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PubMed2002

Interleukin-2-Deficient mice: effect on cytokines and inflammatory cells in chronic colonic disease.

Mice deficient in interleukin-2 (IL-2-/-) develop inflammatory bowel disease resembling human ulcerative colitis. After death, macroscopic and microscopic scores were used to determine colonic inflammation. Both scores were significantly increased in the colon of IL-2-/- mice as compared to wild types mice. The level of IL-1beta 24-week-old was increased in IL-2-/- mice produced by the colon as compared with IL-2+/+ controls. However, the concentrations of IL-6 and IL-10 were not changed. The spleen weight of IL-2-/- mice was significantly increased compared with IL-2+/+ controls. We used immunochemical techniques in low-temperature paraffin-embedded spleen of IL-2-/- mice to examine pathological changes of CD4+ T cells, CD8' T cells, and CD11b+ cells. The tissue was successfully stained and was well preserved. The percentage CD4+ T cells was not significantly changed, while the percentage CD8+ T cells was significantly decreased in IL-2-/- mice compared with IL-2+/+ controls. On the other hand, the percentage CD11b+ cells was significantly increased in the spleen of IL-2-/- mice compared with IL-2+/- controls. As well as the marked difference in CD8+ and CD11b+ cells in the spleen, the increased level of IL-1beta in colonic tissue might indicate that cytotoxic T cells as well as macrophages are involved in the development and/or perpetuation of the inflammatory reactions in IL-2-/- mice.

Animals↗
PubMed2002

In vivo detection of morphological and microvascular changes of the colon in association with colitis using fiberoptic confocal imaging (FOCI).

Using a well-established rodent model of inflammatory bowel disease (IBD), the present study examined changes in the microvasculature of the colonic mucosa in association with ulcerative colitis (UC). The results were compared to microscopic alterations in tissue morphology to establish a temporal relationship between microcirculatory dysfunction and IBD pathology. Mild colitis was induced in rats by the oral consumption of 5% dextran sulfate sodium (DSS) in drinking water. Control animals were provided with water ad libitum. After 3, 5, and 7 days of oral ingestion of DSS, anesthetized rats were laparotomized. The mucosal surface of the distal colon was then examined using fiber optic confocal imaging (FOCI; excitation 488 nm argon ion laser, detection above 515 nm). Changes in the mucosal architecture were examined following the topical application of the fluorescent dye, tetracycline hydrochloride. Tetracycline hydrochloride, an antibiotic used widely in clinical medicine, enabled imaging of the crypts at the surface of the mucosa. Spatial changes in the microvascular structure were assessed following the intravenous administration of fluorescein isothiocyanate dextran (FITC-dextran). Confocal images were correlated with clinical parameters, including weight loss, occult blood, and stool consistency. Attenuation of the colonic epithelium was detected on day 3 colitis. Morphological changes including crypt loss, crypt distortion, and inflammatory cell infiltrate were detected on day 5 and day 7 colitis. Dual channel imaging showed the mucosal capillary network outlining the stromal confines of the mucus-secreting glands in control tissue. Experimental colitis resulted in diffuse hypervascularity and tortuosity of the capillary vessels. Evidence of increased vessel leakiness (leakage of FITC-dextran from the lumen) was first detected on day 5 colitis. Complete disruption of the normal honeycomb pattern of the vessels and capillary dilation was evident after 7 days of DSS ingestion. These findings suggest that the pathogenesis of ulcerative colitis is associated with changes in the vascular architecture as demonstrated in vivo using confocal microscopy.

Animals↗
PubMed1994

Atypical forms of inflammatory bowel disease.

Atypical forms of IBD include the microscopic colitides, collagenous and lymphocytic colitis, and two macroscopic colitides, SRUS and diversion colitis. Clinical presentations include chronic, watery diarrhea and intermittant rectal bleeding. Constitutional symptoms are typically absent; laboratory data are often nonspecific. Colonoscopic evaluation and mucosal biopsy are essential in establishing these diagnoses and excluding more classic forms of IBD (i.e., Crohn's disease or idiopathic ulcerative colitis). Prognosis and response to treatment are variable; potential therapeutic options include dietary manipulations, topical or systemic anti-inflammatory agents, and, in refractory cases, surgical intervention.

Colitis↗
PubMed2005

[Utility and limitations of laboratory diagnosis of amebiasis].

