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Constipation, a gastrointestinal function disorder, is one of the side effects of paclitaxel (PTX) chemotherapy. Shenhuang plaster (SHP) application on the Shenque acupoint promotes gut motility in clinical settings. In this study, we elucidated the ingredients in SHP and evaluated its effects on PTX-induced constipation using a tumour-bearing mouse model. SHP was prepared using the traditional Chinese plaster preparation method. The ingredients were analysed using UPLC-MS/MS and identified via screening in a standard drug database. The gastrointestinal transit was evaluated by the movement of a fluorescein-labelled dextran in the gastrointestinal tract. A histological study of the mucosa was carried out after haematoxylin and eosin staining. mRNA expression was assessed using real-time RT-PCR, and the foetal microbiota composition was elucidated through 16 s rDNA sequencing and BLAST analysis. Our results indicate that the application of SHP attenuated weight gain inhibition by PTX; however, no inhibitory effect was observed on tumour growth. PTX-induced sluggish intestine, villus, and mucosal base layer damage were significantly improved following the application of SHP. Further, SHP enhanced the stimulation efficiency of PTX on TLR4 and its downstream cytokines, as well as on IL-1 β in intestinal cells. SHP combined with PTX reshaped the microbiota, which showed beneficial effects on health. Hence, these results provide evidence that SHP alleviates PTX-induced constipation and intestinal morphological damage but augments the effects of PTX on the expression of cytokines in the TLR4 pathway and IL-1 β . Therefore, we propose that SHP stimulates the host immune response to eradicate cancer cells., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Yanan Shi et al.)

Background and Aim: Prokinetics have been considered the first-line medicine for treating delayed gastric emptying. The aim of this study was to explore the effects and mechanisms of a new 5-HT 4 receptor agonist, YKP10811, on gastric motility in dogs., Methods: Four experiments were performed in dogs: (i) dose-response effects of YKP10811 on liquid gastric emptying; (ii) effects and mechanisms of YKP10811 on solid gastric emptying delayed by glucagon; (iii) effects of low-dose YKP10811 on antral contractions; and (iv) effects of low-dose YKP10811 on gastric accommodation., Results: No adverse events or cardiac dysrhythmia was noted. (i) High-dose YKP10811 (30 mg/kg) accelerated liquid gastric emptying from 15 to 90 min without inducing adverse events or cardiac dysrhythmia. YKP10811 at low doses (0.3, 1, and 3 mg/kg) accelerated gastric emptying in a dose-dependent manner. (ii) YKP10811 (0.1 mg/kg), but not tegaserod (0.3 mg/kg), significantly accelerated glucagon-induced delayed gastric emptying of solid, and the effect was completely blocked by GR113808. (iii) YKP10811 (0.3 mg/kg) enhanced antral contractions. (iv) YKP10811 did not alter gastric accommodation., Conclusions: YKP10811 seems to improve antral contractions and accelerate gastric emptying without altering gastric accommodation in dogs via the 5-HT 4 mechanism and is substantially more potent than tegaserod. No adverse events were noted at a dose 300 times the lowest effective dose. YKP10811 may have a therapeutic potential for gastroparesis., (© 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: It is unknown whether gastric myoelectrical activity (GMA) and autonomic functions are altered in obesity. The aims of this study were to investigate GMA and autonomic functions in obese subjects and to compare their responses to different meals with lean subjects., Methods: The study was performed in 12 lean and 12 obese subjects. GMA was measured using electrogastrography, and autonomic functions were assessed using spectral analysis of heart rate variability., Results: The study achieved the following key results: (1) Compared to lean subjects, obese subjects showed unaltered gastric slow waves at baseline but enhanced responses to both fatty and protein meals. The lean subjects showed a reduced percentage of normal gastric slow waves with a fatty meal, which was not seen in obese subjects; lean subjects showed no changes in the dominant frequency or power of the gastric slow waves with a protein meal, whereas both of these parameters were increased in obese subjects. (2) Autonomic functions were altered in obese subjects in both fasting and fed states. Obese subjects showed an increased sympathetic activity in the fasting state, but absence of a normal postprandial response in sympathovagal balance to both fatty and protein meals., Conclusions: The findings on gastric slow waves demonstrate that obese subjects are more receptive to fatty meals and more responsive to protein meals. Obese subjects have impaired autonomic functions in both fasting and fed states. The alterations in gastric and autonomic functions may contribute to eating disorders in the obese.

