Clinical application of the multigene analysis test in discriminating between ulcerative colitis and Crohn's disease: a retrospective study.

METHODS: The newly described--multigene analysis test (DiBiCol) identifying 7 inflammatory bowel disease (IBD)-specific genes in colonic mucosal biopsy differentiating between ulcerative colitis (UC) and Crohn's disease (CD) with active inflammation--is a new addition to existing methods with a higher stated sensitivity and specificity. Method biopsy material from 78 patients with a complicated course diagnosed as most probably UC in 38, CD in 18 and inflammatory bowel disease unclassified (IBDU) in 22 were investigated by DiBiCol. RESULTS: DiBiCol showed a pattern consistent with CD in 13 patients with UC and led to change of diagnosis in 3 patients and a strong suggestion of CD in 8 patients. A total of 2 patients remained as UC. DiBiCol showed a pattern of UC in 4 patients of 18 with CD leading to a changing of diagnosis to UC in 3 patients, but the fourth remained as CD. In 22 patients with IBDU DiBiCol showed a pattern consistent with UC in 7 cases and with CD in 13 cases. A new evaluation 1 year after the DiBiCol allowed the assessment of clinical diagnosis in 10 patients confirmed in 9 of 10 patients by DiBiCol. In patients with acute flare of colitis the clinical diagnosis corresponded in 10 of 12 UC and in 5 of 6 CD cases. SUMMARY: Adopting the DiBiCol test led to a change of the primary diagnosis in a significant number of patients with the initial diagnosis of UC and CD and suggested a clinically probable diagnosis in most of the patients with IBDU and in those with an acute flare of colitis.

Endogenous prostaglandins are physiological regulators of endocrine cells in the gastroduodenal mucosa of the rat.

BACKGROUND/AIM: To investigate whether endogenous prostaglandins participate in the regulation of the gastrointestinal endocrine cell system. METHODS: Sprague-Dawley rats were treated with 1 mg/kg indomethacin subcutaneously or indomethacin subcutaneously and 500 microg/kg oral prostaglandin E2 or solvents for 2 months. Endocrine cells were visualized by using immunohistochemistry and by the Sevier-Munger silver stain on specimens from the gastroduodenal mucosa, and their total volume was estimated, using standard stereological methods. Plasma and gastrointestinal tissue concentrations of regulatory peptides were analyzed by radioimmunoassay. RESULTS: Fundic mucosa. The total volume of cells stained with the Sevier-Munger silver stain (enterochromaffin-like) was increased by indomethacin, but reduced by the administration of prostaglandin E2 (P < 0.05 vs. indomethacin). Indomethacin increased the total volume of somatostatin-immunoreactive. Similarly, rats given indomethacin and prostaglandin E2 had higher values than controls. Indomethacin increased the tissue concentration of somatostatin in the gastric fundus whereas prostaglandin E2 prevented such changes (P < 0.05 vs. indomethacin). Antral mucosa. The total volume of serotonin-immunoreactive cells was reduced by indomethacin, but increased by prostaglandin E2 (P < 0.05 vs. controls and indomethacin, respectively). Duodenal mucosa. The total volume of somatostatin-immunoreactive cells was reduced in the rats given indomethacin and prostaglandin E2 (P < 0.05 vs. controls and indomethacin). Indomethacin reduced and simultaneous administration of prostaglandin E2 increased the total volume of CCK-immunoreactive cells (P < 0.05 vs. controls and indomethacin). Indomethacin reduced the total volume of serotonin-immunoreactive cells whereas the simultaneous administration of PGE2 comparatively increased their total volumes (P < 0.05 vs. indomethacin), although they were still lower than the control values. The total volume of GIP-immunoreactive cells was slightly increased in the rats given both indomethacin and indomethacin + prostaglandin E2. The tissue concentration of somatostatin in the duodenum was reduced in rats given indometacin and prostaglandin E2 (P < 0.05 vs. controls and indomethacin). CONCLUSION: Endogenous prostaglandins, particularly prostaglandin E2, regulate CCK-, enterochromaffin-like-, somatostatin-, GIP- and enterochromaffin cells in the gastroduodenal mucosa of the rat.

