Cause Of Gastrointestinal Dysfunction Research Articles

Defective development and microcirculation of intestine in Npr2 mutant mice

Intractable gastrointestinal (GI) diseases often develop during infancy. Our group previously reported that natriuretic peptide receptor B (NPR-B)-deficient Npr2slw/slw mice exhibit severe intestinal dysfunction, such as stenosis and distention, which resembles the dysfunction observed in Hirschsprung’s disease-allied disorders. However, the root cause of intestinal dysfunction and the detailed of pathophysiological condition in the intestine are not yet clear. Here, we report that the intestine of preweaning Npr2slw/slw mice showed bloodless blood vessels, and nodes were found in the lymphatic vessel. Additionally, the lacteals, smooth muscle, blood vessel, and nerves were barely observed in the villi of preweaning Npr2slw/slw mice. Moreover, intramuscular interstitial cells of Cajal (ICC-IM) were clearly reduced. In contrast, villi and ICC-IM were developed normally in surviving adult Npr2slw/slw mice. However, adult Npr2slw/slw mice exhibited partially hypoplastic blood vessels and an atrophied enteric nervous. Furthermore, adult Npr2slw/slw mice showed markedly reduced white adipose tissue. These findings suggest that the cause of GI dysfunction in preweaning Npr2slw/slw mice is attributed to defective intestinal development with microcirculation disorder. Thus, it is suggested that NPR-B signaling is involved in intestinal development and control of microcirculation and fat metabolism. This report provides new insights into intractable GI diseases, obesity, and NPR-B signaling.

Effects of Bifidobacterium infantis on cytokine-induced neutrophil chemoattractant and insulin-like growth factor-1 in the ileum of rats with endotoxin injury

BACKGROUNDThe digestive tract is the maximal immunizing tissue in the body, and mucosal integrity and functional status of the gut is very important to maintain a healthy organism. Severe infection is one of the most common causes of gastrointestinal dysfunction, and the pathogenesis is closely related to endotoxemia and intestinal barrier injury. Bifidobacterium is one of the main probiotics in the human body that is involved in digestion, absorption, metabolism, nutrition, and immunity. Bifidobacterium plays an important role in maintaining the intestinal mucosal barrier integrity. This study investigated the protective mechanism of Bifidobacterium during ileal injury in rats.AIMTo investigate the effects of Bifidobacterium on cytokine-induced neutrophil chemoattractant (CINC) and insulin-like growth factor 1 (IGF-1) in the ileum of rats with endotoxin injury.METHODSPreweaning rats were randomly divided into three groups: Control (group C), model (group E) and treatment (group T). Group E was intraperitoneally injected with lipopolysaccharide (LPS) to create an animal model of intestinal injury. Group T was intragastrically administered Bifidobacterium suspension 7 d before LPS. Group C was intraperitoneally injected with normal saline. The rats were killed at 2, 6 or 12 h after LPS or physiological saline injection to collect ileal tissue samples. The expression of ileal CINC mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), and expression of ileal IGF-1 protein and mRNA was detected by immunohistochemistry and RT-PCR, respectively.RESULTSThe ileum of rats in Group C did not express CINC mRNA, ileums from Group E expressed high levels, which was then significantly decreased in Group T (F = 23.947, P < 0.05). There was no significant difference in CINC mRNA expression at different times (F = 0.665, P > 0.05). There was a high level of IGF-1 brown granules in ileal crypts and epithelial cells in Group C, sparse staining in Group E, and dark, dense brown staining in Group T. There was a significant difference between Groups C and E and Groups E and T (P < 0.05). There was no significant difference in IGF-1 protein expression at different times (F = 1.269, P > 0.05). IGF-1 mRNA expression was significantly different among the three groups (P < 0.05), though not at different times (F = 0.086, P > 0.05).CONCLUSIONExpression of CINC mRNA increased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium reduced CINC mRNA expression. IGF-1 protein and mRNA expression decreased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium prevented the decrease in IGF-1 expression. Bifidobacterium may increase IGF-1 expression and enhance intestinal immune barrier function in rats with endotoxin injury.

Parrot bornavirus infection: correlation with neurological signs and feather picking?

Borna disease virus is the causative agent of Borna disease, which is characterised by nonsuppurative meningoencephalomyelitis caused by cellular immune responses against the viral antigens.1 This virus has been extensively...

923 Pediatric Therapeutic Endoscopy: Endoscopic Management of a Congenital Duodenal Web

Congenital duodenal webs are a rare cause of gastrointestinal dysfunction in infants and children. The traditional approach to treatment has been surgical intervention, by way of excision or bypass. We present a case of successful endoscopic management of a congenital duodenal web in an 8 year old girl who presents with a duodenal obstruction.

