Emptying Of Meal Research Articles

Gastric emptying and orocaecal transit time of meals containing lactulose or inulin in men

The H(2) breath test is ideal for orocaecal transit time (OCTT) measurement, as it is non-invasive and inexpensive. Indigestible substrates added to a test meal are metabolised by the colonic bacteria, resulting in the production of H(2) which is detected in end-exhalation breath. However, the substrates themselves can alter the transit times in the gastrointestinal tract. The aim of the present study is to compare OCTT and gastric emptying (GE) when lactulose in liquid (L-L), solid lactulose (L-S) and solid inulin (IN-S) are added to a test meal, and subsequently, to examine if inulin alters GE. Firstly, ten male volunteers were tested on three occasions. Volunteers ate a pancake breakfast containing 100 mg of (13)C-octanoic acid and either 12 g of L-L, 12 g of L-S or 12 g of IN-S in a randomised order. Secondly, seven male volunteers were tested twice with meals containing either 12 g of IN-S or no substrate (NO-S). L-L induced the shortest OCTT (85.3 (sd 42.8) min) compared with L-S (162.4 (sd 62.6) min) and inulin (292.4 (sd 66.7) min; P = 0.007). GE half-time and lag phase (L-L: 61 (sd 9); L-S: 57 (sd 10); IN-S: 52 (sd 10) min; P = 0.005) were also affected, with L-L being the slowest. Thirdly, inulin reduced GE lag and latency phases (P < 0.05) compared with NO-S. Lactulose accelerates OCTT but delays GE compared with inulin. Inulin accelerates the onset of stomach emptying, but it has no effect on GE half-time. For these reasons, inulin is the preferred substrate for the H(2) breath test.

Effect of Endogenous GLP-1 on Insulin Secretion in Type 2 Diabetes

OBJECTIVEThe incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) account for up to 60% of postprandial insulin release in healthy people. Previous studies showed a reduced incretin effect in patients with type 2 diabetes but a robust response to exogenous GLP-1. The primary goal of this study was to determine whether endogenous GLP-1 regulates insulin secretion in type 2 diabetes.METHODSTwelve patients with well-controlled type 2 diabetes and eight matched nondiabetic subjects consumed a breakfast meal containing d-xylose during fixed hyperglycemia at 5 mmol/l above fasting levels. Studies were repeated, once with infusion of the GLP-1 receptor antagonist, exendin-(9–39) (Ex-9), and once with saline.RESULTSThe relative increase in insulin secretion after meal ingestion was comparable in diabetic and nondiabetic groups (44 ± 4% vs. 47 ± 7%). Blocking the action of GLP-1 suppressed postprandial insulin secretion similarly in the diabetic and nondiabetic subjects (25 ± 4% vs. 27 ± 8%). However, Ex-9 also reduced the insulin response to intravenous glucose (25 ± 5% vs. 26 ± 7%; diabetic vs. nondiabetic subjects), when plasma GLP-1 levels were undetectable. The appearance of postprandial ingested d-xylose in the blood was not affected by Ex-9.CONCLUSIONSThese findings indicate that in patients with well-controlled diabetes, the relative effects of enteral stimuli and endogenous GLP-1 to enhance insulin release are retained and comparable with those in nondiabetic subjects. Surprisingly, GLP-1 receptor signaling promotes glucose-stimulated insulin secretion independent of the mode of glucose entry. Based on rates of d-xylose absorption, GLP-1 receptor blockade did not affect gastric emptying of a solid meal.

P.31 FREQUENCY, SYMPTOMS EVOLUTION AND PATHOPHYSIOLOGICAL CORRELATES IN PROSPECTIVELY IDENTIFIED PATIENTS WITH POSTINFECTIOUS DYSPEPSIA

