Effects of Polygala fallax Hemsl Water Extract on a Mouse Model of Gastric Motility Disorders

[Objectives]To explore the effects of Polygona fallax Hemsl water extract on gastrointestinal motility in normal mice and gastric motility disorder model mice and approximate mechanism.[Methods]Using normal mice and mice with gastric motility disorders(modeled with atropine),the effects of different mass concentration groups of P.fallax Hemsl water extract(0.125,0.250,0.500 g/mL)and domperidone groups on gastric residual rate,small intestine propulsion rate,serum motilin(MLT),vasoactive intestinal peptide(VIP),and tissue morphology were studied.[Results]There was a highly significant difference(P<0.01)in the small intestine propulsion rate of liquid in normal mice among the different concentration groups of P.fallax Hemsl water extract compared to the blank group.The small intestine propulsion rate and gastric residue rate of semi-solid paste were statistically significant compared to the blank group(P<0.05).Among them,there was a highly significant difference between the high concentration group(67.75%±7.65%,46.5%±10.62%)and the medium concentration group(60.90%±5.87%,59.27%±7.82%)(P<0.01).There was statistical significance in normal mouse serum MLT content in the high concentration group(P<0.05).There was no effect on serum VIP levels in normal mice;no effect on the morphology of stomach and intestinal tissues of normal mice.The small intestine propulsion rate and gastric residue rate of liquid and semi-solid paste in mice with gastric motility disorders were statistically significant compared to the atropine group,with extremely significant differences(P<0.01).[Conclusions]P.fallax Hemsl water extract has a promoting effect on gastrointestinal motility.One of the specific mechanisms by which P.fallax Hemsl promotes gastrointestinal motility in normal mice may be related to the content of MLT in mouse serum.The mechanism of action in atropine induced gastric paresis mice may be related to the reactivation of M receptors,and the action mechanism of P.fallax Hemsl does not change the original histological basis.It can be inferred that P.fallax Hemsl water extract has a synergistic effect on promoting gastrointestinal motility through other mechanisms,but it is not fully understood and further in-depth research is needed.

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats

BACKGROUND Hydrogen sulfide(H2S)is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems.It exerts its effects through multiple signaling pathways,impacting various physiological activities.The nucleus tractus solitarius(NTS),a vital nucleus involved in visceral sensation,was investigated in this study to understand the role of H2S in regulating gastric function in rats.AIM To examine whether H2S affects the nuclear factor kappa-B(NF-κB)and transient receptor potential vanilloid 1 pathways and the neurokinin 1(NK1)receptor in the NTS.METHODS Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase(CBS)and c-Fos co-expressed positive neurons in the NTS during rat stress.Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus.Changes in gastric motility were observed before and after injecting different doses of NaHS(4 nmol and 8 nmol),physiological saline,Capsazepine(4 nmol)+NaHS(4 nmol),pyrrolidine dithiocarbamate(PDTC,4 nmol)+NaHS(4 nmol),and L703606(4 nmol)+NaHS(4 nmol).RESULTS We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group.Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats(P<0.01).However,injection of saline,first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1(TRPV1)antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes(P>0.05).CONCLUSION NTS contains neurons co-expressing CBS and c-Fos,and the injection of NaHS into the NTS can suppress gastric motility in rats.This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

Neural mechanism of acupuncture-modulated gastric motility

AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism.METHODS: Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and changes of gastric motility induced by acupuncture stimulation were compared with the background activity before any stimulation. Gastro-vagal or splanchnic-sympathetic nerves were recorded or cut respectively for investigating the involvement of autonomic nerve pathways. Spinalization experiment was also performed.RESULTS: Acupuncture-stimulation by exciting Aδ and/or C afferent fibers, could only modulate gastric motility. Acupuncture-stimulation on fore- and hind-limbs evoked a moderate gastric motility followed by increased vagus discharges with unchanged sympathetic activity, while the same stimulus to the acupoints in abdomen resulted in reversed effects on gastric motility and autonomic nervous activities. The inhibitory gastric response was completely abolished by splanchnic denervation, but the facilitative gastric response to stimulation of acupoints in limbs was not influenced, which was opposite to the effect when vagotomy was performed. The similar depressive effects were produced by the stimulation at the acupoints homo-segmental to the gastric innervation in the animals with or without spinalization. However, the facilitation induced by the stimulation at the acupoints hetero-segmental to the gastric innervation was not observed in the spinalized animals.CONCLUSION: Facilitative effects of stimulating hetero-segmental acupoints are involved in the intact preparation of vagal nerves and spinal cord, while the inhibitory response induced by stimulating homo-segmental acupoints is involved in the intact preparation of sympathetic nerves. Only the acupuncture-stimulation with intensity over the threshold of Aδ and/or C afferent fibers can markedly modulate gastrointestinal motility.

