Electroacupuncture ameliorates corticotrophin-releasing factor-induced jejunal dysmotility in a rat model of stress.

BACKGROUND: Central injection of corticotrophin-releasing factor (CRF) mimics the effect of stress on gastrointestinal (GI) responses, including inhibition of GI motility. This study was designed to explore the effects of electroacupuncture (EA) on disordered jejunal motility in a rat model of stress induced by intracisternal (IC) injection of CRF. METHODS: A stress model was established by IC injection of CRF in Sprague-Dawley rats. GI motility was evaluated by assessing gastric emptying (GE), gastrointestinal transit (GIT) and jejunal motility in vivo. EA was performed at ST36. The functional roles of CRF receptor subtype 1 and subtype 2 (CRFr1 and CRFr2) were examined by IC administration of the corresponding selective CRF antagonists. Protein expression of CRFr1 and CRFr2 in the hypothalamus and jejunum was detected by Western blotting. RESULTS: IC injection of CRF significantly inhibited GE, GIT and jejunal motility. EA treatment remarkably improved the disturbed GI motility. Intriguingly, the disordered jejunal motility induced by central CRF was abolished by IC injection of a selective CRFr2 antagonist, indicating the essential role of central CRFr2 in mediating the stress-induced jejunal motor disorder. EA at ST36 decreased central and peripheral expression of CRFr2, which might be one of the potential mechanisms underlying the beneficial effect of EA on jejunal dysmotility in this rat model of stress. CONCLUSION: This study suggested that EA at ST36 could ameliorate disordered jejunal motility induced by stress, and that this might be associated with the down-regulation of CRFr2.

Stenotic Ischemic Enteritis with Concomitant Hepatic Portal Venous Gas and Pneumatosis Cystoides Intestinalis.

A 69-year-old man was admitted to a hospital with complaints of abdominal pain. Computed tomography showed hepatic portal venous gas and pneumatosis cystoides intestinalis. Conservative treatment was effective; however, after discharge, he developed complaints of vomiting. Fluoroscopic enteroclysis revealed a stricture in the jejunum necessitating admission to our hospital. Transoral balloon-assisted enteroscopy showed a circumferential ulcer with a stricture. The stricture was surgically resected, and a histopathological examination was consistent with ischemic enteritis. Stenotic ischemic enteritis should be considered among the differential diagnoses in a patient presenting with hepatic portal venous gas and pneumatosis cystoides intestinalis showing small intestinal obstruction.

Two jenuno-jenunal intussusceptions in a patient with coeliac disease.

We present a case of a 41-year-old woman with severe abdominal pain caused by two jejuno-jejunal intussusceptions. Further investigation showed coeliac disease as the underlying cause. The patient recovered rapidly on a gluten-free diet. So coeliac disease could be the underlying cause of idiopathic intussusception more often than previously thought and intussusception should be suspected in patients with known coeliac disease presenting with abdominal pain. (Acta gastro-enterol. belg., 2016, 79, 000-000).

Nitric oxide-induced oxidative stress impairs pacemaker function of murine interstitial cells of Cajal during inflammation.

The pacemaker function of interstitial cells of Cajal (ICC) is impaired during intestinal inflammation. The aim of this study is to clarify the pathophysiological mechanisms of ICC dysfunction during inflammatory condition by using intestinal cell clusters. Cell clusters were prepared from smooth muscle layer of murine jejunum and treated with interferon-gamma and lipopolysaccharide (IFN-γ+LPS) for 24h to induce inflammation. Pacemaker function of ICC was monitored by measuring cytosolic Ca(2+) oscillation in the presence of nifedipine. Treatment with IFN-γ+LPS impaired the pacemaker activity of ICC with increasing mRNA level of interleukin-1 beta, tumor necrosis factor-alpha and interleukin-6 in cell clusters; however, treatment with these cytokines individually had little effect on pacemaker activity of ICC. Treatment with IFN-γ+LPS also induced the expression of inducible nitric oxide synthase (iNOS) in smooth muscle cells and resident macrophages, but not in ICC. Pretreatment with NOS inhibitor, L-NAME or iNOS inhibitor, 1400W ameliorated IFN-γ+LPS-induced pacemaker dysfunction of ICC. Pretreatment with guanylate cyclase inhibitor, ODQ did not, but antioxidant, apocynin, to suppress NO-induced oxidative stress, significantly suppressed the impairment of ICC function induced by IFN-γ+LPS. Treatment with IFN-γ+LPS also decreased c-Kit-positive ICC, which was prevented by pretreatment with L-NAME. However, apoptotic ICC were not detected in IFN-γ+LPS-treated clusters, suggesting IFN-γ+LPS stimulation just changed the phenotype of ICC but not induced cell death. Moreover, ultrastructure of ICC was not disturbed by IFN-γ+LPS. In conclusion, ICC dysfunction during inflammation is induced by NO-induced oxidative stress rather than NO/cGMP signaling. NO-induced oxidative stress might be the main factor to induce phenotypic changes of ICC.