Background acupuncture (AP) has been shown to have a therapeutic potential for gastrointestinal motility disorders. The aims of this study were to investigate the effects and possible mechanisms of acupuncture on postprandial upper and lower abdominal symptoms induced by rectal distension (RD). Twenty healthy volunteers were involved in a two-session study (AP and sham-AP, AP and no-AP, or sham-AP and no-AP). In 12 of the volunteers, RD was performed for 60 min in the postprandial state, and AP at ST36 or sham-AP was performed during the second 30-min period of RD. Gastric slow waves and heart rate variability (HRV) were recorded using the electrogastrogram and electrocardiogram, respectively. Upper and lower abdominal symptoms were scored during RD with AP and sham-AP. In five of the subjects, an additional experiment with two sessions (with AP and no-AP) was performed. In the remaining eight volunteers, the same experiment was performed with sham-AP and no-AP was performed. The results were, first, RD at an average volume of 171 ml induced upper and lower abdominal symptoms (P < 0.01). AP, but not sham-AP or no-AP, reduced both upper and lower abdominal symptoms (P < 0.05). Second, RD decreased the percentage of normal gastric slow waves (P < 0.05). AP improved gastric slow waves compared with sham-AP or no-AP (P < 0.05). Third, in the larger, but not smaller, sample size experiment, the vagal activity during the RD plus AP period was significantly higher than that during the RD alone period in the same session and the corresponding period with sham-AP or no-AP in other sessions (P < 0.05). Neither sham-AP nor no-AP showed any effects on vagal activity (P > 0.05). Finally, in the experiment with eight volunteers, neither sham-AP nor no-AP showed any effects on RD-induced impairment in gastric slow waves, abdominal symptoms, or vagal activity (P > 0.05). The conclusions are RD induces upper or lower abdominal symptoms and impairs gastric slow waves in healthy volunteers. AP at ST36 is able to improve upper and lower abdominal symptoms and impaired gastric slow waves induced by RD, possibly mediated via the vagal pathway.

Previous studies have shown that gastric tone is inhibited by the electrical stimulation of some parts of the gut. The aims of this study were to investigate the effects of gastric electrical stimulation (GES), duodenal electrical stimulation (DES), ileal electrical stimulation (IES), and colonic electrical stimulation (CES) on gastric tone and the possible mechanism of electrical stimulation on gastric tone. Experiments were performed to study: (1) the effects of the four stimulations (GES, DES, IES, CES) on gastric tone; (2) the role of the nitrergic pathway's involvement in the effect of IES on gastric tone. Each dog was implanted with one pair of gastric, duodenal, ileal, and colonic electrodes and a gastric cannula. A computerized barostat was used to assess gastric tone by measuring the gastric intra-balloon volume. We found that: (1) all methods of stimulation significantly inhibited gastric tone; (2) the percentage of increase in gastric volume was highest with CES and lowest with DES; however, there was no significant difference in the percentage of inhibition among the four stimulations; (3) the inhibitory effect of IES on gastric tone was abolished by intravenous nitric oxide synthase inhibitor. It was concluded that electrical stimulation of the stomach, intestine, or colon with long pulses has an inhibitory effect on gastric tone, and the most effective stimulation is CES. The inhibitory effect is not organ-specific and is unrelated to the distance between the stimulation site and the affected organ. The inhibitory effect of IES on gastric tone is mediated by the nitrergic pathway.

