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Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acid in rats.

Ellagic acid (EA), a naturally occurring plant phenol, has the antioxidant and anti-inflammatory activities. In the present study, we examined the effect of EA contained in microspheres on the ulcerative colitis induced experimentally in rats by dextran sulfate sodium (DSS). Experimental colitis was induced in male Fisher 344 rats by daily treatment with 3% DSS solution in drinking water for 7 days. EA of microspheres (mcEA: 1 approximately 10 mg/kg as EA contents) was administered p.o. twice daily for 6 days. In a preliminary study, we found that these microsphere capsules, when administered p.o., are effectively dissolved in the proximal to the ileo-cecal junction and distributed to the terminal ileum and the colon. The ulceration area, colon length, and mucosal myeloperoxidase (MPO) activity as well as thiobarbituric acid-reactive substances (TBARS) were measured on 7th day after the onset of DSS treatment. The DSS treatment for 7 days caused severe mucosal lesions in the colon, accompanied with the increases of MPO activity and TBARS as well as the decreases of body weight gain and colon length. Administration of mcEA reduced the severity of DSS-induced colitis in a dose-dependent manner, and a significant effect was observed at 10 mg/kg, the ED50 being 2.3 mg/kg. This mcEA treatment also significantly mitigated changes in various biochemical parameters in the colonic mucosa induced by DSS. Although plain EA (without using microspheres) was also effective in reducing the severity of DSS-induced colitis, this effect was much less potent as compared with that of mcEA; the ED50 was about 15 times higher than that of mcEA. In addition, a significant effect on DSS-induced colitis was also obtained by intra-rectal administration of superoxide dismutase, an anti-oxidative agent. These results suggest that EA prevents the ulcerative colitis induced by DSS, probably by radical scavenging and/or anti-oxidative actions. The microspheres used in this study may be useful for delivering an orally administered drug specifically to the colon.

Animals↗

Immunohistologic demonstration of abnormal colonic crypt cell kinetics in ulcerative colitis.

A monoclonal antibody, Ki-67, that reacts with cells in the proliferative phases (G1, G2, S, and M) of the cell cycle was used in an immunohistochemical labeling reaction to examine the colonic crypt epithelium in active ulcerative colitis, inactive ulcerative colitis, and normal mucosa. The proportions of labeled cells in the lower two thirds (proliferative zone) and in the upper quarter of the crypt were determined. The proportions of Ki-67-positive crypt epithelial cells in both the proliferative zone and the upper crypt were higher in biopsy specimens from patients with active ulcerative colitis than from patients with normal mucosa or with inactive ulcerative colitis. In inactive ulcerative colitis the proportion of Ki-67-positive epithelial cells in the proliferative zone of the crypt was higher than in normal mucosa. These results are similar to those obtained in studies using tritiated thymidine to determine the proportion of cells in the DNA-synthesizing thymidine to determine the proportion of cells in the DNA-synthesizing phase of the cell cycle and suggest that immuno-histochemical staining with Ki-67 may be a practical method for measuring the proliferative activity of epithelial cells in patients with ulcerative colitis and other disorders of the gastrointestinal tract.

Antibodies, Monoclonal↗

Collagenous colitis: a study of the distribution of morphological abnormalities and their histological detection.