An Improved Method for Collecting Breath From 3‐ to 7‐Year‐Old Children

Breath sampling and analysis provide healthcare professionals with a practical, noninvasive diagnostic measurement for children with a variety of gastrointestinal (GI) disorders. New biomarkers found in human breath have been investigated and provide the opportunity to diagnose bacterial overgrowth and other underlying causes of GI dysfunction. Although several protocols have been described previously regarding breath sampling, few have demonstrated the feasibility of collection in young children. This communication introduces a simple game that allows for 3- to 7-year-old children to practice breath exhalation to give a proper breath sample in a relaxed and comfortable environment. The technique described offers clinicians a creative approach for obtaining breath samples from a child by reducing the apprehension and anxiety associated with the research and clinical environment.

The Occurrence of Cytomegalovirus Gastrointestinal Disease in Patients with Gastrointestinal Graft-Versus-Host Disease and Its Related Clinical Outcomes in the Era of Preemptive Therapy for Cytomegalovirus Infection

Abstract 492Diagnosis and therapeutic decision of gastrointestinal (GI)-graft-versus-host disease (GVHD) mainly rely upon clinical symptoms and exclusion of other causes of GI dysfunction. Particularly, the presence of CMV-GI-disease should be examined with immunostaining of biopsy. However, there have been few reports about the occurrence of CMV-GI-disease in patients with GI-GVHD in the era of preemptive therapy for CMV infection with real-time quantitative polymerase chain reaction (RQ-PCR) and its related outcomes.Between January 2008 to December 2010, 392 adult patients with AML, ALL, MDS, and CML underwent allogeneic stem cell transplantation (SCT) and all had serial monitoring for CMV DNA based on RQ-PCR followed by initiation of preemptive therapy. Ninety-seven percent of recipients and 84% of donors were CMV-seropositive before SCT. Clinical GI-GVHD based on symptoms, stool studies, and endoscopic findings developed in 114 patients (29%) and they were treated by high-dose systemic steroid. Of these patients, 103 patients performed endoscopic biopsies not only at the time of onset of clinical symptoms but also during the clinical course of GI-GVHD in the absence of response to steroid, and all samples from biopsies were immunohistochemically stained. The median age of the 103 patients was 40 years (range, 15–70). These patients consisted of AML (n=59), ALL (n=29), MDS (n=12), and CML (n=3) transplanted from sibling (n=45), unrelated (n=48), familial-mismatched donors (n=8), and umbilical cord donors (n=2). Conditioning regimens consisted of myeloablative (76%) and reduced-intensity regimens (24%). Anti-thymocyte globulin was given as a part of conditioning in 41 patients (40%). GVHD prophylaxis was based on administering calcineurin inhibitor with short-course methotrexate. GI-GVHD was developed as a manifestation of not only acute GVHD (aGVHD, 87%) but also overlap syndrome (13%). Isolated GI-GVHD was 30%. Eighty-nine patients (86%) initially presented with GI-GVHD, whereas 14 patients (14%) developed GI-GVHD after the treatment of GVHD of other organs.Of the 103 patients, 60 (58%) had histologic findings for GI-GVHD (lower gut, n=41, 40%; lower gut + upper gut, n=10, 10%; upper gut, n=9, 8%) and 26 (25%) had positive immunohistochemical stain for CMV-GI-disease (lower gut, n=13, 13%; lower gut + upper gut, n=4, 4%; upper gut, n=9, 8%). The CMV-GI-disease developed at a median time of 56 days after SCT (range, 20–403). Multivariate analyses revealed that older age over 30 years (RR 4.42, 95%CI 1.10–17.84), HLA-mismatched donors (RR 3.41, 95%CI 1.21–9.60), and higher grade of GVHD (grade III+IV aGVHD or severe cGVHD, RR 3.24, 95% CI 1.22–8.60) were significant risk factors for CMV-GI-disease. Most patients (73%) developed CMV-GI-disease after the treatment of GI-GVHD or other organs of GVHD, whereas CMV-GI-disease developed concurrently with GI-GVHD in other 27%. After the anti-viral therapy with ganciclovir or foscarnet, 14 patients (54%) showed complete resolution of CMV-GI-disease, while 12 patients (46%) failed to show any response.There were 4 patterns of development of pathologically proven GI-GVHD and CMV-GI-disease (Figure). GVHD-specific survival of patients with CMV-GI-disease was significantly lower than patients without CMV-GI-disease (36.2% vs. 79.3%, P = 0.002). Patients with both GI-GVHD and CMV-GI-disease (n=18) had significantly inferior GVHD-specific survival than other 3 patterns of development of GI-GVHD and CMV-GI-disease (24.5% vs. 78.2%, P = 0.001).Our data demonstrate 25 percent of patients with clinical GI-GVHD developed CMV-GI-disease during the treatment or at the time of diagnosis of GI-GVHD even in the era of preemptive therapy for CMV disease based on RQ-PCR, especially in older patients, HAL-mismatched transplants, and higher grade of GVHD. Patients with CMV-GI-disease, especially who concurrently had pathologically proven GVHD, had inferior GVHD-specific survival. Thus, we reemphasize the need of endoscopic biopsy with immunohistochemical stain for CMV disease if ever possible at the diagnosis of GI-GVHD as well as in the absence of response to treatment of GVHD, especially in high risk groups, which can facilitate proper selection of treatment. Additionally, novel prophylactic measures such as immunotherapy and drug prophylaxis should be considered in this specific group of patients. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Autonomic Nervous Dysfunction in Hamsters Infected with West Nile Virus

