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Ischemic colitis associated with hypertension.

A 48-year-old man with accelerated hypertension developed right-sided ischemic colitis. There was no evidence of another cause of vascular inadequacy. Microscopically, the bowel showed ischemic alterations of different stages. The arterial alterations of different stages. The arterial vessels showed minimal changes. In older lesions, fibrosis was prominent and the mucosa was atrophic. In more recent lesions, some vessels of the submucosa were plugged with fibrin and the overlying mucosa was infiltrated by nonorganized hemorrhage and cellular elements.

Arteries↗

Collagenous colitis: report of nine cases and review of the literature.

Collagenous colitis is characterized clinically by chronic watery diarrhea and pathologically by a distinctive band of collagen deposited below the colonic epithelium and an inflammatory cell infiltrate of the lamina propria. Since 1976, more than 100 cases have been described. We report an additional nine cases occurring in five women and four men ranging in age from 18 to 80 years. Diarrhea was present before diagnosis for 2 to 4 months in four cases and for 1 to 25 years in another four cases. One patient did not have diarrhea. Results of radiologic and stool studies were normal in all cases. All patients had flexible sigmoidoscopy or colonoscopy. Microscopic examination of biopsy material was interpreted as characteristic of collagenous colitis. Two cases resolved with psyllium mucilloid therapy alone. Of the five patients treated with azulfidine, three had marked improvement, one had partial response, and one had no change.

Adolescent↗

Epithelial dysfunction associated with the development of colitis in conventionally housed mdr1a-/- mice.

P-glycoprotein, the product of the multidrug resistance protein 1 (MDR1) gene, is a xenobiotic transporter that may contribute to the physiology of the intestinal barrier. Twenty-five percent of mdr1a-deficient (mdr1a(-/-)) mice spontaneously develop colitis at variable ages when maintained under specific pathogen-free conditions. We hypothesized that this disease would result from epithelial dysfunction and that conventional housing would increase incidence and severity of the colitis phenotype. Wild-type congenic FVB (+/+) mice were maintained under the same conditions as controls. Knockout and wild-type mice were matched for age and gender and observed for signs of colitis. Colonic tissues from both groups of mice were examined for macroscopic and microscopic injury and for basal ion transport and transepithelial resistance (TER). Translocation of bacteria across the intestine was assessed by culturing the spleen and mesenteric lymph nodes. Protein analysis was performed by Western blot analysis. All mdr1a(-/-) mice developed weight loss and signs of colitis, whereas wild-type mice never showed such signs. Within the mdr1a(-/-) group, males consistently developed severe colitis earlier than females. Knockout mice showed increased basal colonic ion transport (females, 162.7 +/- 4.6 vs. 49.7 +/- 3.8 muA/cm(2); males, 172.6 +/- 5.6 vs. 54.2 +/- 3.1 muA/cm(2); P < 0.01) and decreased TER (females, 25.4 +/- 0.3 vs. 36.4 +/- 0.8 Omega.cm(2); males, 23.1 +/- 1.0 vs. 38.3 +/- 0.2 Omega.cm(2); P < 0.01) compared with wild-type mice. Barrier dysfunction was accompanied by decreased phosphorylation of tight junction proteins. Expression of cyclooxygenase-2 and inducible nitric oxide synthase in intestinal tissues was increased in the mdr1a(-/-) group (P < 0.01) and correlated with disease severity. Bacterial translocation was greater both in incidence (P < 0.01) and severity (P < 0.001) for the knockout group. With respect to all indexes studied, mdr1a(-/-) males performed worse than females. Our data support the hypothesis that alterations in the intestinal barrier alone, in the absence of immune dysfunction, may rapidly lead to colitis in the setting of a normal colonic flora.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Multiple microcarcinoids arising in chronic ulcerative colitis.