In collagenous colitis, the literature is conflicting concerning where in the colon the lesions are most likely to be present and most severe. Conflicting data furthermore shed doubt on the sensitivity of the histological detection of the morphological abnormalities and the threshold criteria for diagnosis. We addressed these questions in 56 patients with collagenous colitis. Two hundred ninety-one coded biopsy specimens were analyzed according to six standardized sites from cecum to rectum. Subepithelial collagen deposits were subjectively graded in hematoxylin and eosin (H&E) sections and quantitatively measured in trichrome-stained sections, respectively. Semiquantitative grading was also done for inflammatory changes of the lamina propria and abnormalities of the surface and crypt epithelium. The transverse colon yielded the largest percentage of biopsy specimens (83%) interpreted as diagnostic of collagenous colitis and also had the largest percentage of biopsy specimens with inflammatory changes (98%). Biopsy specimens from both the rectosigmoid and the right colon (ascending and cecum) were significantly less likely to be diagnostic (P<.01). Only 66% of specimens obtained from the rectosigmoid were diagnostic, and 18% of these were interpreted as normal. Subepithelial collagen deposits proved to be significantly thicker in the transverse (median, 46.8 microm; range, 12 to 212.4) and descending (median, 49.2 microm; range, 6 to 230.4) than in the rectosigmoid (median, 33.6 microm; range, 9.6 to 178.8) and right colon (median, 35.4 microm; range, 6 to 140.4), respectively (P<.01). Almost all biopsy specimens (97%) had collagen deposits thicker than 10 microm. However, the subjective interpretation "diagnostic of collagenous colitis" proved to be most consistent with a threshold of 30 microm. Our results indicate that biopsy specimens from at least as proximal as the transverse colon should be obtained to definitely rule out collagenous colitis. Furthermore, it is evident that in a given biopsy specimen, markedly abnormal subepithelial collagen deposition had to be present for an unequivocal histological diagnosis of collagenous colitis.

Adult↗

Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial.

BACKGROUND: Ulcerative colitis has been suggested to be caused by infection and there is circumstantial evidence linking Escherichia coli with the condition. Our aim was to find out whether the administration of a non-pathogenic strain of E. coli (Nissle 1917) was as effective as mesalazine in preventing relapse of ulcerative colitis. We also examined whether the addition of E. coli to standard medical therapy increased the chance of remission of active ulcerative colitis. METHODS: This was a single-centre, randomised, double-dummy study in which 120 patients with active ulcerative colitis were invited to take part. 116 patients accepted; 59 were randomised to mesalazine and 57 to E. coli. All patients also received standard medical therapy together with a 1-week course of oral gentamicin. After remission, patients were maintained on either mesalazine or E. coli and followed up for a maximum of 12 months. A two-stage, conditional, intention-to-treat analysis was done. FINDINGS: 44 (75%) patients in the mesalazine group attained remission compared with 39 (68%) in the E. coli group. Mean time to remission was 44 days (median 42) in the mesalazine group and 42 days (median 37) for those treated with E. coli. In the mesalazine group, 32 (73%) patients relapsed compared with 26 (67%) in the E. coli group. Mean duration of remission was 206 days in the mesalazine group (median 175) and 221 days (median 185) in the E. coli group. INTERPRETATION: Our results suggest that treatment with a non-pathogenic E. coli has an equivalent effect to mesalazine in maintaining remission of ulcerative colitis. The beneficial effect of live E. coli may provide clues to the cause of ulcerative colitis.

Adult↗

[Lactose malabsorption in ulcerative colitis. A case-control study].

BACKGROUND: The role of lactose malabsorption in ulcerative colitis is controversial. The aim of this study was to compare the prevalence of lactose malabsorption in a group of ulcerative colitis patients and a control group and to modify lactose consumption in view of the results. METHODS: Lactose malabsorption was studied using the hydrogen breath test in 52 patients with ulcerative colitis and 34 controls after ingestion of 25 g of lactose. A questionnaire on ingestion of milk products was also administered. RESULTS: Of the 52 patients with ulcerative colitis, 13 (25%) presented lactose malabsorption compared with 11 of the 34 (32%) controls (p = 0.45). Twenty-four patients (46%) had been advised to completely eliminate lactose from their diets. Twenty-seven of the 39 patients without malabsorption had reduced or eliminated lactose consumption after being diagnosed with ulcerative colitis. CONCLUSIONS: No significant differences in the prevalence of lactose malabsorption was found between patients with ulcerative colitis and controls. We believe that systematic elimination of lactose from the diets of these patients is erroneous. In our environment, we recommend the hydrogen breath test only in patients with symptoms of lactose intolerance.

