Electroacupuncture improves impaired gastric motility and slow waves induced by rectal distension in dogs

Rectal distension (RD) is known to induce upper gastrointestinal (GI) symptoms. The aim of this study was to investigate the effects and underlying mechanisms of RD on gastric slow waves (GSW) and motor activity and furthermore to investigate the effects and mechanisms of electroacupuncture (EA) on GSW and motor activity. Eight female hound dogs chronically implanted with gastric serosal electrodes and a gastric fistula were studied in six separate sessions. Antral motility, GSW, heart rate variability, and rectal pressure were evaluated for the above purposes. 1) RD at a volume of 120 ml suppressed antral motility significantly. Guanethidine blocked the inhibitory effect of RD. EA at ST36 was able to restore the suppressed antral contractions induced by RD (16.6+/-1.7 vs. 8.0+/-1.4, P<0.001). Naloxone partially blocked the effect of EA on antral contractions. 2) RD reduced the percentage of normal GSW from 98.8+/-0.8% at baseline to 76.1+/-8.6% (P<0.05) that was increased to 91.8+/-3.0% with EA. The effects of EA on the GSW were nullified by the presence of naloxone. 3) EA did not show any significant effect on rectal pressure, suggesting that the ameliorating effects of EA on RD-induced impaired gastric motility were not due to a decrease in rectal pressure. 4) EA increased the vagal activity suppressed by RD. In conclusion, RD inhibits postprandial gastric motility and impairs GSW in dogs, and the inhibitory effects are mediated via the adrenergic pathways. EA at ST36 is able to restore the RD-induced impaired GSW and motor activities, possibly by enhancing vagal activity, and is partially mediated via the opioid pathway. EA may have therapeutic potential for functional gastrointestinal disorders.     

Ameliorating Effects of Auricular Electroacupuncture on Rectal Distention-Induced Gastric Dysrhythmias in Rats

Gastric slow waves (GSW) are known to regulate gastric motility and are impaired with rectal distention (RD). Electroacupuncture (EA) at body acupoints, such as ST 36, has been shown to improve gastric dysrhythmias; however, little is known about the possible effects of auricular electroacupuncture (AEA) on GSW. To study effects and possible mechanisms of AEA on RD-induced gastric dysrhythmias in rats, ten male Sprague-Dawley (SD) rats implanted with gastric serosal electrodes were studied in two different experiments in fed state. Four sessions were performed in experiment 1 as follows: control (RD, no stimulation), RD+AEA, RD+EA at body points and RD+sham AEA. Two sessions were included in experiment 2 to study mechanisms of AEA: RD + atropine and RD + atropine + AEA. It was found that 1) RD significantly decreased the percentage of normal GSW from 89.8±3.5% to 76.0±3.3% (P<0.05); 2) AEA increased the percentage of normal GSW during RD to 94.0±2.1% (P<0.05 vs. RD) via a reduction in the percentages of tachygastria and arrhythmia (P<0.05 vs. RD); 3) atropine blocked the ameliorating effect of AEA on RD-induced gastric dysrhythmias. Our results demonstrated that RD induces gastric dysrhythmias in fed state in rats. AEA improves RD-induced gastric dysrhythmias via the vagal pathway. AEA may have a therapeutic potential in treating gastric dysrhythmias.     

Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans

Glucagon-like peptide-1 (GLP-1) relaxes the stomach during fasting but decreases hunger and food consumption and retards gastric emptying. The interrelationships between volume, emptying, and postprandial symptoms in response to GLP-1 are unclear. We performed, in healthy human volunteers, a placebo-controlled study of the effects of intravenous GLP-1 on gastric volume using (99m)Tc-single photon emission computed tomography imaging, gastric emptying of a nutrient liquid meal (Ensure) using scintigraphy, maximum tolerated volume (MTV) of Ensure, and postprandial symptoms 30 min after MTV. The role of vagal cholinergic function in the effects of GLP-1 was assessed by human pancreatic polypeptide (HPP) response to the Ensure meal. GLP-1 increased fasting and postprandial gastric volumes and retarded gastric emptying; MTV and postprandial symptoms were not different compared with controls. Effects on postprandial gastric function were associated with reduced postprandial HPP levels. GLP-1 does not induce postprandial symptoms despite significant inhibition of gastric emptying and vagal function; this may be partly explained by the increase in postprandial gastric volume.     

