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Induction of nitric oxide synthase and concomitant suppression of superoxide dismutases in experimental colitis in rats.

Reactive oxygen species are thought to play an important role in some bowel diseases. In order to evaluate the participation of nitric oxide and superoxide in such diseases, we examined the expression of nitric oxide synthase (NOS) and superoxide dismutase (SOD) as well as their activities in whole excised colons of rats with colitis induced by intralumenal administration of 2,4,6-trinitrobenzenesulfonic acid. A marked increase in the inducible form of NOS mRNA was detected and NOS activity was coincidentally augmented in the group administered unbuffered TNBS (pH 1.0), in which severe inflammation was revealed by microscopic examination and myeloperoxidase activity of invading neutrophils in the tissues. The levels of the Mn- and Cu,Zn-SOD proteins as well as SOD activity were suppressed, although expression of the Mn-SOD mRNA was enhanced in colitis tissues. The elevation of NOS activity and the suppression of SOD activity occurred concomitantly at the stage of severe inflammation. This would increase peroxynitrite formation from superoxide and nitric oxide and enhance the tissue damage in experimental colitis.

Animals↗

Early mucosal changes in Crohn's disease.

Aphthoid ulceration has been regarded as an early macroscopic feature of Crohn's disease, yet the cause of this mucosal lesion is unknown. Examination of areas of apparently normal and non-inflamed bowel in Crohn's disease has allowed the identification of mucosal changes which occur before macroscopic and microscopic ulceration. Thirty five resection specimens from patients with Crohn's disease were compared with 12 specimens from patients with ulcerative colitis and 13 controls. Specimens were fixed either by immersion in formalin in the routine way or by perfusion fixation with formalin at mean arterial pressure. Immunostaining for macrophages, vessel wall, and blood constituents allowed identification of small mucosal capillaries which were not apparent otherwise. In Crohn's disease damage and rupture of these small capillaries occurred before infiltration of the lamina propria by inflammatory cells. Loss of the overlying epithelium seemed to follow this vascular damage.

Capillaries↗

Ameliorative effect of pyrrolidinedithiocarbamate on acetic acid-induced colitis in rats.

Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. The present study examined the effect of NF-kappaB inhibitor and antioxidant, pyrrolidinedithiocarbamate (PDTC) on experimental ulcerative colitis in rats. Animals were randomly divided into 4 groups, each consisting of 6 animals; normal control group, acetic acid group, PDTC-treated group and sulfasalazine-treated group as a positive control group. Induction of colitis by intracolonic administration of 3% acetic acid produced severe macroscopic inflammation in the colon 24 h after acetic acid administration as assessed by the colonic damage score. Microscopically, colonic tissues showed ulceration, oedema and inflammatory cells infiltration. Biochemical studies revealed increased serum levels of lactate dehydrogenase (LDH), and nitrite/nitrate and colonic concentrations of tumor necrosis factor-alpha (TNF-alpha) and the neutrophil infiltration index, myeloperoxidase (MPO). Oxidative stress was indicated by elevated lipid peroxides formation and depleted reduced glutathione concentrations (GSH) in colonic tissues. Immunohistochemical studies of colonic sections revealed upregulation of inducible nitric oxide synthase (iNOS). Pretreatment with PDTC at a dose of (200 mg/kg/day, i.p.), three days before induction of colitis decreased serum LDH, nitrite/nitrate and TNF-alpha levels, colonic concentrations of MPO and lipid peroxides while increased colonic GSH concentration. Moreover, PDTC pretreatment attenuated colonic iNOS expression. Finally, histopathological changes were nearly restored by PDTC pretreatment. The findings of the present study provide evidence that PDTC may be beneficial in patients with inflammatory bowel disease.

Acetic Acid↗

Solitary ulcer of the rectum: report of a case and review of the literature.

