Reduced Paneth cell alpha-defensins in ileal Crohn's disease
bacteria; expression; gene; human intestinal defensin; inflammatory bowel disease; inflammatory bowel disease; innate; innate immunity; intestine; mechanisms; microflora; mutations; peptides; Science & Technology - Other Topics
The pathogenesis of Crohn's disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human alpha-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC alpha-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CID of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC alpha-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of alpha-defensins was independent of the degree of inflammation in the specimens and was not observed in either CD of the colon, ulcerative colitis, or pouchitis. The functional consequence of alpha-defensin expression levels was examined by using a transgenic mouse model, where we found changes in HD5 expression levels, comparable to those observed in CD, had a pronounced impact on the luminal microbiota. Thus, the specific deficiency of PC defensins that characterizes ileal CD may compromise innate immune defenses of the ileal mucosa and initiate and/or perpetuate this disease.
Wehkamp J; Salzman N H; Porter E; Nuding S; Weichenthal M; Petras R E; Shen B; Schaeffeler E; Schwab M; Linzmeier R; Feathers R W; Chu H T; Lima H; Fellermann K; Ganz T; Stange E F; Bevins C L
Proceedings of the National Academy of Sciences of the United States of America
2005
2005-12
Journal Article
<a href="http://doi.org/10.1073/pnas.0505256102" target="_blank" rel="noreferrer noopener">10.1073/pnas.0505256102</a>
Portal pyelophlebitis identified by CT scan in a patient with ischemic bowel.
Humans; Male; Aged; Necrosis; Fatal Outcome; *Portal System; Ischemia/*complications/pathology; Phlebitis/diagnostic imaging/*etiology; X-Ray Computed; *Tomography; Intestine; Embolism; Air/diagnostic imaging/*etiology; Small/*blood supply
A 65-year-old male was found to have hepatic portal venous gas (HPVG) by computed tomogram secondary to ischemic bowel. Despite aggressive surgical and antibiotic treatment, the patient died within 12 hours. Portal pyelophlebitis, when identified by air in the portal venous system, is a grave indicator of ischemic bowel with a very high mortality rate, except in patients with inflammatory bowel disease.
Ghani A; Kasirajan K; Smith J
The American surgeon
1995
1995-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Bile acids as metabolic regulators.
Bile Acids and Salts/*metabolism; Biological Transport; Cholesterol 7-alpha-Hydroxylase/metabolism; Cytoplasmic and Nuclear/metabolism; Diabetes Mellitus; Energy Metabolism; Homeostasis; Humans; Inflammation/*metabolism; Intestine; Liver/*metabolism/pathology; Obesity/*metabolism; Receptors; Signal Transduction; Small/*metabolism/pathology; Type 2/*metabolism
PURPOSE OF REVIEW: This review focuses on the latest understanding of the molecular mechanisms underlying the complex interactions between intestine and liver bile acid signaling, gut microbiota, and their impact on whole-body lipid, glucose and energy metabolism. RECENT FINDINGS: Hepatic bile acid synthesis is tightly regulated by the bile acid negative feedback mechanisms. Modulating the enterohepatic bile acid signaling greatly impacts the whole-body metabolic homeostasis. Recently, a positive feedback mechanism through intestine farnesoid X receptor (FXR) antagonism has been proposed to link gut microbiota to the regulation of bile acid composition and pool size. Two studies identified intestine Diet1 and hepatic SHP-2 as novel regulators of CYP7A1 and bile acid synthesis through the gut-liver FXR-fibroblast growth factor 15/19-FGF receptor four signaling axis. New evidence suggests that enhancing bile acid signaling in the distal ileum and colon contributes to the metabolic benefits of bile acid sequestrants and bariatric surgery. SUMMARY: Small-molecule ligands that target TGR5 and FXR have shown promise in treating various metabolic and inflammation-related human diseases. New insights into the mechanisms underlying the bariatric surgery and bile acid sequestrant treatment suggest that targeting the enterohepatic circulation to modulate gut-liver bile acid signaling, incretin production and microbiota represents a new strategy to treat obesity and type 2 diabetes.
Li Tiangang; Chiang John Y L
Current Opinion in Gastroenterology
2015
2015-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/MOG.0000000000000156" target="_blank" rel="noreferrer noopener">10.1097/MOG.0000000000000156</a>
Entero mesh vaginal fistula secondary to abdominal sacral colpopexy.
*Surgical Mesh; Abdomen; Female; Gynecologic Surgical Procedures; Humans; Intestinal Fistula/*etiology; Intestine; Middle Aged; Postoperative Complications/*etiology; Sacrum; Small; Uterine Prolapse/surgery; Vaginal Fistula/*etiology
BACKGROUND: Abdominal sacral colpopexy is a popular method for resupporting the vaginal apex. Bleeding and infection are the most common complications. We report a complication resulting in a small bowel fistula. CASE: A 48-year-old woman developed a chronic vaginal discharge 4-6 months after routine abdominal sacral colpopexy in which a velour mesh remained exposed in the pelvis. Conservative measures failed to control the intermittent copious discharge from the upper vaginal vault where the mesh was visualized. At laparotomy, an entero mesh vaginal fistula was discovered. Excellent long-term results were obtained by removal of the mesh along with resection of the involved small intestine. CONCLUSION: At the time of abdominal sacral colpopexy, we recommend that mesh not remain exposed in the pelvis.
Hopkins Michael P; Rooney Christopher
Obstetrics and gynecology
2004
2004-05
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1097/01.AOG.0000127940.45774.b4" target="_blank" rel="noreferrer noopener">10.1097/01.AOG.0000127940.45774.b4</a>