The gastrointestinal tract in hunger and satiety signalling.

BACKGROUND: Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle. METHODS: Narrative review on gastrointestinal mechanisms involved in satiety and hunger signalling. RESULTS: Combined mechano- and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension-sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin as well as motilin and ghrelin contributes to gut-brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP-1 analogues act on these pathways to influence hunger, satiation and food intake. CONCLUSION: Gastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.

The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration.

Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill." However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: 1) the site of administration: intragastrically (IG) or intraduodenally (ID), 2) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and 3) the timing of infusion. Therefore, 14 healthy, female volunteers participated in a randomized, placebo-controlled six-visit crossover study. After an overnight fast, DB (1 µmol/kg), QHCl (10 µmol/kg), or placebo were given IG or ID via a nasogastric feeding tube. Blood samples were taken 10 min before administration and every 10 min after administration for a period of 2 h. Hunger was rated at the same time points on a visual analogue scale. ID bitter administration did not affect hunger sensations, motilin, or acyl-ghrelin release compared with its placebo infusion. IG QHCl infusion tended to suppress hunger increase, especially between 50 and 70 min after infusion, simultaneously with reduced motilin values. Here, acyl-ghrelin was not affected. IG DB did not affect hunger or motilin, however acyl-ghrelin levels were reduced 50-70 minutes after infusion. Plasma values of glucagon-like peptide 1 and cholecystokinin were too low to be properly detected or to have any physiological relevance. In conclusion, bitter tastants should be infused into the stomach to reduce hunger sensations and orexigenic gut peptides. QHCl has the best potential to reduce hunger sensations, and it should be infused 60 min before food intake.NEW & NOTEWORTHY Bitter tastants are a potential new weight-loss treatment. This is a noninvasive, easy approach, which should be received with considerable enthusiasm by the public. However, literature about bitter administration lacks consistency in methods and findings. We summarize how the compound should be given based on: the site of administration, the best bitter compound to use, and at what timing in respect to the meal. This paper is therefore a fundamental step to continue research toward the further development of the "bitter pill."

Serum motilin levels and motilin gene polymorphisms in children with functional constipation.

BACKGROUND: Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal hormone that increases intestinal motility. In this study, we aimed to investigate the serum motilin levels and its relationship with stool consistency and motilin gene polymorphisms in constipated children. METHODS: In this study we investigated 91 constipated patients (mean age 6.84±3.55 years) and 100 healthy controls (mean age 7.78±4.25 years). Serum motilin levels were assessed by sandwich enzyme-linked immunosorbent assay. rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) mutations were evaluated for motilin gene polymorphisms. RESULTS: Serum motilin levels were significantly lower in constipated children than healthy controls (6.20±7.86 vs. 11.54±17.89 pg/mL, respectively, P=0.008). Serum motilin levels were significantly correlated with Bristol stool scale rate (r=0.193, P=0.011) in whole study group, but in the constipation group there was no significant correlation (r=-0.072, P=0.528). There were no differences in terms of presence or distribution of the polymorphisms of rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) in both groups. There was not a significant difference between different polymorphism groups regarding serum motilin concentrations in whole study group and also in both of the study groups. CONCLUSIONS: This study indicated for the first time that serum motilin levels decreased in constipated children. Further studies are needed to clarify whether motilin or motilin gene polymorphisms has a role in pathogenesis of functional constipation.

