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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothesis that a significant reduction in colonic mucosal perfusion, and hence ischemic injury, precedes the development of mucosal ulceration and inflammation is tested in this report. The microcirculatory changes in the rat colonic mucosa within 1 hr of topical exposure to 10% acetic acid were assessed. Colonic mucosal blood flow signals measured by laser Doppler flowmetry were significantly reduced to 61 +/- 8, 52 +/- 10, and 37 +/- 13% (mean +/- SEM) of baseline values at 1 min, 4 min, and 10 min after the colonic mucosa was exposed to 10% acetic acid, respectively, but not in controls exposed to saline. After the start of application of 10% acetic acid (for 4 min), in vivo microscopy studies demonstrated that colonic mucosal ischemia (stasis of the red blood cells in the mucosal capillaries) occurred at 9 +/- 5 min (mean +/- SEM). Evidence of endothelial cell death (failure to exclude a fluorescent dye, propidium iodide, by endothelial cells) developed at 25 +/- 10 min (mean +/- SEM). These findings indicate that within minutes after contact of the colonic mucosa with 10% acetic acid, colonic mucosal ischemia develops, followed shortly by death of endothelial cells. The data do not establish a cause-and-effect relationship between the reductions in mucosal blood flow and loss of endothelial cell viability in response to acetic acid. Nevertheless, because these events occur at such an early time point, they may play a pathogenetic role in the development of the subsequent inflammatory and ulcerative changes in this animal model of colitis. Further studies to define the potential causal relationships between these parameters are warranted.
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PMID:Mucosal vascular stasis precedes loss of viability of endothelial cells in rat acetic acid colitis. 203 12

Reactive oxygen metabolites are potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. To evaluate their role in inflammatory bowel disease, we investigated the effects of lowering the activities of reactive oxygen metabolites in experimental colitis induced by intracolonic administration of acetic acid in rats. Intracolonic administration of 5% acetic acid caused severe inflammation (mean (SEM) inflammatory score was 24.3 (0.7) of a maximum score of 32). Acetic acid at 2.5% produced moderate inflammation (score = 17 (1.4) v 4.0 (0.5) in control rats). This lower dose was used for subsequent experiments. Specific superoxide anion scavenger methoxypolyethylene glycol:superoxide dismutase, and reactive oxygen metabolites scavenger, sulfasalazine, significantly decreased the severity of inflammation (scores: 8 (4.4) and 9.8 (2.2) respectively). The xanthine oxidase inhibitors, tungsten and pterin aldehyde, failed to improve inflammation but another xanthine oxidase inhibitor, allopurinol, a compound with known superoxide anion scavenging effect, did limit the inflammation (10(2)). Inhibition of hydroxyl radical production by deferoxamine or lowering hydroxyl radical values by a scavenger, dimethyl sulfoxide, did not affect the severity of inflammation. These data suggest: (1) that reactive oxygen metabolites play an important role in experimental colitis, (2) that the xanthine oxidase pathway is not a major source of reactive oxygen metabolites in colitis, and (3) that tissue injury in experimental colitis is not caused by generation of hydroxyl radicals.
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PMID:Role of reactive oxygen metabolites in experimental colitis. 186 49

Cell proliferation kinetics of 30 patients affected by extensive ulcerative colitis in remission have been studied with autoradiography of rectal biopsies incubated with tritiated thymidine. The results have been compared with those of 20 control subjects without evidence of colonic diseases, and of 16 patients with multiple nonfamilial colonic adenomas. The labeling index was similar in the three groups (P = NS). On the contrary, the labeling frequency (SEM) in the upper 40% of the crypt (phi h value) was 0.04 +/- 0.01 in controls, 0.16 +/- 0.02 in ulcerative colitis, and 0.10 +/- 0.01 in adenoma patients (P less than 0.001 ulcerative colitis versus controls, P less than 0.01 adenomas versus controls, P = NS ulcerative colitis versus adenomas). The distribution of phi h values in ulcerative colitis showed a bimodal trend with 22 patients having mean phi h values similar to adenoma patients (0.10 +/- 0.01) and 8 with higher values (0.30 +/- 0.02). No relationship was found between phi h values and duration of colitis, age of patients, or age at onset of symptoms. These data show that cell kinetics studies can detect patients at particularly high risk of colon cancer, and that additional factors should determine colon cancer risk level in ulcerative colitis.
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PMID:Rectal cell proliferation and colon cancer risk in ulcerative colitis. 229 64