Background and aim: Functional bowel disorders may follow acute intestinal infection. A single, retrospective study showed that a subset of dyspeptic patients had a history of gastroenteritis. No data are available in patients with prospectively identified postinfectious dyspepsia (PD). We aimed to characterize frequency, symptoms evolution and underlying mechanisms of functional dyspepsia after acute gastroenteritis. Material and methods: A total of 150 consecutive patients with undergoing acute gastroenteritis were screened and followed-up for 1 month (m). In patients with symptoms persistence upper GI endoscopy, breath test-based gastric emptying study and satiety testing (to estimate gastric fundus accommodation) were performed. Pattern and severity of symptoms were scored at 3, 6 and 12 m by standardized questionnaire. Gastric emptying and satiety testing were repeated at 6 m. Patients with previous diagnosis of FGIDs or organic disease were excluded. Normal values of gastric emptying rate and meal-induced satiety (120 min and 890 kcal, respectively) were obtained on 20 age/sex matched healthy subjects. Results: At baseline no signs of infection were found in the majority of the patients, except than giardia lamblia and salmonella tiphy in 3 and 1 patients. Persistence of dyspeptic symptoms at 1 m was observed in 31 subjects (18 male, age 28±10), with postprandial fullness, bloating, belching, nausea, epigastric pain, early satiety and vomiting being reported by 85, 70, 70, 56, 67, 48 and 19% of the patients, respectively; systematic analysis revealed that such pattern of symptoms was quite stable along the times. Although severity was gradually reducing for the majority of the symptoms, only patients reporting severe belching were significantly reduced at 12 m (70 vs. 12%, p<0.05). At baseline, delayed gastric emptying and impaired satiety testing were present in 60% and 85% of the patients with a similar percentage at 6 m (58 and 90%, respectively). Conclusions: We showed that at least 20% of prospectively evaluated patients with acute gastroenteritis develop and maintain dyspeptic symptoms after the resolution of the acute phase. In these patients symptoms severity was gradually reducing, but still persistent up to 1 year. Persistent delayed gastric emptying of solid meal and impaired gastric accommodation are putative mechanisms involved in symptoms generation. # C. Functional disorders 1. Dyspepsia

Gastric emptying evaluation in children with erosive gastroesophageal reflux disease

Delayed gastric emptying may be an important contributing factor to gastroesophageal reflux disease (GERD) in children, but there are limited data on its evaluation in children with erosive-GERD. This study aims to evaluate the gastric emptying of a solid meal in patients with erosive-GERD. Nineteen patients (age range 8.79-17.9 years) with erosive esophagitis and 14 healthy controls (age range from 8.04 to 18.7 years) were compared. Esophagitis was graded according to Los Angeles classification. The gastric emptying was evaluated by (13)C-octanoic breath test, which was performed after a 344 kcal standardized solid test meal. Symptoms were evaluated using a standardized questionnaire. The two most prevalent symptoms were nausea and epigastric pain, which were reported by 12 (63.2%) patients. Irritable bowel syndrome was present in 26.3% (5/19). The median gastric emptying half-time in patients was 160 min (interquartile range [IQR] 140-174 min), which was not different from the controls' figure (median 157 min, IQR 143-170 min). Additionally, the lag time and the gastric emptying coefficient were not significantly different between the study groups. Delayed gastric emptying is not associated with erosive esophagitis in children with GERD, when compared to controls.

Effects of Proton Pump Inhibitors on Gastric Emptying: A Systematic Review

The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes.

Upper gastrointestinal motility changes following spinal cord injury

Spinal cord injury (SCI) is associated with severe autonomic dysfunction in both the acute and chronic phases. Upper gastrointestinal (GI) motor dysfunction has been previously reported in humans and rats. Gastric emptying (GE) of a solid meal--as measured by the [(13)C]-octanoic acid breath test--is delayed in the first 3 weeks after either spinal cord transection (SCT) or contusion (SCC) in rats. This is one of the main findings of a new paper by Qualls-Creekmore et al. in the current issue of this journal. Previous studies in rats only reported impairment of GE, intestinal and GI transit of liquid after SCI, but the authors observed that the delay of the GE of solid was more prominent after SCT than SCC. Recovery of the delay of GE of solid occurred at 6 weeks after SCC, but not after SCT. However, gastric motility changes persisted despite the functional normalization of the GE in rats with SCC. Bowel dysfunction is a major physical and psychological burden for SCI patients. Collaborative efforts, like the development of international standards to evaluate autonomic function after SCI will likely clarify the mechanisms of dysfunction and lead to the development of new therapeutic strategies.