Adolescent↗

[Ulcerative colitis with segmental involvement].

INTRODUCTION: Ulcerative colitis is a chronic inflammatory disease affecting areas of the colon or the full length. From the endoscopic point of view, ulcerative colitis presents lesions that stretch continuously from the rectum to variable colon segments, a characteristic that is of great value when distinguishing it from Crohn's disease. Continuous involvement, without healthy patches, justifies ending endoscopic exploration once the distal end of the lesion has been reached. OBJECTIVE: To retrospectively study the frequency of segmental lesions in the colonoscopies performed in patients with ulcerative colitis. METHODS: Diagnosis of ulcerative colitis and proctitis was established by clinical, endoscopic, histologic, analytical, and radiological criteria. The indication and number of endoscopies was made on the basis of the clinical criteria of diagnosis, acute episodes, refractoriness or dysplasia screening. The extent of the examination also depended on clinical criteria: the severity of the episode, tolerance to colonoscopy or the degree of cleansing. RESULTS: A total of 155 coloscopies were performed. In 113 colonoscopies (73%) the distal end of the lesion was reached and in 70 (45%) the cecum was reached. Of the 80 patients, 27 (33%) presented ulcerative proctitis at diagnosis. Nine of the 80 patients (11.3%) biopsies were performed in healthy colonic patches, which confirmed histological normality. Six of the 9 patients were receiving no treatment. In all patients except two, the cecum was reached in one or more of the colonoscopies. The distribution of the segmental lesions varied but these were mainly found in the periappendicular region and in the cecum in 6 of the 7 patients in whom the cecum was reached. Of the 80 patients, endoscopic evidence of rectal sparing was found in 5 (6.3%); of these, 4 were receiving systemic or topical treatment. Histological analysis confirmed the absence of inflammatory lesions in these patients. The only patient who was not receiving treatment presented microscopic lesions compatible with ulcerative colitis. CONCLUSIONS: Endoscopic segmental lesions in ulcerative colitis were present in 11.3% of patients. Segmental lesions were most frequently found in the cecum and periappendicular region. Endoscopic and histologic evidence of rectal sparing may be the result of systemic or topical treatment.

Adolescent↗

Involvement of CD4+ T cells in the development of dextran sulfate sodium-induced experimental colitis and suppressive effect of IgG on their action.

1. To clarify the role of T cells in the development of dextran sulfate sodium (DSS)-induced colitis, T cells from colitis mice were primed with DSS-pulsed macrophages in vitro and then transferred into normal mice. In addition, to determine whether the target cell of immunoglobulin G (IgG) is the T cell, the extent of T cell proliferation induced by pulsed macrophages was examined after preincubation with IgG. 2. When mice receiving the primed T cells were treated with oral DSS, colitis symptoms were more severe than in animals treated with oral DSS only. This activity of primed T cells was reduced by depletion from the cells of CD4+ but not CD8+ cells. 3. The proliferation of T cells from colitis mice induced by pulsed macrophages was inhibited by T cell preincubation with homologous IgG. 4. The results suggest that CD4+ T cells play an important role in the development of DSS-induced experimental colitis and that IgG may modulate the development of colitis through interaction with pathogenic T cells.

Adoptive Transfer↗

Attenuated mild colonic inflammation and improved survival from severe DSS-colitis of transgenic Cu/Zn-SOD mice.