Electroacupuncture for the treatment of functional dyspepsia: A systematic review and meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a common functional gastrointestinal disease. Acupuncture, including electroacupuncture (EA) is widely used as a complementary and alternative treatment for patients with FD. This study aimed to explore the effectiveness of EA for the treatment of FD. METHODS: We searched Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Cochrane Library) for randomized controlled trials of FD treated by EA from inception to February 3, 2020. Two reviewers will independently screen studies for data extraction and assess the quality and risk of bias. The Cochrane Collaboration's risk of bias tool, RevMan 5.3 software were used for meta-analysis. Data were pooled to calculate relative risk and 95% confidence intervals (CIs) of substantial improvement after treatment for dichotomous data and mean differences (SMDs) and 95% CIs for continuous data. RESULTS: Seven randomized clinical trials included 853 patients. This meta-analysis investigated the effectiveness of EA alone in the treatment of FD relative to sham-EA or pharmacologic medication (PM). The results showed that EA could significantly improve clinical symptoms. Compared with sham-EA, EA was more effective in reducing symptom scores (SMD -3.44, 95% CI -4.21 to -2.67) and increasing normal slow waves of electrogastrogram (SMD 0.93, 95% CI -0.30 to1.55). When EA was combined with PM, there was no significant difference in reducing symptom scores (SMD -0.18, 95% CI -0.51 to 0.16), increasing the effective rate of clinical symptoms (risk ratio 1.04, 95% CI 0.96 to 1.13), enhancing the level of plasma motilin (SMD 0.93, 95% CI -0.30 to1.55), and reducing gastric half-emptying time (SMD 0.02, 95% CI -0.16 to 0.20). The results also showed that there were very few adverse events reported. CONCLUSION: This meta-analysis suggests that EA is better than the placebo (sham-EA) in treating FD, and the therapeutic effect of EA on FD is equivalent to that of PM on FD. Compared with PM, EA for FD is safer and has fewer adverse reactions. Despite limitations due to the quality and number of the included studies, EA might be used as an effective and safe treatment for FD.

[Effect of herb-partitioned moxibustion at fanwei point on plasma motilin and serum gastrin in patients of diabetic gastroparesis].

OBJECTIVE: To explore the clinical therapeutic effect of herb-partitioned moxibustion at fanwei point in patients of diabetic gastroparesis differentiated as spleen and stomach deficiency and retention of turbid dampness as well as its effect mechanism. METHODS: A total of 134 patients with diabetic gastroparesis were randomized into an observation group and a control group, 67 cases in each one. In the observation group, herb-partitioned moxibustion at fanwei point was adopted, 40 min each time, once a day for 5 times a week. In the control group, itopride hydrochloride tablets were prescribed for oral administration, 50 mg each time, three times a day. A total of 6 weeks of treatment was required in the two groups. Before and after treatment, the gastroparesis cardinal symptom index (GCSI) scores, 4-hour gastric emptying rate, TCM symptom score, as well as the levels of plasma motilin and serum gastrin were observed in the patients of the two groups. Additionally, the clinical therapeutic effect was evaluated in the two groups. RESULTS: After treatment, the score of every item of GCSI, TCM symptom scores and the levels of plasma motilin and serum gastrin were all reduced as compared with those before treatment in the patients of the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). Regarding 4-hour gastric emptying rates, which were increased as compared with those before treatment in the two group (P<0.05), and the rate in the observation group was higher remarkably than that in the control group (P<0.05). The total effective rate was 92.5% (62/67) in the observation group, higher than 74.6% (50/67) in the control group (P<0.05). CONCLUSION: Herb-partitioned moxibustion at fanwei point relieves the clinical symptoms in the patients with diabetic gastroparesis and increases the gastric emptying rate, which is probably related to the regulation of the levels of plasma motilin and serum gastrin.

