Lamina muscularis mucosae sitting beneath mucosal surface of the digestive tract has received little attention to date compared with external smooth muscle layers. Motor activity of the muscularis mucosae shows a great regional and species difference. Autonomic innervation profile is also different from esophagus to colon or between animal species. Intracellular transduction mechanisms for motor activity of the muscularis mucosae are also different from those of external longitudinal and circular muscles or from vascular and airway smooth muscles. Since the submucosal area is a major source for eicosanoid production, abnormality of muscularis mucosae motor activity may link with abnormality of mucosal absorption and secretion functions. Inflammatory bowel diseases such as diarrhea, irritable bowel syndrome and Crohn's disease accompanied with altered motor activity of the muscularis mucosae. Much attention should be attracted to the human muscularis mucosae as a new therapeutic target for inflammatory bowel diseases.
Background: Gastrointestinal (GI) symptoms are common in patients with chronic renal failure (CRF). We have previously demonstrated that patients with predialysis end-stage renal disease showed a high prevalence of GI symptoms and gastric hypomotility, and that gastric hypomotility appears to be an important factor in generating GI symptoms. However, it is not clear whether impaired gastric motor function would improve after hemodialytic treatment. Aims: To examine the relationship between gastric motor function and GI symptoms in CRF patients on hemodialysis. Methods: The study was performed in 19 patients with CRF treated with hemodialysis for more than six months and in 12 matched healthy controls. GI symptom severity was quantified in all patients. Gastric motility was evaluated with cutaneously recorded electrogastrography (EGG) and gastric emptying of semi-solid meals using the 13C-acetic acid breath test. Results: Six patients had no symptoms, and 11 had slight GI symptoms with a total symptom score of less than 5. Compared with controls, CRF patients revealed no differences in gastric motility parameters, with the exception of a lower percentage of normogastria in EGG at fasting state. Eleven patients had normal gastric motor function (Group A), and eight showed abnormalities of either gastric myoelectrical activity or gastric emptying (Group B). There was no difference in symptom score between Group A and Group B. Conclusions: More than half of the patients with CRF on hemodialysis demonstrated normal gastric motility, and no or slight GI symptoms. Hemodialytic treatment may improve impaired gastric motility and reduce GI symptoms in patients with CRF.
Diabetic gastropathy is suggested to be the result of not only an autonomic neuropathy but also to disorder of the spontaneous rhythmic motility of the gastric smooth muscle. Attempts were made to investigate the alteration of the effects of endothelin-1 (ET-1), which is known to enhance the spontaneous activity of gastrointestinal smooth muscle, on gastric activity in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were prepared by the injection of Sprague-Dawley (SD) rats with STZ (i.p.). Isometric mechanical responses were recorded in isolated circular smooth muscle strips of the stomach antrum, to measure changes in the rhythmicity of the smooth muscle. ET-1 (10 nM) significantly elevated the resting tension and the frequency of spontaneous contraction, but did not alter the amplitude of the spontaneous oscillatory contractions in normal rats. In diabetic rats, ET-1 elevated the resting tension, and spontaneous contractions were increased in frequency, however they were decreased in amplitude. In normal rats, sarafotoxin S6c (S6c, 10 nM), a selective ETB receptor agonist, elevated the resting tension slightly and increased both the frequency and amplitude of the spontaneous contractions. However, S6c significantly elevated the resting tension alone in STZ-induced diabetic rats. Selective stimulation of endothelin type A (ETA) receptors with ET-1, in the presence of a selective antagonist of ETB receptors, produced similar responses in the gastric muscle of both normal and diabetic rats. These results indicate that ET-1 elevates the resting tension and increases the frequency of the spontaneous oscillatory contractions in both normal and STZ-induced diabetic rats, to a similar extent. However, the specific actions on ETB receptors were quite different between the two: the elevating actions on the resting tension were much greater in STZ-diabetic rats than in normal rats. The results suggested the facilitation of ETB receptor signaling in the antrum during the pathogenesis of diabetic gastropathy.
In the [13C]-octanoate breath test, two popular parameters have been used to quantify gastric emptying rates, namely the time to the maximal [13CO2] excretion (Tmax) and the time to the half-[13CO2] recovery (T1/2b). Although each of Tmax and T1/2b is closely correlated with the scintigraphic half-emptying time, the two parameters occasionally indicate different judgments on a gastric emptying rate. In this study, to clarify which of the two parameters is more reliable, Tmax and T1/2b were compared to the "reference" parameters calculated using the Wagner-Nelson method, which allows accurate estimation of a time-course of gastric emptying from breath data. Ten healthy male volunteers underwent the breath test after ingestion of a muffin meal (320 kcal) containing 100 mg [13C]-octanoate. Breath samples were collected at 15-min intervals for 6 h. According to the conventional analytical algorithm, Tmax and T1/2b were mathematically calculated. By applying Wagner-Nelson analysis to the breath test, the time-percent gastric retention curve was generated and the half-emptying time (T1/2WN) was determined. T1/2WN was more closely correlated with Tmax (r=0.954, P<0.0001) than with T1/2b (r=0.782, P=0.008). Tmax was significantly correlated with the percent gastric retention value in the early (t=0.25 and 0.5 h), the middle (t=1.0 and 1.5 h), and the late (t=2.0 h) postprandial phase. T1/2b was significantly correlated with the gastric retention value in the middle and the late phase, but not with the gastric retention value in the early phase. The present results show that T1/2b has limited capability to reflect gastric emptying in the early postprandial period, suggesting that Tmax is more reliable than T1/2b as a gastric emptying parameter.
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