Transcript levels of Toll-Like receptors 5, 8 and 9 correlate with inflammatory activity in Ulcerative Colitis

<p>Abstract</p> <p>Background</p> <p>Dysregulation of innate immune response by Toll-Like Receptors (TLRs) is a key feature in Ulcerative Colitis (UC). Most studies have focused on <it>TLR2, TLR3</it>, and <it>TLR4 </it>participation in UC. However, few studies have explored other TLRs. Therefore, the aim of this study was to evaluate the mRNA profiles of <it>TLR1 to 9 </it>in colonic mucosa of UC patients, according to disease activity.</p> <p>Methods</p> <p>Colonic biopsies were taken from colon during colonoscopy in 51 patients with Ulcerative Colitis and 36 healthy controls. mRNA levels of <it>TLR1 to 9, Tollip</it>, inflammatory cytokines <it>IL6 </it>and <it>TNF </it>were assessed by RT-qPCR with hydrolysis probes. Characterization of <it>TLR9 </it>protein expression was performed by Immunohistochemistry.</p> <p>Results</p> <p>Toll-like receptors <it>TLR8, TLR9</it>, and <it>IL6 </it>mRNA levels were significantly higher in the colonic mucosa from UC patients (both quiescent and active) as compared to healthy individuals (p < 0.04). In the UC patients group the <it>TLR2, TLR4, TLR8 </it>and <it>TLR9 </it>mRNA levels were found to be significantly lower in patients with quiescent disease, as compared to those with active disease (p < 0.05), whereas <it>TLR5 </it>showed a trend (p = 0.06). <it>IL6 </it>and <it>TNF </it>mRNA levels were significantly higher in the presence of active disease and help to discriminate between quiescent and active disease (p < 0.05). Also, <it>IL6 </it>and <it>TNF </it>mRNA positively correlate with TLRs mRNA with the exception for <it>TLR3</it>, with stronger correlations for <it>TLR5, TLR8</it>, and <it>TLR9 </it>(p < 0.0001). <it>TLR9 </it>protein expression was mainly in the lamina propria infiltrate.</p> <p>Conclusions</p> <p>This study demonstrates that <it>TLR2, TLR4, TLR8</it>, and <it>TLR9 </it>expression increases in active UC patients, and that the mRNA levels positively correlate with the severity of intestinal inflammation as well as with inflammatory cytokines.</p

Update of complications and functional outcome of the ileo-pouch anal anastomosis: overview of evidence and meta-analysis of 96 observational studies

Item does not contain fulltextOBJECTIVE: The objective of this study is to provide a comprehensive update of the outcome of the ileo-pouch anal anastomosis (IPAA). DATA SOURCES: An extensive search in PubMed, EMBASE, and The Cochrane Library was conducted. STUDY SELECTION AND DATA EXTRACTION: All studies published after 2000 reporting on complications or functional outcome after a primary open IPAA procedure for UC or FAP were selected. Study characteristics, functional outcome, and complications were extracted. DATA SYNTHESIS: A review with similar methodology conducted 10 years earlier was used to evaluate developments in outcome over time. Pooled estimates were compared using a random-effects logistic meta-analyzing technique. Analyses focusing on the effect of time of study conductance, centralization, and variation in surgical techniques were performed. RESULTS: Fifty-three studies including 14,966 patients were included. Pooled rates of pouch failure and pelvic sepsis were 4.3% (95% CI, 3.5-6.3) and 7.5% (95% CI 6.1-9.1), respectively. Compared to studies published before 2000, a reduction of 2.5% was observed in the pouch failure rate (p = 0.0038). Analysis on the effect of the time of study conductance confirmed a decline in pouch failure. Functional outcome remained stable over time, with a 24-h defecation frequency of 5.9 (95% CI, 5.0-6.9). Technical surgery aspects did not have an important effect on outcome. CONCLUSION: This review provides up to date outcome estimates of the IPAA procedure that can be useful as reference values for practice and research. It is also shows a reduction in pouch failure over time.1 juli 201

