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Background and Aim: We recently conducted a randomized placebo-controlled trial on the efficacy and safety of rikkunshito, a standardized Japanese herbal medicine, for the treatment of functional dyspepsia (FD). The present post-hoc study aimed to evaluate the differences in clinical characteristics between responders and non-responders among FD patients who received rikkunshito for 8 weeks., Methods: Rikkunshito responders were defined by using a global patient assessment. Candidate predictors included age, gender, smoking, alcohol consumption, body mass index, comorbidity, Helicobacter pylori infection, plasma levels of acyl ghrelin and des-acyl ghrelin, severity of dyspeptic symptoms, FD subgroup, previous medication, and the type of recruiting institution (clinic or hospital). We calculated hazard ratios (HRs) by using Cox regression analysis with the factors that were indicated to be associated with responders., Results: We assigned 83 and 42 patients to responder and non-responder categories, respectively. Lack of alcohol consumption (HR, 2.04; 95% confidence interval, 1.08-3.88) and low plasma des-acyl ghrelin levels (< 177 fmol/mL; HR, 2.42; 95% confidence interval, 1.24-4.73) were significantly associated with the efficacy of rikkunshito. Lack of alcohol consumption was associated with the efficacy of rikkunshito especially among H. pylori-infected participants. On the other hand, the low plasma des-acyl ghrelin was associated with the efficacy of rikkunshito especially among H. pylori-negative participants., Conclusions: A low baseline level of plasma des-acyl ghrelin was associated with an increased treatment efficacy of rikkunshito against FD. Lack of alcohol consumption was also clinically useful for predicting the response to rikkunshito., (© 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Ghrelin has distinct effects on gastrointestinal motility through the vagus nerve and gastric excitatory neural plexus. The objectives of this study were to investigate the dynamics of ghrelin and expression of neuromuscular markers in a newly established surgically manipulated rat model of gastric outlet obstruction (GOO), akin to the pyloric stricture associated with duodenal ulcer, advanced gastric cancer, and other conditions, in the clinical setting., Material and Methods: The rats were divided into two groups, a control group (sham operation) and the GOO group (proximal duodenal stricture). The animals were sacrificed 2 weeks after the operation. Plasma and gastric ghrelin were measured by radioimmunoassay. mRNA expression in the stomach of neural choline acetyltransferase (ChAT), c-kit, and membrane-bound stem cell factor (SCF) were analyzed by quantitative RT-PCR. In addition, gastric mRNA expression of the aforementioned were also evaluated 60 min after intraperitoneal administration of a synthetic GHS-R1a antagonist ([D: -Lys3] GHRP-6 6.0 mg/kg)., Results: Mechanical GOO induced increases of fasting plasma ghrelin levels and hyperplasia of the gastric muscle layers, with enhanced expression of the gastric neuromuscular markers. Administration of [D: -Lys3] GHRP-6 normalized the enhanced expression of c-kit and SCF., Conclusion: GOO stimulates ghrelin dynamics and then enhances the mechanistic expression of gastric cellular communication network molecules between nerves and smooth muscle cells.

Background Rikkunshito, a standardized Japanese herbal medicine, is thought to accelerate gastric emptying and relieve dyspepsia, although no large-scale, randomized, placebo-controlled trials of rikkunshito have been conducted. This study aimed to determine the efficacy and safety of rikkunshito for treating functional dyspepsia ( FD). Methods FD patients received 2.5 g rikkunshito or placebo three times a day for 8 weeks in this multicenter, randomized, placebo-controlled, parallel-group trial. The primary end point was the proportion of responders at 8 weeks after starting test drug, determined by global patient assessment ( GPA). The improvement in four major dyspepsia symptoms severity scale was also evaluated. In addition, plasma ghrelin levels were investigated before and after treatment. Key Results Two hundred forty-seven patients were randomly assigned. In the eighth week, the rikkunshito group had more GPA responders (33.6%) than the placebo (23.8%), although this did not reach statistical significance ( p = 0.09). Epigastric pain was significantly improved ( p = 0.04) and postprandial fullness tended to improve ( p = 0.06) in the rikkunshito group at week 8. Rikkunshito was relatively more effective among Helicobacter pylori-infected participants (rikkunshito: 40.0% vs placebo: 20.5%, p = 0.07), and seemed less effective among H. pylori-uninfected participants (rikkunshito: 29.3% vs placebo: 25.6%, p = 0.72). Among H. pylori-positive individuals, acyl ghrelin levels were improved just in rikkunshito group. There were no severe adverse events in both groups. Conclusions & Inferences Administration of rikkunshito for 8 weeks reduced dyspepsia, particularly symptoms of epigastric pain and postprandial fullness. ( UMIN Clinical Trials Registry, Number UMIN000003954). [ABSTRACT FROM AUTHOR]

