Involvement of endogenous nitric oxide and c-kit—expressing cells in chronic intestinal pseudo-obstruction☆
Section snippets
Tissues
Tissues were obtained from 4 patients undergoing bowel resection or biopsy for CIP at laparotomy. The patients' ages ranged from 1 month to 3 months. All suffered with episodes of functional obstruction and intolerance to enteral feeding. Diagnosis of CIP was confirmed by contrast radiography, laparotomy, and histology with the exclusion of other diseases. For controls, the intestinal specimens were obtained from 4 age-matched patients undergoing intestinal resection for intestinal stricture (n
NOS immunoreactivity
Numerous NOS reactive structures were seen in the tissue sections from control patients (Fig 1A).
Discussion
CIP is a clinical syndrome caused by severe abnormality of gastrointestinal motility in infants and children. The etiology of CIP remains unknown. NO, a vital component of normal GI physiology, is important to GI motility. It has been well reported that NO serves as a nonadrenergic and noncholinergic inhibitory neurotransmitter in the GI tract,21 causing the relaxation of the enteric smooth musculature. Neuronal NOS is expressed in the myenteric neurons and many nerve fibers of the musculature.
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Bowel dysfunction following pullthrough surgery is associated with an overabundance of nitrergic neurons in Hirschsprung disease
2016, Journal of Pediatric SurgeryCitation Excerpt :One possible explanation for these persistent perturbations is an imbalance of neuronal subtypes in the ganglionated proximal colon. Since nitrergic neurons are inhibitory in the gut [18], disproportionately increased expression of this neurotransmitter can lead to colonic dysmotility [13]. We found that the proportion of nitrergic neurons was significantly greater in ganglionic colon of both mice and children with HD and, importantly, a greater proportion of nitrergic neurons in the proximal resection margin was associated with a higher incidence of postoperative constipation and/or HAEC after pullthrough surgery.
Differential responses of VIPergic and nitrergic neurons in paediatric patients with Crohn's disease
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2004, Journal of Pediatric SurgeryDiagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction
2003, Gastroenterology Clinics of North AmericaRole of interstitial cells of cajal in motility disorders of the bowel
2003, American Journal of GastroenterologyCitation Excerpt :It has also been suggested that delayed development of ICC may be associated with neonatal meconium syndrome in patients without cystic fibrosis (36). In two adult patients with myopathic CIIP and two subsequent pediatric subjects with CIIP from Japan, it has been shown that there is a near total absence of c-kit+ ICC in the bowel (4, 37, 38). This finding suggests a major role for ICC in bowel motility and raises the question of whether alterations of the ICC are also associated with other motility disorders of the bowel including sCIP.
Epithelial inducible nitric oxide synthase causes bacterial translocation by impairment of enterocytic tight junctions via intracellular signals of Rho-associated kinase and protein kinase C zeta
2011, Critical Care MedicineCitation Excerpt :Clinically, resected bowel specimens from ileus patients with paralytic intestinal obstruction display increased neuronal NOS immunoreactivity in the myenteric plexus, which correlates with decreased smooth muscle contractility and motility (51, 52). On the other hand, the intestinal epithelial cells in the surgical specimens were strongly labeled with iNOS immunoreactivity (51). Our results here demonstrated that overproduction of epithelial iNOS and NO initiate RhoA/ROCK-dependent MLC phosphorylation in enterocytes, in keeping with a previous report showing that exposure to NO activates RhoA for stress fiber formation in rat small intestinal epithelial IEC-6 cells (53).
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Address reprint requests to Z.Q. Wang, MD, PhD, Department of Pediatric Surgery, Kagawa Medical University Faculty of Medicine, 1750-1, Miki, Kita-gun, Kagawa, 761-07 Japan.