Purpose: A phenomenon of cross-talk has been noted that electrical stimulation of one part of the gut affects another part of the gut. This study was designed to investigate whether the effect of electrical stimulation of one part of the gut on another part of the gut was related to the organ or the distance between the stimulation site and the affected organ, and the mechanism of ileum electrical stimulation on rectal tone., Methods: This study was performed in 13 healthy dogs (16-28 kg) in the fasting state. Experiments were performed to study 1) effects of gastric electrical stimulation, duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation on rectal tone, and 2) the sympathetic and nitrergic pathways involved in the effects of ileum electrical stimulation on rectal tone. A computerized barostat was used to assess rectal tone., Results: All methods of stimulations significantly inhibited rectal tone. Duodenal electrical stimulation was least effective in reducing rectal tone. The percentage of increase in rectal volume was distance-related with duodenal electrical stimulation, ileum electrical stimulation, and colonic electrical stimulation but organ-specific with gastric electrical stimulation. The inhibitory effect of ileum electrical stimulation on rectal tone was abolished by N omega-nitro-L-arginine but not guanethidine., Conclusions: Electrical stimulation of the stomach, intestine, or colon with long pulses has an inhibitory effect on rectal tone. This inhibitory effect is organ-specific as well as associated with the distance between stimulation site and affected organs. The inhibitory effect of ileum electrical stimulation on rectal tone is mediated by the nitrergic but not sympathetic pathway.

Previous studies have shown that sildenafil inhibits the esophageal motility in both humans and animals. The aim of this study was to investigate the effects of sildenafil on intestinal myoelectrical activity and motility. The study was composed of 2 experiments and performed in 7 healthy female dogs with a duodenal cannula 20 cm beyond pylorus (19-26 kg). The first experiment was designed to study the effects of sildenafil on intestinal myoelectrical activity and it included 2 sessions each consisting of 30-minute baseline, 15-minute posttreatment (placebo or 100 mg sildenafil) and 90 minutes after a liquid meal. Intestinal myoelectrical activity was recorded during the entire experiment period. The second experiment was aimed to investigate the effect of sildenafil on intestinal motility and was performed immediately after a solid meal. Intestinal motility was measured by a manometric catheter inserted into the small intestine via the duodenum cannula for 30 minutes at baseline and 60 minutes after sildenafil. Sildenafil significantly reduced the amplitude but had no effect on the frequency and regularity of the intestinal myoelectrical activity. Sildenafil significantly inhibited postprandial intestinal contractions. Although the frequency of the contractions was not altered, the mean area under the curve was significantly reduced during the first 30 minutes (P < .03) and second 30 minutes after sildenafil (P < .03); the power of intestinal contractile activities was also significantly reduced during the first 30 minutes (P < .0004) and second 30 minutes after sildenafil (P < .0003) in comparison with baseline. In conclusion, sildenafil inhibits the amplitude of both intestinal contractile activity and intestinal slow waves.

Objective: To assess the effect of acupressure on gastric myoelectrical activity (GMA) in patients with systemic sclerosis (SSc) and its possible influence on SSc-associated gastrointestinal (GI) dysmotility disorders., Methods: Acupressure to Neiguan point PC6 (GI, antiemetic point) was applied while SSc patients and healthy control subjects were monitored by 4-channel surface electrogastrography (EGG) during 30-minute baseline, acupressure, and recovery intervals. Frequency of GI symptoms and modified Rodnan skin scores (mRSS) of SSc patients were recorded. Acupressure to PC10 (non-GI, sham) was also performed on SSc patients to assess the validity of PC6 as a modulator of GI gastric rhythms., Results: In the SSc patients, PC6 acupressure resulted in significant, persistent percentage mean normal wave decreases with concomitant percentage mean bradygastria and tachygastria increases during the recovery interval. Increases in percentage mean coupling seen in controls were blunted in SSc patients. In SSc patients, PC6 acupressure resulted in significant percentage normal wave and percentage bradygastria changes in the recovery interval that were not obtained with PC10 acupressure. In SSc patients, mRSS were significantly correlated to baseline GMA percentage mean normal waves and bradygastria and frequency of abdominal bloating. The frequency of symptoms for heartburn were significantly correlated with changes in GMA (deltaGMA, baseline vs recovery)., Conclusion: In SSc patients, PC6 acupressure revealed significant, persistent, and possibly unique alterations in GMA during the recovery interval. deltaGMA was significantly correlated with the frequency of heartburn symptoms. Further studies will assess if acupressure to PC6 can provide a therapeutic or prognostic utility with GMA or GI symptoms in SSc patients.