Entamoeba histolytica is an invasive and pathogenic protozoan parasite that causes amebiasis. It must be distinguished from Entamoeba dispar, a nonpathogenic commensal parasite of the human gut lumen that is morphologically identical to Entamoeba histolytica. Diagnosis of amoebic colitis currently requires combination of microscopic examination of stool specimens with another technique allowing positive identification of the two species. Stool culture followed by zymodem analysis is considered as gold standard but is not applicable in routine practice. Detection of specific Entamoeba histolytica antigens in stools is a fast, sensitive technique that should be considered as the method of choice. Stool PCR is a highly sensitive and specific technique but high cost make it unsuitable for use in endemic areas where economic conditions are difficult. The utility of serologic tests in distinguishing Entamoeba dispar from Entamoeba histolytica is controversial. However serology is still considered as the method of choice for diagnosis of extraintestinal amebiasis. Circulating Gal/GalNac lectin antigens can be detected in the serum of 96% of patients with untreated amoebic liver abscess. In the future this method should allow early diagnosis and treatment of extraintestinal amoebiasis in patients who have not yet developed detectable serum antibodies.

Amebiasis↗
PubMed2005

[Study the effect and mechanism of thalidomide in model of inflammatory bowed disease].

OBJECTIVE: To assess the effect of thalidomide on Trinitrobenzensulphonic acid (TNBS)-induced or oxazolone-induced colitis and discuss the possible mechanism of its action. METHODS: Transmural colitis was induced by TNBS in three groups of rats (n=6 each), and distal colitis was induced by oxazolone in three groups of rats (n=6 each). Then the rats of the groups were treated with thalidomide [200 mg/(kg x d)], prednisone [5 mg/(kg x d)] or vehicle (olive oil) respectively by oral gavage. The colitis was allowed to run its course for 7 d after gavage and at that time the following endpoints were assessed. Colitis was evaluated by macroscopic and microscopic score; the expression of NF-kappaB P65 was examined by immunohistchemical (IHC); the expression of TNF-alpha mRNA was assayed by hybridization in situ (ISH); the cytokine TNF-alpha, IL-4, IFN-gamma were estimated by enzyme-linked immunoadsordent assay (ELISA). RESULTS: With respect to TNBS model, in the control, prednisone-treatment and thalidomide-treatment groups, the macroscopic and microscopic scores were 6.33 +/- 1.03, 1.67 +/- 0.82, 2.00 +/- 0.89 and 7.33 +/- 1.03, 2.67s +/- 0.82, 3.17 +/- 0.75 respectively; the expression levels of NF-kappaB P65 and TNF-alpha mRNA in the three groups were 62.45 +/- 12.38, 23.62 +/- 8.54, 34.18 +/- 9.65 and 12.42 +/- 4.63, 9.86 +/- 3.29, 4.35 +/- 1.74 respectively; the levels of TNF-alpha, IL-4, IFN-gamma were 540.32 +/- 80.76, 94.58 +/- 14.45, 486.18 +/- 68.47; 396.53 +/- 92.42, 78.45 +/- 12.69, 347.56 +/- 82.94; and 385.68 +/- 88.57, 123.68 +/- 38.15, 378.27 +/- 90.65 respectively. The results indicated that thalidomide treatment significantly reduced colonic inflammation, suppressed NF-kappaB activation,enhanced TNF-alpha mRNA degradation, inhibited the synthesis of the TNF-alpha, IEN-gamma and increased the production of IL-4. However, with respect to oxazolone model, the macroscopic score and microscopic score were 2.00 +/- 0.89, 0.33 +/- 0.52, 1.83 +/- 0.75 and 7.83 +/- 1.47, 3.33 +/- 0.82, 6.50 +/- 1.22 respectively. Thalidomide appeared not to be effective in reducing the oxazolone-induced chronic colitis. CONCLUSION: Thalidomide may be proposed as a useful drug for Crohn's disease, but further work is needed to clarify whether it is an efficacious agent for ulcerative colitis.

Animals↗
PubMed2004

The comparative effects of calcium channel blockers in an experimental colitis model in rats.