A 13-year-old girl with Prader-Willi syndrome was admitted to our hospital with an 18-month history of anal bleeding and mucus discharge on defecation. Physical examination revealed obesity, hypogonadism, hypotonia and hypomentia. On digital examination, a nodular mass was palpated on the right wall of the ampulla recti, which was suspected to be carcinoma on a barium enema study. Proctoscopic examination revealed a large, irregular ulceration with white slough at the base, surrounded by the nodular and lumpy mucosa. The lesion was excised by the abdomino-anal pull-through method. The resected specimen showed a lesion of large, shallow, irregular ulcer, 5.0 x 2.2 cm in size. Microscopic examination revealed obliterated lamina propria by fibroblasts and muscle fibers derived from the muscularis mucosae, and misplaced cystic dilated glands in the submucosa at the margin of the ulcer. The gross and microscopic appearances are identical to those of "solitary ulcer of the rectum" described by Madigan and others, and similar to those of "colitis cystica profunda" described by Goodall and others. According to these findings, this lesion was diagnosed as solitary ulcer of the rectum. In the present report, the relationship between solitary ulcer of the rectum and colitis cystica profunda was discussed.

Adolescent↗

Campylobacter enteritis in Chelmsford.

During one year, out of 1829 faecal specimens examined at the Chelmsford Public Health Laboratory, campylobacters were isolated from 109 (6%), 21 of the positive cultures were from hospital in-patients and 3 were from hospital staff. The remaining 85 isolates were from specimens sent in by general practitioners. The authors' figures show a marked season variation with most of the infections occurring from June to September. The highest incidence (36%) was in the 20 to 30 age group, 99% of patients had diarrhoea, usually watery, occasionally explosive, and 9% had visible blood in their stools. Eighteen per cent. of patients had abdominal pain, 5 of the 21 hospital in-patients underwent abdominal surgery. Fifty-nine faecal specimens were examined microscopically and 30 of these had blood and pus cells or pus cells alone. Three patients had rectal biopsies showing a nonspecific colitis, 11 patients had recently been abroad.

Adolescent↗

'Microerosions' in rectal biopsies in Crohn's disease.

Small (less than 1 mm), superficial erosions ('microerosions') have been observed stereo-microscopically in surface-stained rectal biopsies in Crohn's disease (CD). Biopsy specimens from 97 patients with CD, 225 with ulcerative colitis (UC), and a control material of 161 patients were investigated to define the occurrence and significance of the microerosions. In CD they were found in 13% of specimens, in UC in 5%, and in the control material not at all. In CD they were observed only in patients with colonic involvement and were most frequent (44%) in patients with this site of affection exclusively. Granulomas were identified in 62% of the biopsies with microerosions and by examination of two consecutive biopsies from each of these patients, in 85% indicating a positive correlation. In patients with microerosions and a primary diagnosis of UC, granulomas were found in 38% and by examination of two biopsies in 54%. Patients with granulomas and a few other patients were reclassified as CD, but there still remained some patients with microerosions, who most probably had UC. In conclusion, microerosions are observed mainly in CD with colonic involvement. There is a high incidence of granulomas in biopsy specimens with microerosions. The demonstration of microerosions in a specimen is suggestive of, but probably not diagnostic of, CD.

Biopsy↗

Germinated barley foodstuff suppresses dextran sulfate experimental colitis in rats: the role of mast cells.

Recent studies have suggested that dietary fiber exerts a therapeutic effect on inflammatory bowel disease patients. The aim of this study was to evaluate the effects of a dietary fiber, germinated barley foodstuff (GBF), derived from the aleurone and scutellum fraction of germinated barley against dextran sulfate sodium (DSS)-induced experimental colitis in rats. Sprague-Dawley rats were fed a 3% DSS diet containing GBF or alpha-cellulose for 8 days. The mucosal damage (macroscopic and microscopic inflammation) was then quantified. In addition, we evaluated the alterations in the mucosal mast cells and connective tissues. GBF effectively prevented mucosal damage. In addition, GBF suppressed the infiltration of the mucosal mast cells, and prevented the distraction of both collagen and elastic fibers. These effects may be closely associated with its inhibitory effects on mucosal mast cells, and the destruction of the mucosal connective tissues.

Animals↗

Increased expression of epidermal growth factor-receptor in an experimental model of colitis in rats.

