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."

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. .

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.

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.

[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.

Enterohormonal disturbances in colorectal cancer patients.

Gastrointestinal (GI) hormonal peptides play a role in the development of gastrointestinal malignancies, and their abnormal levels may contribute to dysmotility. The aim of this study was to analyze plasma concentrations of enterohormones (motilin, ghrelin, gastrin and pancreatic polypeptide) and to verify if their abnormal levels may contribute to the severity of dyspeptic symptoms in colorectal cancer patients. The study included 60 patients with colorectal malignancies (22 men and 38 women), among them 30 individuals with colon cancers (group A) and 30 subjects with rectal tumors (group B). Fasting plasma levels of pancreatic polypeptide (PP), motilin, gastrin and ghrelin were determined by means of ELISA. The results were compared with the respective parameters of healthy volunteers. Colon cancer patients presented with significantly lower concentrations of ghrelin than the subjects with rectal tumors and healthy controls (156.8±86.7 vs. 260.2±87.6 vs. 258.4±94.2 pg/ml, p=0.02), as well as with significantly higher levels of PP (265.5±66.3 vs. 154.1±54.6 vs. 148.3±64.3 pg/ml, p=0.005). Also the levels of motilin turned out to be lower in colon cancer patients than in the subjects with rectal malignancies and healthy controls. No statistically significant intergroups differences were found in plasma levels of gastrin (388.2±98.6 vs. 475.6±88.7 vs. 428.2±91.2 pg/ml, p>0.05). Epigastric bloating was the most frequent dyspeptic symptom, reported by 63.3% and 40% of patients with colon and rectal tumors, respectively. Our findings imply that colon cancer patients may present with abnormal plasma levels of enterohormones significantly more often than individuals with rectal malignancies. Dysmotility observed in colon cancer patients may result not only from anticancer surgery, but also from abnormal release of enterohormones, induced either by neoplastic process or by changes within the autonomic nervous system.

Gastric Activity and Gut Peptides in Patients With Functional Dyspepsia: Postprandial Distress Syndrome Versus Epigastric Pain Syndrome.

GOALS: The goals of the study were to investigate in both postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) the gastric electrical activity and the gastric emptying (GE) time together with the circulating concentrations of motilin, somatostatin, corticotrophin-releasing factor, and neurotensin, and to establish whether the genetic variability in the neurotensin system genes differs between these 2 categories of functional dyspepsia (FD). BACKGROUND: The current FD classification is based on symptoms and it has been proven not to be completely satisfying because of a high degree of symptom overlap between subgroups. STUDY: Gastric electrical activity was evaluated by cutaneous electrogastrography: the GE time by C-octanoic acid breast test. Circulating concentrations of gut peptides were measured by a radioimmunoassay. NTS 479 A/G and NTSR1 rs6090453 SNPs were evaluated by PCR and endonuclease digestion. RESULTS: Fifty-four FD patients (50 female/4 male) were studied. Using a symptom questionnaire, 42 patients were classified as PDS and 12 as EPS, although an overlap between the symptom profiles of the 2 subgroups was recorded. The electrogastrographic parameters (the postprandial instability coefficient of dominant frequency, the dominant power, and the power ratio) were significantly different between the subgroups, whereas the GE time did not differ significantly. In addition, EPS was characterized by a different gut peptide profile compared with PDS. Finally, neurotensin polymorphism was shown to be associated with neurotensin levels. This evidence deserves further studies in consideration of an analgesic role of neurotensin. CONCLUSIONS: Analysis of gut peptide profiles could represent an interesting tool to enhance FD diagnosis and overcome limitations due to a distinction based solely on symptoms.

Effect of XiangBin granules on post-operative gastrointestinal function and brain-gut peptides after transabdominal gynecological surgery.

OBJECTIVES: We conducted a prospective clinical randomized single-blind placebo-controlled trial (ChiCTR-TRC-14004156) to observe the effect of XiangBin granules on the recovery of gastrointestinal function and levels of brain-gut peptide motilin (MTL); vasoactive intestinal peptide (VIP); growth hormone releasing peptide-ghrelin, GHRP-ghrelin, and corticotropin releasing hormone (CRH), after transabdominal gynecological surgery. STUDY DESIGN: Patients undergoing gynecologic abdominal surgery were randomly divided in a 2:1 ratio (according to the data of pre-trial which was a small sample randomized trial in gynecology inpatient) into two groups: the larger treatment group taking XiangBin granules, and the smaller placebo group taking Chinese herbal placebo. The aim was to observe anal exhaust time, time to defecation, and the change in level of brain-gut peptide. RESULT: A significantly shorter time to first postoperative anal exhaust was observed in the treatment group. In the placebo group, the MTL level on the first day after surgery was lower than the preoperative level (P<0.05). In both groups, the GHRP-ghrelin level on the first postoperative day was lower than the preoperative level (P<0.05). In the treatment group, the GHRP-ghrelin level of the third day after surgery was higher than the first day after surgery (P<0.05). The CRH level on the first postoperative day was lower in the treatment group compared to the placebo group (P<0.05). CONCLUSION: XiangBin granules can effectively promote the recovery of gastrointestinal function after surgery for gynecologic abdomen and promote GHRP-ghrelin and MTL recovery, and reduce the postoperative secretion of CRH.