BACKGROUND/AIMS: In this study two calcium channel blockers (CCB), diltiazem and verapamil, which demonstrate their effects on two different receptor blockage mechanisms, were assessed comparatively in an experimental colitis model regarding the local and systemic effect spectrum. METHODS: Eighty male Swiss albino rats were divided into eight groups (n:10 each): Group I) colitis was induced with 1 ml 4% acetic acid without any medication. Group II) Sham group. Group III) Intra-muscular (IM) diltiazem was administered daily for five days before inducing colitis. Group IV) IM verapamil was administered daily for five days before inducing colitis. Group V) Transrectal (TR) diltiazem was administered with enema daily for two days before inducing colitis. Group VI) TR saline was administered four hours before inducing colitis. Group VII) TR diltiazem was administered with enema four hours before inducing colitis. Group VIII) TR verapamil was administered with enema four hours before inducing colitis. All subjects were sacrificed 48 hours after the colitis induction. The distal colon segment was assessed macroscopically and microscopically for the grade of damage, and myeloperoxidase (MPO) activity was measured. RESULTS: All the data of the control colitis group (group I), including the microscopic, macroscopic and MPO activity measurements, were significantly higher than in the groups in which verapamil and diltiazem were administered over seven days (3.100+/-0.7379 to 1.300+/-0.9487 and 1.600+/-0.9661) (p<0.05). The data of the Sham group, group II, were less than the other groups in which colitis was induced (p<0.05). For the local effect spectrum, after the assessment of groups V-VIII, the control colitis group (group I) and group VI had significantly higher values than the others (3.300+/-0.4830 to 1.800+/-0.6325 and 1.700+/-0.8233 (p<0.05). CONCLUSIONS: Calcium channel blockage has systemic and local effects on the colitis model.

Animals↗
PubMed1996

An orally active non-selective endothelin receptor antagonist, bosentan, markedly reduces injury in a rat model of colitis.

Activation of endothelial cells by vasoactive mediators, such as endothelins, may be an early, strategically important step in the initiation of inflammation in the intestine. In view of recent evidence that inflammatory bowel disease is associated with elevated intestinal concentrations of endothelins and upregulated expression of endothelin receptors on vascular endothelium in intestine, endothelins may become therapeutic targets in inflammatory bowel disease. The recent availability of an orally active, mixed endothelin receptor antagonist, bosentan, allowed us to examine the role of endothelins in a rat model of colitis. Colitis was induced by intra-rectal administration of trinitrobenzene sulphonic acid. In each treatment group, rats were treated with bosentan (10-60 mg/kg p.o.) 24 and 2 h prior to (pre-dose) or 1 h after the induction (post-induction) of colitis and all animals were treated every 24 h thereafter for 5 days. On day 6, stool consistency and the presence of adhesions in the peritoneal cavity were accessed. Colonic tissue samples were removed for determination of macroscopic and microscopic tissue injury, and myeloperoxidase activity. Colitis was typified by tissue ulceration in the distal colon and a corresponding 35-fold increase in myeloperoxidase activity compared to non-inflamed controls. Daily treatment with bosentan dose-dependently reduced colonic damage and myeloperoxidase activity when bosentan was given prior to induction of colitis. In the pre-dose group, the greatest beneficial effect of bosentan was observed at 60 mg/kg; colonic damage and granulocyte infiltration were attenuated by > 80%. A partial therapeutic effect of bosentan was also observed at 60 mg/kg when the pre-treatment regimen was excluded. These findings demonstrate that an orally active, mixed endothelin receptor antagonist has marked protective and therapeutic effects in an animal model of colitis.

Administration, Oral↗
PubMed1999

The effect of antioxidant therapy on colonic inflammation in the rat.

Under normal physiological conditions, chemical and antioxidant defenses protect tissues from the damaging effects of reactive oxygen metabolites (ROM). It has been proposed that ROMs are involved in the development of tissue injury in many inflammatory diseases and also in patients with colitis. In the present study we aimed to investigate the effects of antioxidant therapy on the extent of colonic inflammation and ROM levels in the injured tissues in a trinitrobenzene sulfonic acid-induced colitis model in the rat. Sprague-Dawley rats were pretreated with the antioxidants superoxide dismutase (30,000 U/kg s.c.) or catalase (400,000 U/kg s.c.) prior to induction of colitis and they were decapitated 24 h (acute group) or 6 days (chronic group) after the induction of colitis (each group consists of eight to ten rats). Pretreatment with the antioxidants reduced the macroscopic damage score significantly in both acute and chronic groups compared with untreated colitis groups, whereas they reduced the microscopic damage score and colonic wet weight only in the chronic group. The chemiluminescence assay - a technique to assess the presence of reactive oxygen species in the tissues - values of the groups pretreated with the antioxidants showed a tendency to decrease compared with the untreated colitis group, but they were not statistically significant. Based on these findings, pretreatment with the antioxidants superoxide dismutase or catalase has beneficial effects on the extent of colonic inflammation, particularly in the chronic period, and this may support the importance of antioxidant therapy to reduce the severity of inflammatory bowel disease in humans.

Animals↗
PubMed2003

Gastral antral biopsy in the differentiation of pediatric colitides.