A 50-year-old man who had chronic ulcerative colitis with dysplasia and two synchronous carcinomas had a total colectomy. Microscopic examination of the resected specimen revealed multiple microcarcinoids that were all smaller than 2 mm in diameter and not visible with gross examination. Histologic examination revealed that they were similar to microcarcinoids of the stomach encountered in patients with pernicious anemia. In this patient, however, there was no associated endocrine cell hyperplasia in the overlying mucosa, and the carcinoids may have arisen from dysplastic stem cells in the colonic crypts.

Adenocarcinoma↗

Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking IkappaB kinase and ameliorates acute murine colitis.

BACKGROUND/AIMS: The plant sterol guggulsterone has been shown to have anti-inflammatory properties. It remains unknown, however, whether guggulsterone is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of guggulsterone on intestinal epithelial cells (IEC) and on experimental murine colitis models and elucidated its molecular mechanisms. METHODS: Human Caco-2 cells and rat non-transformed IEC-18 cells were stimulated with interleukin (IL)-1beta or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-kappaB signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-kappaB transcriptional activity assay, Western blotting for IkappaB phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro IkappaB kinase (IKK) assay. For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with or without guggulsterone. Colitis was quantified by disease activity index and evaluation of macroscopic and microscopic findings. Phosphorylation of IkappaB and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry. RESULTS: Guggulsterone significantly inhibited LPS- or IL-1beta-induced ICAM-1 gene expression, NF-kappaB transcriptional activity, IkappaB phosphorylation/degradation, and NF-kappaB DNA binding activity in IEC. Moreover, guggulsterone strongly blocked IKK activity. Administration of guggulsterone significantly reduced the severity of DSS-induced murine colitis as assessed by clinical disease activity score, colon length, and histology. Furthermore, tissue upregulation of IkappaB and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice. CONCLUSION: Guggulsterone blocks NF-kappaB signaling pathway by targeting IKK complex in IEC and attenuates DSS-induced acute murine colitis, which suggests that guggulsterone could be an attractive therapeutic option in the treatment of IBD.

Animals↗

Development of dextran sulfate sodium-induced colitis is aggravated in mice genetically deficient for complement C5.

The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement system in inflammatory bowel disease (IBD), we evaluated the development of dextran sulfate sodium (DSS)-induced colitis in genetically complement C5-deficient mice. We used DBA2/J mice, which are genetically deficient in complement C5. DBA1/J mice have a normal complement system, and were used as controls. Experimental colitis was induced by the oral administration of 3.5% (w/v) DSS in their drinking water for 10 days. On day 10, all mice were sacrificed and their colons were collected. The development of colitis was assessed by the histological score, disease activity index, myeloperoxidase (MPO) activity, and macroscopic changes of the colon. Body weight loss was more apparent in the DBA2/J mice than in control DBA1/J mice. The colon length was shorter in the DBA2/J mice than in DBA1/J mice. The disease activity index, histological colitis score, and MPO activity were all significantly higher in the DBA2/J mice than in DBA1/J mice. Microscopically, mucosal edema, cellular infiltration and disruption of the epithelium were much more severe in the DBA2/J mice than in DBA1/J mice. The development of DSS colitis was aggravated in genetically C5-deficient DBA2/J mice. These findings suggest that the complement system might play a protective role in the development of DSS-induced experimental colitis.

Animals↗

Hemangioendothelioma with intravascular coagulation and ischemic colitis.

An infant who presented with a thigh mass and coagulopathy was found to have a hemangioendothelioma. The tumor rapidly enlarged despite accepted therapeutic modalities, and the child died after a sudden cardiac arrest. Postmortem examination revealed a highly invasive tumor mass that had infiltrated the bowel and involved the inferior mesenteric artery, resulting in ischemic colitis of the left colon. A discussion regarding the pathophysiology with respect to endothelial cell properties and other microscopic features of the tumor is presented.

Abdomen↗

Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice.

