used to measure the tissue concentrations of 5-ASA and its metabolites. We compared the 5-ASA concentrations of the sulfasalazine group with the mesalamine group. Furthermore, we analyzed the relationship between tissue 5-ASA concentrations and the Disease Activity Index (DAI). RESULTS: The concentrations of 5-ASA and acetyl-5-ASA in the sulfasalazine group were higher than those in the group taking oral mesalamine alone (p < 0.01). The concentration of 5-ASA was much higher in the patients who received oral and rectal mesalamine in an enema than in the patients who had oral mesalamine alone. There was a significant inverse correlation between the DAI and concentrations of 5-ASA in the rectum (r = 0.712, p < 0.001). CONCLUSIONS: We demonstrated that the colonic mucosal concentration of 5-ASA was significantly higher in the sulfasalazine group than in the mesalamine group. Furthermore, the concentrations of mucosal 5-ASA may be a good marker for the estimation of its efficacy in the treatment of ulcerative colitis.     

Excessive production of reactive oxygen metabolites by inflamed colon: analysis by chemiluminescence probe.

Reactive oxygen metabolites (ROMs) are involved in inflammatory diseases and are postulated to contribute to tissue injury in colitis. To determine whether excessive ROMs are generated by inflamed colonic mucosa and to identify possible sources and type of ROMs, mucosal ROMs were estimated in rats and humans using a chemiluminescence probe. Colitis was induced in rats by intracolonic injection of acetic acid or intraperitoneal injection of mitomycin C. Intact, inflamed colon in rats produced more ultraweak chemiluminescence than normal colon. Inflamed mucosal scrapings from both rat models produced significantly more luminol-enhanced chemiluminescence. Addition of catalase, an H2O2 scavenger, or azide, a myeloperoxidase inhibitor, into the media significantly decreased chemiluminescence from inflamed mucosal scrapings. Indomethacin, an antioxidant cyclo-oxygenase inhibitor, also decreased chemiluminescence, but MK-866, a 5-lipoxygenase inhibitor, had no effect. Colonic biopsy specimens obtained during colonoscopy from patients with ulcerative colitis also produced more catalase-inhibitable chemiluminescence than normal colonic mucosa. These data indicate that excessive ROMs are produced by inflamed colonic mucosa in both humans and rats, which may contribute to tissue injury.     

Enhanced colonic nitric oxide generation and nitric oxide synthase activity in ulcerative colitis and Crohn's disease.

Recent studies have suggested that nitric oxide (NO.), the product of nitric oxide synthase in inflammatory cells, may play a part in tissue injury and inflammation through its oxidative metabolism. In this study the colonic generation of oxides of nitrogen (NOx) and nitric oxide synthase activity was determined in ulcerative colitis and Crohn's disease. Colonic biopsy specimens were obtained from inflammatory bowel disease patients and from normal controls. Mucosal explants were cultured in vitro for 24 hours and NOx generation was determined. Nitric oxide synthase activity was monitored by the conversion of [3H]-L-arginine to citrulline. Median NOx generation by inflamed colonic mucosa of patients with active ulcerative colitis and Crohn's colitis was 4.2- and 8.1-fold respectively higher than that by normal human colonic mucosa. In ulcerative colitis and Crohn's colitis nitric oxide synthase activity was 10.0- and 3.8-fold respectively higher than in normal subjects. Colonic NOx generation is significantly decreased by methylprednisolone and ketotifen. The decrease in NOx generation by cultured colonic mucosa induced by methylprednisolone suggests that NO synthase activity is induced during the culture and the steroid effect may contribute to its therapeutic effect. Enhanced colonic NOx generation by stimulated nitric oxide synthase activity in ulcerative colitis and Crohn's disease may contribute to tissue injury.     

Infliximab is effective in the treatment of ulcerative colitis with dermatomyositis: A case report

BACKGROUNDJoint, skin, oral cavity, and eye lesions are the most common extraintestinal manifestations of ulcerative colitis that can occur before or after its onset. The cases of ulcerative colitis with dermatomyositis (DM) are rare. In this study, we report a rare case of ulcerative colitis with DM that was effectively treated with infliximab.CASE SUMMARYThe patient was a 57-year-old female with a 2-year history of DM. The patient was admitted to hospital with abdominal pain, diarrhea, and blood in stool lasting for more than 2 mo. Colonoscopy revealed multiple erosions and ulcers in the entire colon and rectum. Pathological sections showed chronic inflammatory cell infiltration, especially neutrophil infiltration, in the colonic mucosa; therefore, the patient was diagnosed with ulcerative colitis. Preparations of 5-aminosalicylic acid was added to her treatment based on the original treatment for DM, but its effect was unsatisfactory. The patient’s discomfort was relieved after infliximab treatment.CONCLUSIONInfliximab can improve DM in the treatment of ulcerative colitis. Specialists need to raise awareness about patients with inflammatory bowel disease who have rare extraintestinal manifestations.