Mucosal tissue damage in chronic inflammatory bowel disease (IBD) is partly caused by an enduring exposure to excessive amounts of reactive oxygen metabolites (ROM). To protect themselves from the toxic effects of ROM, most intestinal cell types constitutively express the highly specific, key ROM-neutralizing cytosolic enzyme Cu/Zn-superoxide dismutase (SOD). Under inflammatory conditions, however, its protein and activity levels have consistently been reported as being decreased. To elucidate a direct functional relationship between intracellular Cu/Zn-SOD expression and intestinal inflammation, we investigated the effects of transgenic human Cu/Zn-SOD overexpression in acute and chronic murine dextran sodium sulfate (DSS)-induced colitis. When subjected to a mild form of acute colitis, the Cu/Zn-SOD overexpressing mice showed a significantly lower colonic activity of neutrophilic myeloperoxidase (MPO) than their nontransgenic littermates. This difference was particularly evident in the male animals. In contrast, a severe acute colitis did not lead to any differences in MPO activity between both groups. Yet, when the animals were subsequently allowed to recover, MPO levels were again significantly lower in the transgenes, suggesting an involvement of Cu/Zn-SOD in, particularly, the clearance of neutrophils. Specific, immunohistochemical identification of neutrophils confirmed the validity of the MPO activity measurements. In addition, transgenic animals showed a remarkable survival benefit from severe DSS colitis over their nontransgenic littermates, particularly during or shortly after the acute inflammatory phase. During the chronic inflammatory phase, which was not characterized by massive neutrophil infiltration, no effects of Cu/Zn-SOD overexpression were noted. Paradoxically, overexpression of Cu/Zn-SOD did not obviously improve the colitis-related (oxidative) injury or symptoms at any stage of the experiment. Surprisingly, however, we did observe a pronounced male gender preference for DSS susceptibility that was reflected by increased male colitis mortality. Our findings provide direct in vivo evidence for a protective, neutrophil-related role for Cu/Zn-SOD in intestinal inflammation. As such, they support the concept of SOD-based (adjunct) antioxidant treatment strategies for inflammatory bowel disease.

Acute Disease↗

Long-term maintenance treatment in ulcerative colitis: a 10-year follow-up.

BACKGROUND: With the extensive use of mesalamine, the natural history of ulcerative colitis is probably changed. AIM: To evaluate the relapse rate and the duration of remission in patients with ulcerative colitis on maintenance treatment with mesalamine. PATIENTS AND METHODS: Enrolled in the study were 95 patients divided into 4 groups according to macroscopic location of the disease and treated with the same therapy starting from the date of enrolment. Patients in all 4 groups were followed-up until relapse occurred. The disease activity was evaluated by the Clinical Activity Index and Endoscopic Index. Patients suitable for recruitment showed a Clinical Activity Index and Endoscopic Index lower than 6 and 4, respectively. The patients with ulcerative pancolitis or left-sided colitis were treated with 1.6 g/day while the cases with proctosigmoiditis or proctitis were treated with 5-acetylsalicylic acid enemas 4 g/day Each patient was evaluated with clinical and endoscopic assessment at a 6-month interval. Relapse was defined as an increase in Clinical Activity Index and Endoscopic Index, of more than 6 and 4, respectively. RESULTS: Five patients dropped-out. All enrolled patients showed a clinical and/or endoscopic relapse within 10 years, the majority 2 or 3 years after diagnosis: pancolitis and left-sided colitis within 2-3 years and patients with distal colitis within 9-10 years. CONCLUSIONS: A relapse was observed in most cases within 3 years, and in all recruited patients within a space of ten years. The extent of the disease in the colon is an important prognostic factor, as patients with distal colitis showed a lesser tendency to relapse.

Adult↗

Oral and topical 5-aminosalicylic acid (mesalazine) in inducing and maintaining remission in mild-moderate relapse of ulcerative colitis: one-year randomised multicentre trial.