Clinical studies and case reports clearly document that West Nile virus (WNV) can cause respiratory and gastrointestinal (GI) complications. Other functions controlled by the autonomic nervous system may also be directly affected by WNV, such as bladder and cardiac functions. To investigate how WNV can cause autonomic dysfunctions, we focused on the cardiac and GI dysfunctions of rodents infected with WNV. Infected hamsters had distension of the stomach and intestines at day 9 after viral challenge. GI motility was detected by a dye retention assay; phenol red dye was retained more in the stomachs of infected hamsters as compared to sham-infected hamsters. The amplitudes of electromygraphs (EMGs) of intestinal muscles were significantly reduced. Myenteric neurons that innervate the intestines, in addition to neurons in the brain stem, were identified to be infected with WNV. These data suggest that infected neurons controlling autonomic function were the cause of GI dysfunction in WNV-infected hamsters. Using radiotelemetry to record electrocardiograms and to measure heart rate variability (HRV), a well-accepted readout for autonomic function, we determined that HRV and autonomic function were suppressed in WNV-infected hamsters. Cardiac histopathology was observed at day 9 only in the right atrium, which was coincident with WNV staining. A subset of WNV infected cells was identified among cells with hyperplarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) as a marker for cells in the sinoatrial (SA) and atrioventricular (AV) nodes. The unique contribution of this study is the discovery that WNV infection of hamsters can lead to autonomic dysfunction as determined by reduced HRV and reduced EMG amplitudes of the GI tract. These data may model autonomic dysfunction of the human West Nile neurological disease.

Gastric and small intestinal ileus as a cause of acute colic in the post parturient mare

Ileus (functional obstruction of aboral gastrointestinal transit) is an uncommon cause of gastrointestinal dysfunction and colic in the horse. A number of specific conditions have been previously reported in association with ileus. This report describes the recognition of primary gastric and small intestinal ileus of undetermined cause in a series of post parturient mares. To describe the clinical features, treatment and outcome of a series of episodes of primary gastric and small intestinal ileus. A retrospective study was performed of colic episodes seen in an equine practice in Newmarket, UK over a 6 year period (2002-2007). Seventeen episodes of gastric and small intestinal ileus were identified, which occurred in 15 horses. All episodes occurred in post parturient mares. No previously reported cause of ileus was identified in any of the episodes. Fifteen of the 17 episodes received medical treatment (medical support and nasogastric decompression) and, in addition, surgical decompression was performed in 9 episodes. Two mares were subjected to euthanasia before treatment due to the presence of gastric rupture and the remaining 13 mares survived with a follow-up period of at least 10 months. Two mares suffered a further episode of gastric and small intestinal ileus, one 4 days and the other 2 years after the initial episode. Gastric and small intestinal ileus of, as yet, unknown aetiology appears to be a potential cause of acute colic in the post parturient mare. The outcome following treatment by decompression is good.

Myenteric Plexus in Streptozotocin-Treated Rats

Adrenergic, cholinergic, and serotoninergic nerves were studied in the myenteric plexus of ileum and colon from streptozotocin-treated rats, an animal model of juvenile-onset diabetes. In view of clinical reports implicating diabetic autonomic neuropathy as the cause of gastrointestinal dysfunction in diabetes mellitus, neurochemical and histochemical techniques were used to study changes in the innervation of the gut. In the myenteric plexus of the ileum from diabetic animals, adrenergic nerves displayed signs of degeneration and the brightness of fluorescence in serotoninlike immunoreactive nerves was lower. Cholinergic nerves, however, did not display any signs of reduction in the ileum, and both choline acetyltransferase and acetylcholinesterase activities per centimeter were increased. In contrast, in the proximal colon 8 wk after induction of diabetes, neurochemical assays revealed significant increases in noradrenaline and serotonin levels as well as choline acetyltransferase activity, although no obvious changes in the pattern of innervation could be detected histochemically. The results indicate that changes do occur in the innervation of the gut of the streptozotocin-diabetic model shortly after the induction of diabetes, although they differ significantly in the ileum and colon; these may be of relevance to the types of gastrointestinal dysfunction displayed in human diabetes.