dinoprost and Colitis--Ulcerative

Topics: Arachidonic Acids; Colitis, Ulcerative; Dinoprost; Dinoprostone; Eicosanoids; Gastrointestinal Motility; Humans; Leukotriene B4; Platelet Activating Factor

Intestinal microvessels of patients with inflammatory bowel disease (IBD) show microvascular endothelial dysfunction. It may contribute to reduced perfusion, poor ulcer healing, and sustained chronic inflammation. The aim of the study was to assess endothelial dysfunction and oxidative stress markers in patients with IBD.. Serum levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine, and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) were measured in 31 consecutive patients with ulcerative colitis (UC) and 32 with Crohn's disease (CD). Apparently healthy subjects served as age- and sex-matched controls. Associations between these markers and the disease activity and laboratory variables were evaluated.. ADMA, SDMA, and 8-iso-PGF2alpha levels were increased in the IBD group as compared to the control group and higher in patients with CD than UC (P < 0.05 for all comparisons). Arginine levels were similar in all the groups. In the CD and UC groups ADMA and SDMA showed positive correlation with 8-iso-PGF2alpha (r from 0.47-0.67; P < 0.01 for all comparisons). ADMA and SDMA correlated positively with the CD activity (r = 0.4, P = 0.025; r = 0.4, P = 0.024, respectively) and the 8-iso-PGF2alpha level correlated positively with the UC activity (r = 0.4, P = 0.026).. This is the first study to show that in patients with IBD there is enhanced ADMA generation that might be associated with oxidative stress, and these effects are more pronounced in the CD group.

Topics: Adolescent; Adult; Aged; Arginine; Biomarkers; Case-Control Studies; Colitis, Ulcerative; Crohn Disease; Dinoprost; Female; Humans; Male; Middle Aged; Oxidative Stress; Young Adult

To compare the local release of arachidonic acid metabolites in inflammatory diarrheal disease, in vivo equilibrium dialysis of the rectum was done in consecutive untreated patients with ulcerative colitis (n = 20), Crohn's colitis (n = 10), and Clostridium difficile colitis (n = 7). All patients had endoscopically proven rectal inflammation. Eicosanoid profiles were determined in rectal dialysates by radioimmunoassay after preliminary purification. Concentrations of prostaglandin E2, prostaglandin F2 alpha, and thromboxane B2, but not 6-keto-prostaglandin F1 alpha, were raised in all groups and compared with healthy controls. The highest levels within each group were obtained in patients with widespread epithelial damage, as judged by endoscopy. In patients with ulcerative colitis, an extreme rise in prostaglandin E2 and thromboxane B2 were observed. Similarly, concentrations of leukotriene B4 were substantially increased in ulcerative colitis, but in Crohn's colitis and Clostridium difficile colitis only those patients with rectal ulcerations showed elevations. These findings probably reflect more severe tissue damages in ulcerative colitis, but differences between disease groups in cell-to-cell interaction may also contribute. The data suggest, therefore, that therapeutic inhibition of lipoxygenase pathways may prove more effective in ulcerative colitis than in Crohn's disease.

Topics: Adolescent; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Colitis; Colitis, Ulcerative; Crohn Disease; Dialysis; Dinoprost; Dinoprostone; Eicosanoic Acids; Enterocolitis, Pseudomembranous; Female; Humans; Leukotriene B4; Male; Middle Aged; Prostaglandins E; Prostaglandins F; Rectum; Thromboxane B2

It has been proposed that anti-inflammatory actions of corticosteroids rely on promotion of a natural peptide phospholipase A2 inhibitor, lipocortin, but in vivo effects on arachidonic acid metabolism have not been shown. Equilibrium dialysis of the rectum in patients with ulcerative colitis was used to determine whether cyclooxygenase and lipoxygenase products released from the inflamed rectal mucosa could be differentially inhibited by systemic treatment with prednisolone and indomethacin, respectively. In 10 patients with severe disease luminal concentrations of prostaglandin E2, prostaglandin F2 alpha, and leucotriene B4 were markedly raised (p less than 0.05) on comparison with 10 healthy controls, and they decreased significantly (p less than 0.05) within 72 hours after administration of prednisolone 1.5 mg/kg/day orally. In contrast prostaglandin, but not leucotriene B4 concentrations decreased (p less than 0.05) within 72 hours after administration of indomethacin 150 mg/day in another 10 patients with distal disease. These prompt reductions in concentrations of arachidonic acid metabolites more likely are caused by direct drug actions, rather than being secondary to decreased tissue damage. The data accord with the theory explaining anti-inflammatory effects of corticosteroids through lipocortin activity and support the belief that leucotrienes are more important than prostaglandins as mediators of inflammation in ulcerative colitis.

Topics: Adult; Aged; Colitis, Ulcerative; Dinoprost; Dinoprostone; Female; Humans; Indomethacin; Intestinal Mucosa; Leukotriene B4; Male; Middle Aged; Prednisolone; Prostaglandins; Prostaglandins E; Prostaglandins F; Rectum