Background & Aims: The pylorus plays an important role in regulating gastric emptying. The aim of this study was to investigate the therapeutic potential of pyloric electrical stimulation (PES) for obesity in dogs., Methods: The study was composed of 3 separate experiments. The first experiment was designed to study the effects of PES with various parameters on gastric emptying and gastric slow waves in 5 sessions. The second experiment was used to test the effects of PES on antral contractions. The acute effect of PES on food intake was studied in the third experiment., Results: (1) Pyloric myoelectrical recording showed dual frequencies. The lower frequency was identical to the frequency of the gastric slow waves, and the higher frequency was similar to that of the intestinal slow waves. (2) Gastric emptying was significantly delayed with PES, and the delay in gastric emptying was significantly and negatively correlated with stimulation energy ( r = -.673; P < .001). (3) PES significantly impaired the regularity and coupling of the intrinsic gastric myoelectrical activity in an energy-dependent manner. The delayed gastric emptying was significantly correlated with the impairment of the coupling of gastric myoelectrical activity ( r = .441; P < .02). (4) Antral contractions on the fed state were significantly and substantially inhibited with PES. (5) Acute PES significantly reduced food intake., Conclusions: PES reduces food intake that may be attributed to its inhibitory effects on intrinsic gastric myoelectrical activity, antral contractions, and gastric emptying.

The aim of this study was to record gastric myoelectric activity using multichannel electrogastrography (EGG) and to determine if there are differences due to age, gender, body mass, and study location. In 61 normal subjects from four centers, fasting multichannel EGG was recorded for 1 h, followed by two 1-h postprandial recordings after a test meal. Variables assessed included dominant frequency (DF) and its power, percentage time in 2- to 4-cpm frequency, and percentage slow-wave coupling (%SWC). There were no significant differences in EGG parameters with respect to gender or age. Subjects with a BMI > 25 had a decrease in the absolute DF power but a similar increase in the postprandial DF power. Subjects with a BMI > 25 had a postprandial decrease in the %SWC compared to those with a BMI < 25. There was a decrease in postprandial %SWC in European/Asian centers compared to American centers. In conclusion, multichannel EGG provides assessment of electrical slow-wave coupling in addition to determining dominant frequency, power, and percentage normal rhythm. This multicenter study of normal subjects shows similar multichannel EGG values among different genders and ages. Body mass and ethnicity may impact on some of the EGG values.

Background/aim: The aim of this study was to investigate the anti-dysrhythmic effect of long-pulse gastric electrical stimulation (GES) in dogs., Methods: The study was performed in 7 healthy dogs implanted with 4 pairs of serosal gastric electrodes. Each dog was studied in three sessions on 3 separate days in a randomized order with recordings of gastric slow waves. In session 1 or 2, infusion of either saline or glucagon (0.1 U/kg in 20 ml saline instilled in 40 min) was given during the 2nd and 3rd 20-min periods. The protocol of session 3 was the same as that of session 2 except that GES was performed during the 2nd 20-min period., Results: (1) Glucagon induced gastric dysrhythmia and decreased gastric slow-wave coupling (ANOVA, p < 0.001). The long-pulse GES normalized glucagon-induced gastric dysrhythmia and the uncoupling of slow waves. (2) Glucagon induced symptoms and behaviors suggestive of nausea and the symptoms were not improved by long-pulse GES., Conclusion: (1) Glucagon induces gastric dysrhythmias, slow-wave uncoupling and symptoms, and (2) long-pulse GES normalizes glucagon-induced gastric dysrhythmia and slow-wave uncoupling with no improvement in symptoms., (Copyright 2004 S. Karger AG, Basel)

