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Antioxidant therapy with N-acetylcysteine plus mesalamine accelerates mucosal healing in a rodent model of colitis.

The aims of this study were to examine the ability of the antioxidant N-acetylcysteine (NAC) and mesalamine (5-ASA) alone and in combination to affect TNBS-induced colitis in rat. Three days following induction of TNBS colitis rats were randomized to receive daily intracolonic treatment with NAC, 5-ASA, and NAC plus 5-ASA for 5 or 8 days. At the end of the treatment period macroscopic and microscopic colonic injuries were scored. Myeloperoxidase (MPO) activity and cytokine gene expression were measured in colonic tissues. Results indicated that treatment with NAC plus 5-ASA caused a significantly greater reduction in colonic injury than either agent alone. Furthermore, combination therapy inhibited significantly MPO activity and inflammatory cytokine gene expression in the distal colon of TNBS-treated animals. The beneficial effects of NAC plus 5-ASA on reduction of colonic injury and promotion of healing were most evident after 8 days of treatment.

Acetylcysteine↗

Antibiotics with a selective aerobic or anaerobic spectrum have different therapeutic activities in various regions of the colon in interleukin 10 gene deficient mice.

BACKGROUND AND AIMS: Multiple rodent models implicate resident intestinal bacteria in the pathogenesis of chronic immune mediated intestinal inflammation. Specific pathogen free (SPF) interleukin 10 gene deficient (IL-10(-/-)) mice develop colitis, which does not occur in the germ free (GF) state. We investigated whether broad or narrow spectrum antibiotics affect onset and progression of disease in various regions of IL-10(-/-) mice. METHODS: Metronidazole, ciprofloxacin, vancomycin-imipenem (50 mg/kg/day), or water (control) was administered orally before (prevention) or two weeks after (treatment) colonisation of GF IL-10(-/-) mice with SPF bacteria. After four weeks, colonic histology scores and cytokine production by colonic explants were determined. Caecal and colonic contents were collected for quantitative bacterial analysis. RESULTS: In the prevention study, all antibiotics decreased inflammation in the caecum and colon. However, in the treatment study, ciprofloxacin and vancomycin-imipenem decreased caecal inflammation, and reduced Escherichia coli and Enterococcus faecalis concentrations, whereas only vancomycin-imipenem lowered direct microscopic bacterial counts. In contrast, metronidazole and vancomycin-imipenem reduced colonic injury and eliminated anaerobic bacteria, including Bacteroides spp. CONCLUSIONS: Both narrow and broad spectrum antibiotics can prevent disease but treatment of established colitis is more selective. Ciprofloxacin is most effective in the treatment of caecal inflammation, metronidazole preferentially treats the colon, whereas vancomycin-imipenem definitively treats both regions. These results suggest that subsets of aerobic or anaerobic bacteria show regional differences in their capacity to mediate experimental colitis in IL-10(-/-) mice.

Animals↗

Clinically silent inflammatory gut lesions in undifferentiated spondyloarthropathies.

Gastrointestinal inflammation or infection can be associated with various forms of arthritis, such as, acute reactive arthritis triggered by enteritis due to gram-negative bacteria or ankylosing spondylitis and peripheral arthritis in relation to Crohn's disease and ulcerative colitis. Using colonoscopy, we have found a high prevalence of clinically silent inflammatory lesions in 38 patients (24 males and 14 females) affected by undifferentiated spondyloarthropathies (SpA). Microscopic inflammatory lesions were present in all the patients. Three patterns of nonspecific chronic inflammatory alterations were observed. No difference was noted between patients taking or not taking nonsteroidal anti-inflammatory drugs. Direct immunofluorescence demonstrated the presence of IgG, IgA, IgM, C3, C4 and fibrinogen in 75% of the specimens examined. The finding of chronic inflammatory gut lesions hypothesizes that a local activation of the immune system depending on the persistence of intestinal microbial antigens or toxins, due to impaired elimination or increased exposition, may have a part in the pathogenesis of SpA.

Adult↗

Pentax confocal endomicroscope: a novel imaging device for in vivo histology of the upper and lower gastrointestinal tract.

With advances in endoscopic imaging tools, it is becoming increasingly possible to find, assess and treat numerous gastrointestinal (GI) pathologies at the time of endoscopy. This article focuses on the newly developed Pentax confocal endomicroscope that enables in vivo microscopic imaging of the upper and lower GI tract in histological detail at the time of patient examination without the collection of biopsies. The optical imaging technique has the potential to revolutionize clinical workflows in endoscopy through high-resolution fluorescence imaging of cellular and subcellular detail from the surface and subepithelial layers of the GI mucosa. The device incorporates a full screen, high-resolution charge coupled device as well as a confocal microscope. Preliminary data from blinded clinical studies suggests that the use of this device can increase the diagnostic yield for disease detection in conditions such as ulcerative colitis and Barrett's esophagus, where diagnosis using white light endoscopy is problematic. The early detection and diagnosis of GI abnormalities through the collection of 'optical' biopsies or targeted mucosal excisional biopsies has the potential to improve patient outcomes and enable early therapeutic intervention.