BACKGROUND & AIMS: Effective therapeutics for treating acute colitis, caused by disruption of the intestinal epithelial barrier, are scarce. Trefoil factors (TFF) are cytoprotective and promote epithelial wound healing and reconstitution of the gastrointestinal tract, which makes them good candidate therapeutics for acute colitis. However, orally administered TFF stick to the mucus of the small intestine and are absorbed at the cecum. METHODS: We have engineered the food-grade bacterium Lactococcus lactis to secrete bioactive murine TFF. The protective and therapeutic potentials of these TFF-secreting L. lactis were evaluated in parallel with purified TFF in the dextran sodium sulfate (DSS)-induced murine model for acute colitis and in established chronic colitis in interleukin (IL)-10(-/-) mice. Disease was evaluated by blinded macroscopic and microscopic inflammatory scores and by myeloperoxidase activity. RESULTS: Intragastric administration of TFF-secreting L. lactis led to active delivery of TFF at the mucosa of the colon and, in contrast to administration of purified TFF, proved to be very effective in prevention and healing of acute DSS-induced colitis. The in situ secreted murine TFF significantly decreased morbidity and mortality and stimulated prostaglandin-endoperoxide synthase 2 expression, which represents a major therapeutic pathway. In addition, this approach was successful in improving established chronic colitis in IL-10(-/-) mice. CONCLUSIONS: We have positively evaluated a new therapeutic approach for acute and chronic colitis that involves in situ secretion of murine TFF by orally administered L. lactis. This novel approach may lead to effective management of acute and chronic colitis and epithelial damage in humans.

Acute Disease↗

The effect of recombinant human growth hormone (rhGH) on trinitrobenzene sulfonic acid-induced colitis in rats: an experimental study.

The limited efficacy of standard medical therapies for inflammatory bowel diseases has resulted in a continuing search for alternative treatments. Growth hormone (GH) has shown to have mutagenic and proliferative effects on intestinal cells. This study was designed to identify the effect of growth hormone on trinitrobenzene slfonic acid-induced colitis (TNBSIC) in rats. This study was carried out on 30 rats, divided in 3 groups: group 1: TNBSIC+ GH, group 2: TNBSIC, group 3: saline enema. Colitis was induced in male Sprague-Dawley rats (200 g-250 g) by intracolonic installation of 2, 4, 6-trinitrobenzene sulphonic acid in 50% ethanol. GH treatment has been started and continued throughout the study after inducing colitis. All rats were killed after 5 weeks and colonic segments were examined histopathologically. Microscopic and macroscopic damage scores were caulculated. Intestinal damage scores were found higher in Goups II when compared with treatment group (P < 0.05). There was no damage in group 3 as expected. Both macroscopic and microscopic scores were highest in group 2 (P < 0.05). The myloperoxidase activity was found lower comparing to group 2 (P < 0.05). In conclusion, growth hormone replacement had protective effects against colonic inflammation while reducing intestinal damage on TNB-induced colitis.

Analysis of Variance↗

Effects of statins on experimental colitis in normocholesterolemic rats.

OBJECTIVE: The results of previous studies suggest that statins have a direct anti-inflammatory effect that is not directly related to their cholesterol-lowering activity. The aim of this study was to investigate the effect of simvastatin (SIM) and fluvastatin (FLU) on trinitrobenzene sulfonic acid (TNBS)-induced colonic inflammation in rats. MATERIAL AND METHODS: The drugs were given for 3 days (0.1 and 1 mg/kg day-1; intraperitoneally) after induction of colitis. The lesions in the distal colon were scored at the macroscopic and microscopic level. Tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content were assessed and formation of reactive oxygen species and peroxynitrite was monitored by chemiluminescence (CL) assay. Trunk blood was collected for the measurement of serum tumor necrosis factor (TNF)-alpha level. RESULTS: Treatment with SIM reduced the lesion score of the colitis group at macroscopic level (p<0.05), but there was no effect of treatment with FLU. The increase in colonic MDA level of the colitis group was reduced by both drugs at all doses (p<0.05-0.001). The decrease in GSH and the an increase in MPO activity in the colitis group were reversed by SIM at all doses (p<0.01), but FLU had no effect. An increase in colonic lucigenin CL value in the colitis group was reduced by SIM and FLU at all doses (p<0.001) and an increase in peroxynitrite ratio in the colitis group showed a significant reduction in SIM-treated groups; FLU reduced this effect at a dose of 1 mg/kg (p<0.01). An increase in tissue collagen content and serum TNF-alpha level in the colitis group was reversed by both drugs at all doses (p<0.001). CONCLUSIONS: SIM and FLU seemed to be beneficial in a TNBS-induced rat colitis model through the prevention of lipid peroxidation, superoxide generation, cytokine production and neutrophil accumulation.