BACKGROUND: Epidermal growth factor and related proteins share some structural homology and bind to one common receptor. We have shown previously that exogenously applied EGF protects colonic mucosa against injury in an experimental model of colitis in rats and that the endogenously expressed ligands for the EGF-receptor are predominantly transforming growth factor alpha precursors. The aim of our present study was to evaluate the EGF-receptor expression in response to mucosal injury in the same model of colitis. METHODS: The trinitrobenzene sulphonic acid (TNBS)/ethanol-induced model of colitis in rats was used and EGF-receptor expression was evaluated using ribonuclease protection assay and Western blot analysis. The extent of mucosal injury and inflammation was characterized by using a microscopic and macroscopic damage score and by estimation of the myeloperoxidase activity in colonic specimens. RESULTS: Irritation of the colonic mucosa leads to severe colonic inflammation with tissue oedema, erosions and mucosal ulcers and to a significant increase in myeloperoxidase activity expressed by neutrophil granulocytes and macrophages. A significant increase in EGF-receptor mRNA expression was obtained at 8-24 h followed by an increased expression of the EGF-receptor protein at 1-5 days after the induction of colitis. On Western blot analysis only one immunoreactive band with a molecular weight of approximately 170 kDa was detected. CONCLUSIONS: Mucosal inflammation leads to a significant increase in the EGF-receptor expression in the early phases of colitis. These findings support our hypothesis that EGF and related proteins and their common receptor play a pivotal role in mucosal defence and repair.

Actins↗

Haemorrhagic colitis: detection of verotoxin producing Escherichia coli O157 in a clinical microbiology laboratory.

Faeces (n = 1319) were examined over three months for the presence of non-sorbitol fermenting, verotoxin producing Escherichia coli (serotype O157). Seven isolates were found, four from patients with bloodstained diarrhoea and three from patients with no evidence of blood in the faeces. Screening of all faecal samples with specific O157 antiserum for non-sorbitol fermenting organisms and agglutination was an important adjunct to clinical and microscopic findings and helped detect cases of verotoxin producing E coli which might otherwise have been missed.

Bacterial Toxins↗

Cases from the Osler Medical Service at Johns Hopkins University.

A 47-year-old white woman with a history of stage III squamous cell carcinoma of the anus was transferred to Johns Hopkins Hospital for further evaluation of renal failure, hemolytic anemia, and thrombocytopenia. The patient was first diagnosed with squamous cell carcinoma of the anus 1 year before admission. She was treated with external beam radiation of the pelvis and two cycles of mitomycin C-based chemotherapy (a cumulative dose, 34 mg/m(2)). Her clinical course was complicated by Clostridium difficile colitis and myositis successfully treated with prednisone. Three months before admission, the patient developed dysuria. Her creatinine increased from normal to 1.7 mg/dL, and microscopic hematuria was present. A renal ultrasound and an abdominal computed tomographic scan showed no abnormalities or obstruction. One month before admission, she underwent a cystoscopy, which showed only radiation-induced changes in the bladder. Two weeks before admission, the patient became delirious and was taken to a hospital, where she was found to be anemic, with a hematocrit level of 23.7%, and thrombocytopenic with a platelet count of 110,000/mm(3). Her creatinine level was 5.9 mg/dL. Previous values of hematocrit, platelet count, and serum creatinine were normal. On admission at Johns Hopkins Hospital the patient had no complaints. She was afebrile on physical examination and had normal vital signs. Head, neck, chest, cardiovascular, and abdominal examinations were normal. There was skin pallor, but no echymoses or petechiae. She was alert and oriented with normal mental status. Her neurologic examination was normal. Laboratory data showed a white blood cell count of 6390/mm(3), a hematocrit level of 26.5%, and a platelet count of 26,000/mm(3). Her blood urea nitrogen level was 57 mg/dL, creatinine level was 4.0 mg/dL, and lactate dehydrogenase was 550 U/L (reference, 115 to 275 U/L). Urinalysis showed innumerable red blood cells and large protein. A peripheral blood smear showed fragmented red blood cells, schistocytes, no abnormal white blood cells, and few platelets. There was no radiographic or clinical evidence of relapse of her squamous cell carcinoma. What is the diagnosis?

Anemia, Hemolytic↗

Distinct differences in autoantigen specificity of anti-neutrophil cytoplasm antibodies in systemic vasculitides and other inflammatory diseases.