BACKGROUND: The association of oral 5-aminosalicylic acid (mesalazine) and enema is effective in treatment of mild-moderate forms of ulcerative colitis. However no study has been aimed at determining optimal duration of this association in active ulcerative colitis. AIM: To determine whether longer duration of therapy: 1. increases the rate of patients achieving remission, and 2. reduces relapse rate during the maintenance period in patients in remission. PATIENTS AND METHODS: A total of 149 patients, (89 male, 60 female), were randomly assigned to a regimen with 5-aminosalicylic acid tablets 2.4 g/day associated with 5-aminosalycilic enema 2 g/day for a 4-week (n = 73) or 8-week regimen (n = 76). After this acute therapy, patients were submitted to clinical, endoscopic and histological examinations and those in remission were assigned to a follow-up (maintenance) period with oral mesalazine alone at a dosage of 1.2 g/day. A clinical visit, including laboratory tests, at 6 months and an endoscopic-histological control at 12 months were carried out to exclude symptoms and endoscopic-histological signs of activity. Relapse of disease, i.e., presence of clinical symptoms or abnormal laboratory tests, was confirmed by endoscopy and histology. RESULTS: At end of acute phase, clinical, endoscopic and histological remission was comparable in the two groups: 42/76 (55%), in the 4-week, and 47/73 patients (64%), in the 8-week regimen. No difference was found stratifying patients according to extension of disease. Of these 89 patients in remission, 75 (34 from 4-week regimen; 41 from 8-week regimen) completed 12 months' follow-up. At end of follow-up, a similar percentage of patients in the 4-week regimen (50%) and 8-week regimen (51%) were still in remission. No significant difference between cumulative relapse rates of the two groups was found. Stratifying patients according to extension of disease, in the 8-week regimen group, those with left-sided colitis showed a higher remission rate than that of patients with diffuse colitis (66% versus 35%, p < 0.05). All regimens were well tolerated by most patients during the entire study period. CONCLUSIONS: An additional 4 weeks of topical treatment does not increase the remission rate in patients with mild-moderate active ulcerative colitis but seems to reduce the probability of relapse in patients with left-sided colitis.

Administration, Oral↗

Association of susceptibility locus for inflammatory bowel disease on chromosome 16 with both ulcerative colitis and Crohn's disease.

A susceptibility locus for inflammatory bowel disease (IBD) on chromosome 16 (IBD1) has been linked to Crohn's disease in genome-wide linkage studies. We performed a case-control study with two markers for this locus using leukocyte DNA from 127 Crohn's patients, 83 ulcerative colitis patients, and 74 control patients. Allele, genotype, and haplotype frequencies of the polymerase chain reaction products were determined using autoradiography. Haplotype frequencies differed for ulcerative colitis and Crohn's disease, particularly for haplotype CC (22% ulcerative colitis vs 10% Crohn's disease, P = 0.002 Chi2 = 10.0) and haplotype CD (18% Crohn's disease vs 9% ulcerative colitis, P = 0.025 Chi2 = 5.02). These data demonstrate the association of the IBD1 locus with both ulcerative colitis and Crohn's disease in a group of unrelated IBD patients. The use of such microsatellite markers when combined with others, might help distinguish ulcerative colitis from Crohn's disease in patients with ambiguous clinical and histological features.

Adolescent↗

Cytomegalovirus colitis after administration of docetaxel-5-fluorouracil-cisplatin chemotherapy for locally advanced hypopharyngeal cancer.

We present the case of a patient with a locally advanced hypopharyngeal carcinoma who developed a severe cytomegalovirus (CMV) colitis after his first chemotherapy course with 5-fluorouracil (5-FU), docetaxel and cisplatin. The most probable cause of his CMV colitis is the impaired immunity during a phase of neutropenia after the chemotherapy. Although there was amelioration of the colitis and clinical status after treatment with ganciclovir, the patient later deteriorated and died due to recurrent bacterial infections. This is the third reported case of CMV colitis treated with ganciclovir in a patient with a solid tumour. It is the first report of CMV colitis after docetaxel containing chemotherapy. Although CMV colitis is most frequently observed in immunosuppressed patients such as those with acquired immune deficiency syndrome (AIDS), transplants and corticosteroid treatment, it has also been reported in less immunosuppressed (elderly, malnourished,...) and even non-immunosuppressed patients. CMV infection should therefore be included in the differential diagnosis of GI disease in all patients, and when suspected, the clinician should pursue appropriate diagnostic and therapeutic interventions.