Dumping Syndrome: Establishing Criteria for Diagnosis and Identifying New Etiologies

To investigate the current incidence and identify the current etiologies of rapid gastric emptying (dumping syndrome) in patients with a spectrum of gastrointestinal symptoms, including nausea, vomiting, abdominal pain, or diarrhea. The results for a 4-h radionuclide gastric emptying test (GET) using a standardized scintigraphic technique were reviewed in 545 patients to see which patients met criteria for rapid gastric emptying, defined as >50% emptying of isotope-labeled solid meal at 1 h. Forty-eight of 545 (8.8%) patients (28 females, mean age 46 +/- 2 years, range 32-58 years) had rapid GET. Seventeen of 59 (35%) met Rome III diagnostic criteria for cyclic vomiting syndrome (CVS). Twelve of these 59 (25%) patients were regarded as non-ulcer dyspepsia and six (13%) had dyspepsia in the setting of diabetes mellitus. Five (10.5%) were post-fundoplication surgery, where an accidental vagotomy was confirmed by sham meal challenge; previous gastric bypass surgery for obesity had been performed in three (6%) patients. Five (10.5%) patients with unexplained abdominal pain and diarrhea had the working diagnosis of irritable bowel syndrome. Rapid gastric emptying can be identified in a sizeable subset (9%) of patients with unexplained nausea, vomiting, abdominal pain, and diarrhea when criteria are applied to the standardized scintigraphic gastric emptying meal.

Gastric Emptying

Gastric Emptying

Deletion of P2X3 receptors blunts gastro‐oesophageal sensation in mice

Prior studies have demonstrated P2X receptor expression in the majority of nodose neurons. Immunoreactivity for P2X receptors has also been seen in putative gastric mechanoreceptors, the intraganglionic laminar endings. We therefore hypothesized that deletion of P2X3 receptors will blunt responses to gastric distension in vagal sensory neurons. Using wildtype and P2X3(-/-) mice, we examined responses to purinergic agonists in retrogradely labelled gastric sensory neurons with patch-clamp techniques. Activation of gastro-oesophageal neurons by fluid distension was studied with intracellular electrodes. Distension-evoked ATP release into the gastric lumen was determined with the luciferase assay and intake and gastric emptying of a solid meal was assessed. ATP triggered inward currents in 80% of gastric nodose neurons. In P2X3(-/-) mice, the peak current density was lower compared to controls. Ten of 14 controls but none of 30 neurons from P2X3(-/-) mice responded to alpha,beta-metATP. Gastro-oesophageal sensory neurons of P2X3(-/-) mice showed a blunted response to fluid distension of oesophagus and stomach. This difference was not explained by differences in distension-evoked ATP release, which did not differ between knockout mice and controls. Food intake during a 3-h period was lower in P2X3(-/-) mice. Gastric emptying of a solid meal was slightly faster in knockout mice after 1.5 h, but did not differ between groups at 3 h. Our data support a role of purinergic signalling in gastric vagal afferents. Considering the role of vagal input in sensations of fullness or nausea, P2X receptors may be interesting treatment targets for dyspeptic symptoms.

Gastric Emptying of Semisolids and Pouch Motility Following Laparoscopic Adjustable Gastric Banding

Laparoscopic adjustable gastric banding (LAGB) has been popularized as an effective, safe, minimally invasive surgical technique for the treatment of morbid obesity. We performed a pilot study to evaluate gastric emptying of semisolid meals and antral motility following LAGB. Gastric emptying half-time was compared in normal volunteers and morbidly obese patients before and 6-12 months after LAGB using sulfur colloid-labeled semisolid meals. There was no difference in mean age between groups. Women were prevalent in the group of obese patients. BMI was higher in patients before surgery (p < 0.001). Patients following LAGB demonstrated prolonged gastric pouch emptying (T1/2 = 36.6 +/- 9.8 min) compared to subjects without surgery (23.8 +/- 4.7 min) and healthy volunteers (22.8 +/- 6.8 min; p < 0.001). Similar gastric contractility was found all groups (3.3 +/- 0.4; p = 0.968). No cases of band slippage or pouch dilatation were observed during mean follow-up of 11.4 months. A standard normal gastric pouch emptying rate of semisolids in asymptomatic patients after LAGB was established. Postoperative prolongation of gastric emptying is a matter of mechanical delay without gastric pouch denervation. This study provides a first step of future functional evaluation of complications following this type of bariatric surgery.

