Colitis ulcerosa con afectación periapendicular. Estudio de casos y controles

La colitis ulcerosa (CU) es caracteritza per una afectació contínua de la mucosa rectal en sentit proximal cap a altres zones del còlon. Hi ha formes de CU amb afectació distal i periapendicular (CU-PA). Objectius: avaluar la prevalença de la CU-PA, i comparar les seves característiques clíniques, terapèutiques i evolutives. Mètodes: 14 pacients amb CU-PA van ser comparats en termes d'evolució clínica amb 25 pacients amb CU distal sense afectació periapendicular. Resultats: Es va trobar una major freqüència de CU-PA en homes (p = 0,047), sense diferències en la resta de les variables comparades entre els dos grups de pacients.La colitis ulcerosa (CU) se caracteriza por una afectación continua de la mucosa rectal en sentido proximal hacia otras zonas del colon. Existen formas de CU con afectación parcheada distal y periapendicular (CU-PA). Objetivos: evaluar la prevalencia de la CU-PA, y comparar sus características clínicas, terapéuticas y evolutivas. Métodos: 14 pacientes con CU-PA fueron comparados en términos de evolución clínica con 25 pacientes con CU distal sin afectación periapendicular. Resultados: Se halló una mayor frecuencia de CU-PA en hombres (p=0,047), sin diferencias en el resto de las variables comparadas en ambos grupos de pacientes

Evolució clínica després de la retirada d'infliximab en pacients amb MII en remissió clínica i endoscòpica sota tractament combinat amb tiopurines

Objectius: Avaluar la retirada d'infliximab en pacients amb MII, en remissió mantinguda i curació mucosa sota tractament combinat. Mètodes: Pacients amb MC luminal o CU sota tractament combinat (infliximab i azatioprina) durant mínim un any, als quals se'ls retira l'infliximab per remissió clínica, biològica i endoscòpica. Resultats: S'inclogueren 26 pacients. Un 73% es van mantenir en remissió. La recidiva no s'associà al fracàs previ d'immunomoduladors. A les recidives se'ls va reiniciar infliximab amb bona resposta. Cap factor va associar-se a la recidiva. Conclusions: La retirada de l'infliximab en aquests pacients, s'acompanya d'una baixa probabilitat de recidiva a mig termini

Plasma polyunsaturated fatty acid pattern in active inflammatory bowel disease

Plasma fatty acid patterns were assessed by gas liquid chromatography in 73 patients with active inflammatory bowel disease and 107 healthy controls. The influence of the disease activity on fatty acid profile was also investigated. Plasma fatty acid patterns in patients with ulcerative colitis and Crohn's disease were similar. Plasma C18:3n3 and C22:6n3 were significantly higher in active ulcerative colitis (p = 0.0143 and p < 0.00001 respectively) and in Crohn's disease (p < 0.00001 for both) than in controls, whereas C20:3n6 was significantly lower in patients than in controls, both in ulcerative colitis (p = 0.0001) and in Crohn's disease (p = 0.0041). In more severe disease, plasma polyunsaturated fatty acid concentrations fell with a significant stepwise decrease in the desaturation index (p = 0.0031 in ulcerative colitis and p = 0.0355 in Crohn's disease). Even in patients with severe disease, however, plasma n3 fatty acids (C18:3n3 and C22:6n3) never fell below those of healthy controls. These findings suggest that in active inflammatory bowel disease, an increased biosynthesis might coexist with an increased consumption of polyunsaturated fatty acids. These observations may be of relevance in the pathogenesis of the disease as polyunsaturated fatty acids are involved in tissue eicosanoid synthesis and cellular membrane function, including that of immunocompetent cells. These results also question the rationale of using n3 polyunsaturated fatty acids in the treatment of inflammatory bowel disease

Enteral nutrition as primary therapy in Crohn's disease

The developments in enteral feeding for Crohn's disease in the past decade are critically reviewed. The advent of amino acid based chemically defined elemental diets signalled the end of 'total bowel rest' in the management of these patients. Subsequently, controlled clinical trials showed that elemental diets were as effective as corticosteroids in inducing clinical remission in patients with acute exacerbations of Crohn's disease. The later use of peptide based elemental diets, in Crohn's disease produced somewhat conflicting results. The initial uncontrolled studies suggest that polymeric whole protein diets might also be effective in the management of acute exacerbations of the disease, casting in turn doubts concerning the role of dietary antigens in the pathogenesis of Crohn's disease. Results of controlled studies comparing the use of elemental and polymeric diets as primary therapy in Crohn's disease have, however, also produced conflicting results. The results of one recent controlled trial in whic

Effect of olive oil on early and late events of colon carcinogenesis in rats: modulation of arachidonic acid metabolism and local prostaglandin E2 synthesis.