Antineoplastic Combined Chemotherapy Protocols↗

Novel antioxidants zolimid and AEOL11201 ameliorate colitis in rats.

The mechanism of tissue damage in ulcerative colitis (UC) is unknown. However, recent evidence suggests that reactive oxygen species (ROS) are critical mediators of inflammation, and tissue damage in UC and antioxidants could be beneficial in the treatment of UC. Our aim was to evaluate the effects of two new antioxidants, Zolimid and AEOL11201 on experimental colitis. Antioxidants or vehicle were given to rats for five days after induction of colitis by intrarectal administration of 4% acetic acid. Severity of colitis was assessed on day 5. Zolimid and AEOL11201 significantly improved acetic acid-induced colitis. Both Zolimid and AEOL11201 significantly decreased the severity of diarrhea, and severity of macroscopic and histological changes in the colon. Both agents also significantly decreased colonic MPO levels. In conclusion, Zolimid and AEOL11201 are effective antiinflammatory agents in an animal model of colitis. Further studies are needed to evaluate their beneficial therapeutic effects in patients with UC.

Acetic Acid↗

Increased nitric oxide production and inducible nitric oxide synthase activity in colonic mucosa of patients with active ulcerative colitis and Crohn's disease.

It is postulated that an enhanced production of nitric oxide by inflamed intestine plays a role in the pathophysiology of active inflammatory bowel disease. In this study, systemic NOx concentrations and colonic nitric oxide synthase activity were determined in patients with ulcerative colitis or Crohn's disease. The relationship between these two parameters and disease activity, as well as differences in nitric oxide synthase activity between ulcerative colitis and Crohn's disease, were areas of specific focus. Patients with active ulcerative colitis and Crohn's disease had significantly elevated plasma NOx concentrations; a positive correlation was found between NOx values and inducible nitric oxide synthase activities in the active mucosa of these patients. In active ulcerative colitis, levels of inducible nitric oxide synthase were significantly elevated in both normal and inflamed mucosa, although inducible nitric oxide synthase activity was higher in the latter. These colonic inducible nitric oxide synthase activities correlated well with the results of endoscopic and histologic grading of inflammation. There was no increase in constitutive nitric oxide synthase activity in patients with active ulcerative colitis. However, constitutive nitric oxide synthase activity was significantly increased in the inflamed mucosa in patients with Crohn's disease. In Crohn's disease, elevated inducible nitric oxide synthase activity was found in both normal and inflamed mucosa, with no significant difference between the tissues. Such differences in nitric oxide production in the colonic mucosa possibly reflect the significant differences in the pathophysiology and characteristic clinical features between ulcerative colitis and Crohn's disease.

Adult↗

Low plasma protein Z levels in patients with ischemic colitis.

Hypercoagulable states have been suggested to play an important role in the pathogenesis of ischemic colitis. Since protein Z is, as recently demonstrated, important in the regulation of coagulation, we investigated the plasma levels of protein Z in connection to factor V Leiden (FVL) and anti-phospholipid antibodies in patients with a definite diagnosis of ischemic colitis. The plasma levels of protein Z were measured using a commercially available enzyme-linked immunosorbent assay in 33 patients with ischemic colitis, 13 patients with diverticulitis, and 33 healthy controls. Mean plasma protein Z levels were 1.38 +/- 0.52 microg/ml in patients with ischemic colitis and were significantly lower compared to healthy controls (1.86 +/- 0.49 microg/ml) and patients with diverticulitis (1.72 +/- 0.53 microg/ml) (P = 0.001). Protein Z deficiency was found in patients cases with ischemic colitis (18.2%) compared to one with diverticulitis (7.7%) and one healthy control (3.0%). In conclusion, our results suggest that low plasma protein Z levels may play a role in the disease development in some cases with ischemic colitis.