Predictors of Gastric Myoelectrical Activity in Type 2 Diabetes Mellitus

Previous studies have clearly demonstrated the delayed gastric emptying of solid meals in diabetics, whereas their gastric myoelectrical activity, which primarily determines gastric motility, has not yet been fully confirmed. This study aimed to clarify the characteristics and potential predictors of gastric myoelectrical activity in type 2 diabetics. Twenty-eight diabetics and 18 healthy controls participated. Duodenal biopsy sample was used for reverse transcription-polymerase chain reaction to evaluate cholecystokinin and motilin mRNA contents. Electrogastrography was performed before and after the test meal, and was assessed in terms of dominant frequency; dominant frequency instability coefficient; and the percentage of bradygastria, normogastria, and tachygastria. Over the entire recording period, dominant frequency was significantly lower, and dominant frequency instability coefficient and the percentage of bradygastria were significantly higher in diabetics than in controls. In diabetics, the multiple regression analysis demonstrated that dominant frequency instability coefficient and the percentage of tachygastria in the fasting period were dependent on fasting plasma glucose level and HbA1c, respectively. Moreover, dominant frequency over the entire period and the postprandial percentage of bradygastria were significantly associated with body mass index; the fasting percentage of bradygastria and postprandial dominant frequency instability coefficient were associated with fasting serum leptin level; the postprandial percentage of bradygastria was also associated with cholecystokinin mRNA content. Gastric myoelectrical activity in type 2 diabetics is impaired on dominant frequency, dominant frequency instability coefficient, and the percentage of bradygastria and predicted by body mass index, fasting serum leptin level, and cholecystokinin mRNA content besides the glycemic status.

Gastric emptying of carbohydrate meals.

Gastric emptying of carbohydrate meals.

Influence of Quercetin on Diabetes-Induced Alteration in CYP3A Activity and Bioavailability of Pioglitazone in Rats

Problem statement: Quercetin-a common bioflavonoid, is present in herbal preparations consumed by diabetic patients along with routine anti-diabetic agents. We recently showed that quercetin increases the bioavailability of pioglitazone in non-diabetic rats. Thus, present study investigated whether this pharmacokinetic interaction is also evident in diabetic animals, especially because diabetic subjects have altered gastrointestinal (GI) function and CYP3A activity. Approach: The study was carried out in alloxan-induced (40 mg kg-1, i.v.) diabetic rats. After 2 weeks of diabetes induction, rats were treated for 2 weeks with quercetin (10 mg kg-1, p.o.) or vehicle (5% methyl cellulose, 10 mL kg-1). At the end of 4 weeks, these rats were used to investigate: (1) GI function in terms of gastric emptying and intestinal transit of semisolid barium sulphate meal; (2) CYP3A activity in liver and intestinal microsomes by erythromycin N-demethylase assay; (3) Plasma levels of orally and intravenously administered pioglitazone (10 mg kg-1, p.o.; 5 mg kg-1, i.v.). Results: The results revealed that diabetic rats exhibited: (1) Delayed gastric emptying and intestinal transit; (2) Decreased CYP3A activity and (3) A significant increase in the oral and intravenous AUC0-∞ of pioglitazone as compared to non-diabetic rats. Quercetin treatment prevented the diabetes-induced GI dysfunction, whereas diabetes-induced decrease in CYP3A activity and increased bioavailability of pioglitazone remained unaffected. Conclusion: The results suggested that quercetin attenuated GI dysfunction but did not affect the bioavailability of pioglitazone in diabetic rats contrary to the increase reported in non-diabetic rats. However, the safety of co-joint use of quercetin containing herbs and pioglitazone in clinical practice requires further pharmacokinetic substantiation.