Effects of Zuojin pill on depressive behavior and gastrointestinal function in rats with chronic unpredictable mild stress: Role of the brain-gut axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Zoujin pill (ZJP), a medication used to treat gastrointestinal disorders since the 15th Century in China, have been reported to exert anti-depressant effects in various models. STUDY AIM: To assess the effects of ZJP on gastrointestinal function and depressive behavior in rats under chronic unpredictable mild stress (CUMS), and to examine the underlying mechanisms related to brain-gut axis. METHODS: The rats suffered the stressor once daily for 5 weeks. ZJP (0.6 and 1.2 g/kg) and fluoxetine (15 mg/kg) as positive control were administered to the rats through gastric intubation once daily for 5 consecutive weeks. The anti-depression effects were compared by performing sucrose preference tests and open field tests. Gastrointestinal motility was investigated by determining the gastrointestinal transit rate and by electrogastrogram. The serum levels of the gastrointestinal hormone (GAS, MOT, VIP, SP), inflammatory cytokine (IL-1ß, IL-6; , TNFα) and glucagon-like peptide-1 (GLP-1) were assayed by enzyme-linked immunosorbent assay. For monoamine neurotransmitters (NE, 5-HT, DA), the levels were determined by high-performance liquid chromatography and electrochemical detection in conjunction, which was applied on the samples taken from the hypothalamus, hippocampus, and striatum. RESULTS: The depression-like symptoms among rats under CUMS were significantly relieved by ZJP administration (0.6 and 1.2 g/kg). Gastrointestinal motility was also improved by restoring gastric electrical rhythm and promoting gastrointestinal propulsion. The ZJP at 0.6 g/kg dosage obviously up-regulated 5-HT and DA levels in hippocampus. The ZJP at 1.2 g/kg dosage could increase 5-HT and DA levels in hypothalamus, striatum, and hippocampus, while down-regulated the NE level in hypothalamus and hippocampus. ZJP also reversed the alterations in serum gastrointestinal hormones. Furthermore, treatment with ZJP significantly reduced levels of IL-1ß, IL-6 and TNF-α and increased serum GLP-1 compared with the CUMS group. Fluoxetine also exerted similar anti-depressant effects in the absence of effects on gastrointestinal motility and the levels of serum hormone, inflammatory cytokine and GLP-1. CONCLUSION: ZJP imposed anti-depressant and gastrointestinal regulating functions in rats under CUMS, suggesting potential clinical application. .

Elevated Circulating Levels of Motilin are Associated with Diabetes in Individuals after Acute Pancreatitis.

AIM: The study aimed to investigate the associations between glycaemic control after acute pancreatitis and gastrointestinal motility, using plasma motilin concentration and gastroparesis cardinal symptom index score as proxies. METHODS: This cross-sectional study recruited a total of 93 individuals after acute pancreatitis. Gastroparesis cardinal index scores, demographic and anthropometric factors, as well as pancreatitis-related factors were analysed. Fasting venous blood was collected to measure motilin, glycated haemoglobin, and fasting blood glucose. Linear regression analyses were conducted to investigate the associations between glycaemic control and gastrointestinal motility in unadjusted and adjusted models. RESULTS: Motilin was significantly higher in individuals with diabetes across all adjusted models, with the highest ß-coefficient (95% confidence interval) of 588.89 (138.50, 1039.28); P=0.010. Fasting blood glucose was significantly associated with motilin across all models, with the highest ß-coefficient (95% confidence interval) of 156.30 (55.49, 257.10); P=0.002. Glycated haemoglobin was significantly associated with motilin in one adjusted model with ß-coefficient (95% confidence interval) of 18.78 (1.53, 36.02); P=0.033. Gastroparesis cardinal symptom index was not significantly associated with any measure of glycaemic control. CONCLUSIONS: Diabetes in individuals after acute pancreatitis appears to be characterised by elevated plasma motilin but not gastroparesis cardinal symptom index. The role of motilin in this setting warrants further investigations.

Effect of acute Δ9-tetrahydrocannabinol administration on subjective and metabolic hormone responses to food stimuli and food intake in healthy humans: a randomized, placebo-controlled study.