Indomethacin influences regulatory peptides and increases DNA synthesis in the gastrointestinal tract of the rat.

OBJECTIVE: To examine the effect of long-term administration of indomethacin on regulatory peptides and DNA synthesis. DESIGN: Sprague-Dawley rats were treated with 1 mg/kg indomethacin subcutaneously or indomethacin and 500 micrograms/kg oral prostaglandin E2 or solvents for 2 months before labelling with methyl-3H-thymidine. METHODS: The labelling index, growth fraction and the number of epithelial cells were determined on autoradiographs of the stomach small intestine and colon. Plasma and gastrointestinal tissue concentrations of regulatory peptides were analysed by radioimmunoassay. RESULTS: Indomethacin increased the concentration of somatostatin in the gastric fundus and ileum and reduced it in the colon. Prostaglandin E2 reduced the somatostatin concentration in the duodenum and colon. Indomethacin increased the concentration of neurotensin neurokinin A and glucagon in the distal small intestine and reduced the glucagon level in the colon. Prostaglandin E2 prevented such changes. Indomethacin increased DNA synthesis in the small intestine and produced hypoplasia of the villi. These changes were prevented by prostaglandin E2, except for the villous hypoplasia observed in the distal small intestine. Prostaglandin E2 reduced the labelling index in the antrum and colon. CONCLUSION: Endogenous prostaglandins selectively modulate the synthesis and/or release of regulatory peptides and regulate the outflow of cells from the epithelial surface. Indomethacin induces hypoplasia, which triggers a secondary trophic reaction in the epithelium that may, at least partially, be mediated by regulatory peptides.

Prostaglandin E2 modulates serotonin- and gastrin/CCK-immunoreactive cells in the duodenal mucosa of the rat.

Groups of Sprague-Dawley rats were given placebo or prostaglandin E2 (PGE2) at 25 or 5,000 micrograms/kg or 15,R,15-methyl-PGE2 (MePGE2) at 5 or 50 micrograms/kg, twice daily, orally, for 1 month. Histological sections from the proximal duodenum were processed for immunohistochemistry and the volume density of immunoreactive endocrine cells was determined using point-counting grids. The surface density of the villous lining was estimated by using a cycloid test system. Thereafter, the total volumes of endocrine cells and the total surface area of the villous lining were calculated after estimating the mucosal volume. The volume density of serotonin-immunoreactive cells was increased in the duodenum of rats given 25 or 5,000 micrograms/kg PGE2 (p < 0.05). The total volume of these cells increased in the animals given 25 micrograms/kg PGE2 (p < 0.05). The total volume of gastrin/CCK-immunoreactive cells was higher in rats given 25 micrograms/kg PGE2 or 50 micrograms/kg MePGE2 than in controls (p < 0.05). The volume density of somatostatin-immunoreactive cells increased in rats given 5 micrograms/kg MePGE2, but the total volumes were not different between the groups. The area of somatostatin-immunoreactive cell profiles was enlarged in the animals given 5,000 micrograms/kg PGE2 (p < 0.05). The mucosal volume was enlarged by prostaglandins. The epithelial thickness increased in rats given the highest doses of PGE2 (p < 0.05). The concentration of motilin-like immunoreactivity increased in the duodenum of rats given 5 micrograms/kg MePGE2 (p < 0.05). We conclude that oral administration of PGE2 for 1 month increased the total volumes of serotonin- and gastrin-CCK-immunoreactive cells and the tissue concentration of motilin-like immunoreactivity, which indicates that prostaglandins modulate endocrine cells in a stable steady-state condition.

Indomethacin inhibits cell proliferation and increases cell losses in rat gastrointestinal epithelium.