Expression of clusterin in Crohn's disease of the terminal ileum

Crohn's disease (CD) is a chronic inflammatory intestinal disorder with disturbance and injury of the intestinal mucosal barrier, in which various proinflammatory molecules as well as molecules with antiinflammatory activity and cytoprotective function are found to be expressed. We investigated whether clusterin, a multifunctional cytoprotective protein, is upregulated in Crohn's disease, because augmented expression of clusterin is seen in many organs following various forms of tissue injury. Human actively and inactively inflamed ileal tissues from CD patients as well as normal intestinal specimens from control patients (normal ileum) were investigated by Western blot analysis, immunohistochemisty and in situ hybridization. As compared with controls, a strongly enhanced expression of clusterin was found in CD tissues, correlating with disease activity. Immunohistochemistry and in situ hybridization analysis revealed foci of crypts almost completely lined by clusterin expressing enterocytes in CD, a feature that was never seen in controls. Such crypts appeared especially within the morphologically intact mucosa apart from erosive or ulcerative lesions. Besides epithelia, clusterin was also expressed by inflammatory mononuclear cells. Enhanced expression of clusterin by crypt epithelia might reflect a cytoprotective function of the protein in order to prevent further injury of the intestinal mucosal barrier in CD

Expression of clusterin in Crohn's disease of the terminal ileum

Crohn's disease (CD) is a chronic inflammatory intestinal disorder with disturbance and injury of the intestinal mucosal barrier, in which various proinflammatory molecules as well as molecules with antiinflammatory activity and cytoprotective function are found to be expressed. We investigated whether clusterin, a multifunctional cytoprotective protein, is upregulated in Crohn's disease, because augmented expression of clusterin is seen in many organs following various forms of tissue injury. Human actively and inactively inflamed ileal tissues from CD patients as well as normal intestinal specimens from control patients (normal ileum) were investigated by Western blot analysis, immunohistochemisty and in situ hybridization. As compared with controls, a strongly enhanced expression of clusterin was found in CD tissues, correlating with disease activity. Immunohistochemistry and in situ hybridization analysis revealed foci of crypts almost completely lined by clusterin expressing enterocytes in CD, a feature that was never seen in controls. Such crypts appeared especially within the morphologically intact mucosa apart from erosive or ulcerative lesions. Besides epithelia, clusterin was also expressed by inflammatory mononuclear cells. Enhanced expression of clusterin by crypt epithelia might reflect a cytoprotective function of the protein in order to prevent further injury of the intestinal mucosal barrier in CD

Suicidal ideation in remitted major depressive disorder predicts recurrence

Introduction: Each year almost 800.000 people die from suicide, of which up to 87% are affected by major depressive disorder (MDD). Despite the strong association between suicidality and MDD, it remains unknown if suicidal symptoms during remission put remitted recurrent MDD patients (rrMDD) at risk for recurrence. Methods: At baseline we compared sociodemographic characteristics and suicidal symptoms in un-medicated rrMDD participants to matched never-depressed controls. We used the HDRS17 and IDS-SR30 to assess suicidal symptoms and depressive symptomatology. Next, we studied the longitudinal association between baseline suicidal symptoms and time to recurrence(s) in rrMDD during a 2.5-year follow-up period using cox regression analyses. Further, we studied with longitudinal data whether suicidal symptoms and depressive symptomatology were cross-sectionally associated using mixed model analysis. Results: At baseline, rrMDD participants (N = 73) had higher self-reported suicidal symptoms than matched never-depressed controls (N = 45) (χ2 = 12.09 p <.002). Self-reported suicidal symptoms were almost four times higher (27.9% versus 6.9%) compared to clinician-rated suicidal symptoms in rrMDD at baseline. Self-reported baseline suicidal symptoms, but not clinician-rated symptoms, predicted earlier MDD-recurrence during follow-up, independent of other residual depressive symptoms (χ2 = 7.26, p <.026). Higher suicidal symptoms were longitudinally related to higher depressive symptoms (HDRS17; F = 49.87, p <.001), IDS-SR30; (F = 22.36, p <.001). Conclusion: This study showed that self-reported – but not clinician-rated - suicidal symptoms persist during remission in rrMDD and predict recurrence, independent from residual symptoms. We recommend to monitor both suicidal and depressive symptomatology during remission in rrMDD, preferably also including self-reported questionnaires apart from clinician-rated. It would be beneficial for future research to assess suicidality using questionnaires primarily designed for measuring suicidal ideation