Browsing by Subject "Intestinal Diseases"
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Item Characterization of VIBRIO Parahaemolyticus-Induced Intestinal Inflammation in the Mouse(2009-09-04) Lee, Olivia; Orth, KimThe Gram-negative marine bacterium Vibrio parahaemolyticus is a leading cause of gastroenteritis from the consumption of contaminated seafood. Some recent outbreaks are attributed to a rise in ocean temperatures, a trend that is likely to continue as a result of global warming and emphasizes the need to study the virulence mechanisms of the pathogen. V. parahaemolyticus utilizes a type III secretion system to inject effectors that disrupt signal transduction in eukaryotic hosts during infection. Herein, we describe an in vivo model of infection by V. parahaemolyticus using germfree mice. V. parahaemolyticus is recovered from the cecum and colon of mice infected by oral gavage. Mice infected with a pathogenic, wild type strain of V. parahaemolyticus exhibit intestinal inflammation characterized by epithelial damage, submucosal edema, crypt abscess and hyperplasia, and infiltration of the lamina propria by neutrophils. Using mutant strains of V. parahaemolyticus, we have determined that thermostable direct hemolysin, the most well characterized virulence factor produced by V. parahaemolyticus, and T3SS2, one of the two type III secretion systems present in this bacterium, both contribute to enteropathogenesis. Analysis of the expression of inflammatory cytokines IL-1? and IFN-gamma and chemokines KC, MIP-2 alpha, and CXCL-9 reveals that the duration of the inflammatory response is extended in the presence of TDH. In addition to delineating the roles of the virulence factors TDH, type III secretion system 1, and type III secretion system 2, in the infection process, we have developed an experimental system that will enable further characterization of type III effectors of V. parahaemolyticus.Item Epithelial Cell Autophagy in Antibacterial Defense of the Small Intestine(2013-10-14) Benjamin, Jamaal Louis; Yarovinsky, Felix; Hooper, Lora V.; Levine, Beth; Sperandio, VanessaThe intestines of all mammals are colonized with a diverse microbiota that provide metabolic benefits to their hosts. However, this symbiotic relationship can break down when resident bacteria opportunistically invade the intestinal barrier, leading to pathologies such as inflammatory bowel disease (IBD), and bacteremia. As a result, epithelial cell innate immune responses play an essential role in preventing bacterial invasion of host tissues and maintaining a symbiotic host-bacterial relationship. Autophagy is emerging as an important component of innate immunity. Mounting evidence suggests that dysregulation of the autophagy-independent function of autophagy genes can lead to inflammatory bowel disease. However, little is known about the role of autophagy-dependent gene function in controlling interactions between intestinal bacteria and the intestinal epithelium in vivo. In this study, I have demonstrated that small intestinal epithelial cell autophagy is essential for protection against tissue invasion by intestinal pathogens and opportunistically invasive commensals. I have shown that small intestinal autophagy is an early innate immune response that functions in an epithelial cell-intrinsic MyD88-dependent, NOD2-independent manner. Utilizing mice deficient in small intestinal epithelial cell autophagy (Atg5∆IEC), I have determined that epithelial cell autophagy is required to limit pathogen dissemination to extraintestinal sites. This study thus shows that autophagy is a critical mechanism of innate immune defense that protects intestinal epithelial surfaces from bacterial invasion. My findings may lead to new insights into how autophagy protects against gastrointestinal infections and maintains homeostasis with the intestinal microbiota.Item Intestinal ischemia(1991-07-18) Harford, William V.Item Intestinal ischemia(1983-09-08) Westergaard, HenrikItem Ischemic bowel disease(1975-07-10) Goyal, Raj K.Item Urine Sodium Concentration as a Marker of Poor Growth in Children with Intestinal Failure(2017-01-17) Casson, Cameron; Piper, Hannah; Pace, JesseBACKGROUND: Children who have had a significant small bowel resection often have difficulty growing adequately due to fluid and electrolyte losses in their stool. Specifically, growth is impaired when total body sodium depletion occurs. Urinary sodium concentration (UNa) is a more sensitive marker than serum sodium (less than or equal to 30 mmol/L considered low), and is used to monitor total body sodium status. The objective of this study was to determine the frequency of low UNa in children after significant bowel resection, and determine if it is associated with poor growth. METHODS: After IRB approval (Protocol #032016-015), a retrospective chart review of children (<19 years) who underwent small bowel resection (requiring parenteral nutrition for > 6 weeks post-operatively) cared for at Children's Health from 2010 to 2016 was performed. Patient characteristics, reason for small bowel resection, intestinal anatomy, nutritional intake, anthropometric measurements, and urine and serum electrolytes were collected. Z-scores were calculated from WHO and CDC standard growth charts. Anthropometric values were compared between children with a UNa less than or equal to 30 mmol/L and > 30 mmol/L. Statistical analysis was completed using Mann-Whitney and Pearson's correlation coefficient, providing both 95% confidence intervals and p-values. Analysis was performed with SAS 9.4 (Cary, NC). RESULTS: Thirty-eight children with significant bowel resection were included in the study. Patients had a median small bowel length of 50 cm (5-315 cm) and median % expected small bowel remaining of 27% (2-91%). The median UNa was 44 mmol/L, and 10 patients (26%) had a UNa less than or equal to, to 30 mmol/L. Only 1 patient demonstrated hyponatremia (serum Na = 130 meq/L). There was a positive correlation between UNa and both sodium intake (0.32, 95% CI [0.01, 0.57], p=.04), and body mass index (0.35, 95% CI [0.05, 0.60], p=.03), but no significant correlation with small bowel length. Children with UNa less than or equal to 30mmol/L had significantly lower Z-scores for weight (median -2.5 vs. -0.44, p=.0252) compared to those with UNa > 30mmol/L. CONCLUSION: Children with malabsorption after significant small bowel resection are at increased risk for sodium depletion and impaired growth. Patients with UNa less than or equal to 30 mmol/L should receive additional sodium supplementation to maximize growth.