[Effect of Transcutaneous Electrical Acupoint Stimulation on Post-surgical Gastrointestinal Function, Autonomic Nerve Activities and Plasma Brain-gut Peptide Levels in Patients Undergoing Gastrointestinal Surgery].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on ileus-postope-rative gastrointestinal functions and plasma ghrelin, motilin, and gastrin contents, and heart rate variability (HRV) in patients undergoing gastrointestinal surgery, so as to explore the interaction of vagus-brain-gut peptide. METHODS: A total of 58 patients undergoing elective gastrointestinal surgery were randomly assigned to TEAS (n=29) and sham-TEAS group (n=29, patients had no subjective sensation to 1 mA TEAS, thus, being considered to be sham-TEAS). TEAS (2 Hz/100 Hz, 6-8 mA for LI 4-PC 6, 12-18 mA for ST 36-SP 6) was applied to bilateral Hegu (LI 4)-Neiguan (PC 6) from 30 min pre-operation to the end of the operation and to bilateral LI 4-PC 6 and Zusanli (ST 36)-Sanyinjiao (SP 6) for 30 minutes twice daily in 3 consecutive post-operative days. ECGs of 12 leads were recorded to analyze different parameters of HRV from 2 days before and 4 days after surgery. Plasma ghrelin, motilin and gastrin contents were assayed by radioimmunoassay, and the patients' first bowel sound, first independent walk, first flatus, first solid food-intake and first defecation were recorded to evaluate the recovery state of gastrointestinal motility. RESULTS: Postoperative gastrointestinal motility:compared with the sham-TEAS group, the first bowel sound and the first defecation after surgery appeared apparently earlier in the TEAS group (P<0.05), but no significant differences were found between the two groups at the time of the first independent walk, first flatus and the first solid food-intake in patients undergoing gastrointestinal surgery. Plasma brain-gut peptides:the plasma ghrelin and motilin contents 4 days post-surgery were significant increased in the TEAS group than in the sham-TEAS group (P<0.05). No significant difference was found between the two groups in plasma gastrin contents (P>0.05). HRV domains:in comparison with pre-surgery, the levels of low frequency (LF) and high frequency (HF) of frequency domain (FD) and root mean square of successive differences (rMSSD) of the time domain (TD) of HRV 4 days after surgery were significantly decreased in the sham-TEAS group (P<0.05), but no significant changes were found in both FD and TD domains of the TEAS group 4 days after surgery (P>0.05). Compared with the sham-TEAS group, the HF and rMSSD levels were significantly increased in the TEAS group 4 days after the surgery (P<0.05). No significant differences were found between the two groups in the levels of very low frequency, LF and LF/HF levels of FD, and standard deviation of NN (beat-to-beat) intervals, the standard deviation of the average NN intervals and the proportion of NN 50 (the number of pairs of successive NNs that differ by more than 50 ms) divided by total number of NNs of TD. CONCLUSIONS: TEAS can promote gastrointestinal activities (i.e., reducing the time spending of first bowel sound and the first defecation) in gastrointestinal surgery patients, which may be related to its effects in up-regulating ghrelin and motilin contents and parasympathetic activity.

Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger.

OBJECTIVE: Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores. DESIGN: Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery. 20 min after the end of the second phase III, obese patients received an intravenous infusion of 40 mg erythromycin. Hunger was scored every 5 min. Hedonic hunger was assessed in obese patients with the Power of Food Scale questionnaire. RESULTS: Obesity caused a switch in the origin of phase III from antrum to duodenum. Obese patients had significantly higher motilin levels compared with controls during the MMC but tended to lack the motilin peak prior to phase III necessary to trigger hunger. Hunger scores during phase III were significantly lower in obese patients, but could be restored to control levels through the administration of a low dose of the motilin agonist, erythromycin. After RYGB surgery motilin, but not ghrelin, levels decreased in parallel with hedonic hunger scores. CONCLUSIONS: Motilin may be an important regulator involved in the pathogenesis of obesity.