Background Ghrelin, growth-hormone-releasing peptide, has been reported to accelerate food intake and gastrointestinal motility. Aim The present study was designed to investigate the plasma ghrelin levels in patients with functional dyspepsia (FD). Patients and Methods Ninety-seven patients, who showed no evidence of peptic ulcer disease or gastrointestinal cancer on upper gastrointestinal endoscopy, were recruited. Seventeen patients who had no gastrointestinal symptoms were recruited as controls. Forty-seven patients were diagnosed to be suffering from FD, based on the Rome II criteria. The FD patients were further subdivided into those with ulcer-like FD, dysmotility-like FD and non-specific-type FD, based on their Gastrointestinal Symptom Rating Scale (GSRS) scores. Fourteen patients were categorized as having gastro-oesophageal reflux disease, and 19 patients were excluded as having the irritable bowel syndrome, based on the GSRS. The plasma ghrelin levels were measured by radioimmunoassay. Results The plasma ghrelin levels were significantly higher in FD patients, especially in those with dysmotility-like FD, as compared with those in controls. The plasma ghrelin levels were also correlated well with the indigestion scores. Conclusion Plasma ghrelin levels are significantly higher in patients with dysmotility-like FD, suggesting that this parameter could become useful as a novel supportive marker for the diagnosis of FD. [ABSTRACT FROM AUTHOR]

Background Ghrelin, a recently discovered peptide hormone, has been shown to be produced mainly by the A-like cells of the gastric mucosa. Ghrelin not only stimulates growth hormone (GH) release but also promotes gastric motility. While the effect of ghrelin on the gastric acid secretion in rats has been reported, no such reports appeared to date from studies in humans. Aim To investigate the effect of ghrelin administration on the gastric pH in humans, using a novel wireless pH capsule (Bravo, Medtronic, Shoreview, MN, USA). Methods Four healthy volunteers (male; average age, 35.0 years; Helicobacter pylori-negative) were enrolled. The pH capsule was attached endoscopically to the gastric mucosa and the data were transmitted to a portable receiver. Thirty minutes after a stabilization period, synthetic ghrelin (5 μg/kg body weight) was injected intravenously into the subjects and the data were monitored for more than 120 min while the subjects lay supine. Results The average minimum gastric pH in four cases (1.2 ± 0.10) was significantly decreased after injection of ghrelin, as compared with the basal pH value (1.8 ± 0.06). The serum gastrin level, however, showed no change after the ghrelin injection. Conclusion These results suggest that exogenous ghrelin could enhance gastric acid secretion in humans. [ABSTRACT FROM AUTHOR]

Background Ghrelin is a novel appetite-promoting peptide secreted primarily from the A-like cells in the gastric fundic mucosa. As gastric inflammation caused by Helicobacter pylori infection extends, the number of ghrelin-producing A-like cells is diminished and gastric ghrelin content decreases significantly. We previously reported that plasma levels of ghrelin, which correlated well with the serum levels of pepsinogen (PG) I and PG I/II ratio, decreased as gastric mucosal atrophy increased in non-ulcerogenic conditions and that plasma ghrelin level increased in rats with cysteamine-induced duodenal ulcer. Aim To investigate the plasma levels of ghrelin in patients with peptic ulcer disease. Patients and Methods Two hundred and eighty-six patients with epigastric symptoms, who underwent upper gastrointestinal endoscopy, were enrolled. Blood samples were collected after a 12-h fast before endoscopy. Patients were divided into four groups, namely chronic gastritis with high PG ( n = 197), chronic gastritis with low PG ( n = 58), duodenal ulcer ( n = 14) and gastric ulcer ( n = 17) and plasma concentrations of total and active ghrelin as well as serum concentrations of PG I and PG II were measured by radioimmunoassay. Six patients with duodenal ulcer and seven with gastric ulcer were also examined after ulcer healing. Results Plasma ghrelin levels were significantly higher in patients with duodenal ulcer or gastric ulcer than in those without ulcers. Elevated plasma total ghrelin levels did not significantly change after the healing of ulcers. Conclusions Plasma ghrelin levels were significantly higher in patients with peptic ulcer than in those with gastritis without ulcer. This finding suggests a possible relationship between mucosal injury susceptibility and elevated fasting plasma ghrelin. [ABSTRACT FROM AUTHOR]