The pathogenesis of enteric changes was studied in gnotobiotic piglets which, after hysterectomy had been infected orally with Campylobacter jejuni on the first day of their life. The involvement of the entire large intestine became clinically manifest by scouring on days post infection (DPI) 4 to DPI 5, and pathomorphologically, by simultaneous inflammation and severe edema of the intestinal wall. Histology and SEM revealed inflammatory edema with abundant neutrophils, microulcerations, focal propagation and activation of goblet cells, and a presence of mucin-positive material within the intestinal lumen. TEM examination revealed disconnected interdigitating folds and wide dilated intercellular spaces between enterocytes. The endothelial cells of small blood vessels in the lamina propria showed hypertrophy with increase in the thickness of their basal lamina. Ultrastructural lesions of the large intestinal microcirculation also support the hypothesis that disturbances in the vascular system are responsible for edema in the cecum and colon. Gnotobiotic piglets may be used as a suitable animal model to study colitis induced by C. jejuni.
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PMID:The gnotobiotic piglet as a model for the pathogenesis of Campylobacter jejuni infection. 276 93

Lymphocytes, isolated by the enzymatic technique, from colonic mucosal specimens obtained from eight patients with ulcerative colitis (UC), two with ischemic colitis, two with antibiotic-associated colitis, and 15 controls by colonoscopic biopsy were used to examine T and B cells. In control biopsy specimens, the mononuclear cell yield averaged 3.6 +/- 0.3 (SEM) X 10(6)/g with a viability of 93 +/- 1%, while T and B cells expressed as a percentage of total lymphocyte counts were 65 +/- 1% and 15 +/- 1%, respectively. T and B cells in the ascending, transverse, and sigmoid colon and rectum did not present any differences. In involved tissue at the active stage of UC, the mononuclear cell yield averaged 11.4 +/- 2.1 X 10(6)/g, and T and B cells constituted 49 +/- 3% and 43 +/- 4%, respectively. After treatment for two months with salazosulfapyridine, mononuclear cell yields in five cases of UC were significantly reduced to an average of 3.9 +/- 0.8 X 10(6)/g as compared to the pretreatment level (P less than 0.01). The percentage of T cells was significantly increased from 48 +/- 2% to 62 +/- 2% (P less than 0.01), and that of B cells was significantly reduced from 39 +/- 2% to 27 +/- 3% (P less than 0.01). These results revealed a significant difference in the subpopulations of mucosal lymphocytes in the involved sites in the active stage of UC as compared to normal controls, suggesting that immunological abnormalities may be implicated in the etiology of this disease and that disease remission on salazosulfapyridine treatment is associated with a correction of the colonic lymphocyte abnormalities.
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PMID:Studies on lymphocyte subpopulations in human colonic biopsy specimens by colonoscopy. 285 19

Enhanced production of arachidonic acid metabolites by colonic mucosa has been reported in ulcerative colitis as well as in experimental models of colitis. However, production of these compounds by colonic smooth muscle from colitis subjects has not been described. To evaluate arachidonic acid metabolism in colonic tissue, we studied the production of prostaglandin E2 (PGE2) by mucosa and muscularis propria in two experimental models of acute colitis in which inflammation was virtually confined to the mucosa. Colitis was induced in New Zealand white rabbits by either of two methods, dinitrochlorobenzene (DNCB) sensitization or formalin followed by intravenous soluble immune complexes (F-IC). Arachidonic acid metabolites were identified from in vitro incubations of tissue with [14C] arachidonic acid by thin layer chromatography followed by autoradiography. The major eicosanoid metabolites of colitis mucosa and muscularis were 14C-labeled prostaglandin E2, prostaglandin F2a and 6-keto prostaglandin F1 alpha. PGE2 was quantitated from incubations without labeled arachidonic acid by radio-immunoassay. PGE2, expressed as picograms per milligram protein per 20 min (mean +/- SEM), was increased in F-IC mucosa (1093 +/- 141 vs 645 +/- 189, P less than 0.05) and DNCB mucosa (1354 +/- 487 vs 527 +/- 222, P less than 0.05) compared to normals. PGE2 production by uninflamed colitis muscularis propria was also increased five- to eightfold compared to normals for F-IC muscularis (1594 +/- 329 vs 189 +/- 35, P less than 0.005) and DNCB muscularis (1287 +/- 171 vs 225 +/- 72, P less than 0.005). Thus, the adjacent inflammation in colonic mucosa may induce increased eicosanoid production by the uninflamed smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Exaggerated prostaglandin production by colonic smooth muscle in rabbit colitis. 316 42