Gastric emptying of liquid and solid meals at various temperatures

Patients with functional dyspepsia frequently show delayed gastric emptying, and dietary advice is frequently given for its improvement. If meal temperature influences gastric emptying, advice regarding the meal temperature may become a possible component of dietary therapy. However, little information exists concerning the thermal effect of meals on gastric emptying. The aim of this study was to determine the thermal effect of liquid and solid meals on gastric emptying. The gastric emptying of liquid and solid test meals was examined in healthy volunteers (liquid, n = 25, mean age = 35.7 +/- 9.6 years, male-to-female ratio = 22:3; solid, n = 25, mean age = 35.2 +/- 8.8 years, male-to-female ratio = 20:5). Gastric emptying after the ingestion of liquid or solid meals at three different temperatures (4, 37, and 60 degrees C) was investigated with the [(13)C]-labeled acetate breath test. The lag phase time (T (max-calc)) and the half-emptying time (T (1/2)) were calculated from the (13)CO(2) breath excretion curve as indices of gastric emptying. The values of T (max-calc) at 60 degrees C with both the liquid and solid meals were significantly smaller than those at 37 degrees C (P < 0.05). However, there was no difference in the T (1/2) values. In the analysis of the percent excretion of (13)CO(2) in 1 h (% dose/h) data with the liquid meal test in the earlier phase within 30 min, significantly larger values were found at 60 degrees C than at the other temperatures. These findings suggest that a hot meal significantly accelerates gastric emptying. Meal temperature may be considered as a component of dietary therapy for patients with functional dyspepsia.

Monosodium l-glutamate added to a high-energy, high-protein liquid diet promotes gastric emptying

BackgroundFree glutamate activates taste receptors on nerves in the oral cavity to elicit a unique taste known as umami. Recently, umami taste receptors were also found in the gastric mucosa. Although reports suggest that mucosal receptors may respond to free glutamate to modulate gastric function, no evidence of any effect on gastric emptying has been documented. ObjectiveWe hypothesized that glutamate may act as a modulator of gastric function. We studied the effects of l-glutamate enrichment of a protein-rich liquid meal, and similar enrichment of an equicaloric carbohydrate meal or noncaloric water, on gastric emptying. DesignTen healthy men were enrolled. Nine of the 10 subjects included in the study ingested all test meals with and without monosodium l-glutamate (MSG), and the remaining subject ingested only the protein-rich meals with and without MSG. All experimental and control liquid meals included [1-13C]sodium acetate as a tracer. After a test meal or water was ingested, 13C breath tests were performed to estimate gastric emptying. ResultsMSG enrichment not only resulted in a significant decrease in the mathematically simulated half-excretion (emptying) time of a protein-rich meal, but also increased the area under the curve (%dose/h) significantly. In contrast, MSG had no significant effect on the gastric emptying of a carbohydrate meal or a noncaloric water meal. ConclusionsEnrichment with MSG facilitated gastric emptying of a protein-rich meal exclusively, which suggests that free glutamate is important for protein digestion and may be helpful in the management of delayed gastric emptying.

Physiological Significance of Glutamate Signaling in Gut-Brain Communication

L -Glutamate is involved in the perception of umami taste, intermediary metabolism, and excitatory neurotransmission. In addition, recent studies have uncovered a variety of physiological roles for dietary glutamate, as evidenced by the fact that intragastric glutamate infusions induce flavor preference learning in rats. Moreover, glutamate increases digestive juice secretion and gastric emptying of protein-rich meals. Glutamate levels in blood and brain remain stable all day long even after the food intake since most of glutamate absorbed is oxidized in the mucosa of the small intestine as a primary energy source. Chronic ad libitum ingestion of glutamate solution contributes to reducing weight gain, fat deposition, and plasma leptin levels in comparison to ingestion of water. Glutamate receptors and their cellular transduction molecules have recently been identified in gut epithelial cells. Stimulation of gut glutamate receptors enhances the apical expression of glutamate transporters and also triggers the release of nitric oxide. Nitric oxide in its turn induces gut serotonin release, which increases vagal afferent inputs to different brain regions. Notably, three brain areas, i.e., the medial preoptic area, the dorsomedial nucleus of the hypothalamus, and the habenular nucleus are activated by intragastric glutamate infusions. Total subdiaphragmatic vagotomy abolishes this response. Consistent with the above, vagotomy specifically reduces the overall intake of glutamate. Taken together, these findings contribute to the growing body of evidence indicating that glutamate signaling via dedicated taste and gut receptors influences multiple physiological functions including gut secretion, motility, digestion, absorption, metabolism and energy homeostasis.