Inhibitory effects of desvenlafaxine on gastric slow waves, antral contractions, and gastric accommodation mediated via the sympathetic mechanism in dogs

Desvenlafaxine succinate (DVS; Pristiq) is a new antidepressant, serotonin-norepinephrine reuptake inhibitor. Antidepressants have been widely used for the treatment of functional gastrointestinal disorders. Possible roles of DVS on gastrointestinal motility have not been studied. The aim of this study was to investigate the effects of DVS on gastric slow waves (GSW), antral contractions, and gastric accommodation in dogs. Fifteen healthy dogs implanted with gastric serosal electrodes and a gastric cannula were studied in four separate sessions: control, DVS (50 mg), propranolol (1 mg·kg(-1)·h(-1)), and propranolol + DVS. GSW were measured via the gastric serosal electrodes. Antral contractions were assessed via an intraluminal manometric catheter inserted via the gastric cannula. The sympathovagal activity was assessed from the spectral analysis of the heart rate variability signal. Gastric tone was measured by barostat via an intragastric balloon inserted into the fundus via the gastric cannula. In the postprandial period, in comparison with the control, DVS reduced the percentage of normal GSW (P=0.001) and increased the percentage of tachygastria (P=0.005) and bradygastria (P=0.002). Simultaneously, DVS increased the sympathetic activity (P=0.006) and the sympathovagal ratio (low frequency/high frequency; P=0.044). These effects were blocked by propranolol. DVS attenuated postprandial antral contractions and gastric accommodation. The postprandial antral contractile index (area under the curve) was decreased by 26% with DVS (P=0.013), and gastric accommodation was decreased by about 50% with DVS (P < 0.001). The inhibitory effect of DVS on gastric accommodation was blocked by propranolol. DVS inhibits gastric contractions, slow waves, and accommodation in the fed state. These inhibitory effects are associated with an increased sympathetic modulation in the gastrointestinal system. Cautions should be made when DVS is used for treating patients with depression and gastric motility disorders.     

Glucose sensing by gut endocrine cells and activation of the vagal afferent pathway is impaired in a rodent model of type 2 diabetes mellitus

Glucose in the gut lumen activates gut endocrine cells to release 5-HT, glucagon-like peptide 1/2 (GLP-1/2), and glucose-dependent insulinotropic polypeptide (GIP), which act to change gastrointestinal function and regulate postprandial plasma glucose. There is evidence that both release and action of incretin hormones is reduced in type 2 diabetes (T2D). We measured cellular activation of enteroendocrine and enterochromaffin cells, enteric neurons, and vagal afferent neurons in response to intestinal glucose in a model of type 2 diabetes mellitus, the UCD-T2DM rat. Prediabetic (PD), recent-diabetic (RD, 2 wk postonset), and 3-mo diabetic (3MD) fasted UCD-T2DM rats were given an orogastric gavage of vehicle (water, 0.5 ml /100 g body wt) or glucose (330 μmol/100 g body wt); after 6 min tissue was removed and cellular activation was determined by immunohistochemistry for phosphorylated calcium calmodulin-dependent kinase II (pCaMKII). In PD rats, pCaMKII immunoreactivity was increased in duodenal 5-HT (P < 0.001), K (P < 0.01) and L (P < 0.01) cells in response to glucose; glucose-induced activation of all three cell types was significantly reduced in RD and 3MD compared with PD rats. Immunoreactivity for GLP-1, but not GIP, was significantly reduced in RD and 3MD compared with PD rats (P < 0.01). Administration of glucose significantly increased pCaMKII in enteric and vagal afferent neurons in PD rats; glucose-induced pCaMKII immunoreactivity was attenuated in enteric and vagal afferent neurons (P < 0.01, P < 0.001, respectively) in RD and 3MD. These data suggest that glucose sensing in enteroendocrine and enterochromaffin cells and activation of neural pathways is markedly impaired in UCD-T2DM rats.     

Effect of Somatostatin Analog on Postprandial Satiation in Obesity

Objective: Altered satiation may impact postprandial symptoms and potentially change food intake in obesity. Our aim was to compare effects of octreotide and placebo on postprandial symptoms, satiation, and gastric volumes in obesity. Research Methods and Procedures: In a randomized, parallel‐group, double‐blind, placebo‐controlled study, 26 obese but otherwise healthy participants received 100 μg of octreotide or placebo subcutaneously 30 minutes before each study. Studies were performed on 2 separate days and included validated non‐invasive techniques: ^99mTc‐single photon emission computed tomography imaging to measure fasting stomach volume and gastric volume changes after 90 mL of water and 240 mL of Ensure and a standardized nutrient drink test to measure the maximum tolerated volume and postprandial symptoms. Results: Relative to placebo, octreotide increased gastric volume after 90 mL of water; however, fasting and gastric volume change post‐Ensure and maximum tolerated volume of Ensure were not different. Octreotide decreased sensations of fullness (p = 0.035) and bloating (p = 0.05) and tended to reduce aggregate symptoms (p = 0.07) after the fully satiating meal. Discussion: In obese individuals, somatostatin analog significantly reduced postprandial sensations after a satiating meal without altering maximum tolerated meal volume or postnutrient gastric volume, suggesting an effect on upper gut sensation. The role of somatostatin as a permissive factor in the development of obesity by reducing postprandial sensations deserves further study.     