BACKGROUND: The endocannabinoid system (ECS) is considered a key player in the neurophysiology of food reward. Animal studies suggest that the ECS stimulates the sensory perception of food, thereby increasing its incentive-motivational and/or hedonic properties and driving consumption, possibly via interactions with metabolic hormones. However, it remains unclear to what extent this can be extrapolated to humans. OBJECTIVE: We aimed to investigate the effect of oral Δ9-tetrahydrocannabinol (THC) on subjective and metabolic hormone responses to visual food stimuli and food intake. METHODS: Seventeen healthy subjects participated in a single-blinded, placebo-controlled, 2 × 2 crossover trial. In each of the 4 visits, subjective "liking" and "wanting" ratings of high- and low-calorie food images were acquired after oral THC or placebo administration. The effect on food intake was quantified in 2 ways: via ad libitum oral intake (half of the visits) and intragastric infusion (other half) of chocolate milkshake. Appetite-related sensations and metabolic hormones were measured at set time points throughout each visit. RESULTS: THC increased "liking" (P = 0.031) and "wanting" ratings (P = 0.0096) of the high-calorie, but not the low-calorie images, compared with placebo. Participants consumed significantly more milkshake after THC than after placebo during oral intake (P = 0.0005), but not intragastric infusion, of milkshake. Prospective food consumption ratings during the food image paradigm were higher after THC than after placebo (P = 0.0039). THC also increased plasma motilin (P = 0.0021) and decreased octanoylated ghrelin (P = 0.023) concentrations before milkshake consumption (i.e., in both oral intake and intragastric infusion test sessions), whereas glucagon-like peptide 1 responses to milkshake intake were attenuated by THC during both oral (P = 0.0002) and intragastric (P = 0.0055) administration. CONCLUSIONS: These findings suggest that the ECS drives food intake by interfering with anticipatory, cephalic phase, and metabolic hormone responses. This trial was registered at clinicaltrials.gov as NCT02310347.

Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms.

Objectives: Intragastric bitter tastants may decrease appetite and food intake. We aimed to investigate the gut-brain signaling and brain mechanisms underlying these effects.Methods: Brain responses to intragastric quinine-hydrochloride (QHCl, 10 µmol/kg) or placebo infusion were recorded using functional magnetic resonance imaging in 15 healthy women. Appetite-related sensations, plasma levels of gastrointestinal hormones and hedonic food intake (ad libitum drink test) were assessed.Results: Lower octanoylated ghrelin (P<0.04), total ghrelin (P<0.01), and motilin (P<0.01) plasma levels were found after QHCl administration, along with lower prospective food consumption ratings (P<0.02) and hedonic food intake (P<0.05). QHCl increased neural activity in the hypothalamus and hedonic (anterior insula, putamen, caudate, pallidum, amygdala, anterior cingulate cortex, orbitofrontal cortex, midbrain) regions, but decreased activity in the homeostatic medulla (all pFWE-corrected<0.05). Differential brain responses to QHCl versus placebo covaried with subjective and hormonal responses and predicted differences in hedonic food intake.Discussion: Intragastric QHCl decreases prospective and actual food intake in healthy women by interfering with homeostatic and hedonic brain circuits in a ghrelin- and motilin-mediated fashion. These findings suggest a potential of bitter tastants to reduce appetite and food intake, through the gut-brain axis.

STORE-gastrointestinal functions and gastrointestinal hormones in patients with liver failure.

This study aims to investigate the gastrointestinal functions of patients with liver failure (LF) based on gastrointestinal dysfunction (GD) scores and serum gastrointestinal hormone levels.The GD in LF patients was scored using the gastrointestinal dysfunction scoring criteria. Serum gastrin (GAS), cholecystokinin (CCK), and motilin (MTL) levels were determined in LF patients. In addition, liver function and prothrombin activity were detected, and ultrasonography was performed.The GD score was significantly higher in the LF groups than in the control group. Compared with the control group, serum GAS, CCK, and MTL levels significantly increased in the LF groups, and was positively correlated with the severity of LF. Furthermore, in the LF groups, GD was positively correlated with the severity of LF. However, the GD score and serum GAS, CCK, and MTL levels in the acute LF group were not statistically different, when compared with those in the subacute LF group, acute-on-chronic LF group and chronic LF group.LF plays a key role in the development of GD, and may be the main cause of obvious gastrointestinal symptoms, such as abdominal distension, nausea, vomiting and anorexia, in LF patients. The severity of GD is not associated with LF type, but is positively correlated with the severity of LF, suggesting that GD in LF patients may have complicated mechanisms.