Glucose absorption in small intestinal diseases.

Recent developments in the field of diabetes and obesity management have established the central role of the gut in glucose homeostasis; not only is the gut the primary absorptive site, but it also triggers neurohumoral feedback responses that regulate the pre- and post-absorptive phases of glucose metabolism. Structural and/or functional disorders of the intestine have the capacity to enhance (e.g.: diabetes) or inhibit (e.g.: short-gut syndrome, critical illness) glucose absorption, with potentially detrimental outcomes. In this review, we first describe the normal physiology of glucose absorption and outline the methods by which it can be quantified. Then we focus on the structural and functional changes in the small intestine associated with obesity, critical illness, short gut syndrome and other malabsorptive states, and particularly Type 2 diabetes, which can impact upon carbohydrate absorption and overall glucose homeostasis.

Surgical treatment of retrograde peristalsis following laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Retrograde Roux limb peristalsis following laparoscopic Roux-en-Y gastric bypass is a rare complication that can be difficult to identify. It may present as persistent nausea, vomiting, abdominal pain, or even gastrointestinal bleeding related to an anastomotic ulcer. Upper gastrointestinal (UGI) series is an important diagnostic modality to identify this motility disorder; however, it may not be readily identifiable without specific delayed imaging. The etiology of this phenomenon is unclear, but attributing factors include the presence of ectopic pacemaker cells, variable lengths of the Roux limb and misconstructions. When this problem is identified, revisional surgery is indicated. CASE DESCRIPTION: A 51-y-old female with morbid obesity presented with persistent nausea and vomiting following a laparoscopic gastric bypass. A CT scan showed a dilated Roux limb. Reverse peristalsis from the jejunojejunostomy toward the gastric pouch was identified on a UGI. Two laparoscopic revisions of the jejunojunostomy were attempted to correct this dysfunction. DISCUSSION: An attempt at widening and relaxing the anastomosis was unsuccessful at providing relief of symptoms. A second revision with an anastomosis between the Roux limb and common channel provided long-term improvement. Identifying complications of gastric bypass surgery can be challenging. Imaging studies may be limited, and often diagnostic and revisional surgery is indicated.

Adenosine A2A receptor contributes to the anti-inflammatory effect of the fixed herbal combination STW 5 (Iberogast®) in rat small intestinal preparations.

STW 5 (Iberogast®), an established herbal combination, was effective in randomized, double blind clinical studies in functional dyspepsia and irritable bowel syndrome. Since STW 5 was found to influence intestinal motility and has anti-inflammatory properties, this study investigated the expression of adenosine receptors and characterized their role in the control of the anti-inflammatory action of STW 5 and its fresh plant component STW 6 in inflammation-disturbed rat small intestinal preparations. The inflammation was induced by intraluminal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 0.01 M). The effects of coincubation with selective receptor agonists and antagonists, STW 5, STW 6, or combinations of these compounds on acetylcholine (ACh)-evoked contraction of ileum/jejunum preparations were tested. Adenosine receptor mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). In untreated preparations, RT-PCR revealed the presence of all adenosine receptor subtypes. Suppressed expression was detected for all subtypes in inflamed tissues, except for A(2B)R mRNA, which was unaffected. STW 5 reversed these effects and enhanced A(2A)R expression above control levels. Radioligand binding assays confirm the affinity of STW 5 to the A(2A)R, and the A(2A)R antagonist was able to prevent the effect of STW 5 on TNBS-induced attenuation of the ACh contraction. Our findings provide evidence that STW 5, but not STW 6 interacts with A(2A)R, which is involved in the anti-inflammatory action of STW 5. STW 6 did not contribute to adenosine A(2A)R-mediated anti-inflammatory effect of STW 5. Other signaling pathways could be involved in the mechanism of action of STW 6.