OBJECTIVES: Differentiation of Crohn's disease (CD) from ulcerative colitis (UC) is problematic, primarily when inflammation is confined to the colon. In a historical cohort study, we evaluated the usefulness of baseline gastric antral biopsies in the differentiation of pediatric chronic colitides. METHODS: During initial investigation for suspected inflammatory bowel disease, 39 children and adolescents with colitis but normal small bowel radiography underwent pretreatment upper endoscopy concurrently with colonoscopy. Two reviewers assigned a colonoscopic diagnosis (colonic CD, UC, or indeterminate colitis) based on the macroscopic and microscopic appearances of the colonic mucosa. Antral histological findings were compared between groups using Fisher's exact test. RESULTS: Five (14%) of colonoscopic diagnoses (four indeterminate, one UC) were changed to CD by the finding of granulomatous inflammation in antral biopsies. Nonspecific antral gastritis was found in similar proportions of children and adolescents with Crohn's colitis and UC (92% vs 75%). Focal antral gastritis was more common in patients with Crohn's colitis than UC (52% vs 8%). CONCLUSIONS: Nonspecific antral gastritis is common in all forms of chronic colitis. Nevertheless, upper gastrointestinal endoscopy with biopsy is useful in the differentiation of inflammatory bowel disease confined to the colon, particularly when colonoscopic findings are indeterminate.

Adolescent↗
PubMed2004

Prophylactic administration of topical glutamine enhances the capability of the rat colon to resist inflammatory damage.

Glutamine is an important nutrient for the GI tract and has been shown to exert a protective effect on the bowel. Nonetheless, in the context of IBD, data demonstrating a therapeutic role for glutamine has been inconclusive. IBD is associated with oxidative stress caused by reactive oxygen species. We aimed to investigate the effect of topical glutamine administration in rats before or after induction of colitis by trinitrobenzenosulfonic acid. In study I glutamine enemas were given beginning 2 days before or on the same day of induction of colitis. Inflammation severity was assessed by macroscopic and microscopic score and tissue myeloperoxidase activity. In study II glutamine enemas were given for 3 days without induction of colitis: mitotic index and colonic crypt length were measured, as well as water-soluble low molecular weight antioxidants and energy-rich phosphate levels (by HPLC). Results showed that glutamine significantly decreased indexes of inflammation when administered before induction of colitis. Glutamine caused an increase in the mitotic index and the levels of water-soluble low molecular weight antioxidants and energy-rich phosphates. We conclude that glutamine exerts a beneficial effect only when administered before induction of colitis, by increasing the resistance of the colonic tissue to inflammatory injury. This effect is probably mediated by increasing the antioxidant capacity and energy level of the tissue.

Adenosine Triphosphate↗
PubMed1996

Eosinophilic colitis and hepatitis in a horse with colonic intramucosal ciliated protozoa.

Tissues from a 9-year-old American Standardbred gelding with a history of anorexia, mild colic, and unexpected death were submitted to the Laboratories of Veterinary Diagnostic Medicine at the University of Illinois for histopathologic examination. Microscopic diagnoses were severe subacute, diffuse eosinophilic colitis with intralesional protozoa and a subacute to chronic eosinophilic portal hepatitis with granuloma formation. Two tissue-invading, ciliated protozoa were identified in large numbers within the colonic mucosa. The ciliates were Polymorphella ampulla and Cycloposthium sp., Phylum:Ciliophora. The eosinophilic colitis and portal hepatitis in association with the overpopulation and invasion by the ciliated protozoa suggests a causal etiology.

Animals↗
PubMed1989

Criteria of case definition in Crohn's disease and ulcerative colitis.

The diagnosis of inflammatory bowel disease is usually made on a combination of clinical, radiologic, endoscopic, and histologic grounds. In the differential diagnosis, endoscopy and histologic evaluation of biopsy specimens can help to make a specific diagnosis. Site of disease is important in documentation and can determine drug choice and clinical course. Disease activity indices are important to assess a patient objectively, particularly in multicentre studies. There is poor correlation between disease activity indices and macroscopic and histologic findings. The Severity Activity Index for Crohn's disease has both clinical and laboratory variables and is a valuable tool for the definition of Crohn's disease. An ulcerative colitis activity index that correlates significantly with microscopic and macroscopic scores, using both clinical symptoms and laboratory findings, is proposed.

Colitis, Ulcerative↗
PubMed2000

[Chronic abdominal pain and eosinophilia in a young African patient].

