Peptidoglycan Suppresses Phagocytic Activities and Apoptosis of Macrophages in Colonic Mucosa Tissues of Crohn's Disease Patients and In Vitro.

BACKGROUND Rac1 signaling plays a crucial role in controlling macrophage functions in CD. Peptidoglycan triggers several intracellular signaling pathways, including activation of Rac1, to regulate the function of macrophage. Suppressed Rac1 signaling in non-inflamed colonic mucosa of Crohn's disease patients has been shown to correlate with increased innate immunity. MATERIAL AND METHODS We examined the effect of peptidoglycan on Rac1 signaling in macrophages and mucosal tissue samples collected from 10 patients with active Crohn's disease and further investigated the effects of peptidoglycan on apoptosis and phagocytic activities of macrophages in vitro. RESULTS Macrophage infiltration and Rac1 signaling was increased in inflamed mucosal tissues of Crohn's disease patients. Immunoblotting assays revealed that peptidoglycan dose- and time-dependently increased the expression of Rac1-GTP, phosphorylated VAV1, and phosphorylated PAK1in RAW264.7 macrophages, which, however, was attenuated by 6-thioguanine. Peptidoglycan also dose-dependently inhibited phagocytic activities of human peripheral blood monocytic cells (PBMCs), which were partially abated by 6-thioguanine or NSC23766. Flow cytometry showed that peptidoglycan (3 µg/mL) decreased the proportion of apoptotic human PBMCs versus controls. The addition of 6-thioguanine or NSC3766 to peptidoglycan led to a sharper rise in the proportion of apoptotic human PBMCs than 6-thioguanine or NSC3766 alone. CONCLUSIONS Our findings suggest that Rac1 signaling is a common molecular target shared by peptidoglycan and immunosuppressive treatment in intestinal macrophages. Inhibiting Rac1 activation may be crucial for optimizing macrophage immunity for treatment of Crohn's disease.

Association of Helicobacter pylori infection with diabetic complications: a meta-analysis.

UNLABELLED: BACKGROUND. Helicobacter pylori (HP) infects more than half of the world's population. The aim of the study was to quantify the association between HP and the risk of diabetic complications. METHODS: A literature search was performed to identify studies published between 1998 and 2012 for relevant risk estimates. Fixed and random effect meta-analytical techniques were conducted for ischemic heart disease, retinopathy, neuropathy and nephropathy. RESULTS: Eight studies were included. HP was associated with an increase risk of nephropathy and neuropathy (relative risk [RR]: 1.35, 95% CI: 1.06-1.73, p = 0.45 and RR: 1.20, 95% CI: 1.03-1.40, p = 0.29). We also discovered significant associations between bacterial infection and nephropathy risk in Oriental people (RR: 1.73, 95% CI: 1.19-2.50, p = 0.82) and in type 2 diabetic patients (RR: 1.50, 95% CI: 1.11-2.02, p = 0.29). CONCLUSIONS: Our meta-analyses suggest a possible relationship between HP and the risk of nephropathy and neuropathy. Our results also suggest that the effect of HP on the risk of nephropathy is stronger in Oriental people and in type 2 DM patients.

Association of Helicobacter pylori infection with diabetes mellitus and diabetic nephropathy: a meta-analysis of 39 studies involving more than 20,000 participants.

BACKGROUND: Helicobacter pylori infects more than half of the world's population. The aim of this study was to quantify the association between H. pylori infection and the risk of diabetes mellitus and diabetic nephropathy, and to detect at which stage the infection might have higher pathogenicity in the disease-free status-diabetes mellitus-diabetic nephropathy process. METHODS: A literature search was performed to identify studies published between 1997 and 2012 for relative risk estimates. Fixed and random effects meta-analytical techniques were conducted for diabetes mellitus and diabetic nephropathy. RESULTS: Thirty-seven case-control studies and 2 cohort studies were included. H. pylori was associated with an increased risk of each type of diabetes mellitus (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.82-2.20, p for heterogeneity = 0.07). The infection was also associated with increased risks of type 1 and type 2 diabetes mellitus, separately (OR 1.99, 95% CI 1.52-2.60, p for heterogeneity = 0.15, and OR 2.15, 95% CI 1.81-2.55, p for heterogeneity = 0.24, respectively). In addition, we found a significant association between H. pylori infection and diabetic nephropathy risk (OR 1.60, 95% CI 1.10-2.33, p for heterogeneity = 0.44). CONCLUSIONS: Our meta-analyses suggest a relationship between H. pylori infection and the risk of diabetes mellitus and diabetic nephropathy. The bacterium may be able to play its pathogenic role in the whole disease process, and this action may be stronger in type 2 diabetic patients than in type 1 diabetic patients.

Mechanical intestinal obstruction due to isolated diffuse venous malformations in the gastrointestinal tract: A case report and review of literature.

BACKGROUND: Isolated gastrointestinal venous malformations (GIVMs) are extremely rare congenital developmental abnormalities of the venous vasculature. Because of their asymptomatic nature, the diagnosis is often quite challenging. However, as symptomatic GIVMs have nonspecific clinical manifestations, misdiagnosis is very common. Here, we report a case of isolated diffuse GIVMs inducing mechanical intestinal obstruction. A literature review was also conducted to summarize clinical features, diagnostic points, treatment selections and differential diagnosis in order that doctors may have a comprehensive understanding of this disease. CASE SUMMARY: A 50-year-old man presented with recurrent painless gastrointestinal bleeding for two months and failure to pass flatus and defecate with nausea and vomiting for ten days. Digital rectal examination found bright red blood and soft nodular masses 3 cm above the anal verge. Computed tomography showed that part of the descending colon and rectosigmoid colon was thickened with phleboliths in the intestinal wall. Colonoscopy exhibited bluish and reddish multinodular submucosal masses and flat submucosal serpentine vessels. Endoscopic ultrasonography showed anechoic cystic spaces within intestinal wall. The lesions were initially thought to be isolated VMs involving part of the descending colon and rectosigmoid colon. Laparoscopic subtotal proctocolectomy, pull-through transection and coloanal anastomosis and ileostomy were performed. Histopathology revealed intact mucosa and dilated, thin-walled blood vessels in the submucosa, muscularis, and serosa involving the entire colorectum. The patient recovered with complete symptomatic relief during the 52-mo follow-up period. CONCLUSION: The diagnosis of isolated GIVMs is challenging. The information presented here is significant for the diagnosis and management of symptoms.