Impairment of gastric accommodation induced by water-avoidance stress is mediated by 5-HT2B receptors.

BACKGROUND: Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5-HT2B receptors in a guinea pig model of stress-induced impairment of GA. METHODS: Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water-avoidance stress. The role of 5-HT2B receptors in impairment of GA was investigated by administering a 5-HT2B receptor agonist (BW723C86) or antagonist (SB215505), the traditional Japanese medicine rikkunshito (RKT), a muscarinic M3 receptor antagonist (1,1-dimethyl-4-diphenylacetoxypiperidium iodide [4-DAMP]), or a nitric oxide synthase inhibitor (Nω -nitro-L-arginine [L-NNA]). KEY RESULTS: In normal animals, liquid meal-induced GA was inhibited by BW723C86, but was not affected by SB215505. The inhibition of GA by BW723C86 was reversed by co-administration of 4-DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB215505 and RKT significantly suppressed stress-induced impairment of GA. After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L-NNA was suppressed by SB215505 or RKT. At a dose that did not affect GA in normal animals, BW723C86 exacerbated the impairment of GA in stressed animals. CONCLUSIONS AND INFERENCES: Stress-induced impairment of GA may be mediated by an increased responsiveness of 5-HT2B receptors, and activation of the 5-HT2B receptor signaling pathway may have an inhibitory effect on nitric oxide function.

Effect of rikkunshito on the expression of substance P and CGRP in dorsal root ganglion neurons and voluntary movement in rats with experimental reflux esophagitis.

BACKGROUND: While there are reports that the herbal medicine rikkunshito (RKT) relieves upper gastrointestinal disease symptoms, the effect of RKT on primary afferent neurons is unknown. METHODS: A model of reflux esophagitis (RE) was implemented using male Wistar rats aged 6-7 weeks. Ten days after surgery, the total area of esophageal mucosal erosion sites was determined. Th8-10 dorsal root ganglia (DRG) were dissected out and the expression of substance P (SP), calcitonin gene-related peptide (CGRP), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) was determined in DRG using immunohistochemistry. RKT (0.6%/WV) or omeprazole (OME) (10 mg/kg) was administered for 10 days beginning on the day after surgery. Voluntary movement was measured with an infrared sensor for 22 h each day. KEY RESULTS: RE rats showed esophageal mucosal erosion and significantly increased number of SP/CGRP- and p-ERK1/2-immunoreactive neurons in DRG. Treatment with OME improved the size of erosive lesions in the esophageal mucosa of RE rats, while RKT did not. Treatment with RKT or OME significantly reduced the expression of SP/CGRP and p-ERK1/2 in DRG, and significantly increased voluntary movement in RE rats. CONCLUSIONS & INFERENCES: RKT inhibited the activation of ERK1/2 and decreased the expression of SP and CGRP in DRG of RE rats, which may be associated with the observed amelioration of voluntary movement.

Early nonpolypoid colorectal cancer: radiographic diagnosis of depth of invasion.

PURPOSE: To diagnose depth of invasion of early flat and depressed nonpolypoid colorectal cancers with double-contrast barium enema examination. MATERIALS AND METHODS: Ninety-seven early nonpolypoid colorectal cancers, initially identified with colonoscopy, were investigated with double-contrast barium enema examination. Depth of invasion in resected specimens obtained with endoscopic mucosal or surgical resection was determined. Cancer confined to the mucosal layer or with focal extension to the submucosal layer was defined as Ca-m; moderate to massive extension of cancer into the submucosal layer was classified Ca-sm. RESULTS: In flat elevated and depressed cancers, converging folds and semilunar deformity were observed significantly more frequently in Ca-sm than in Ca-m tumors (P < .05 and P < .01, respectively). Sensitivities and specificities of these findings for Ca-sm tumor were 42%, 93% and 86%, 85%, respectively. Deep depression, irregular surface of the depression, and tumor size larger than 20 mm were also predictive findings for depressed Ca-sm tumors (P < .05); the specificity of each was 100%. With use of these radiographic predictors, overall accuracy for diagnosing depth of invasion was 85%. CONCLUSION: Findings on double-contrast barium enema study are highly predictive of depth of invasion of early nonpolypoid colorectal cancer. Radiographic findings of converging folds, semilunar deformity, deep depression, irregular surface of the depression, and tumor size are predictors of Ca-sm tumor.

[An infradian rhythm of weight increment velocity in patients with Crohn's disease during nutritional therapy].

We examined the rhythm of weight velocity in eight patients with Crohn's disease. In this paper we used the spline smoothing technique to study the cycle in the weight increment velocity curves derived from individual data during nutritional therapy. As a result of the weight measurement at four-day intervals, an infradian rhythm with the average cycle of 9.6 +/- 0.7 was recognized in all of the subjects in terms of the weight increment velocity. This rhythm was especially conspicuous in three adolescent patients with serious nutritional lesion. The cycle of the rhythm was unaffected by any of the following factors: energy intake, contents of nutritional therapy, medical examination during the period. Our findings of a common cycle in the process of convalescence from a low nutritious stage in patients with Crohn's disease suggest that, in others as well, the weight increment velocity might have an infradian rhythm with a kind of inherent periodicity.