BACKGROUND Animal model studies have shown that the colon tumour promoting effect of dietary fat depends not only on the amount but on its fatty acid composition. With respect to this, the effect of n9 fatty acids, present in olive oil, on colon carcinogenesis has been scarcely investigated. AIMS To assess the effect of an n9 fat diet on precancer events, carcinoma development, and changes in mucosal fatty acid composition and prostaglandin (PG)E2 formation in male Sprague-Dawley rats with azoxymethane induced colon cancer. METHODS Rats were divided into three groups to receive isocaloric diets (5% of the energy as fat) rich in n9, n3, or n6 fat, and were administered azoxymethane subcutaneously once a week for 11 weeks at a dose rate of 7.4 mg/kg body weight. Vehicle treated groups received an equal volume of normal saline. Groups of animals were colectomised at weeks 12 and 19 after the first dose of azoxymethane or saline. Mucosal fatty acids were assessed at 12 and 19 weeks. Aberrant crypt foci and the in vivo intracolonic release of PGE2 were assessed at week 12, and tumour formation at week 19. RESULTS Rats on the n6 diet were found to have colonic aberrant crypt foci and adenocarcinomas more often than those consuming either the n9 or n3 diet. There were no differences between the rats on the n9 and n3 diets. On the other hand, administration of both n9 and n3 diets was associated with a decrease in mucosal arachidonate concentrations as compared with the n6 diet. Carcinogen treatment induced an appreciable increase in PGE2 formation in rats fed the n6 diet, but not in those fed the n3 and n9 diets. CONCLUSIONS Dietary olive oil prevented the development of aberrant crypt foci and colon carcinomas in rats, suggesting that olive oil may have chemopreventive activity against colon carcinogenesis. These effects may be partly due to modulation of arachidonic acid metabolism and local PGE2synthesis

Interleukin-10 enhances the intestinal epithelial barrier in the presence of corticosteroids through p38 MAPK activity in Caco-2 monolayers : a possible mechanism for steroid responsiveness in ulcerative colitis

Altres ajuts: 2012 Spanish Gastroenterological Association i CIBER G0034Glucocorticosteroids are the first line therapy for moderate-severe flare-ups of ulcerative colitis. Despite that, up to 60% of patients do not respond adequately to steroid treatment. Previously, we reported that low IL-10 mRNA levels in intestine are associated with a poor response to glucocorticoids in active Crohn's disease. Here, we test whether IL-10 can favour the response to glucocorticoids by improving the TNFα-induced intestinal barrier damage (assessed by transepithelial electrical resistance) in Caco-2 monolayers, and their possible implications on glucocorticoid responsiveness in active ulcerative colitis. We show that the association of IL-10 and glucocorticoids improves the integrity of TNFα-treated Caco-2 cells and that p38 MAPK plays a key role. In vitro, IL-10 facilitates the nuclear translocation of p38 MAPK-phosphorylated thereby modulating glucocorticoids-receptor-α, IL-10-receptor-α and desmoglein-2 expression. In glucocorticoids-refractory patients, p38 MAPK phosphorylation and membrane desmoglein-2 expression are reduced in colonic epithelial cells. These results suggest that p38 MAPK-mediated synergism between IL-10 and glucocorticoids improves desmosome straightness contributing to the recovery of intestinal epithelium and reducing luminal antigens contact with lamina propria in ulcerative colitis. This study highlights the link between the intestinal epithelium in glucocorticoids-response in ulcerative colitis

Bacterial translocation in cirrhotic rats. Its role in the development of spontaneous bacterial peritonitis