Shuidouchi (Fermented Soybean) Fermented in Different Vessels Attenuates HCl/Ethanol-Induced Gastric Mucosal Injury.

Shuidouchi (Natto) is a fermented soy product showing in vivo gastric injury preventive effects. The treatment effects of Shuidouchi fermented in different vessels on HCl/ethanol-induced gastric mucosal injury mice through their antioxidant effect was determined. Shuidouchi contained isoflavones (daidzein and genistein), and GVFS (glass vessel fermented Shuidouchi) had the highest isoflavone levels among Shuidouchi samples fermented in different vessels. After treatment with GVFS, the gastric mucosal injury was reduced as compared to the control mice. The gastric secretion volume (0.47 mL) and pH of gastric juice (3.1) of GVFS treated gastric mucosal injury mice were close to those of ranitidine-treated mice and normal mice. Shuidouchi could decrease serum motilin (MTL), gastrin (Gas) level and increase somatostatin (SS), vasoactive intestinal peptide (VIP) level, and GVFS showed the strongest effects. GVFS showed lower IL-6, IL-12, TNF-α and IFN-γ cytokine levels than other vessel fermented Shuidouchi samples, and these levels were higher than those of ranitidine-treated mice and normal mice. GVFS also had higher superoxide dismutase (SOD), nitric oxide (NO) and malonaldehyde (MDA) contents in gastric tissues than other Shuidouchi samples. Shuidouchi could raise IκB-α, EGF, EGFR, nNOS, eNOS, Mn-SOD, Gu/Zn-SOD, CAT mRNA expressions and reduce NF-κB, COX-2, iNOS expressions as compared to the control mice. GVFS showed the best treatment effects for gastric mucosal injuries, suggesting that glass vessels could be used for Shuidouchi fermentation in functional food manufacturing.

Efficacy of Gum Chewing on Bowel Movement After Open Colectomy for Left-Sided Colorectal Cancer: A Randomized Clinical Trial.

BACKGROUND: Prolonged intestinal paralysis can be a problem after gastrointestinal surgery. Several systematic reviews and meta-analyses have suggested the efficacy of gum chewing for the prevention of postoperative ileus. OBJECTIVE: The purpose of this study was to examine the efficacy of gum chewing for the recovery of bowel function after surgery for left-sided colorectal cancer and to determine the physiological mechanism underlying the effect of gum chewing on bowel function. DESIGN: This was a single-center, placebo-controlled, parallel-group, prospective randomized trial. SETTINGS: The study was conducted at a general hospital in Japan. PATIENTS: Forty-eight patients with left-sided colorectal cancer were included. INTERVENTIONS: The patients were randomly assigned to a gum group (N = 25) and a control group (N = 23). Four patients in the gum group and 1 in the control group were subsequently excluded because of difficulties in continuing the trial, resulting in the analysis of 21 and 22 patients in the respective groups. Patients in the gum group chewed commercial gum 3 times a day for ≥5 minutes each time from postoperative day 1 to the first day of food intake. MAIN OUTCOME MEASURES: The time to first flatus and first bowel movement after the operation were recorded, and the colonic transit time was measured. Gut hormones (gastrin, des-acyl ghrelin, motilin, and serotonin) were measured preoperatively, perioperatively, and on postoperative days 1, 3, 5, 7, and 10. RESULTS: Gum chewing did not significantly shorten the time to the first flatus (53 ± 2 vs. 49 ± 26 hours; p = 0.481; gum vs. control group), time to first bowel movement (94 ± 44 vs. 109 ± 34 hours; p = 0.234), or the colonic transit time (88 ± 28 vs. 88 ± 21 hours; p = 0.968). However, gum chewing significantly increased the serum levels of des-acyl ghrelin and gastrin. LIMITATIONS: The main limitation was a greater rate of complications than anticipated, which limited the significance of the findings. CONCLUSIONS: Gum chewing changed the serum levels of des-acyl ghrelin and gastrin, but we were unable to demonstrate an effect on the recovery of bowel function.

Preventive Effect of Lactobacillus fermentum Zhao on Activated Carbon-Induced Constipation in Mice.

The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1×10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1×10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.

[Irritable bowel syndrome with extraintestinal manifestations from a position of neuroendocrine pathology].