Correlation between Predictors for Diabetic Gastroparesis and Gastric Emptying Scintigraphy

The objective of this study was to evaluate the prevalence of gastroparesis in diabetic patients with severe upper gastrointestinal symptoms and to examine the predictors of diabetic gastroparesis to improve the efficiency of gastric emptying scintigraphy. Gastric emptying of a solid meal (scintigraphy) was measured in 40 patients with diabetes (10 type 1 and 30 type 2) who had severe upper abdominal symptoms. All patients were evaluated for anthropometry, lipid profiles, glycated hemoglobin, cardiac autonomic neuropathy, and other chronic diabetic complications. Of the 40 patients who underwent scintigraphy, the gastric emptying of solids was delayed in 16 (40%) patients, and 24 (60%) patients had cardiac autonomic neuropathy. The BBV cardiac beat-to-beat variability test score correlated positively with the gastric emptying time [OR=6.78 (1.53-30.04), p=0.018]. The deep breathing test (abnormal E/I ratio), one of the BBV tests, correlated positively with the gastric emptying rate of solids [OR=7.00 (1.27-38.36), p=0.025]. However, delayed gastric emptying was not related to the type or duration of diabetes, abdominal symptoms, glycated hemoglobin, body mass index, lipid profiles, or other chronic diabetic complications. Our results suggest that the BBV test, especially the abnormal deep breathing test, is associated with an increased risk of diabetic gastroparesis in diabetic patients with gastrointestinal symptoms.

Orlistat accelerates gastric emptying and attenuates GIP release in healthy subjects

Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of obesity. Previous reports on the effect of orally ingested orlistat together with a meal on gastric emptying and secretion of gut peptides that modulate postprandial responses are controversial. We investigated the effect of ingested orlistat on gastric emptying and plasma responses of gut peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of orlistat in pellet form in random order. Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve. Orlistat significantly attenuated the secretion of glucose-dependent insulinotropic polypeptide (GIP) but did not alter the plasma responses of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and insulin. There was no peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP (r=0.786) in orlistat and was negatively correlated with integrated plasma response of GLP-1 (r=-0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal. Orlistat administered similar to its use in obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK, GLP-1, and PP. Since GIP is being implemented in the development of obesity, its role in weight control attained by orlistat awaits further investigation.

Effect of Rikkunshito, a Chinese Herbal Medicine, on Stasis in Patients After Pylorus‐Preserving Gastrectomy

Distal gastrectomy (DG) and pylorus-preserving gastrectomy (PPG) have been employed for gastric cancer, with PPG having been reported to be superior to DG in regard to postoperative quality of life. Some patients with these operations still suffer from gastric stasis, however. In this study, we aimed to examine the clinical effects of rikkunshito on patients who were to undergo PPG. A total of 11 patients who were scheduled to undergo PPG for early gastric cancer at the Osaka University Hospital were enrolled. The patients were randomly assigned to the crossover study with and without rikkunshito 7.5 g/day. Questionnaires and emptying tests using (111)In-labeled liquid scintigraphy and (99m)Tc-labeled solid scintigraphy were performed at the end of each treatment period. Stasis-related symptoms were significantly reduced during rikkunshito treatment (p = 0.043). The emptying test showed that rikkunshito improved emptying of solid meals (p = 0.0003) from the remnant stomach but did not accelerate gastric empting of liquid meals. Rikkunshito improved gastric emptying and ameliorated postoperative symptoms of patients who had undergone a PPG.

Corticotropin-Releasing Factor-Overexpressing Mice Exhibit Reduced Neuronal Activation in the Arcuate Nucleus and Food Intake in Response to Fasting

Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulating ghrelin levels, and gastric emptying of a nonnutrient meal. CRF-OE mice injected ip with saline showed a 47 and 44% reduction of 30-min and 4-h cumulative food intake response to an overnight fast, respectively, compared with WT. However, the 30-min food intake decrease induced by ip cholecystokinin (3 microg/kg) and increase by ghrelin (300 microg/kg) were similar in CRF-OE and WT mice. Overnight fasting increased the plasma total ghrelin to similar levels in CRF-OE and WT mice, although CRF-OE mice had a 2-fold reduction of nonfasting ghrelin levels. The number of Fos-immunoreactive cells induced by fasting in the arcuate nucleus was reduced by 5.9-fold in CRF-OE compared with WT mice whereas no significant changes were observed in other hypothalamic nuclei. In contrast, fasted CRF-OE mice displayed a 5.6-fold increase in Fos-immunoreactive cell number in the dorsal motor nucleus of the vagus nerve and a 34% increase in 20-min gastric emptying. These findings indicate that sustained overproduction of hypothalamic CRF in mice interferes with fasting-induced activation of arcuate nucleus neurons and the related hyperphagic response.