BACKGROUND: Anti-neutrophil cytoplasm antibodies in necrotizing vasculitides need to be distinguished from ANCAs in other inflammatory conditions to avoid clinical misinterpretation. OBJECTIVES: To help clinicians and laboratory scientists recognize and utilize vasculitis-related ANCAs as an aid in diagnostic workup and patient follow-up, and be aware that ANCAs with different characteristics are commonly found in other chronic inflammatory conditions that persistently engage neutrophils in the inflammatory process. METHODS: Indirect immunofluorescence and enzyme immunoassay methods were used to detect ANCAs with both known and unknown neutrophil autoantigenic targets. RESULTS: Primary necrotizing small vessel vasculitides such as Wegener's granulomatosis, Churg-Strauss syndrome, microscopic polyangiitis, and renal-limited rapidly progressive necrotizing glomerulonephritis target either the serine protease proteinase 3 or myeloperoxidase in azurophilic granules. In ulcerative colitis and rheumatoid arthritis, we found multiple ANCA targets contained in azurophilic and specific granules, the cytosol and the nucleus, whereas PR3 and MPO were not, or only weakly, recognized. CONCLUSIONS: ANCAs typically found in active SVV are demonstrable both by indirect immunofluorescence and antigen-specific enzyme immunoassay, and strong reactivity to either PR3 or MPO is characteristic. Strong ANCA with MPO reactivity is also found in some patients with drug-induced syndromes (lupus, vasculitis). Intermediate to strong perinuclear ANCAs are found in a substantial proportion of patients with UC (40-60%) and RA (30-70%), but in these conditions the ANCAs have many antigen targets that are only weakly recognized.

Antibodies, Antineutrophil Cytoplasmic↗

Crohn's disease, ulcerative colitis or indeterminate colitis--how important is it to differentiate?

In most patients coming to the general practitioner or specialist with a history of bloody diarrhoea, bacteria or drugs are the most likely causative agents and it will be possible to make a diagnosis fairly easily. Because of differences in treatment, ulcerative colitis (UC) and Crohn's disease (CD) must however seriously be considered especially in younger patients, with severe symptoms and whenever the history is prolonged. A variety of colitides may indeed be clinically confused with UC and CD. Pathological mimics that should not be missed include infectious diseases such as Campylobacter colitis, yersiniosis, amoebiasis and others; drug-induced diseases (due to nonsteroidal antiinflammatory drugs...); diverticular disease-associated colitis; intestinal endometriosis; intestinal vasculitis and Behçet's disease and iatrogenic conditions such as graft-versus-host-disease and radiation colitis. In most situations a precise diagnosis of these conditions should be possible when all data are available. The term "indeterminate colitis" is used, when a diagnosis of chronic idiopathic inflammatory bowel disease (IBD) is suggested, but the differential diagnosis between UC and CD can not be solved. This occurs in approximately 5% of all patients with IBD. Diagnostic problems can occur in acute fulminant colitis, acute prolonged colitis, chronic relapsing disease and pouchitis. Indeterminate colitis is essentially a temporary diagnosis. Surgical and medical treatment of these patients can be difficult. When surgical treatment is indicated, the type of surgery must be seriously considered. The clinical course of patients with indeterminate colitis is usually more severe when compared with classical UC and these patients require often more severe medical treatment. Diagnostic problems can also arise in longstanding IBD, either UC and CD. Relapse of symptoms can be due to intercurrent infection (CMV is one of the candidates). Medical treatment can influence the microscopic features and induce a discontinuous inflammation in UC, reminiscent of CD. In cases of doubt, the original biopsies should be reviewed to ascertain the diagnosis, and orient treatment.

Colitis↗

Colitis cystica profunda: an unusual surgical problem.

Colitis cystica profunda is a rare, benign, non-neoplastic condition which usually presents as a mass in the rectum associated with bloody, mucoid diarrhea. This clinical presentation associated with the microscopic finding of mucus cysts in the submucosa has led to the mistaken diagnosis of adenocarcinoma of the rectum and unnecessarily radical operative procedures. Attention to the completely normal cellular architecture provides the key to the correct diagnosis. Local excision is curative, and there is no propensity to develop malignancy in these patients. Experience with one case is reported, and the medical literature on the subject is reviewed.

Adenocarcinoma↗

Mistaken diagnosis of eosinophilic colitis.