A 20-year-old African female was hospitalized several times for diffuse chronic abdominal pain. The following exclusions were made: Acute adnexitis (by laparoscopy), acute appendicitis (by appendectomy), gastric ulcerations (by esophagogastroduodenoscopy) as well as Crohn's disease and ulcerative colitis. However, once taking a closer microscopical look at the mucosa, that otherwise appeared colonoscopically to be normal, multiple eggs of schistosomiasis mansoni (S. mansoni) were found in the colon as well as the rectum. Thus, the diagnosis of an intestinal bilharziosis was finely established. In retrospect even the sample taken for the appendix could have indicated this diagnosis already earlier on. Both the antibodies (ELISA/IFAT) and the specific immunoglobulins (IgE) for S. mansoni proved significantly positive. Therapy of choice was a single oral dosage of praziquantel. Migration and tourism have considerably increased the range of tropical and infectious diseases that need to be included into differential diagnosis. This case report focuses on intestinal bilharziosis as a potential underlying cause of chronic abdominal pain in immigrants of endemically affected areas. Direct diagnosis is the most important diagnostic method. The adult worms are usually inaccessible, so the method of choice to assess both diagnosis and the degree of activity of a chronic infection is evidence of living eggs in the stool. Alternatively, in case of lack of direct evidence diagnosis can be established by endoscopy and rectal biopsy.

Abdominal Pain↗
PubMed2003

The colon single-stripe sign and its relationship to ischemic colitis.

OBJECTIVES: Endoscopic findings may assist in the clinical diagnosis of ischemic colitis but have not been systematically characterized. We noted that a single linear colonic ulcer could on occasion be found endoscopically after hypotension and proceeded to investigate its relationship to ischemic colitis. METHODS: Twenty-six patients (19 female and seven male, mean age 71 yr) with endoscopic evidence of a single linear ulcer running along the longitudinal axis of the colon (colon single-stripe sign (CSSS) were retrospectively studied. Colitis etiologies were determined in the CSSS patients and in 58 consecutive patients without a stripe forming a colitis comparison group; clinical course and outcome in CSSS patients subsequently were compared with those in 22 patients with circumferentially involved ischemic colitis. RESULTS: The CSSS was >/=5 cm in length in all instances and isolated to a segment of the left colon in 89%. Evidence of a preceding ischemic event was noted significantly more often in the CSSS (62%) patients than in the colitis comparison group (7%) (p < 0.0001). On blinded histopathological examination, 75% of CSSS cases had microscopic evidence of ischemic injury compared with 13% in the colitis comparison group (p < 0.0001). None of the CSSS patients required surgical intervention, whereas six (27%) patients from the circumferential ischemic colitis group underwent exploration (p < 0.05). Nine patients (41%) in the circumferential ischemic colitis group died, whereas there was one death in the CSSS group (4%) (p < 0.05). CONCLUSIONS: Ischemia can manifest endoscopically as the CSSS. This sign seems to characterize milder disease in the clinical spectrum of ischemic colitis.

Aged↗
PubMed1993

Detection of Entamoeba histolytica antigens in stool in amebiasis.

BACKGROUND: Stool microscopy, the conventional method of diagnosing intestinal amebiasis, fails to detect Entamoeba histolytica in more than 30-40% of clinically suspected cases. Demonstration of parasite products in clinical specimens has been suggested as an alternative. However, the usefulness of demonstrating amebic antigen in the stools of clinical cases needs to be assessed. METHODS: A double-antibody sandwich enzyme linked immunosorbent assay (ELISA) using anti-trophozoite antibodies to capture E histolytica specific coproantigen(s) was carried out on stools obtained from 31 patients with microscopically confirmed non-dysenteric amebic colitis, 18 patients with intestinal parasites other than E histolytica and 41 apparently healthy subjects. RESULTS: The assay detected E histolytica specific coproantigen(s) in stools of 23 (74.2%) of 31 subjects with non-dysenteric amebic colitis, none of 18 with other parasitic infections and 1 (2.4%) of 41 apparently healthy subjects. CONCLUSION: Our results provide evidence for the presence of E histolytica specific coproantigen(s) in stool eluates from patients with amebic infection; this finding can be exploited for confirming ongoing amebic infection. However, the sensitivity of the assay needs to be improved by the use of relevant monospecific/monoclonal antibodies.

Animals↗
PubMed1985

Cocaine colitis. Is this a new syndrome?

An unusual case of colitis in a 37-year-old cocaine addict is described. The patient presented with right-sided abdominal pain and diarrhea exacerbated by his use of cocaine. Significant antibiotic ingestion was denied. At laparotomy, an edematous cecum and ascending colon were found, the cut surface of which revealed diffuse superficial ulcerations and yellowish fibrinous material. Microscopic examination demonstrated findings consistent with pseudomembranous colitis with an ischemic component. A mechanism involving catecholamine-induced mucosal ischemia is postulated to explain the findings seen in this patient.

Adult↗