Antibodies, Antiphospholipid↗

The effect of local attachment of cationized antioxidant enzymes on experimental colitis in the rat.

PURPOSE: To investigate the possibility of local treatment of colitis with the adhesive antioxidant enzymes catalase and superoxide dismutase (SOD). METHODS: The net electric charge of the enzymes' surfaces was modified from negative to positive, to cause their adherence to the colon epithelium. The effects of this local administration were assessed in inflamed rat colon. Inflammation severity (colitis) was assessed by measuring colonic tissue myeloperoxidase (MPO) activity, amounts of tumour necrosis factor alpha (TNFalpha) and concentrations of reduced glutathione (GSH). The measurements were carried out in two types of protocols: preventive (pre-colitis induction) and treatment (post-colitis induction). In addition, the efficacy of treatment with the cationized enzymes was compared to 5-aminosalicylic acid (5-ASA) and betamethasone with similar administration routes. RESULTS: The two cationized antioxidant enzymes were found to be efficient in both prevention and treatment of experimental colitis. The two cationized enzymes caused a significant reduction in MPO activity. A reduction in TNFalpha concentration was noted only after the treatment protocol. No correlation was found between inflammation severity and tissue levels of GSH. In most cases the cationized enzymes were more effective than 5-ASA and betamethasone. CONCLUSION: Cationized catalase and cationized SOD have the potential to be efficient therapeutic tools in the local treatment of colitis.

Animals↗

Influence of feces from patients with ulcerative colitis on butyrate oxidation in rat colonocytes.

An impaired oxidation of butyrate has been suggested as a causative factor of ulcerative colitis and, moreover, agents present in colonic luminal contents impair butyrate oxidation in both rat and human colonocytes. To evaluate the overall effect of feces on the production of CO2 and ketone bodies from butyrate oxidation in rat colonocytes, fecal homogenates from 10 healthy subjects and 10 patients with quiescent and 10 patients with active ulcerative colitis were sterile filtrated and added to rat colonocytes incubated with 2, 4, and 10 mmol/liter of stock butyrate, respectively. Addition of fecal filtrate from healthy subjects and patients with quiescent and active ulcerative colitis to colonocytes incubated with 2, 4, and 10 mmol/liter of stock butyrate, respectively, tended to decrease the production of CO2 from butyrate oxidation, whereas ketogenesis was unaffected. The decrease in CO2 production was not explained by the simultaneous addition of fecal short-chain fatty acids (SCFAs). However, a difference in the ability to decrease CO2 production was not found between filtrates from healthy subjects and patients with quiescent and active ulcerative colitis. In conclusion, feces from healthy subjects and patients with quiescent and active ulcerative colitis contain inhibitor(s) of the production of CO2 from butyrate oxidation in colonocytes. However, a specific inhibitory effect of feces from patients with ulcerative colitis on the production of CO2 could not be identified.

Adult↗

Effect of icatibant, a bradykinin B2 receptor antagonist, on the development of experimental ulcerative colitis in mice.

Dextran sulfate sodium-induced colitis in mice has been recognized as a model for human ulcerative colitis. Using this model, we carried out a study on the preventive effect of Icatibant, a bradykinin B2 receptor antagonist previously called HOE 140, on the development of colitis. Subcutaneous administration of Icatibant (0.3 or 1.5 mg/kg) significantly suppressed shortening of the large intestine and worsening of the general health. Oral administration of Icatibant (50 mg/kg) significantly suppressed shortening of the large intestine, the onset of diarrhea, and worsening of the general health. In addition, the oral treatment significantly inhibited the development of colitis that was observed histopathologically. These results indicate a role of BK in the development of dextran sulfate sodium-induced colitis in mice, and suggest that BK could be important in human ulcerative colitis.

Administration, Oral↗