Role of vasoactive intestinal peptide and nitric oxide in the modulation of electroacupucture on gastric motility in stressed rats

AIM: To investigate the effects and mechanisms of vasoactive intestinal peptide (VIP) and nitric oxide (NO) in the modulation of electroacupucture (EA) on gastric motility in restrained-cold stressed rats. METHODS: An animal model of gastric motility disorder was established by restrained-cold stress. Gastric myoelectric activities were recorded by electrogastroent erography (EGG). VIP and NO concentrations in plasma and gastric mucosal and bulb tissues were detected by radioimmunoassay (RIA). VIP expression in the gastric walls was assayed using avidin-biotin-peroxidase complex (ABC) and image analysis. RESULTS: In cold restrained stressed rats, EGG was disordered and irregular. The frequency and amplitude of gastric motility were higher than that in control group (P < 0.01). VIP and NO contents of plasma, gastric mucosal and bulb tissues were obviously decreased (P < 0.01). Following EA at “Zusanli” (ST36), the frequency and amplitude of gastric motility were obviously lowered (P < 0.01), while the levels of VIP and NO in plasma, gastric mucosal and bulb tissues increased strikingly (P < 0.01, P < 0.05) and expression of VIP in antral smooth muscle was elevated significantly (P < 0.01) in comparison with those of model group. CONCLUSION: VIP and NO participate in the modulatory effect of EA on gastric motility. EA at “Zusanli” acupoint (ST36) can improve gastric motility of the stressed rats by increasing the levels of VIP and NO.

Effective regularity in modulation on gastric motility induced by different acupoint stimulation

AIM： To investigate whether manual acupuncture at representative acupoints in different parts of the body can modulate responses of gastric motility in rats and regular effects in different acupoint stimulation. METHODS： The gastric motor activity of rats was recorded by the intrapyloric balloon. The changes of gastric motility induced by the stimulation were compared with the background activity in intragastric pressure and/or waves of gastric contraction recorded before any stimulation. Morphological study was also conducted by observing the Evans dye extravasation in the skin after mustard oil injection into the intragastric mucous membrane to certify cutaneous innervations of blue dots related to gastric segmental innervations. RESULTS： In all six rats that received mustard oil injections into intragastric mucosa, small blue dots appeared in the skin over the whole abdomen, but mainly in peri-midline upper- and middle- abdomen and middle-back, a few in thigh and groin. It may speculate that cutaneous innervations of blue dots have the same distribution as gastric segmental innervations. Acustimulation in acupoints of head-neck, four limbs, upper chest-dorsum and Iower-dorsum induced markedly augmentation of gastric motility （acupoints on headneck such as St-2： n = 16, 105.19 ± 1.36 vs 112.25 ± 2.02 and St-3： n = 14, 101.5 ± 1.75 vs 109.36 ± 1.8; acupoints on limbs such as Sp-6： n = 19, 100.74 ± 1.54 vs 110.26 ± 3.88; St-32： n = 17, 103.59 ± 1.64 vs 108.24 ± 2.41; St-36： n = 16, 104.81 ± 1.72 vs 110.81 ± 2.74 and U-11： n = 17, 106.47 ± 2.61 vs 114.77 ± 3.77, P 〈 0.05-0.001）. Vigorous inhibitory regulations of gastric motility induced by acu-stimulation applied in acupoints on whole abdomen and middle-dorsum were significantly different as compared with the controls before acu-stimulation （abdomen acupoints such as Cv-12： n = 11, 109.36 ± 2.09 vs 101 ± 2.21; Cv-6： n = 18, 104.39 ± 1.42 vs 91.83 ± 3.22 and St-21： n = 12, 107 ± 2.97 vs 98.58 ± 2.81; acupoints on middledorsum such as BI-17： n = 19, 100.63 ± 1.4 vs 92.21 ± 2.07 and BI-21： n = 19, 103.84 ± 1.48 vs 97.58 ± 2.16, P 〈 0.05-0.001）. CONCLUSION： Regular regulatory effects of facilitation and inhibition on gastric motility appear to be somatotopically organized in the acupoints of whole body, and the effective regularity of site-special acupoints on gastric motility is involved in segmental innervations between stomach and acupoints.