Animals↗

[Parallel morphological, enzyme and immunological research on the jejunal mucosa in patients with gluten enteropathy, chronic nonspecific enteritis and ulcerative colitis].

The results are reported from the study on 120 patients, 30 of them with gluten enteropathy, 50--with chronic unspecified enteritis and 40--with chronic ulcerous colitis. Small intestinal aspiration biopsy was performed to all patients with histomorphological, electron microscopic, enzymatic and immune-fluorescent study. The secretory immunoglobulins in the jejunal juice were studied in 40 patients. Morphological changes, various degrees, were established, that correlate with the increased number of IgG and IgM secretory cells. The exclusion of gluten from the diet in case of gluten enteropathy was followed by normalization of the number and percentage ratio of IgSC and of secretory immunoglobulins. The enzymatic and immune disorders, in chronic unspecific enteritis correlate with the electron microscopic and precede the histologic ones. The role of immune system of small intestine in the etiology and pathogenesis of the various intestinal diseases is discussed.

Adult↗

The costs of colonoscopy in patients with ulcerative pan-colitis in Sweden.

The costs of colonoscopy examinations at a hospital in Sweden were calculated in ten consecutive patients with ulcerative pan-colitis. Since colonoscopy in such patients is incomplete if not followed by microscopic study of the state of the colon mucosa, the costs of both the endoscopic and histological examinations were calculated together. The costs of the material used (disposable items, recycled items and durable items) and the wages for personnel involved (endoscopists, pathologists, nurses, laboratory technicians, secretaries and clerks) were calculated for each colonoscopic and histological examination. The mean cost per complete examination was US$223, which is moderate despite the high personnel costs in Sweden. Since the biopsy material obtained in an endoscopic examination is of value not only for conventional histological study but also for DNA analysis, periodic colonoscopy is still to be recommended in patients with long-standing ulcerative pan-colitis until new methods of cancer detection and prevention become available.

Adult↗

[Un- classifiable types of ulcerative colitis].

10-15% of cases of non-specific inflammatory bowel disease cannot be classified. In a retrospective study of 35 colectomy specimens during a ten-year period, we observed 5 such cases. These cases of so-called "unclassified colitis" or "indeterminate colitis" nearly always follow, a fulminating course and require urgent surgery. On macroscopic examination there is marked dilatation of the colon with perforations. The colon is continuously involved, the right colon sometimes more so. Microscopically there is transmural inflammation with acute fissuring and extensive ulcerations. No specific criteria of ulcerative colitis or Crohn's disease are present. "Unclassified colitis" is not a definitive diagnosis. Followup studies sometimes serve for final classification of a case.

Adult↗

Obstructing carcinomas of the colon and rectum: clinicopathologic analysis of 40 cases.

A review of 40 cases of obstructing colorectal carcinoma selected from 1,786 cases of surgically resected colorectal carcinomas was undertaken. The average age of the patients was 63 years, and there were 22 women and 18 men. Twenty-three lesions (58%) arose in the sigmoid colon and nine (23%) in the transverse colon, and obstructing rectal carcinomas were significantly rare. All of the obstructing tumors displayed a circumferential growth, 32 being examples of the annular constricting type. Obstructive colitis was caused by a combined lesion in only three cases. Microscopic characteristics of the obstructing carcinomas were as follows: 1) invasion of the whole thickness of the colorectal wall by the malignant tissue, 2) complete discontinuance of the muscularis propria in the affected area, 3) striking fibrous stromal reaction in the tumor, 4) upward rising, not descending, of both stumps of the discontinuous muscularis propria, 5) infiltrative growth of the tumor into the subserosa with scar-like fibrosis. It is indicated from the present study that obstructing carcinomas have features promising construction of the bowel lumen, but patients with such a tumor are not appreciably different in prognostic, histologic nor immunohistochemical aspects from those with a non-obstructing carcinoma.