Effects of hydromorphone and morphine intravenous analgesia on plasma motilin and postoperative nausea and vomiting in patients undergoing total hysterectomy.

OBJECTIVE: To observe the effects of hydromorphone and morphine intravenous analgesia on plasma motilin and postoperative nausea and vomiting in patients undergoing a total hysterectomy. PATIENTS AND METHODS: 80 patients who underwent hysterectomy from April 2015 to June 2016 were randomly divided into two groups, with 40 patients in each group. The two groups received an intravenous infusion of hydromorphone or morphine for analgesia. The VAS pain score and Ramsey sedation score were recorded 4, 8, 12, 24, and 48 hours after the first dose of analgesia. The scores of nausea and vomiting were recorded. The levels of motilin were determined by radioimmunoassay before anesthesia, after anesthesia, during hysterectomy and 1 day after the operation. The results showed that the analgesic effect of hydromorphone was more rapid than morphine. RESULTS: There were significant differences in VAS scores between the two groups at each time point (p<0.05), indicating that the analgesic effect of hydromorphone was better than morphine's one. The scores of Ramsay sedation were less than 6 points at each time point within 48 hours after the operation. The content of plasma motilin in the hydromorphone group was higher than that in the morphine group during the first day after anesthesia. There were 34 cases (85%) of mild nausea and vomiting within 24 hours after the operation in the hydromorphone group. In the morphine group, there were 16 cases (40%) of mild nausea and vomiting within 24 hours after the operation, 10 cases (25%) of severe nausea and vomiting. CONCLUSIONS: The occurrence of severe malignant vomiting after the use of morphine was more than that after the use of hydromorphone. Normal level and function of motilin is the basis of avoiding nausea and vomiting. Too fast or too slow gastrointestinal motility can induce postoperative nausea and vomiting.

A correlation between gastrointestinal dysfunction and cirrhosis severity.

This study aims to investigate the relationship between gastrointestinal dysfunction (GD) and cirrhosis severity in cirrhotic patients, to provide evidences for the prevention and treatment of GD in cirrhotic patients.A total of 95 cirrhotic inpatients and outpatients, who were treated in the Department of Gastroenterology of Xinqu Hospital of the First Affiliated Hospital of Henan University of Science and Technology, were enrolled in the present study, and assigned as the experimental group (cirrhosis group). According to Child-Pugh classification, these patients were divided into 3 groups: group A (n = 45), group B (n = 23), and group C (n = 27). Forty healthy adults who received health check-ups during the same period served as the control group. The gastrointestinal (GI) symptoms of cirrhotic patients were scored, and the fasting serum gastrin (GAS), motilin (MTL), and vasoactive intestinal peptide (VIP) levels were measured in all subjects.The potential correlations of GI symptom scores of patients in these cirrhosis groups with GI hormone levels and cirrhosis severity were analyzed. In cirrhotic patients, the GI symptom scores significantly increased. Furthermore, the symptom scores gradually increased along with the aggravation of liver damage. Moreover, serum GAS and VIP levels were significantly higher in the cirrhosis groups than in the control group, whereas MTL levels were significantly lower. These changes were significantly correlated with cirrhosis severity. The linear correlation analysis revealed that the GI symptom score was positively correlated with GAS and VIP levels, and negatively correlated with MTL level. In addition, the linear correlation analysis revealed that GI symptom score and GAS and VIP levels were positively correlated with cirrhosis severity, whereas MTL level was negatively correlated with cirrhosis severity.Cirrhotic patients have more obvious GI symptoms and higher GI hormone levels, which are closely correlated with the progression of liver cirrhosis and the degree of liver function damage.

The Relations Among Serum Ghrelin, Motilin and Gastric Emptying and Autonomic Function in Autoimmune Gastritis.