Noninvasive assessment of the effects of glucagon on the gastric slow wave

Hyperglycemic effects on the gastric slow wave are not well understood, and no studies have examined the effects that hyperglycemia has on gastric slow wave magnetic fields. We recorded multichannel magnetogastrograms (MGGs) before and after intravenous administration of glucagon and subsequent modest hyperglycemia in 20 normal volunteers. Normal slow waves were evident in baseline MGG recordings from all 20 subjects, but within 15 min after glucagon had been given, we noted significant effects on MGG signals. In addition to an overall decrease in the slow wave frequency from 2.9 +/- 0.5 cycles per min (cpm) to 2.2 +/- 0.1 cpm (P < 0.05), we observed significant changes in the number and range of spectral peaks recorded. Furthermore, the propagation velocity determined from surface current density maps computed from the multichannel MGG decreased significantly (7.1 +/- 0.8 mm/s to 5.0 +/- 0.3 mm/s, P < 0.05). This is the first study of biomagnetic effects of hyperglycemia in normal subjects. Our results suggest that the analysis of the MGG provides parameter quantification for gastric electrical activity specific to and characteristic of slow wave abnormalities associated with increased serum glucose by injection of glucagon.     

Abnormal gastric slow waves in patients with functional dyspepsia assessed by multichannel electrogastrography

The aim of this study was to utilize multichannel electrogastrography to investigate whether patients with functional dyspepsia had impaired propagation or coordination of gastric slow waves in the fasting state compared with healthy controls. The study was performed in 10 patients with functional dyspepsia and 11 healthy subjects. Gastric myoelectrical activity was measured by using surface electrogastrography with a specially designed four-channel device. The study was performed for 30 min or more in the fasting state. Special computer programs were developed for the computation of the propagation and coupling of the gastric slow wave. It was found that, compared with the healthy controls, the patients showed a significantly lower percentage of slow wave propagation (58.0 +/- 8.9 vs. 89.9 +/- 2.6%, P < 0.002) and a significantly lower percentage of slow wave coupling (46.9 +/- 4.4 vs. 61.5 +/- 6.9%, P < 0.04). In addition, the patients showed inconsistencies in the frequency and regularity of the gastric slow wave among the four-channel electrogastrograms (EGGs). It was concluded that patients with functional dyspepsia have impaired slow wave propagation and coupling. Multichannel EGG has more information than single-channel EGG for the detection of gastric myoelectrical abnormalities.     

Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers

CCK influences satiation and gastric and gallbladder emptying. GI181771X is a novel oral CCK-1 agonist; its effects on gastric emptying of solids, accommodation, and postprandial symptoms are unclear. Effects of four dose levels of the oral CCK-1 agonist GI181771X and placebo on gastric functions and postprandial symptoms were compared in 61 healthy men and women in a randomized, gender-stratified, double-blind, double-dummy placebo-controlled, parallel group study. Effects of 0.1, 0.5, and 1.5 mg of oral solution and a 5.0-mg tablet of GI181771X on gastric emptying of solids by scintigraphy, gastric volume by (99m)Tc-single photon emission computed tomographic imaging, maximum tolerated volume of Ensure, and postprandial nausea, bloating, fullness, and pain were studied. On each of 3 study days, participants received their randomly assigned treatment. Adverse effects and safety were monitored. There were overall group effects of GI181771X on gastric emptying (P < 0.01) and fasting and postprandial volumes (P = 0.036 and 0.015, respectively). The 1.5-mg oral solution of GI181771X significantly delayed gastric emptying of solids (P < 0.01) and increased fasting (P = 0.035) gastric volumes without altering postprandial (P = 0.056) gastric volumes or postprandial symptoms relative to placebo. The effect of the 5.0-mg tablet on gastric emptying of solids did not reach significance (P = 0.052). Pharmacokinetic profiles showed the highest area under the curve over 4 h for the 1.5-mg solution and a similar area under the curve for the 0.5-mg solution and 5-mg tablet. Adverse effects were predominantly gastrointestinal and occurred in a minority of participants. GI181771X delays gastric emptying of solids and exhibits an acceptable safety profile in healthy participants. CCK-1 receptors can be modulated to increase fasting gastric volume.     