Barrett Esophagus↗

Mycobacterium paratuberculosis and inflammatory bowel disease: frequency distribution in serial colonoscopic biopsies using the polymerase chain reaction.

An association between Mycobacterium paratuberculosis and Crohn's disease is suspected but the evidence remains controversial. Using a one-step DNA extraction procedure with the thermophilic protease PRETAQ and amplification by the polymerase chain reaction, M. paratuberculosis DNA was detected in 22% of patients with Crohn's disease, and in 13% of patients with ulcerative colitis. M. paratuberculosis DNA was not found in any biopsy tissue from control non-inflammatory bowel disease patients. The biopsy tissues in which M. paratuberculosis was detected all came from regions which were inflamed when viewed microscopically. Overall, 7.7% of biopsies from such inflamed areas were positive. This low frequency of detection could be explained on the basis of extremely low abundance of the organism in relation to the area of mucosa sampled, or be consistent with a non-aetiological role for M. paratuberculosis in inflammatory bowel disease.

Animals↗

A microscopic and immunodiagnostic search for giardiasis in patients with gastrointestinal disorders.

Direct microscopy and an ELISA technique were used to determine the prevalence of Giardia lamblia and its antigen in stool samples from patients with Crohn's disease, ulcerative colitis, acute-onset diarrhoea, or dyspepsia. Cysts of Giardia lamblia were observed by microscopy of faeces from two of the patients with acute-onset diarrhoea and one with dyspepsia. Giardia antigen was detected in the faeces of five patients, including all three in whom cysts had been identified by microscopy. No evidence of giardiasis was found in any patient with Crohn's disease or ulcerative colitis. It is concluded that the ELISA can reliably distinguish giardiasis from a range of other gastrointestinal disorders.

Antibodies, Protozoan↗

Histomorphometric evaluation of experimentally induced colitis with trinitrobenzene-sulphonic acid in rats.

Colitis was induced with trinitrobenzene-sulphonic acid (TNB) in rats and a histomorphometric study was performed as a possible scoring system for disease activity. The affected colon was examined 10, 20, 40 and 60 days after TNB administration. Quantitative microscopic analysis was performed on the following histologic parameters: necrosis, mucosal epithelium, muscularis fibres, inflammation, granulation tissue and fibrosis. Clinically, the rats were sick, especially on days 10 and 20 after TNB injection. Concomitantly, a peak necrosis score involving the full thickness of the colonic wall was recorded on day 10. The inflammatory reaction was most intense 20 days after TNB injection. After 60 days, marked epithelial regeneration was seen and most of the inflammatory reaction had subsided. A good correlation was found between clinical features and quantitative histomorphometric characteristics of colitis. The criteria described allow a precise description and quantification of the inflammatory and healing process of TNB-induced colitis in rats.

Acute Disease↗

[Preservation of anal transitional zone in restorative proctocolectomy].

Since 1980, restorative proctocolectomy has been established for surgical therapy to ulcerative colitis. The crucial points of this procedure are mucosectomy of the anorectal mucosa and pouch anal anastomosis. Mucosectomy is often difficult due to long standing acute and chronic inflammation and incomplete microscopically and leakage of pouch anal anastomosis is relatively high probably due to steroid given prior to surgery or direct effect of anorectal mucosal inflammation. Regards to postoperative bowel function, nocternal soiling is frequently recognized in the patients who received this operation. To overcome these technical and functional disadvantages, anal transitional zone preservation without mucosectomy and stapled anastomosis between pouch and the upper rim of the puborectalis muscle has been performed. Our series of 84 cases with this modified method, anastomotic leakage was significantly decreased and nocternal soiling was completely disappeared within 7 months postoperatively. And one stage procedure became possible unless severe, or high doses of steroid given prior to surgery. Only one case of mild dysplasia was experienced in the remaining rectal mucosa which was disappeared at the next examination. Medical treatment to the remaining lesion was not necessary in the most of cases. Anal canal preservation is superior to mucosectomy in the points of bowel function and minimizing postoperative complications.

Anal Canal↗

A case of Behçet's disease with multiple longitudinal ulcers all over the colon.

