dinoprost and Crohn-Disease

In healthy gut enteric glial cells (EGC) are essential to intestinal epithelial barrier (IEB) functions. In Crohn's Disease (CD), both EGC phenotype and IEB functions are altered, but putative involvement of EGC in CD pathogenesis remains unknown and study of human EGC are lacking. EGC isolated from CD and control patients showed similar expression of glial markers and EGC-derived soluble factors (IL6, TGF-β, proEGF, GSH) but CD EGC failed to increase IEB resistance and healing. Lipid profiling showed that CD EGC produced decreased amounts of 15-HETE, 18-HEPE, 15dPGJ2 and 11βPGF2α as compared to healthy EGC. They also had reduced expression of the L-PGDS and AKR1C3 enzymes. Produced by healthy EGC, the 11βPGF2 activated PPARγ receptor of intestinal epithelial cells to induce cell spreading and IEB wound repair. In addition to this novel healing mechanism our data show that CD EGC presented impaired ability to promote IEB functions through defect in L-PGDS-AKR1C3-11βPGF2α dependent pathway.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aldo-Keto Reductase Family 1 Member C3; Caco-2 Cells; Cells, Cultured; Coculture Techniques; Crohn Disease; Dinoprost; Eicosapentaenoic Acid; Epithelial Cells; Female; Humans; Hydroxyeicosatetraenoic Acids; Intestinal Mucosa; Intestines; Male; Middle Aged; Prostaglandin D2; Wound Healing; Young Adult

Breath analysis and exhaled breath condensate (EBC) collection are simple and noninvasive processes whereby inflammatory mediators and other biomarkers can be assessed in diseases that affect the lung. It was hypothesised that markers of epithelial dysfunction and secretion, such as a low pH, 8-isoprostane, and release of epithelial factors such as trefoil factor 2 (TFF2) and mucin, would be elevated in the breath of those with inflammatory bowel disease (IBD). The aim was to compare the levels of these biomarkers in EBC and the fraction of expired nitric oxide (FENO) in children with Crohn disease (CD), in those with asthma, and in normal individuals in a pilot study.. EBC was collected from patients in the 3 groups mentioned above in a cross-sectional design. pH, 8-isoprostane, TFF2, and mucin levels were measured in the EBC. Spirometry was performed in asthmatic patients and patients with IBD, whereas FENO and skin prick tests were performed in patients with IBD.. Breath samples including EBC were collected from 80 patients (30 CD, 30 asthma, 20 controls). Compared with controls, EBC pH was lower in children with IBD (P < 0.0001) or asthma (P = 0.0041). 8-Isoprostane levels differed between the 3 groups (P < 0.05). EBC TFF2 was mainly less than the limit of detection, whereas mucin levels did not differ significantly between the 3 groups. FENO was measurable in children with IBD, but did not correlate with disease activity or serum markers of inflammation.. A lower EBC pH may reflect inflammatory events either in the lung or systemically. 8-Isoprostane, FENO, and mucin were detected for the first time in the EBC of children with IBD. Further studies are required to assess the value of these assessments.

Topics: Adolescent; Asthma; Biomarkers; Breath Tests; Child; Crohn Disease; Cross-Sectional Studies; Dinoprost; Exhalation; Female; Humans; Hydrogen-Ion Concentration; Inflammation; Inflammation Mediators; Isoprostanes; Lung; Male; Mucins; Nitric Oxide; Peptides; Pilot Projects; Reference Values; Trefoil Factor-2

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

In Crohn disease (CD), the increased production of reactive oxygen species from activated neutrophils may reduce plasma concentrations of antioxidant vitamins and result in increased oxidative stress.. We compared lipid peroxidation, a measure of reactive-oxygen-species production, and plasma antioxidant vitamin concentrations between CD patients and healthy control subjects.. Thirty-seven nonsmoking CD patients (22 women and 15 men) were compared with an equal number of healthy control subjects who were matched by age, sex, and body mass index. In patients the mean CD activity index (CDAI) was 141.2 +/- 18.7 (range: 9.0-514), and 11 of 37 patients (30%) had a CDAI > or =150. Seventy-eight percent of patients were taking > or = 1 medication. Medication use by subjects included the following: 5-aminosalicylic acid (40% of subjects), antibiotics (22%), oral corticosteroids (30%), and immunosuppressants (19%).. Lipid peroxidation as measured by breath pentane output (CD patients, 7.47 +/- 0.98 pmol x kg(-1) x min(-1); control subjects, 4.97 +/- 0.48 pmol x kg(-1) x min(-1); P < or = 0.025), breath ethane output (CD patients, 11.24 +/- 1.17 pmol x kg(-1) x min(-1); control subjects, 5.46 +/- 0.71 pmol x kg(-1) x min(-1); P < or = 0.0005) and F2-isoprostane (CD patients, 78.6 +/- 8.0 ng/L; control subjects, 60.6 +/- 3.7 ng/L; P < or = 0.047) were significantly higher in CD patients than in control subjects. Plasma antioxidant vitamins (ascorbic acid, alpha- and beta-carotene, lycopene, and beta-cryptoxanthin) were all significantly lower in CD patients than in control subjects. There were no significant differences in macro- and micronutrient intakes between groups.. Patients with CD are oxidatively stressed, which was observed even though 70% of patients had a CDAI < or =150 and 78% of them were taking medications to treat CD.

Topics: Adult; Alkenes; Antioxidants; Ascorbic Acid; beta Carotene; Breath Tests; Carotenoids; Case-Control Studies; Crohn Disease; Dinoprost; Ethane; F2-Isoprostanes; Female; Humans; Lipid Peroxidation; Lycopene; Male; Oxidative Stress; Reactive Oxygen Species

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