The aim of this study was to investigate the mechanism (s) of action of gastrointestinal hormones in the pathogenesis of irritable bowel syndrome (IBS), and the correlation between gastrointestinal hormones and psychological factors. Patients with IBS were divided into IBS with normal emotional state ratings and IBS in anxiety-depressive states groups. The two groups were then subdivided into IBS-constipation predominant (IBS-C) and IBS-diarrhea predominant (IBS-D) groups. Non-IBS patients with normal depression and anxiety ratings were recruited as controls. The expression of somatostatin (SS) and vasointestinalpeptid (VIP), motilin in the colonic mucosa was detected by immunohistochemistry and radioimmunoassay. The anxiety-depression scores of patients with IBS were significantly different from those of the control group. The expression levels of SS and VIP, motilin colonic mucosa of the patients with IBS were higher compared with those of the control.group. Furthermore, the expression level of SS in the IBS-C group demonstrated a significantly larger increase than that in the IBS-D group; however, there was no significant difference in the expression of VIP between the IBS-C and IBS-D groups. In addition, the expression levels of SS and VIP, motilin in the IBS groups with normal emotional state ratings were notably different from those in the IBS groups in anxiety-depressive states. Anxiety-depressive states may lead to changes in the secretion of SS and VIP, motilin, and subsequently to changes in gastrointestinal motility and function.

Prolonged treatment with transcutaneous electrical nerve stimulation (TENS) modulates neuro-gastric motility and plasma levels of vasoactive intestinal peptide (VIP), motilin and interleukin-6 (IL-6) in systemic sclerosis.

PURPOSE: We assessed the effects of transcutaneous electrical nerve stimulation (TENS) on neurogastric functioning in scleroderma patients. METHODS: Seventeen SSc patients underwent 30 min TENS treatment >10Hz at GI acupuncture points PC6 and ST36, once (acute TENS) and then after two weeks of TENS sessions for 30 min twice daily (prolonged TENS). Data collected at Visits 1 and 2 included gastric myoelectrical activity (GMA) by surface electrogastrography (EGG), heart rate variability (HRV) by surface electrocardiography (EKG), GI specific symptoms and health related SF-36 questionnaires. Plasma VIP, motilin and IL-6 levels were determined. Statistical analyses were performed by Student's t-test, Spearman Rank and p-values <0.05 were considered significant. RESULTS: 1. Only after prolonged TENS, the percentages of normal slow waves and average slow wave coupling (especially channels 1, 2 reflecting gastric pacemaker and corpus regions) were significantly increased; 2. the percentage of normal slow waves was significantly correlated to sympathovagal balance; 3. Mean plasma VIP and motilin levels were significantly decreased after acute TENS, (vs. baseline), generally maintained in the prolonged TENS intervals. Compared to baseline, mean plasma IL-6 levels were significantly increased after acute TENS, but significantly decreased after prolonged TENS. 4. After prolonged TENS, the frequency of awakening due to abdominal pain and abdominal bloating were significantly and modestly decreased, respectively. CONCLUSIONS: In SSc patients, two weeks of daily TENS improved patient GMA scores, lowered plasma VIP, motilin and IL-6 levels and improved association between GMA and sympathovagal balance. This supports the therapeutic potential of prolonged TENS to enhance gastric myoelectrical functioning in SSc.

Ghrelin and motilin levels in hyperemesis gravidarum.

PURPOSE: Ghrelin, an endogenous ligand for the growth hormone secratogogue receptor, and its receptors are found in the reproductive organs and placenta. Motilin is produced from the endocrine cells of the duodeno jejunal mucosa and considered to be a regulator of interdigestive migrating contractions. Aim of this study is to investigate ghrelin and motilin levels in patients with hyperemesis gravidarum. METHODS: A total of 56 patients with singleton pregnancies in the first trimester were recruited in the study, 39 with hyperemezis gravidarum and 17 normal pregnant women. Patients with medical complications and body mass index <18 or >25 were excluded. Fasting plasma ghrelin and motilin concentrations were measured. Fasting blood glucose, liver enzymes, blood urea nitrogen, creatinin, estradiol, progesterone, human chorionic gonadotropin, and thyroid function tests were also investigated. RESULTS: Ghrelin levels were significantly higher in patients with hyperemesis group than the normal pregnant women (p = 0.025). Serum estradiol levels were also higher in the hyperemesis group (p = 0.001). No significant difference was observed in plasma motilin levels between the two groups. In correlation analyses, maternal ghrelin was positively correlated with estradiol (r = 0.29, p = 0.029) in the whole cohort. CONCLUSION: There are a few studies about the course of circulating ghrelin levels during human pregnancy. Ghrelin administration increases food intake through central mechanisms but its effects on appetite in relation to human pregnancy is unknown. The increased levels of ghrelin in hyperemesis gravidarum might be a compensatory mechanism to restore the energy metabolism of the pregnant women.

Influence of acute exposure to high altitude on basal and postprandial plasma levels of gastroenteropancreatic peptides.

Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.