Postoperative ileus (POI), a gastrointestinal function disorder, is a complication that arises from surgery. Shenhuang plaster (SHP) application to the Shenque acupoint (CV8) to promote the recovery of gastrointestinal function has achieved definite curative effects in clinical settings; however, the underlying pharmacological mechanism remains unknown. In this study, we evaluated the effects of SHP using a Sprague Dawley rat POI model. Then, gastrointestinal transit in different rat groups was evaluated by the movement of fluorescein-labelled dextran. Ghrelin, obestatin, motilin (MTL), and vasoactive intestinal peptide (VIP) plasma concentrations were measured via a radioimmunoassay. The expression of the ghrelin and obestatin receptors (GHS-R1α and GPR39) in the intestinal muscularis of rats in different groups was comparatively identified via western blotting. The results indicated that SHP application improved gastrointestinal motility in POI model rats. SHP application significantly increased ghrelin concentration and the expression of its receptor and inhibited obestatin concentration and the expression of its receptor in blood. Further, ghrelin concentration and the capability of gastrointestinal transit were positively correlated. Simultaneously, SHP application also promoted the secretion of other gastrointestinal motility hormones, such as MTL and VIP. Hence, these results provide evidence that SHP can promote the recovery of gastrointestinal transmission in POI rat models through regulation of ghrelin and other intestinal hormones. [ABSTRACT FROM AUTHOR]

Background and Aim Prokinetics have been considered the first-line medicine for treating delayed gastric emptying. The aim of this study was to explore the effects and mechanisms of a new 5-HT4 receptor agonist, YKP10811, on gastric motility in dogs. Methods Four experiments were performed in dogs: (i) dose-response effects of YKP10811 on liquid gastric emptying; (ii) effects and mechanisms of YKP10811 on solid gastric emptying delayed by glucagon; (iii) effects of low-dose YKP10811 on antral contractions; and (iv) effects of low-dose YKP10811 on gastric accommodation. Results No adverse events or cardiac dysrhythmia was noted. (i) High-dose YKP10811 (30 mg/kg) accelerated liquid gastric emptying from 15 to 90 min without inducing adverse events or cardiac dysrhythmia. YKP10811 at low doses (0.3, 1, and 3 mg/kg) accelerated gastric emptying in a dose-dependent manner. (ii) YKP10811 (0.1 mg/kg), but not tegaserod (0.3 mg/kg), significantly accelerated glucagon-induced delayed gastric emptying of solid, and the effect was completely blocked by GR113808. (iii) YKP10811 (0.3 mg/kg) enhanced antral contractions. (iv) YKP10811 did not alter gastric accommodation. Conclusions YKP10811 seems to improve antral contractions and accelerate gastric emptying without altering gastric accommodation in dogs via the 5-HT4 mechanism and is substantially more potent than tegaserod. No adverse events were noted at a dose 300 times the lowest effective dose. YKP10811 may have a therapeutic potential for gastroparesis. [ABSTRACT FROM AUTHOR]