EFFECTS OF ENTERAL AND PARENTERAL NUTRITION ON GASTROENTERIC HORMONES AND GASTRIC MOTILITY AFTER SUBTOTAL GASTRECTOMY

Objective To investigate the effects of enteral nutrition （EN） and parenteral nutrition （PN） on gastric motility and gastroentefic hormones after subtotal gastrectomy. Methods Forty-one patients underwent gastrectomy were randomly divided into EN group （n=20） and PN group （n=21 ）. From the first postoperative day to the seventh day, patients received either EN （EN group） or PN （PN group） with isocalofic （84.9kJ·kg^-1·d^-1） and isonitrogenous （0.11g·kg^-1·d^-1） intake. Serum gastrin （GAS）, plasma mofilin （MTL）, and plasma cholecystokinin （CCK） were measured on preoperative day, the first and seventh postoperative day. Electrogastrography （EGG） was measured on preoperative day and the seventh postoperative day. Results Compared with preoperafion, blood GAS, MTL, and CCK levels of 41 patients decreased significantly on the first day after subtotal gastrectomy （ P 〈 0. 001 ）, but returned to the preoperative levels one week later. EGG after gastrectomy showed that gastric basal electrical rhythm was significantly restrained （ P 〈 0. 001 ）. On the seventh day after subtotal gastrectomy, plasma MTL and CCK levels in EN group were higher than those in PN group （ P 〈 0.05 ）. There was no difference in GAS level between two groups. EGG in EN group was better than that in PN group postoper- atively. Conclusions The levels of gastroentefitic hormones and the gastric motility decrease significantly after subtotal gastrectomy. In contrast with PN, EN can accelerate the recovery of MTL, CCK, and gastric motility after subtotal gastrectomy.

Role of Enteric Glial Cells in Gastric Motility in Diabetic Rats at Different Stages

Summary： Diabetes patients tend to have the gastrointestinal motility disorder. Although the relationship between the motility disorder and both the neurons and Cajal cells in the enteric nervous system （ENS） is well established, little is known about the role of enteric glial cells （EGCs） in gastric motility in diabetes. This study aimed to examine the expression of the glial marker S100B and morphology of EGCs in gastric tissues and the relationship between activated EGCs and the damage of gastric emptying in diabetic models. The diabetic model of rat was induced with 1% streptozotocin （STZ）. The model rats at 7-14 days and at 56-63 days were defined as early diabetic rats and advanced diabetic rats, re- spectively, and normal rats at the two time periods served as their corresponding controls. The gastric emptying rate of the rats was tested by using the phenol red solution. The ultrastructure of EGCs in the gastric antrum was observed by the transmission electron microscopy, and the expression of S100B in the myenteric plexus was immunohistochemically detected. The results showed that the gastric emptying rate was significantly increased in the early diabetic rats and decreased in the advanced diabetic rats when compared with their corresponding control rats （P〈0.01 for both）. The ultrastructure of EGCs was mostly normal in both the early diabetic and control groups. Vacuolization of mitochondria and expan- sion of endoplasmic reticulum occurred in both the advanced diabetic group and its control group, and even the structure of smooth muscle cells and intestinal neurons was destroyed in the advanced diabetic group. The expression level of S100B in the advanced diabetic group was significantly decreased com- pared with its control group （P〈0.05）. It was obviously increased in the early diabetic control group when compared with the advanced diabetic control group （P〈0.05）. However, there was no significant difference in the S 100B expression between the early diabetic group and its control group （P〉0.05）. The findings suggested that the gastric motility dysfunction in diabetes may be associated with the changes of morphology and number of EGCs in the myenteric plexus.