The association of hepatobiliary disorders with colonic inflammation is well recognized. Although the pathophysiology is obscure, increased permeation of toxic bacterial products across the inflamed gut to the portal circulation might be one mechanism. Potentially toxic metabolites include N-formylated chemotactic peptides that are produced by several species of intestinal bacteria and can be detected in colonic fluid in vivo. To investigate the metabolic fate of one of these low molecular weight proinflammatory peptides, N-formyl L-methionine L-leucine 125I-L-tyrosine was introduced into colon loops of healthy rats (n = 10) and rats with experimental colitis (n = 15) induced by rectal instillation of 15% (vol/vol) acetic acid. Gut, liver, and blood radioactivity were monitored by external gamma-counting and radioactivity in bile was measured by biliary catheter drainage into a well counter. Bile was processed by high-performance liquid chromatography to determine the amount of intact, bioactive peptide excreted over 3 h. After colonic instillation of 1 nmol of peptide, the mean (+/- SEM) biliary excretion of intact peptide was 6.4 +/- 2.0 pmol in normal rats and 49.0 +/- 20 pmol in rats with colitis (p less than 0.01). An enterohepatic circulation of synthetic N-formyl L-methionine L-leucine L-tyrosine has been demonstrated in the rat. Experimental colitis was associated with an eightfold increase in biliary excretion of this proinflammatory bacterial peptide. Proinflammatory bacterial peptides synthesized by colonic bacteria could be important in the pathophysiology of colon inflammation and its frequently associated hepatobiliary complications.
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PMID:Enterohepatic circulation of bacterial chemotactic peptide in rats with experimental colitis. 334 70

The impairment of bowel healing that is characteristic of inflammatory bowel disease (IBD) is poorly understood. Because bowel healing is related to the adequacy of perfusion in other circumstances, we studied bowel surface oxygen tension (PSO2), which is related to bowel perfusion, in rabbits with IBD. Both cell-mediated (n = 17) and immune complex-mediated (n = 10) colitis caused marked attenuation of colon PSO2. Control (n = 13) left colon PSO2 was 36 +/- 5 (SEM) torr. In mild colitis, left colon PSO2 fell to 11 +/- 5 torr, and in severe colitis it fell to 4 +/- 1 torr (p less than 0.01 for each compared with control). These changes occurred irrespective of the mechanism of induction of colitis. Gastric and small intestinal PSO2 were unaffected. Hepatic and renal PSO2 were decreased in severe colitis only. The presence of decreased PSO2 was a better marker for the presence of IBD than was histologic evaluation. It is suggested that attenuation of PSO2 may be a marker for the physiologic activity of IBD. If this is so, PSO2 may prove a useful adjunct in the operative management of IBD.
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PMID:Visceral surface oxygen tension in experimental colitis in the rabbit. 339 58

Whole colon perfusion studies and measurements of luminal prostaglandin E2 were carried out in a 41-year-old female with collagenous colitis to investigate pathophysiological mechanisms for the diarrhea. Biopsies of the colorectal mucosa had revealed a continuous 25- to 60-micron subepithelial collagenous layer, but normal junctional complexes and capillaries. When the patient fasted, the diarrhea persisted and fecal electrolytes, as estimated from the concentration of sodium, potassium, and their anions, accounted for all the osmolality (284 mosm/kg) of stool water, the pH of which was above 8.0. The lumen-negative electrical potential difference in the rectum was -64 mV vs -45 +/- 2 mV (mean +/- SEM) in healthy controls. Profuse secretion of fluid and electrolytes occurred during colonic perfusion with saline. Transport of sodium appeared to be passive with flux ratios equal to those predicted for passive sodium movements, while chloride transport against a steep electrical gradient indicated active secretion. Perfusion with an "ileal output"-like solution decreased fluid and electrolyte secretion, suggesting that bicarbonate, in addition to chloride, may be a major determinant of secretion rates. Since immunoreactive prostaglandin E2 levels following in vivo equilibrium dialysis of feces ranged from 555 to 650 pg/ml vs 55 to 235 pg/ml (99% confidence limits) in healthy controls, it is speculated that prostaglandins synthesized locally in response to mucosal hypoxia might be the mediators of anion secretion.
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PMID:Colonic transport of water and electrolytes in a patient with secretory diarrhea due to collagenous colitis. 658 Oct 38

Patients with Crohn's disease seen in the Gastro-intestinal Clinic of Groote Schuur Hospital between 1975 and 1980 were studied to establish the incidence and clinical features of this disease. There were 117 patients and the mean (+/- SEM) follow-up was 6,1 +/- 0,5 years. Of these patients 72% were White, 37% Coloured and 1% Black. The incidence for the Coloured and White population groups was calculated to be 0,4 and 0,9/100 000 per year during 1970-1974 and 1,3 and 1,2/100 000 per year during 1975-1980 respectively. In Jews the rates were 5,0 and 7,2/100 000 per year for the two periods. Insufficient data are available to calculate an incidence for the Black population. The disease involved the ileum in 39%, the colon in 17% and both areas in 44% of patients. At presentation 18% of patients had mild, 37% moderate, and 45% severe disease. The severity of symptoms was not related to the extent of the disease. A peri-anal fistula was present in 24% of patients. There was no difference in clinical features between the different population groups. Surgical resection had been performed in 50% of patients and 29% of these had had two or more resections. The surgical rate in the ileitis group was 63%, in the ileocolitis group 49% and in those with colitis 20%.
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PMID:Inflammatory bowel disease in Cape Town, 1975-1980. Part II. Crohn's disease. 682 38


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