Previous studies have shown that gastric tone is inhibited by the electrical stimulation of some parts of the gut. The aims of this study were to investigate the effects of gastric electrical stimulation (GES), duodenal electrical stimulation (DES), ileal electrical stimulation (IES), and colonic electrical stimulation (CES) on gastric tone and the possible mechanism of electrical stimulation on gastric tone. Experiments were performed to study: (1) the effects of the four stimulations (GES, DES, IES, CES) on gastric tone; (2) the role of the nitrergic pathway's involvement in the effect of IES on gastric tone. Each dog was implanted with one pair of gastric, duodenal, ileal, and colonic electrodes and a gastric cannula. A computerized barostat was used to assess gastric tone by measuring the gastric intra-balloon volume. We found that: (1) all methods of stimulation significantly inhibited gastric tone; (2) the percentage of increase in gastric volume was highest with CES and lowest with DES; however, there was no significant difference in the percentage of inhibition among the four stimulations; (3) the inhibitory effect of IES on gastric tone was abolished by intravenous nitric oxide synthase inhibitor. It was concluded that electrical stimulation of the stomach, intestine, or colon with long pulses has an inhibitory effect on gastric tone, and the most effective stimulation is CES. The inhibitory effect is not organ-specific and is unrelated to the distance between the stimulation site and the affected organ. The inhibitory effect of IES on gastric tone is mediated by the nitrergic pathway. [ABSTRACT FROM AUTHOR]

Cold or emotional stress was reported to affect gastric myoelectrical activity. The aim of this study was to investigate the effects of music or noise on gastric myoelectrical activity and autonomic function in healthy volunteers. Material and methods The study was performed in 10 fasted healthy volunteers and included 30 min at baseline, 30 min of classical music via headphones and 30 min of loud household noises via headphones. The electrogastrogram (EGG) readings were recorded simultaneously with the electrocardiogram (ECG) recording. Results Both classical music and noise altered the regularity of gastric slow waves. The percentage of normal 2–4 cycles/min (cpm) waves was reduced from 77.9±4.7% at baseline to 66.9±5.4% during music (p<0.006) and 67.7±5.4% during noise (p<0.05). The reduction was attributed to a significant increase in bradygastria (15.8±3.9% versus 9.8±2.6%, p<0.04) with the music and a significant increase in arrhythmia (7.4±1.6% versus 2.0±1.1%, p<0.02) with the noise. The dominant frequency and power of the EGG were, however, not altered with either music or noise. Neither music nor noise had any effect on the autonomic function assessed by the heart rate variability. Conclusions Audio stimulation, with both music and noise, alters the rhythmicity of gastric slow waves. Classical music seems to increase bradygastria, whereas, household noise may increase arrhythmia. The effect of audio stimulation on the gastric slow wave does not seem to involve sympathetic or vagal efferent pathways assessed by the spectral analysis of heart rate variability. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the correlation of gastric emptying with gastric myoelectrical activity recorded from internal serosal electrodes and with gastric motility measured from strain gauges. The study was performed in eight healthy dogs chronically implanted with four pairs of electrodes and two strain gauges on the gastric serosa and equipped with a duodenal fistula for the assessment of gastric emptying. Each dog was fed four liquid test meals on four separate days with identical calories (320 kcal) and volume (473 ml). A correlation was found between gastric emptying and the energy of contraction in the frequency band of 3.75-7.50 cycles/min during the first 30 min after the meal (r = 0.46, P < 0.05). While none of the parameters of gastric myoelectrical activity was correlated with gastric emptying, two major parameters, percentage of regular gastric slow waves and percentage of slow-wave coupling, were found to be associated with delayed gastric emptying. A significant correlation was found between the frequency of gastric slow waves and that of the contractions in both fasting (r = 0.83, P < 0.001) and fed state (r = 0.70, P < 0.001 at 30 min, r = 0.86, P < 0.001 at 60 min). It was concluded that gastric emptying is correlated with the strength of gastric contractions in a frequency range identical to that of the gastric slow waves, and there is no one-to-one correlation between gastric emptying of liquids and any parameters of gastric myoelectrical activity. However, major parameters of gastric myoelectrical activity are associated with gastric emptying. [ABSTRACT FROM AUTHOR]