BACKGROUND: Gastric emptying (GE) of solids is delayed and autonomic dysfunction is detected in autoimmune gastritis (AIG). The goals of this study were to: (1) compare serum levels of ghrelin and motilin in subjects with delayed and normal GE and (2) investigate whether circulating antimyenteric antibodies (CAA), serum ghrelin levels and motilin levels have any effect on autonomic function. MATERIALS AND METHODS: Noninvasive cardiovascular reflex tests were used in order to evaluate the autonomic function. GE was evaluated by a standard 2-hour scintigraphic test. Serum ghrelin and motilin levels were tested by enzyme-linked immunosorbent assay and CAA were tested by immunofluorescence. RESULTS: The serum ghrelin and motilin levels in the patients with delayed GE (n = 22) were significantly decreased compared to the normal GE patients (n = 19), (67.55 ± 8.81 versus 126.79 ± 25.81pg/mL, P < 0.001 and 279.59 ± 111.12 versus 500.42 ± 155.95pg/mL, respectively, P < 0.001). Whereas, the serum ghrelin and motilin levels in the patients with deranged autonomic function (n = 26) were significantly decreased compared to the patients with normal autonomic function (n = 15), (80.73 ± 28.46 versus 127.79 ± 28.06pg/mL, P < 0.001 and 316.92 ± 160.47 versus 490.20 ± 141.02pg/mL, P < 0.001, respectively).  None of the patients were positive for CAA. CONCLUSIONS: Ghrelin and motilin levels in AIG subjects with delayed GE and deranged autonomic function were significantly decreased. The decrease in serum ghrelin and plasma motilin levels in AIG suggest their potential role in the delayed GE observed in these subjects.

Evaluation of a modified rat model for functional dyspepsia.

Background/Aim: The purpose of this study was to establish a modified rat model with functional dyspepsia (FD) and analyze the changes in gastrointestinal motility and brain-gut peptide levels in serum and brain-gut axis. Materials and Methods: Male Wistar rats were divided into control group (Con) and FD model group. FD model was established by stimulating semi-starvation rats via tail damping, provocation, and forced exercise fatigue until gastrointestinal motility disorder appeared, and then levels of motilin, leptin, cholecystokinin (CCK), and vasoactive intestinal peptide (VIP) were detected in serum by enzyme linked immunosorbent assay and in duodenum, antrum, and hypothalamus by immunohistochemistry, reverse transcriptase-polymerase chain reaction, and Western blot. Results: The results showed rates of intestinal propulsion and gastric emptying slowed down markedly compared to Con (P < 0.05), the gastrointestinal electric activity attenuated, and migrating motor complex (MMC) interrupted in the model group. The levels of leptin and VIP markedly increased, but motilin decreased as compared to the Con (P < 0.05) in serum and in the above tissues. It is interesting that the level of CCK decreased in the antrum and duodenum but increased in the hypothalamus as compared to Con (P < 0.05). Conclusions: The modified rat model meets the diagnostic criteria of FD and can be used as a method for studying FD in animals.

Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation.

Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.

Intragastric infusion of the bitter tastant quinine suppresses hormone release and antral motility during the fasting state in healthy female volunteers.

BACKGROUND: Intragastric administration of the bitter tastant denatonium benzoate inhibits the increase of motilin plasma levels and antral contractility. While these findings suggest that gastrointestinal bitter taste receptors could be new targets to modulate gastrointestinal motility and hormone release, they need confirmation with other bitter receptor agonists. The primary aim was to evaluate the effect of intragastric administration of the bitter tastant quinine-hydrochloride (QHCl) on motilin and ghrelin plasma levels. Secondly, we studied the effect on interdigestive motility. METHODS: Ten healthy female volunteers were recruited (33±4 y; 22±0.5 kg/m²). Placebo or QHCl (10 µmol/kg) was administered intragastrically through a nasogastric feeding tube after an overnight fast in a single-blind randomized fashion. Administration started 20 min after the first phase III of the migrating motor complex. The measurement continued for another 2 h after the administration. Blood samples were collected every 10 min with the baseline sample taken 10 min prior to administration. KEY RESULTS: The increase in plasma levels of motilin (administration; P=.04) and total ghrelin (administration; P=.02) was significantly lower after QHCl. The fluctuation of octanoylated ghrelin was reduced after QHCl (time by administration; P=.03). Duodenal motility did not differ. The fluctuation of antral activity differed over time between placebo and QHCl (time by administration; P=.03). CONCLUSIONS AND INFERENCES: QHCl suppresses the increase of both motilin and ghrelin plasma levels. Moreover, QHCl reduced the fluctuation of antral motility. These findings confirm the potential of bitter taste receptors as targets for modifying interdigestive motility in man.