Pathogenesis of NSAID-induced gastric damage:Importance of cyclooxygenase inhibition and gastric hypermotility

This article reviews the pathogenic mechanism of nonsteroidal anti-inflammatory drug(NSAID)-induced gastric damage,focusing on the relation between cyclooxygenase(COX) inhibition and various functional events.NSAIDs,such as indomethacin,at a dose that inhibits prostaglandin(PG) production,enhance gastric motility,resulting in an increase in mucosal permeability,neutrophil infiltration and oxyradical production,and eventually producing gastric lesions.These lesions are prevented by pretreatment with PGE 2 and antisecretory drugs,and also via an atropine-sensitive mechanism,not related to antisecretory action.Although neither rofecoxib(a selective COX-2 inhibitor) nor SC-560(a selective COX-1 inhibitor) alone damages the stomach,the combined administration of these drugs provokes gastric lesions.SC-560,but not rofecoxib,decreases prostaglandin E 2(PGE 2) production and causes gastric hypermotility and an increase in mucosal permeability.COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib.The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility.In addition,selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions,including adrenalectomy,arthritis,and Helicobacter pylori-infection.In summary,gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage,and the response,causally related with PG deficiency due to COX-1 inhibition,occurs prior to other pathogenic events such as increased mucosal permeability;and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2,the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility,and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition.

Electrical bioimpedance gastric motility measurement based on an electrical-mechanical composite mechanism

AIM： To introduce a bioimpedance gastric motility mea- surement method based on an electrical-mechanical composite concept and a preliminary clinical application. METHODS： A noninvasive gastric motility measure- ment method combining electrogastrograrn （EGG） and impedance gastric motility （IGM） test was used. Prelim- inary clinical application studies of patients with func- tional dyspepsia （FD） and gastritis, as well as healthy controls, were carried out. Twenty-eight FD patients （mean age 40.9±9.7 years） and 40 healthy volun- teers （mean age 30.9±7.9 years） were involved. IGM spectrum was measured for both the healthy subjects and FD patients, and outcomes were compared in the FD patients before treatment and 1 wk and 3 wk after treatment. IGM parameters were obtained from 30 erosive gastritis patients （mean age 50.5±13.0 years） and 40 healthy adults, and IGM and EGG results were compared in the gastritis patients before treatment and 1 wk after treatment.RESULTS： There were significant differences in the IGM parameters between the FD patients and healthy subjects, and FD patients had a poorer gastric motility [percentage of normal frequency （PNF） 70.8±25.5 in healthy subjects and 28.3 =t= 16.9 in FD patients, P 〈 0.01]. After 1 wk administration of domperidone 10 mg, tid, the gastric motility of FD patients was not im- proved, although the EGG of the patients had returned to normal. After 3 wk of treatment, the IGM rhythm of the FD patients became normal. There was a significant difference in IGM parameters between the two groups （PNF 70.4：1：25.5 for healthy subjects and 36.1 4- 21.8 for gastritis patients, P 〈 0.05）. The EGG rhythm of the gastritis patients returned to normal （frequency insta- bility coefficient 2.22±0.43 before treatment and 1.77 ：t： 0.19 one wk after treatment, P 〈 0.05） after 1 wk of treatment with sodium rabeprazole tablets, 10 mg, qd, po, qm, while some IGM parameters showed a tenden- cy toward improvement but had not reached statistical significance. CONCLUSION： The electrical-mechanical composite measurement method showed an attractive clinical appli- cation prospect in gastric motility research and evaluation.