We experienced a rare case of intestinal Behçet's disease simulating Crohn's colitis. A 70-yr-old female presented oral and genital ulcers, erythema nodosum, arthralgias, and abdominal pain. Regardless of our efforts, she died of septic shock. Autopsy showed punched-out ulcers in the terminal ileum and multiple longitudinal ulcers with inflammatory polyposis spreading from the ascending to the descending colon. The differential diagnosis of intestinal Behçet's disease versus Crohn's disease was difficult. However, microscopic findings showed nonspecific ulceration, and no evidence of Crohn's disease could be found. Clinically, the patient met the criteria of Behçet's disease, and punched-out ulcers in the ileocecal region, which is characteristic of intestinal Behçet's disease, confirmed the diagnosis of Behçet's colitis. Although rarely encountered, multiple longitudinal ulcers can involve all of the colon in Behçet's disease, like Crohn's disease.

Aged↗

Histiocytic ulcerative colitis in three non-boxer dogs.

Histiocytic ulcerative colitis (HUC) is described in three non-boxer dogs. Clinical signs were typical of large-bowel diarrhea and included soft stool, hematochezia, tenesmus, and an increased frequency of defecation. Diagnosis in each case was made by light microscopic evaluation of endoscopically obtained colonic biopsy specimens. Treatment regimes varied, but included immunosuppressive agents, anti-inflammatory drugs, antimicrobials, and dietary modification. Clinical response was substantial in two patients, while the third patient was euthanized due to treatment failure. The authors' observations indicate that HUC may be encountered in non-boxer dogs.

Animals↗

Further studies of HLA-DR antigens on colonic epithelium in ulcerative colitis.

The aim of this study was to determine whether HLA-DR antigens are expressed on colonic epithelium in macroscopically involved areas in all cases of ulcerative colitis and whether the expression precedes inflammation (colitis). Thirty-four cases of active ulcerative colitis were studied including two cases in which island-like lesions were observed proximally apart from the main lesion, and three cases in which distal colitis became entire colitis in 8 months or less. Detection of HLA-DR antigens on colonic epithelium was performed with the immunoperoxidase method using anti-HLA-DR monoclonal antibodies. HLA-DR antigens were expressed on colonic epithelium in macroscopically involved areas in all 34 cases. In the macroscopically normal areas, the antigens were modestly expressed in six of 16 specimens (cases) in the presence of microscopic inflammation. The antigens were expressed on colonic epithelium in island-like lesions, but not in the intervening mucosa between the proximal island-like lesions and the distal main lesion. HLA-DR antigens were not expressed on colonic epithelium in the proximal non-inflamed mucosa where colitis later developed. These results lead to the conclusion that HLA-DR antigen expression does not precede, but is associated with the inflammation.

Adolescent↗

Can ischemic colitis be differentiated from C difficile colitis in biopsy specimens?

Pseudomembranous colitis is often caused by Clostridium difficile; however, it may also be due to ischemia. To determine if any histologic features could be used to differentiate C difficile from ischemia, 49 biopsies of pseudomembranous colitis (25 from patients with C difficile colitis and 24 from patients with ischemic colitis) were coded, randomized, and evaluated for the presence of numerous variables, including the amount and distribution of mucosal necrosis, lamina propria hyalinization, and atrophic "micro-crypts." Hyalinization of the lamina propria was seen in 19 cases of ischemia but not in C difficile colitis (p < 0.0001). Atrophic-appearing micro-crypts were seen in 18 ischemic cases and 6 C difficile cases (p < 0.0006). Lamina propria hemorrhage, full-thickness mucosal necrosis, and a diffuse microscopic distribution of pseudomembranes were significantly more common in ischemia than C difficile. Endoscopic examination identified pseudomembranes significantly more often with C difficile than ischemia, while the endoscopic appearance of masses or polyps was seen exclusively in cases of ischemia. The presence of a hyalinized lamina propria appeared to be a specific and sensitive marker for ischemia in colon biopsies with pseudomembranes. The presence of atrophic micro-crypts, lamina propria hemorrhage, full-thickness mucosal necrosis, diffuse involvement of all the surface of all biopsies by pseudomembranes, and the endoscopic impression of a localized process, polyp, or mass were also markers of ischemia, while the endoscopic identification of diffuse pseudomembranes favored the diagnosis of C difficile.

Adult↗

Case report: haemorrhagic colitis associated with royal jelly intake.

The case report of a 53-year-old woman with abdominal pain and bloody diarrhoea is described. Prior to the onset of symptoms the patient had taken royal jelly for 25 days. Colonoscopy revealed that the mucosa was haemorrhagic and oedematous throughout the 20 cm long sigmoid colon. Histopathologically, mucosal haemorrhage, oedema, and infiltration of inflammatory cells were observed. Transmission electron microscopic examination revealed platelet aggregation in 30% of capillaries in the mucosal lesions. The drug-induced lymphocyte stimulation test was slightly positive for royal jelly (847 c.p.m., SI = 147%) compared with the control (576 c.p.m.). The patient's signs and symptoms disappeared within a few days after the initiation of conservative therapy, and the colonic lesions disappeared after 2 weeks of this therapy. This is the first reported case of haemorrhagic colitis associated with royal jelly intake.