Effects of allopurinol and preconditioning on apoptosis due to ischemia-reperfusion on a double jejunum-segment canine model.

PURPOSE: To investigate the duration of apoptosis caused by ischemia-reperfusion in the intestine in a new double jejunum-segment model, and to analyze the protective effects of allopurinol or ischemic preconditioning (IPC). METHODS: In Experiment I for harvesting the double jejunum-segment model after laparotomy a 30-cm-long jejunum part was selected on mongrel dogs (n=24). End-to-end anastomoses were performed at both ends and in the middle of the jejunum part, creating two equal segments. In one segment ischemia was induced by occluding the supplying vessels, the other segment served as control. Tissue samples for detecting apoptosis were taken at 30th minutes, 1st, 2nd, 4th, 6th, 8th, 12th and 24th hours of reperfusion. In Experiment II using the same model the 4-hour reperfusion time period, allopurinol (50 mg/kg) pre-treated and IPC (3 cycles of 5x1) groups (n=5 per each) were also investigated. RESULTS: In Experiment I the greatest apoptotic activity was detected at the 4th and 6th hour of reperfusion (14.2 ± 1.31 and 16.3 ± 1.05 per visual field at 40x magnification). In Experiment II Using the 4-hour reperfusion time period allopurinol pre-treatment increased the apoptotic activity (10.72 ± 0.47 per 50 intestinal villi) approximately two-fold than the IPC (6.72 ± 0.46 per 50 intestinal villi) did (p<0.05). CONCLUSIONS: Apoptotic activity has a characteristic time curve, reaching the highest values between the 4th and 6th hours after 30-minute intestinal ischemia. Ischemic preconditioning seemed to be protective against the morphological changes caused by intestinal ischemia-reperfusion.

Involvement of cannabinoid-1 and cannabinoid-2 receptors in septic ileus.

BACKGROUND Cannabinoid (CB) receptors are involved in the regulation of gastrointestinal (GI) motility under physiological and pathophysiological conditions. We aimed to characterize the possible influence of CB(1) and CB(2) receptors on motility impairment in a model of septic ileus. METHODS Lipopolysaccharide (LPS) injections were used to mimic pathophysiological features of septic ileus. Spontaneous jejunal myoelectrical activity was measured in rats in vivo, and upper GI transit was measured in vivo by gavaging of a charcoal marker into the stomach of mice, in absence or presence of LPS, and CB(1) and CB(2) receptor agonists and antagonists. Tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were measured using enzyme-linked immunosorbent assay. Histology was performed with haematoxylin-eosin staining. KEY RESULTS Lipopolysaccharide treatment significantly reduced amplitude and frequency of myoelectric spiking activity and GI transit in vivo in a dose-dependent manner. TNF-alpha and IL-6 were increased in LPS-treated animals and histology showed oedema and cell infiltration. Both, the CB(1) agonist HU210 and the CB(2) agonist JWH133 reduced myoelectrical activity whereas the CB(1) antagonist AM251 caused an increase of myoelectrical activity. Pretreatment with AM251 or AM630 prevented against LPS-induced reduction of myoelectrical activity, and also against the delay of GI transit during septic ileus in vivo. CONCLUSIONS & INFERENCES The LPS model of septic ileus impairs jejunal myoelectrical activity and delays GI transit in vivo. Antagonists at the CB(1) receptor or the CB(2) receptor prevent the delay of GI transit and thus may be powerful tools in the future treatment of septic ileus.