Xiangbinfang granules enhance gastric antrum motility via intramuscular interstitial cells of Cajal in mice

BACKGROUND Interdigestive migrating motor complexes(MMC)produce periodic contractions in the gastrointestinal tract,but the exact mechanism of action still remains unclear.Intramuscular interstitial cells of Cajal(ICC-IM)participate in gastrointestinal hormone and neuromodulation,but the correlation between ICCIM and MMC is also unclear.We found that xiangbinfang granules(XBF)mediated the phase III contraction of MMC.Here,the effects of XBF on gastric antrum motility in W/Wv mice and the effects of ICC-IM on gastric antrum MMC are reported.AIM To observe the effects of ICC-IM on gastric antrum motility and to establish the mechanism of XBF in promoting gastric antrum motility.METHODS The density of c-kit-positive ICC myenteric plexus(ICC-MP)and ICC-IM in the antral muscularis of W/Wv and wild-type(WT)mice was examined by confocal microscopy.The effects of XBF on gastric antrum slow waves in W/Wv and WT mice were recorded by intracellular amplification recording.Micro-strain-gauge force transducers were implanted into the gastric antrum to monitor the MMC and the effect of XBF on gastric antrum motility in conscious W/Wv and WT mice.RESULTS In the gastric antrum of W/Wv mice,c-kit immunoreactivity was significantly reduced,and no ICC-IM network was observed.Spontaneous rhythmic slow waves also appeared in the antrum of W/Wv mice,but the amplitude of the antrum slow wave decreased significantly in W/Wv mice(22.62±2.23 mV vs 2.92±0.52 mV,P<0.0001).MMCs were found in 7 of the 8 WT mice but no complete MMC cycle was found in W/Wv mice.The contractile frequency and amplitude index of the gastric antrum were significantly increased in conscious WT compared to W/Wv mice(frequency,3.53±0.18 cpm vs 1.28±0.12 cpm;amplitude index,23014.26±1798.65 mV·20 min vs 3782.16±407.13 mV·20 min;P<0.0001).XBF depolarized smooth muscle cells of the gastric antrum in WT and W/Wv mice in a dose-dependent manner.Similarly,the gastric antrum motility in WT mice was significantly increased after treatment with XBF 5 mg(P<0.05).Atropine(0.1 mg/kg)blocked the enhancement of XBF in WT and W/Wv mice completely,while tetrodotoxin(0.05 mg/kg)partially inhibited the enhancement by XBF.CONCLUSION ICC-IM participates in the regulation of gastric antrum MMC in mice.XBF induces MMC III-like contractions that enhance gastric antrum motility via ICCIM in mice.

Effects of metoclopramide on gastric motility measured by short-term bio-impedance

AIM:To analyze the accuracy of short-term bio-impedance as a means of measuring gastric motility.METHODS: We evaluated differences in the short-term electrical bio-impedance signal from the gastric region in the following conditions: (1) fasting state, (2) after the administration of metoclopramide (a drug that induces an increase in gastric motility) and (3) after food ingestion in 23 healthy volunteers. We record-ed the real component of the electrical impedance signal from the gastric region for 1000 s. We performed a Fast Fourier Transform (FFT) on this data and then compared the signal among the fasting, medicated, and postprandial conditions using the median of the area under the curve, the relative area under the curve and the main peak activity.RESULTS: The median of the area under the curve of the frequency range in the region between 2-8 cycles per minute (cpm) decreased from 4.7 cpm in the fasting condition to 4.0 cpm in the medicated state (t=3.32, P=0.004). This concurred with the decrease seen in the relative area under the FFT curve in the region from 4 to 8 cpm from 38.3% to 26.6% (t=2.81, P=0.012) and the increase in area in the region from 2 to 4 cpm from 22.4% to 27.7%, respectively (t=-2.5, P=0.022). Finally the main peak position also decreased in the region from 2 to 8 cpm. Main peak activity in the fasting state was 4.72 cpm and declined to 3.45 cpm in the medicated state (t=2.47, P=0.025). There was a decrease from the fasting state to the postprandial state at 3.02 cpm (t=4.0, P=0.0013). CONCLUSION: Short-term electrical bio-impedance can assess gastric motility changes in individuals experiencing gastric stress by analyzing the area medians and relative areas under the FFT curve.