[Effects of auricular point sticking on plasma motilin in patients after gynecological laparoscopic operation under general anesthesia].

OBJECTIVE: To observe the clinical efficacy of auricular point sticking on prevention and treatment of gastrointestinal complications after gynecological laparoscopic operation of general anesthesia, and to explore whether it is achieved by regulating the secretion of plasma motilin (MTL). METHODS: Sixty patients who received selective gynecological laparoscopy under general anesthesia were randomly assigned into an observation group and a control group, 30 patients in each one. The patients in the observation group were treated with auricular point sticking at each morning and night, 30 min before anesthesia, revival after surgery and 24 h after surgery. The adhesive fabric with vaccaria seeds was pressed at shenmen (TF4), wei (CO4), benmen (CO3), jiaogan (AH6a) and pizhixia (AT4) for 3 to 5 min until the sensation of sourness, distension and numb appeared. The treatment was given for one week. The patients in the control group were treated only with similar adhesive fabric at auricular points at identical time points; each auricular point was pressed for 3 to 5 min. The anus exhaust time, defecating time and borborygmus were recorded; the level of plasma MTL was tested 30 min before anesthesia, 24 h after o-peration and 48 h after operation; the occurrence of nausea and vomiting from the end of operation to the end of treatment were also recorded. RESULTS: Compared with the control group, the occurrence of nausea after operation was reduced in the observation group (P<0.05), and the anus exhaust time and defecating time were shortened (both P<0.05), and the recovery of borborygmus was improved (P<0.05). The levels of MTL 24 h and 48 h after surgery were higher than those before operation in the two groups (all P<0.05); The levels of MTL 24 h and 48 h after surgery in the observation group were significantly lower than those in the control group (both P<0.05). CONCLUSIONS: The assist of auricular point sticking could reduce the occurrence of nausea-vomiting and accelerate the recovery of gastrointestinal function in gynecological laparoscopic operation under general anesthesia, which is likely to be related with the inhibition on excess secretion of MTL.

Colonic Transit Time and Gut Peptides in Adult Patients with Slow and Normal Colonic Transit Constipation.

PURPOSE: To investigate whether pathophysiological differences exist among healthy controls (HC) and patients with slow and normal transit constipation (STC and NTC), we evaluated (1) gastrointestinal (GI) symptoms using validated questionnaires; (2) circulating concentrations of neurotensin, motilin, corticotrophin-releasing factor (CRF), and somatostatin; and (3) possible differences in frequency distribution of the neurotensin rs1800832 A/G and Neurotensin Receptor 1 rs6090453 C/G SNPs. METHODS: Fifty-one patients with severe functional constipation and 20 HC completed the study. Symptoms were evaluated by GSRS and Constipaq scoring system. Plasma concentrations of GI peptides were evaluated by ELISA on fasting and six sequential blood samples after a standard meal. Genotyping was performed by PCR and endonuclease digestion. RESULTS: Symptom profiles largely overlapped between NTC and STC patients. As for peptide profiles, neurotensin showed lower concentrations at 60 and 90 min in STC versus HC, and motilin showed throughout the curve 85% and 82% lower levels in STC than HC and NTC, respectively. Finally, neurotensin polymorphism resulted in being associated with the peptide levels. CONCLUSIONS: Symptom profile is not a reliable tool to discriminate STC, whilst the GI peptide profiles might help in identifying it.

[Effect of extensively hydrolyzed formula on growth and development of infants with very/extremely low birth weight].