Effect of ghrelin on gastric myoelectric activity and gastric emptying in rats

Ghrelin is a recently discovered peptide in the endocrine cells of the stomach, which may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not been clearly defined. The purpose of this study was to investigate the pharmacological effects of ghrelin on gastric myoelectrical activity and gastric emptying in rats, and to investigate whether cholinergic activity is involved in the effects of ghrelin. The study was performed on Sprague-Dawley rats implanted with serosal electrodes for electrogastrographic recording. Gastric slow waves were recorded from fasting rats at baseline and after injection of saline, ghrelin, atropine, or atropine+ghrelin. Gastric emptying of non-caloric liquid was measured by the spectrophotometric method in conscious rats. Intravenous administration of rat ghrelin (20 microg/kg) increased not only dominant frequency, dominant power and regularity of the gastric slow wave but also the gastric emptying rate when compared with the control rats (P<0.01, P<0.05, P<0.05, P<0.001 respectively). These stimulatory actions of ghrelin on both gastric myoelectrical activity and gastric emptying were not fully eliminated by pretreatment with atropine sulphate. These results taken together suggest that ghrelin may play a physiological role in the enteric neurotransmission controlling gastric contractions in rats.     

Influence of sildenafil on gastric sensorimotor function in humans

After a meal, the proximal stomach relaxes probably through the activation of nitrergic neurons in the gastric wall. Nitric oxide-induced smooth muscle relaxation involves activation of soluble guanylate cyclase, with cGMP production, which is then degradated by phosphodiesterase-5 (PDE-5). The aim of this study was to investigate the effect of sildenafil, a selective PDE-5 inhibitor, on fasting and postprandial proximal gastric volume and on gastric emptying rates in humans. A gastric barostat was used to study gastric compliance and perception to isobaric distension in healthy subjects before and after placebo (n = 13) or sildenafil, 50 mg (n = 15). In 10 healthy subjects, two gastric barostat studies were performed in randomized order to study the effect of placebo or sildenafil on postprandial gastric relaxation. Similarly, solid and liquid gastric emptying rates were studied in 12 healthy subjects. Sildenafil significantly increased fasting intragastric volume (141 +/- 15 vs. 163 +/- 15 ml, P < 0.05) and volumes of first perception. Sildenafil induced a higher and prolonged gastric relaxation either at 30 min (357 +/- 38 vs. 253 +/- 42 ml, P < 0.05) or 60 min (348 +/- 49 vs. 247 +/- 38 ml, P < 0.05) after the meal. Sildenafil did not alter solid half-emptying time but significantly delayed liquid emptying (43 +/- 4 vs. 56 +/- 4 min, P < 0.01). In conclusion, sildenafil significantly increases postprandial gastric volume and slows liquid emptying rate, confirming that meal-induced accommodation in humans involves the activation of a nitrergic pathway. The effect of sildenafil on gastric fundus suggests a therapeutic potential for phosphodiesterase inhibitors in patients with impaired gastric accommodation.     

Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers

Chloride channels modulate gastrointestinal neuromuscular functions in vitro. Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces intestinal secretion and has been shown to relieve constipation in clinical trials; however, the effects of lubiprostone on gastric function and whole gut transit in humans are unclear. Our aim was to compare the effects of the selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic transit in humans. We performed a randomized, parallel-group, double-blind, placebo-controlled study evaluating the effects of lubiprostone (24 microg bid) in 30 healthy volunteers. Validated methods were used: scintigraphic gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the nutrient drink ("satiation") test to measure MTV and postprandial symptoms. Lubiprostone accelerated small bowel and colonic transit, increased fasting gastric volume, and retarded gastric emptying. MTV values were reduced compared with placebo; however, the MTV was within the normal range for healthy adults in 13 of 14 participants, and there was no significant change compared with baseline measurements. Lubiprostone had no significant effect on postprandial gastric volume or aggregate symptoms but did decrease fullness 30 min after the fully satiating meal. Thus the ClC-2 activator lubiprostone accelerates small intestinal and colonic transit, which confers potential in the treatment of constipation.     