Effects of Infrasound on Gastric Motility, Gastric Morphology and Expression of Nitric Oxide Synthase in Rat

Infrasound widely condition, productive exists in nature, our living and traffic environment. Gastrointestinal tract is relatively sensitive to infrasound. However, the effect of infrasound on gastrointestinal function is unclear. Therefore, the purpose of our study was to observe the effects of infrasound on gastric motiliW and gastric morphology and to assess the expression of nitric oxide synthase （NOS） in gastric antrum after exposure to infrasound of 8 Hz - 130 dB for 2 hours per day for 14 consecutive days. Gastric motility was assessed by gastric fluid-emptying rate. Gastric morphology was evaluated by HE. The expression of NOS was measured by tissue microarray technology. The results would contribute to understand the role of infrasound in gastroenterology, and help to explain the mechanism of infrasound on gastroenterology.

Parameters Analysis of Gastric Motility Signals in Time Domain and Frequency Domain

In order to assess gastric motility, a new noninvasive method was addressed. Firstly, bio-impedance and stomach electric signals were recorded from the healthy control group and the pathologic stomach group. Wavelet transform was used to remove the influence of the heart activity signals. By analyzing and processing the two signals of the time domain and frequency domain, we get the corresponding parameters of the two groups. According to all the parameters, several verification tests have been carried out, from the result of the statistics, we can find that in both time and frequency domains, impedance signal and synchronize EGG （electrogastrogram） have some similar features. However synchronize EGG cannot be totally instead by gastric motility, especially in morbid state, EGG is not correspondence to impedance signal. The gastric contraction or gastric emptying is a complex procedure including electrical and mechanical activity. Electrical impedance （EIP） and the synchronous EGG should be analyzed together. In conclusion, the parameters have the value to evaluate gastric motility.

Effect of acupuncture at Foot-Yangming Meridian on gastric mucosal blood flow, gastric motiiity and brain-gut peptide

AIM： To observe the effect of acupuncture at Foot- Yangming Meridian on gastric mucosal blood flow （GMBF）, gastric motility and brain-gut peptide. METHODS： Sixty SD rats were randomly divided into 6 groups： normal control group, model group （group with gastric mucosal damage, GMD）, Sibai group （with acupuncture at Sibai point ＋ GMD）, Tianshu group （with acupuncture at Tianshu point ＋ GMD）, Zusanli group （with acupuncture at Zusanli point ＋ GMD） and non-acupoint group （with acupuncture at non-acupoint ＋ GMD）. The GMD model group was induced by infusing pure alcohol into gastric cavity. H2 Gas Clearance Test （HGCT） was used to measure GMBF, the frequency and amplitude of gastric motility were measured by the method of aerocyst, the content of brain-gut peptide in sinus ventriculi and bulbus medullae were detected by radioimmunoassay. RESULTS： Inhibitory effect of the frequency and amplitude of gastric motility were shown in model group, and the rates of frequency and amplitude changes were remarkably different from the normal control group （-19.41 ± 17.21 vs-4.71 ± 10.32, P 〈 0.05; -51.61 ± 29.02 vs 1.81 ± 14.12, P 〈 0.01）. In comparison with control group, the GMBF was 0.52 ± 0.161 mL vs 1.03 ± 0.255 mL per 100g tissue/min, P 〈 0.01, the content of motilin in sinus ventriculi and bulbus medullae was 63.04 ± 7.77 pg/mL vs 72.91 ± 8.42 pg/mL, P 〈 0.05 and 50.96 ± 8.77 pg/mL vs 60.76 ± 8.05 pg/mL, P 〈 0.05, but the content of somatostatin in sinus ventriculi and bulbus medullae was 179.85 ± 43.13 ng/g vs 90.54 ± 40.42 ng/g, P 〈 0.01 and 532.86 ± 122.58 ng/g vs 370.91 ± 76.29 ng/g, P 〈 0.05,respectively. In comparison with model group, the amplitude of gastric motility was 1.52 ± 20.13, -6.52 ± 23.31, 6.92 ± 25.21 vs -51.61 ± 29.02, P 〈 0.01 and GMBF was 0.694 ± 0.160 mL vs 0.893 ± 0.210 mL, 1.038 ± 0.301 mL vs 0.52 ± 0.161 mL per 100g tissue/rain, P 〈 0.01, respectively in Tianshu, Sibai and Zusanli groups, the content of motilin in sinus ventriculi and bulbus medullae was 71.64 ± 9.35 pg/mL vs 63.04 ± 7.77 pg/mL, P 〈 0.05; 58.96 ± 6.69 pg/mL vs 50.96 ± 8.77 pg/mL, P 〈 0.05 in Zusanli group and 72.84 ± 8.62 pg/mL vs 63.04 ± 7.77 pg/mL, P 〈 0.05 in Sibai group, while the content of somatostatin in bulbus medullae in Tianshu, Sibai and Zusanli groups was 480.62 ± 151.69 ng/g, 388.53 ± 155.04 ng/g, 365.76 ± 143.93 ng/g vs 532.86 ± 122.58 ng/g, P 〈 0.05, respectively. CONCLUSION： Electro-acupuncture at acupoints of Foot-Yangming Meridian could enhance the gastric motility, improve GMBF, and regulate the content of motUin and somatostatin in sinus ventriculi and bulbus. The effects of acupuncture on GMBF and gastric motility may be related to the content of brain-gut peptide.