Jejunal disorders: potentially lethal causes of acute abdomen are still overlooked.

OBJECTIVE: To highlight the importance of considering jejunal disorders in the differential diagnosis of acute abdomen. Although these conditions are relatively uncommon, we should keep in mind that jejunum still occurs, and deserves consideration. METHOD: This study was carried out at King Abdullah University Hospital, Jordan. Medical records of 7 patients with uncommon jejunal disorders that were encountered between 2001 and 2007 were retrospectively evaluated. We had 1 patient with jejunal diverticulitis, 1 with jejunal intussusception, 2 with jejuno-ileal tuberculosis complicated by intestinal obstruction, and 3 with acute mesenteric ischemia. All of these patients presented with acute abdominal pain of nonspecific features. Radiologic workup, along with surgical intervention, was necessary to reach a final diagnosis. RESULTS: Only 1 patient matched preoperative diagnosis, in which computed tomography scan revealed the presence of intussusception. The remaining patients were diagnosed intraoperatively. Laparoscopy and/or laparotomy with resection were performed. Morbidity was within acceptable range. There was no mortality. CONCLUSIONS: Jejunal disorders are potentially serious, and are underestimated. They are considered important causes of acute abdomen. Although they should not be at the top of a differential diagnostic list, they should always be ruled out when there is no apparent cause.

Intestinal afferent nerve sensitivity is increased during the initial development of postoperative ileus in mice.

INTRODUCTION: Neuronal reflex inhibition of gastrointestinal motility is a key mechanism in the development of postoperative ileus (POI). The aim of our study was to determine whether intestinal afferent nerve fibers are sensitized during the first hours after surgery contributing to this mechanism. METHODS: Under enflurane anesthesia, C57BL/6 mice underwent laparotomy followed by sham treatment or standardized small bowel manipulation to induce POI. After 1, 3, or 9 h, extracellular multi-unit mesenteric afferent nerve recordings were performed in vitro from 2 cm segments of jejunum (subgroups n = 6) superfused with Kreb's buffer (32 degrees C, gassed with O(2)/CO(2) mixture). Segments were cannulated to monitor luminal pressure and intestinal motility. Afferent impulses as response to bradykinin (0.5 microM) and to mechanical ramp distension of the intestinal lumen from 0 to 80 cmH(2)O were recorded. RESULTS: At 1 h, amplitudes of intestinal contractions were 0.8 +/- 0.2 cmH(2)O after induction of POI and 5.0 +/- 0.8 cmH(2)O in sham controls (mean +/- SEM; p < 0.01). A similar difference was observed for segments harvested at 3 and 9 h. Afferent firing to serosal bradykinin was increased at 1, 3, and 9 h in POI segments compared to sham controls (p < 0.05 at 1 h, p < 0.01 at 3 and 9 h). During distension with high pressures, afferent firing rate was increased at 1 and 3 h in segments after induction of POI compared to sham controls. Nine hours postoperatively, contracted and dilated segments were observed during POI that were investigated separately. While afferent firing in dilated segments was increased to 176 +/- 16 imp s(-1) at 80 cmH(2)O luminal distension (p < 0.01), it was 46 +/- 5 imp s(-1) in contracted segments (p < 0.001) compared to 77 +/- 4 imp s(-1) in sham controls. CONCLUSIONS: Afferent firing to bradykinin and high threshold distension is augmented in the early phase of POI. As these stimuli are known to sensitize predominantly spinal afferents, this mechanism may contribute to reflex inhibition of intestinal motility during POI.

Differential sensitization of afferent neuronal pathways during postoperative ileus in the mouse jejunum.