OBJECTIVE: To study the effect of extensively hydrolyzed formula on the growth and development in very low birth weight (VLBW) and extremely low birth weight (ELBW) infants. METHODS: A total of 375 VLBW or ELBW infants were enrolled and divided into an observation group (187 infants) and a control group (188 infants) using a random number table. The infants in the observation group were given extensively hydrolyzed formula, and when the amount of extensively hydrolyzed formula reached 10 mL/time, it was changed to the standard formula for preterm infants. The infants in the control group were given standard formula for preterm infants. Both groups were fed for 4 consecutive weeks and were compared in terms of incidence rate of feeding intolerance, time to establish full enteral feeding, time to complete meconium excretion, number of spontaneous bowel movements, growth and development, motilin level at 4 and 10 days after feeding, and incidence rate of infection. RESULTS: Compared with the control group, the observation group had a lower rate of feeding intolerance (P<0.05), a shorter duration to full enteral feeding and time to complete meconium excretion (P<0.05), a higher mean number of daily spontaneous bowel movements (P<0.05), higher body weight (1 793±317 g vs 1 621±138 g; P<0.05), head circumference (30.5±1.1 cm vs 30.0±1.6 cm; P<0.05), and body length (43.9±1.2 cm vs 42.1±2.0 cm; P<0.05), a higher motilin level at 4 and 10 days after feeding (P<0.05), and a significantly lower infection rate (P<0.05). CONCLUSIONS: Extensively hydrolyzed formula can increase motilin level, improve gastrointestinal feeding tolerance, promote early growth and development, and reduce the incidence of infection in VLBW and ELBW infants.

Effects of Chinese herbal medicine Xiangbin prescription on gastrointestinal motility.

AIM: To investigate the effects of Xiangbin prescription (XBP), a Chinese herbal concoction, on gastrointestinal motility. METHODS: Forty healthy volunteers were recruited for this randomized controlled trial of XBP. Antroduodenojejunal manometry was used to monitor gastrointestinal motility in these subjects. After the subjects had fasted for at least 12 h, XBP (n = 30) or placebo (n = 10) was orally administrated and gastrointestinal motility was recorded for 4 h. Plasma motilin and ghrelin were measured by enzyme-linked immunosorbent assay. RESULTS: Oral administration of XBP significantly increased the amplitude of duodenal contractions [19.5 (13.0-26.7) vs 16.9 (12.3-23.9), P < 0.05], jejunal contractions [18.3 (15.3-25.0) vs 15.4 (11.7-23.9), P < 0.01], and the motility index of duodenal contractions [522.0 (146.0-139.0) vs 281.0 (76.5-1006.0), P < 0.01] in phase II of the migratory motor complex (MMC), which subsequently initiated the MMC cycle [74.0 (30.0-118.0) vs 116.5 (24.0-219.0), P < 0.05], shortened the duration of phase I of the MMC [42.0 (0.0-90.0) vs 111.5 (42.0-171.0), P < 0.01], and lengthened the duration of phase II of the MMC [120 (21-240) vs 58 (16-170), P < 0.01] compared to the duration before XBP administration. There were significant differences in the amplitude of jejunal contractions [19.8 (14.0-30.0) vs 18.0 (13.0-28.5), P < 0.05], the motility index of duodenal contractions [236.0 (115.0-306.0) vs 195.0 (109.0-310.0), P < 0.05)], and jejunal contractions [214.0 (95.0-403.0) vs 178.0 (55.0-304.0), P < 0.01] in phase III of the MMC. Oral administration of XBP greatly increased plasma motilin (57.69 ± 9.03 vs 49.38 ± 8.63, P < 0.01) and ghrelin (279.20 ± 104.31 vs 238.73 ± 115.59, P < 0.01) concentrations compared to concentrations after oral administration of the placebo. CONCLUSION: XBP can stimulate duodenal and jejunal motility and increase the concentrations of plasma motilin and ghrelin. The clinical applicability of XBP in treating GDIM deserves investigation.