Gastric electrical stimulation for gastroparesis:A goal greatly pursued,but not yet attained

The lack of an effective medical treatment for gastroparesis has pushed the research of new techniques of gastric electrical stimulation (GES) for nearly half a century of experimentation with a large variety of electrical stimuli delivered to the gastric wall of animals and patients with gastroparesis. Three principal methods are currently available: gastric low-frequency/high-energy GES with long pulse stimulation, high-frequency/low-energy GES with short pulse stimulation and neural sequential GES. The first method aims to reset a regular slow wave rhythm, but has variable effects on contractions and requires devices with large and heavy batteries unsuitable for implantation. High-frequency/low-energy GES, although inadequate to restore a normal gastric electro-mechanical activity, improves dyspeptic symptoms, such as nausea and vomiting, giving patients a better quality of life together with a more satisfactory nutritional status and is suitable for implantation. Unfortunately, the numerous clinical studies using this type of GES, with the exception of two, were not controlled and there is a need for definitive verification of the effectiveness of this technique to justify the cost and the risks of this procedure. The last method, which is neural sequential GES, consists of a microprocessor-controlled sequential activation of a series of annular electrodes along the distal two thirds of the stomach and is able to induce propagated contractions causing forceful emptying of the gastric content. The latter method is the most promising, but has been used only in animals and needs to be tested in patients with gastroparesis before it is regarded as a solution for this disease.

Dendroaspis natriuretic peptide relaxes gastric antral circular smooth muscle of guinea-pig through thecGMP/cGMP-dependent protein kinase pathway

AIM: To systematically investigate if cGMP/cGMP- dependent protein kinase G (PKG) signaling pathway may participate in dendroaspis natriuretic peptide (DNP)-induced relaxation of gastric circular smooth muscle. METHODS: The content of cGMP in guinea pig gastric antral smooth muscle tissue and perfusion solution were measured using radioimmunoassay; spontaneous contraction of gastric antral circular muscles recorded using a 4-channel physiograph; and Ca2+-activated K+ currents (IK(Ca)) and spontaneous transient outward currents (STOCs) in isolated gastric antral myocytes were recorded using the whole-cell patch clamp technique. RESULTS: DNP markedly enhanced cGMP levels in gastric antral smooth muscle tissue and in the perfusion medium. DNP induced relaxation in gastricantral circular smooth muscle, which was inhibited by KT5823, a cGMP-dependent PKG inhibitor. DNP increased IK(Ca). This effect was almost completely blocked by KT5823, and partially blocked by LY83583, an inhibitor of guanylate cyclase to change the production of cGMP. DNP also increased STOCs. The effect of DNP on STOCs was abolished in the presence of KT5823, but not affected by KT-5720, a PKA-specific inhibitor. CONCLUSION: DNP activates IK(Ca) and relaxes guinea-pig gastric antral circular smooth muscle via the cGMP/PKG-dependent singling axis instead of cAMP/ PKA pathway.

Intragastric injection of botulinum toxin for the treatment of obesity. Where are we?

Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A (BT-A) in gastric antrum by means of endoscopy for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BT-A in laparatomized rats induced a significant reduction of food intake and body weight. Nowadays, 6 studies have been published yielding conflicting results. Differences in selection of patients, doses of BT-A, method of administration of the toxin and instruments of evaluation of some parameters among these studies may be the cause of divergent results. We discuss herein some important features of these studies pointing out on differences among them. At the same time, based on the knowledge of physiological characteristics of normal and abnormal gastric function related with feeding, we discuss the probable causes of failure observed in these trials. Finally, we give some guidelines concerning the way that future research in this field may follow, not without calling attention to disadvantages of this treatment.

Can adiponectin have an additional effect on the regulation of food intake by inducing gastric motor changes?

The regulation of food intake is a complex mechanism,and the hypothalamus is the main central structure implicated.In particular,the arcuate nucleus appears to be the most critical area in the integration of multiple peripheral signals.Among these signals,those originating from the white adipose tissue and the gastrointestinal tract are known to be involved in the regulation of food intake.The present paper focuses on adiponectin,an adipokine secreted by white adipose tissue,which is reported to have a role in the control of feeding by acting centrally.The recent observation that adiponectin is also able to influence gastric motility raises the question of whether this action represents an additional peripheral mechanism that concurs with the central effects of the hormone on food intake.This possibility,which represents an emerging aspect correlating the central and peripheral effects of adiponectin in the hunger-satiety cycle,is discussed in the present paper.

Glucagon-like peptide-2 modulates the nitrergic neurotransmission in strips from the mouse gastric fundus

AIM To investigate whether glucagon-like peptide-2(GLP-2) influences the neurally-induced responses in gastric strips from mice, since no data are available. METHODS For functional experiments, gastric fundal strips were mounted in organ baths containing Krebs-Henseleit solution. Mechanical responses were recorded via forcedisplacement transducers, which were coupled to a polygraph for continuous recording of isometric tension. Electrical field stimulation(EFS) was applied via two platinum wire rings through which the preparationwas threaded. The effects of GLP-2(2 and 20 nmol/L) were evaluated on the neurally-induced contractile and relaxant responses elicited by EFS. Neuronal nitric oxide synthase(n NOS) enzyme was evaluated by immunohistochemistry.RESULTS In the functional experiments, electrical field stimulation(EFS, 4-16 Hz) induced tetrodotoxin(TTX)-sensitive contractile responses, which were reduced in amplitude by GLP-2(P < 0.05). In the presence of the nitric oxide(NO) synthesis inhibitor L-NNA, GLP-2 no longer influenced the neurally-evoked contractile responses(P > 0.05). The direct smooth muscle response to methacholine was not influenced by GLP-2(P > 0.05). In the presence of guanethidine and carbachol, the addition of GLP-2 to the bath medium evoked TTX-sensitive relaxant responses that were unaffected by L-NNA(P > 0.05). EFS induced a fast NO-mediated relaxation, whose amplitude was enhanced in the presence of the hormone(P < 0.05). Immunohistochemical experiments showed a significant increase(P < 0.05) in n NOS immunoreactivity in the nerve structures after GLP-2 exposure. CONCLUSION The results demonstrate that in gastric fundal strips, GLP-2 influences the amplitude of neurally-induced responses through the modulation of the nitrergic neurotransmission and increases n NOS expression.

Mechanisms underlying feed intolerance in the critically ill: Implications for treatment

Malnutrition is associated with poor outcomes in critically ill patients. Although nutritional support is yet to be proven to improve mortality in non-malnourished critically ill patients, early enteral feeding is considered best practice. However, enteral feeding is often limited by delayed gastric emptying. The best method to clinically identify delayed gastric emptying and feed intolerance is unclear. Gastric residual volume （GRV） measured at the bedside is widely used as a surrogate marker for gastric emptying, but the value of GRV measurement has recently been disputed. While the mechanisms underlying delayed gastric emptying require further investigation, recent research has given a better appreciation of the pathophysiology. A number of pharmacological strategies are available to improve the success of feeding. Recent data suggest a combination of intravenous metoclopramide and en/thromycin to be the most successful treatment, but novel drug therapies should be explored. Simpler methods to access the duodenum and more distal small bowel for feed delivery are also under investigation. This review summarises current understanding of the factors responsible for, and mechanisms underlying feed intolerance in critical illness, together with the evidence for current practices. Areas requiring further research are also highlighted.