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• Oxylipin profile/pathways are disturbed in inflammatory bowel diseases (IBD). • IBD are associated with increased pro-inflammatory and pro-resolving oxylipins. • Targeting oxylipin pathways could be an adjuvant or alternative therapy in IBD. We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 ​​and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases. [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: The role of hyperhomocysteinemia (HHC) and its determinants in Crohn''s disease (CD) remain uncertain. This study was aimed to determine the prevalence of HHC and its main risk factors in Tunisian patients with CD. Methods: This study included 89 patients with CD and 103 age- and sex-matched healthy subjects. Fasting venous blood was collected in all subjects allowing the assessment of homocysteine, folate, vitamin B12, C-reactive protein and creatinine levels. Logistic regression models were applied to identify factors associated with HHC in CD patients. Results: Plasma homocysteine was higher (13.69±4.84μmol/l vs. 10.77±2.80μmol/l; p <0.01) and HHC was more frequent (31.5% vs. 7.8%; p <0.001) in patients compared with controls. The association between HHC and CD persisted after adjustment for smoking, body mass index and serum folate, vitamin B12, creatinine and C-reactive protein. In patients with CD, multivariate analysis showed that HHC was positively associated with age [multi-adjusted odds-ratio (95% confidence interval): 1.14 (1.06–1.24); p <0.001], active disease [7.54 (1.15–49.3); p =0.03], disease duration >2years [8.69 (1.53–49.3); p =0.02] and inversely related to plasma folate [0.64 (0.48–0.84); p =0.002] and vitamin B12 (0.993 (0.987–0.999); p =0.02]. Conclusion: HHC is common in Tunisian patients with CD and is related to B vitamins deficit, as well as disease activity and duration. Further studies should test the effect of correction of HHC by vitamin B supplementation on progression and complications of CD. [Copyright &y& Elsevier]

Abstract: Background: Evaluation of activity of Crohn''s disease is based on CDAI. Several other tools have been studied to assess disease activity with more accuracy. Aims: To assess the correlation between Doppler parameters of superior mesenteric artery and disease activity and to assess the accuracy of these parameters in discriminating between active and quiescent Crohn''s disease. Material and methods: We perform a prospective study including non-operated and non-complicated Crohn''s disease patients involving terminal ileum and/or right colon and sex and age-matched controls. Doppler sonography of superior mesenteric artery was performed in all subjects. Results: We studied 41 patients and 15 controls. There was no statistical difference between patients and controls according to the studied US parameters. The difference in resistance index between the three groups using analysis of variance is not significant (p =0.064). Resistance index was significantly lower in patients with active disease compared to inactive disease patients (0.82+/−0.04 vs 0.85+/−0.03; p =0.01). Pulsatility index was also lower in patients with active disease compared to inactive disease patients (1.37+/−0.21 vs 1.53+/−0.15; p =0.01). A value of resistance index less than 0.79 predicted active disease with a sensitivity of 35.3% and specificity of 95.7%. A value of pulsatility index less than 1.56 predicted active disease with a sensitivity of 94.1% and specificity of 43.5%. In case of resistance index less than 0.79 and pulsatility index less than 1.56 in the same patient, the probability of active disease was 86%. However, in case of resistance index over than 0.79 and pulsatility index over than 1.56, this probability was only 9%. In Crohn''s disease patients, correlation study showed that resistance index value was significantly correlated with CDAI (r =−0.46; p =0.003). Pulsatility index value was also correlated with CDAI (r =−0.39; p =0.01). Conclusion: Doppler sonographic parameters of superior mesenteric artery are significantly correlated with disease activity in non-operated and non-complicated Crohn''s disease. [Copyright &y& Elsevier]

Selected mucosal and plasma polyunsaturated fatty acids (PUFAs) and related oxylipins and endocannabinoids were determined in 28 Crohn's disease (CD) patients and 39 controls. Fasting blood and colonic biopsies were collected in all participants, during a disease flare for the patients. Thirty-two lipid mediators including PUFAs, oxylipins, and endocannabinoids were assessed by LC-MS/MS. The pattern of lipid mediators in CD patients is characterized by an increase in arachidonic acid-derived oxylipins and endocannabinoids and a decrease in n-3 PUFAs and related endocannabinoids. A model combining increased 6-epi-lipoxin A4 and 2-arachidonyl glycerol with decreased docoasapentaenoic acid in plasma fairly discriminates patients from controls and may represent a lipidomic signature for CD flare. The study findings suggest that lipid mediators are involved in CD pathophysiology and may serve as biomarkers for disease flare. Further research is required to confirm the role of these bioactive lipids and test their therapeutic potential in CD. • Crohn's disease is associated with high n-6 OxLs and eCBs, but low n-3 PUFAs and endocannabinoids eCBS. • High 6-epi-LA4 and 2-AG and low DPA represent useful lipidomic signatures for Crohn's disease. • PUFAs, OxLs and eCBs are likely involved in Crohn's disease and may serve as biomarkers and therapeutic targets for it. [ABSTRACT FROM AUTHOR]