Gastrointestinal cell proliferation was estimated in histological sections of rats treated with low and high doses of parenteral indomethacin for 3 to 60 days. Mitoses were arrested with vincristine and cells in S phase were labeled with tritiated thymidine. Short-term, low-dose treatments reduced the mitotic activity in the oxyntic and small intestinal epithelium, whereas moderate doses restored the mitotic index and high doses increased the proliferative activity and produced epithelial hyperplasia. Long-term, low-dose treatments increased cell proliferation in the small intestine and reduced the number of villous cells. Indomethacin did not affect the proliferative response elicited by refeeding in the oxyntic mucosa, but the simultaneous administration of prostaglandin E2 analog increased the number of arrested mitoses. The turnover of labeled cells was accelerated by indomethacin, particularly in the small intestine. These findings indicate that prostaglandins are regulators of the cell kinetics of the gastrointestinal epithelium but, at the same time, they disclose the presence of trophic mechanisms that are independent of the synthesis of endogenous prostaglandins.

Oral prostaglandin E2 influences the enterochromaffin-like and somatostatin cell populations in the oxyntic mucosa of the rat.

Our aim was to study the effects of long-term oral administration of different doses of prostaglandin E2 (PGE2) and of a synthetic analogue on the endocrine cells and on selected epithelial cells of the rat oxyntic mucosa. The endocrine cells were visualized by immunohistochemical staining and by the Sevier-Munger method. Quantification of the mucosal cells was performed at a light-microscopic level using stereological methods. The highest dose of 15-R-15-methylprostaglandin E2 (MePGE2) increased the total volume of enterochromaffin-like (ECL) cell profiles whereas no changes were observed after treatment with PGE2. On the other hand, the total mucosal volume of chromogranin A-immunoreactive cells was significantly reduced by both doses of natural PGE2. The highest dose of PGE2 increased the total volume of somatostatin-immunoreactive cells. The serotonin-immunoreactive cells were very few and unaffected by treatments. E2 prostaglandins induced hyperplasia and hypertrophy of epithelial cells. A selective trophic action on the mucous but not on the parietal cells was observed. The area of the parietal cells was increased in rats treated with the analogue. The gastric acid content was increased in rats treated with the highest doses of E2 prostaglandins. The plasma level of somatostatin was significantly increased in rats given MePGE2 and the highest dose of PGE2. The cell population of chromogranin A-immunoreactive cells did not reach the levels of the NECL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Trophic doses of E2 prostaglandins do not influence the exocrine and endocrine pancreas in the presence of high levels of plasma somatostatin.

The aim of the present investigation was to study the effect of a long-term and a short-term treatment regimen with 15-R-15-methyl prostaglandin E2 and natural prostaglandin E2 (PGE2) on the endocrine cell populations of the rat pancreas. Graded oral doses of the analogue (5 and 50 micrograms/kg) and PGE2 (5000 micrograms/kg) were given twice daily for 4 weeks. The pancreas was carefully excised and weighed. Sections from randomly taken pancreatic biopsy specimens were processed for immunohistochemistry or hematoxylin and eosin staining before quantitative estimations were made, using stereologic methods. The total pancreatic volumes of insulin-, glucagon-, polypeptide P-, somatostatin-, and chromogranin A-immunoreactive cells were not affected by E2 prostaglandins. Neither the total volume of the islets of Langerhans nor that of the pancreatic cell nuclei was affected. The size of pancreatic cell nuclei was the same in the groups. The plasma levels of the antitrophic peptide somatostatin were significantly increased in rats treated with doses of both the analogue and PGE2 (p less than 0.05). In an additional short-term study rats were given oral placebo or 5000 micrograms/kg PGE2 twice daily for 5 days. The total endocrine pancreatic volume was not affected by PGE2. As in the long-term study, natural PGE2 did not affect the total pancreas volume or the total volume of pancreatic cell nuclei. These findings indicate that E2 prostaglandins produce no changes in the exocrine or endocrine pancreas in a dose range known to induce hyperplasia in the gastrointestinal epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)