A 69-year-old male chronic alcohol abuser suffering from diarrhoea and with a number of discrete pruriginous and erythematous lesions of the trunk was referred to our Unit with a diagnosis of idiopathic eosinophilic colitis in order that we might determine corticosteroid treatment. Diagnosis was based on the presence of marked peripheral eosinophilia and massive eosinophilic infiltration at colonic biopsy, and the exclusion of parasitic infection by means of two different microscopic stool examinations of five samples. However, repeated stool examinations of ten samples collected on separate days and evidence of impaired cell-mediated immunity allowed a definite diagnosis of Strongyloides stercoralis autoinfection or hyperinfection. Due to the poor sensitivity of stool examination in the diagnosis of Strongyloides stercoralis infection, a careful search for this parasite should be made in all patients with comparable clinical findings before formulating a diagnosis of idiopathic eosinophilic colitis, because consequent steroid treatment may have a fatal outcome by inducing widespread dissemination of the parasite.

Aged↗

Prolonged ileus as a sole manifestation of pseudomembranous enterocolitis.

BACKGROUND: Pseudomembranous colitis usually manifests as fever and diarrhea in hospitalized patients treated with systemic antibiotics. We present a case that represents a unique variant. CASE PRESENTATION: The 44-year-old man suffered of several weeks of abdominal pain, low-grade fever, nausea, vomiting, and lack of bowel movements. Upper gastrointestinal barium swallow and passage series revealed evidence of severe intestinal hypomotility. A thorough evaluation for the cause of the patient's ileus and abdominal pain was unrevealing, and symptomatic treatment was ineffective. Following the administration of opiates and dietary fiber supplementation the patient's abdominal pain and distention rapidly worsened, requiring an urgent subtotal colectomy. The macroscopic and microscopic appearance of the excised colon as well as results of the colonic cytotoxin essay and fecal enzyme-linked immunosorbent assay essay confirmed the diagnosis of severe Clostridium difficile induced pseudomembranous colitis as the cause of the patient's illness. CONCLUSION: To our knowledge, this is the first reported case of Clostridium-difficile induced disease consisting of prolonged ileus in the absence of diarrhea in a patient not previously taking antibiotics.

Adult↗

The dietary combination of germinated barley foodstuff plus Clostridium butyricum suppresses the dextran sulfate sodium-induced experimental colitis in rats.

BACKGROUND: Recent studies have suggested that dietary fiber exerts a therapeutic effect on IBD patients. The aim of this study was to evaluate the effects of a dietary combination of germinated barley foodstuff (GBF), derived from the aleurone and scutellum fraction of germinated barley, plus Clostridium butyricum against dextran sulfate sodium (DSS)-induced experimental colitis in rats. METHODS: Sprague-Dawley rats were fed a 3% DSS diet containing GBF only, GBF plus C. butyricum, cellulose only (control) or cellulose plus C. butyricum for 8 days. The mucosal damage (macroscopic and microscopic inflammation) and fecal short-chain fatty acid (SCFA) levels were then determined. RESULTS: The combination of GBF plus C. butyricum most effectively prevented bloody diarrhea and mucosal damage. The GBF-only diet also showed some preventive effects. With respect to fecal SCFAs, the combination of GBF plus C. butyricum most effectively increased the fecal SCFA level. CONCLUSION: The dietary combination of GBF plus C. butyricum most effectively suppressed DSS-induced experimental colitis in rats. These effects may be closely associated with its high activity to increase SCFA levels in the gut lumen. The potential clinical efficacy of GBF in IBD patients is also discussed.

Animals↗

Colonic perforation in unsuspected amebic colitis.

Unsuspected amebic colitis presenting as inflammatory bowel disease, as in our patient, has been previously reported (4, 7, 8). Misdiagnosis, delay in antibiotic treatment, and institution of immunosuppression were the result of failure to identify the parasite in stool specimens and have resulted in suffering, morbidity, mortality, and surgery. In all previously reported cases, routine stool studies failed to identify E. histolytica (4, 7, 8). The correct diagnosis was only established after reviewing the surgical specimen or biopsies obtained endoscopically. Because the erroneous diagnosis of inflammatory bowel disease can lead to disastrous complications, it is imperative to exclude amebic colitis prior to undertaking steroid therapy, especially in patients with a prior history of travel to or residence in areas with endemic E. histolytica (17). We recommend obtaining at least three stool specimens for microscopic examination, as well as testing for serum amebic antibody. Patients should submit fresh stool specimens directly to the laboratory to allow for prompt diagnostic evaluation. Such an approach might lead to the improved diagnosis of amebiasis.

Acute Disease↗