Adenocarcinoma↗

Collagenous colitis: an unrecognised entity.

A patient is reported with chronic abdominal pain, diarrhoea, and associated radiological and endoscopic abnormalities of the sigmoid colon. Light and electron microscopic study of colorectal mucosa showed abnormal collagenous thickening of the subepithelial basement membrane. The authors felt that the clinical and morphological features justified a diagnosis of collagenous colitis. Review of the literature suggested that collagenous colitis was still an unrecognised entity.

Colitis↗

Mycobacteria as a possible cause of inflammatory bowel disease.

Mesenteric lymph-nodes from 27 patients with Crohn's disease, 13 with ulcerative colitis, and 11 without inflammatory bowel disease were cultured for mycobacteria. A node from a patient with Crohn's disease yielded a strain of Mycobacterium kansasii. Cultures from 22 other patients with Crohn's disease, 7 with ulcerative colitis, and 1 control subject yielded pleomorphic organisms with the electron-microscopic appearances of cell-wall-deficient organisms. Further culture and characterisation of these organisms has so far proved unsuccesful. Skin tests with tuberculin were positive in a smaller proportion of patients with Crohn's disease than in healthy control subjects. Conversely, the patients gave a higher proportion of positive reactions to a reagent prepared from the strain of M. kansasii isolated. No differences in the proportion of positive test were found between patients and controls with reagents prepared from 16 other mycobacteria. Cell-wall-deficient mycobacteria are a possible causative agent of inflammatory bowel disease.

Adolescent↗

[Colitis in the non-functioning rectosigmoid after establishment of an end-sigmoid colostomy].

In 11 patients with a sigmoid end colostomy (and one additional patient with an end ileostomy), we examined the endoscopic and microscopic aspects of both the dysfunctioned bowel and the colon proximal to the colostomy. The latter showed in none of the cases signs of inflammation, while in 7 patients a remarkable or even severe colitis (mimicking ulcerative colitis) could be demonstrated endoscopically and/or histologically - irrespective to the duration of the dysfunction (one month up til 11 years). In the four patients with restoration of the intestinal continuity, macroscopic and microscopic findings of the rectal mucosa became normal as soon as two weeks after reoperation. We conclude, that the "dysfunctioned bowel-colitis" is somehow related to the mucosa's contact to the fecal stream.

Aged↗

Protective effect of epidermal growth factor in an experimental model of colitis in rats.

BACKGROUND/AIMS: The role of epidermal growth factor (EGF) in the maintenance of mucosal integrity in the lower gastrointestinal tract is unknown. The aim of this study was to determine the effect of EGF in experimental colitis. METHODS: Colitis was induced with 2,4,6-trinitrobenzenesulfonic acid/ethanol enemas. Rats were pretreated with intraperitoneal administration of recombinant human EGF (600 micrograms/kg) or vehicle 1 hour before induction of colitis and daily thereafter until killed at 8 hours, 48 hours, and 1 week. A separate group received an identical dosage and administration of EGF or vehicle for 1 week with treatment initiated 24 hours after the induction of colitis. Colonic tissue was evaluated macroscopically, histologically, and for myeloperoxidase activity. RESULTS: Pretreatment with EGF reduced microscopic erosions at 8 and 48 hours by 74% and 54%, respectively (P < 0.05). At 1 week, microscopic ulcerations and myeloperoxidase activity were reduced by 65% in the EGF-pretreated group (P < 0.05). No significant difference in macroscopic injury, histological damage, or myeloperoxidase activity was noted when EGF treatment was initiated after the induction of colitis. CONCLUSIONS: Systemic EGF administration reduces mucosal damage and inflammation in a trinitrobenzenesulfonic acid/ethanol model of colitis in rats through a mechanism involving mucosal protection.

Animals↗