BACKGROUND: Postoperative ileus induces reflex inhibition of gastrointestinal motility and an intestinal inflammatory response. We aimed to determine whether afferent sensitivity is increased during postoperative ileus and whether alterations are cyclooxygenase-2 (COX-2)-dependent. METHODS: C57BL/6 mice underwent laparotomy followed by standardized small bowel manipulation to induce ileus or sham treatment. After 24 hours, extracellular multiunit mesenteric afferent nerve discharge was recorded in vitro from 2-cm segments of jejunum. Fos immunoreactivity was determined for neuronal activation in the vagal nucleus of the solitary tract (nTS) of the brain stem and leukocyte infiltration in the intestinal muscularis by myeloperoxidase stains. RESULTS: Serosal bradykinin (1 microM) was followed by an increase in afferent discharge to 65 +/- 5 imp x s(-1) in ileus segments compared with 37 +/- 6 imp x s(-1) in sham controls (P < 0.05). The response was attenuated to 31 +/- 7 imp x s(-1) after the selective COX-2 inhibitor 5,5-dimethyl-3-(flurorophenyl)-4-(4-methylsulfonyl) phenyl-2(5H)-furanone (DFU) in ileus segments. Afferent firing during ileus was augmented at luminal distension at 20 mm Hg but not at pressures up to 60 mm Hg. The number of Fos-positive neurons in the nTS was 110 +/- 45 during ileus compared with 7 +/- 4 in sham controls (-7.32 mm from bregma, P < 0.05) and did not differ after DFU. The intestinal muscularis contained more leukocytes during ileus compared with ileus segments after DFU and controls (both P < 0.05). CONCLUSION: This study provides direct evidence from afferent nerve recordings that sensitivity to bradykinin, which stimulates predominantly spinal afferents, is augmented during postoperative ileus involving a COX-2 pathway. Vagal afferents were also sensitized because low-threshold mechanosensitivity and neuronal activation in the nTS were increased.

Cine magnetic resonance imaging evaluation of peristalsis of small bowel with longitudinal ulcer in Crohn disease: preliminary results.

OBJECTIVE: To evaluate peristalsis of the small bowel with a longitudinal ulcer in Crohn disease using cine magnetic resonance imaging (MRI). METHODS: Fifteen patients with suspected or diagnosed Crohn disease were examined by cine MRI using a multislice and multiphase method. Inclusion criteria were pathological evidence of Crohn disease and confirmation of longitudinal ulceration in the small bowel by ileocolonoscopy, single- or double-contrast radiography of the small bowel, or surgery. Six of these patients were included in this study. Cine MRI findings of the small bowels were retrospectively reviewed by 2 radiologists. RESULTS: Asymmetric involvement or mesenteric rigidity with antimesenteric flexibility was seen in all patients by cine MRI. This finding was not seen in normal small bowel segments. A combination of ileocolonoscopy and contrast radiography detected longitudinal ulcers in 5 of the 6 patients, and surgery revealed ulceration in the remaining patient. CONCLUSIONS: Cine MRI was a feasible approach for detecting a longitudinal ulcer in small-bowel Crohn disease.

Duodeno-jejunal junction dyssynergia: description of a novel syndrome.

AIM: To investigate the hypothesis that duodeno-jejunal dyssynergia existed at the duodeno-jejunal junction. METHODS: Of 112 patients who complained of epigastric distension and discomfort after meals, we encountered nine patients in whom the duodeno-jejunal junction did not open on duodenal contraction. Seven healthy volunteers were included in the study. A condom which was inserted into the 1st duodenum was filled up to 10 mL with saline in increments of 2 mL and pressure response to duodenal distension was recorded from the duodenum, duodeno-jejunal junction and the jejunum. RESULTS: In healthy volunteers, duodenal distension with 2 and 4 mL did not produce pressure changes, while 6 and up to 10 mL distension effected significant duodenal pressure increase, duodeno-jejunal junction pressure decrease but no jejunal pressure change. In patients, resting pressure and duodeno-jejunal junction and jejunal pressure response to 2 and 4 mL duodenal distension were similar to those of healthy volunteers. Six and up to 10 mL 1st duodenal distension produced significant duodenal and duodeno-jejunal junction pressure increase and no jejunal pressure change. CONCLUSION: Duodeno-jejunal junction failed to open on duodenal contraction, a condition we call 'duodeno-jejunal junction dyssynergia syndrome' which probably leads to stagnation of chyme in the duodenum and explains patients' manifestations.