Colitis↗

Staphylococcus aureus in inflammatory bowel disease.

BACKGROUND: The potential role of superantigens in inflammatory bowel disease (IBD), particularly Crohn disease, has been broached in studies of the functions of T cell receptors. Staphylococcal cells have been found in intestinal lymph follicles of IBDs. To clarify a role of staphylococcal superantigens in IBD, we attempted to determine whether Staphylococcus aureus could be detected in intestinal mucosa, including surgical specimens and lymph follicles of initial cases. METHODS: One-hundred-and-six colonic and ileal specimens were obtained from 38 Crohn disease, 25 ulcerative colitis and 36 non-IBD patients through therapeutic surgery or endoscopic biopsy. In Crohn disease, 23 surgical specimens and 11 biopsy specimens from initial cases were included. DNA was extracted with phenol-chloroform after homogenization and proteinase K treatment in 73 mucosal specimens. Using an inverted microscope, lymph follicle tissue was microdissected from the remaining 33, mostly biopsy, specimens. DNA was then extracted by freeze-thawing. A coagulase gene characteristic of S. aureus was sought. A nested polymerase chain reaction was performed utilizing primers that amplify a region of the coagulase gene. Polymerase chain reaction products were analyzed with polyacrylamide gel electrophoresis. RESULTS: Only one surgically resected colonic specimen, from a 42-year-old male ulcerative colitis patient, registered positive staphylocoagulase amplification. CONCLUSIONS: Staphylococcal superantigens are not involved in either the early lesions or the established lesions of Crohn disease. However, S. aureus infection occasionally may occur during the course of IBD.

Adult↗

Preserving the ascending colon as an alternative surgical option in ulcerative colitis.

Six patients with ulcerative colitis were studied to assess the histologic appearance of the ascending colon which was preserved at the initial operation performed more than ten years previous. Inflammatory cells were increased in all patients, but ulceration was not present microscopically. Most patients had less than five bowel movements a day. Because of good long term survival of the mucosa, wider use of a surgical approach is proposed, based upon excising the colonic mucosa most prone to ulceration and metabolic derangement. The procedure entails subtotal colectomy, mucosectomy of the rectal mucosa and preservation of the ascending colon as a neorectum. Prime advantages are the lack of a stoma and fewer bowel movements than result from other operations.

Adult↗

[Effect of plaunotol on trinitrobenzene sulfonic acid and acetic acid induced colonic lesions in rats].

The aim of this study was to assess the effect of plaunotol, an anti-ulcer agent, on trinitrobenzene sulfonic acid (TNB)- and acetic acid-induced colonic lesions in rats. Plaunotol significantly reduced the severity of colonic mucosal lesions induced by TNB at a dose of 600 mg/kg/day. Moreover, plaunotol, at a dose of 600 mg/kg/day, significantly depressed the myeloperoxidase activity of the lesioned area induced by TNB of the rat colon. In the model of colitis induced by acetic acid, plaunotol reduced the area of lesions dose-dependently and significantly at doses of 60, 200 and 600 mg/kg/day as assessed by macroscopic observation. Microscopic observation showed obvious changes by administration of plaunotol such as reduction of epithelial cell necrosis, decreased mucin production and a decreased infiltration of a large number of neutrophils. In conclusion, plaunotol showed a protective effect against colonic lesion formation induced by TNB and acetic acid in rats. This study suggests the possibility that plaunotol may be effective and useful for treatment of inflammatory bowel disease in humans.

Acetic Acid↗

[Development of colonic lesions caused by occlusion of paracolic marginal artery and/or vein--an experimental study using the model of ischemic colitis].

Paracolic marginal artery and/or vein of rabbit descending colon were ligated at two points with a distance of 3cm each other. The animals were sacrificed 1, 4 and 7 days after the operative procedure. The colonic segment including the vessel-ligated region was removed and studied macroscopically and microscopically. The impairment of arterial blood supply was more responsible for the development of colonic lesions. Especially, ulcerative lesions occurred only in artery-ligated and both of artery and vein-ligated groups. All the lesions occurred in the vein-ligated group were those showing only edema. Three types of mucosal folds with different etiology appeared in the vessel-ligated region of the colon, i. e., longitudinal and transverse folds and those converging to the ulcerative lesion. The morphological features of colonic lesions changed gradually. In the artery-ligated group, a variety of lesions including multiple ulcers and petechiae appeared with a longer lapse of time.

Animals↗