Bacterial translocation occurs in ascitic cirrhotic rats, but its association with ascites infection is unknown. The aim of this study was to assess the relation between bacterial translocation and ascites infection in cirrhotic rats. Male Sprague-Dawley rats were induced to cirrhosis with intragastric CCl4. Ascitic fluid, portal and peripheral blood, mesenteric lymph nodes, liver and spleen samples were cultured before death in those cirrhotic rats with less (group A) or more (group B) than 250 polymorphonuclear neutrophils/mm3 in ascitic fluid, as well as in healthy control rats. Histological examination of jejunum, ileum, and caecum was also performed. Bacterial translocation occurred in 45% of ascitic rats (without differences between groups A and B), but in 0% controls (p = 0.01). Bacterial translocation was associated with positive ascitic fluid culture in 60% of the cases. In all of them the same bacterial species was isolated in both mesenteric lymph node and ascitic fluid. Submucosal caecal oedema (100%), ileal lymphangiectasia (41%), and caecal inflammatory infiltrate (41%) occurred in ascitic rats, the last being associated with ascitic fluid positive culture (p = 0.04). These results suggests that bacterial translocation occurs frequently in ascitic cirrhotic rats, and may play a permissive, but not unique, part in a number of ascites infections. Whether histological changes seen in cirrhotic ascitic rats favour bacterial translocation remains to be elucidated

Abnormal plasma polyunsaturated fatty acid pattern in non-active inflammatory bowel disease

An abnormal plasma polyunsaturated fatty acid pattern (PUFA) (increased n3 and decreased n6 PUFA) has been reported in active inflammatory bowel disease (IBD). The possibility of a primary defect in the PUFA metabolism in IBD was hypothesised. The aim of this study was to assess plasma PUFA pattern in inactive inflammatory bowel disease and to ascertain whether patients who had had a colectomy and who were suffering from ulcerative colitis have a similar PUFA pattern than those patients with non-active ulcerative colitis and who had not had a colectomy. Plasma fatty acids were analysed by semi-capillary column gas-liquid chromatography in three groups of patients with inactive IBD (24 patients with inactive ulcerative colitis who had not had a colectomy, 15 patients with ulcerative colitis who had had a colectomy, and 27 patients with Crohn's disease). Plasma concentration and percentage of C22:6n3 and unsaturation index were significantly higher in patients with inactive ulcerative colitis without a colectomy and the Crohn's disease group (p < 0.0001) than in controls. Plasma concentration and percentage of C22:6n3 and the unsaturation index remained significantly higher, in both the operated and non-operated ulcerative colitis patients when compared with controls (p < 0.0001). These results suggest that in inactive IBD, an increased PUFA biosynthesis might be the cause of the high values of n3 compounds. These findings although seen in active disease, are more noticeable in remission because of the lack of artefactual factors (malnutrition, steroids, inflammation). In addition, persistence of high values in both groups of ulcerative colitis patients--that is, those who had had a colectomy and those who had not suggests the existence of a primary abnormality in the PUFA metabolism in IBD

Adhesion Molecules Associated with Female Genital Tract Infection

Altres ajuts: Marie Curie Career Integration Grant i una beca Fundació Dexeus Salut de la DonaEfforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes

Changes of the mucosal N3 and N6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence

Despite data favouring a role of dietary fat in colonic carcinogenesis, no study has focused on tissue n3 and n6 fatty acid (FA) status in human colon adenoma-carcinoma sequence. Thus, FA profile was measured in plasma phospholipids of patients with colorectal cancer (n = 22), sporadic adenoma (n = 27), and normal colon (n = 12) (control group). Additionally, mucosal FAs were assessed in both diseased and normal mucosa of cancer (n = 15) and adenoma (n = 21) patients, and from normal mucosa of controls (n = 8). There were no differences in FA profile of both plasma phospholipids and normal mucosa, between adenoma and control patients. There were considerable differences, however, in FAs between diseased and paired normal mucosa of adenoma patients, with increases of linoleic (p = 0.02), dihomogammalinolenic (p = 0.014), and eicosapentaenoic (p = 0.012) acids, and decreases of alpha linolenic (p = 0.001) and arachidonic (p = 0.02) acids in diseased mucosa. A stepwise reduction of eicosapentaenoic acid concentrations in diseased mucosa from benign adenoma to the most advanced colon cancer was seen (p = 0.009). Cancer patients showed lower alpha linolenate (p = 0.002) and higher dihomogammalinolenate (p = 0.003) in diseased than in paired normal mucosa. In conclusion changes in tissue n3 and n6 FA status might participate in the early phases of the human colorectal carcinogenesis