Effect of solid meal on gastric emptying of,and glycemic and cardiovascular responses to,liquid glucose in older subjects

Gastric emptying is a determinant of the postprandial glycemic and cardiovascular responses to oral carbohydrate. We evaluated the effects of a solid meal on gastric emptying and the glycemic and cardiovascular responses to oral glucose in healthy older subjects. Ten subjects aged 72.1 +/- 1.9 yr were studied. Each subject had measurements of gastric emptying, blood glucose, serum insulin, blood pressure, and heart rate after ingestion of a 50-g glucose drink (300 ml) with (mixed meal) or without (liquid only) a solid meal (300 g ground beef). Gastric emptying of liquid was initially slightly more rapid (P < 0.05) after the mixed meal compared with liquid only at 5 min (92.0 +/- 1.5 vs. 96.0 +/- 1.3%) and much slower (P < 0.05) after 120 min. The time to peak blood glucose was less (39.0 +/- 4.0 vs. 67.5 +/- 10.3 min; P < 0.01) and blood glucose subsequently lower (P < 0.01) after the mixed meal. The increase in serum insulin was greater (P < 0.001) after the mixed meal. Blood pressure fell (P < 0.05) in the first 30 min, with no difference between the two meals. Increase in heart rate after both meals (P < 0.005), was greater (P < 0.05) after the mixed meal. The presence of a noncarbohydrate solid meal had discrepant effects on early and subsequent emptying of a nutrient liquid, which affects postprandial glycemia and increased heart rate.     

Influence of acute tryptophan depletion on gastric sensorimotor function in humans

Peripheral serotonin (5-hydrodytryptamine; 5-HT) is involved in the regulation of gastrointestinal motility and sensation, whereas centrally it plays a role in mood regulation. A dysfunctional serotonergic system may provide a plausible link between functional dyspepsia symptoms and its high psychosocial comorbidity such as anxiety and depression. The aim of this study was to evaluate the effect of decreased 5-HT synthesis by acute tryptophan depletion (ATD) on gastric sensorimotor function and nutrient tolerance, anxiety scores, and gastrointestinal mucosal 5-HT concentrations in healthy volunteers. All subjects were studied under a control condition and during ATD. Gastric sensorimotor function and nutrient tolerance were assessed using a barostat (n = 16, mean age 28.8 ± 1.4 yr) and a satiety drinking test (n = 13, mean age 27.3 ± 1.4 yr). Anxiety during the barostat was evaluated using State-Trait Anxiety Inventory (STAI) questionnaire. 5-HT concentrations were measured in fundic and duodenal mucosal biopsies by means of ELISA and immunohistochemistry. ATD significantly decreased plasma tryptophan levels compared with control in every experiment. ATD did not affect gastric sensitivity and compliance but decreased the sensation of nausea during balloon distension (AUC: 17.4 ± 4.3 vs. 11.4 ± 3.4 mm·mmHg, P = 0.030). ATD enhanced the postprandial volume increase (ANOVA, P < 0.05), but this was not accompanied by augmented nutrient tolerance (848 ± 110 vs. 837 ± 99 ml, nonsignificant). ATD had no effect on STAI state anxiety scores. No evidence was found for an effect on the number of enterochromaffin cells, but ATD reduced 5-HT levels in the duodenal mucosa. ATD alters gastric postprandial motor function and distension-induced nausea. These findings confirm involvement of 5-HT in the control of gastric accommodation and sensitivity.     

Enhancement of intragastric acid stability of a fat emulsion meal delays gastric emptying and increases cholecystokinin release and gallbladder contraction

Preprocessed fatty foods often contain calories added as a fat emulsion stabilized by emulsifiers. Emulsion stability in the acidic gastric environment can readily be manipulated by altering emulsifier chemistry. We tested the hypothesis that it would be possible to control gastric emptying, CCK release, and satiety by varying intragastric fat emulsion stability. Nine healthy volunteers received a test meal on two occasions, comprising a 500-ml 15% oil emulsion with 2.5% of one of two emulsifiers that produced emulsions that were either stable (meal A) or unstable (meal B) in the acid gastric environment. Gastric emptying and gallbladder volume changes were assessed by MRI. CCK plasma levels were measured and satiety scores were recorded. Meal B layered rapidly owing to fat emulsion breakdown. The gastric half-emptying time of the aqueous phase was faster for meal B (72 +/- 13 min) than for meal A (171 +/- 35 min, P < 0.008). Meal A released more CCK than meal B (integrated areas, respectively 1,095 +/- 244 and 531 +/- 111 pmol.min.l(-1), P < 0.02), induced a greater gallbladder contraction (P < 0.02), and decreased postprandial appetite (P < 0.05), although no significant differences were observed in fullness and hunger. We conclude that acid-stable emulsions delayed gastric emptying and increased postprandial CCK levels and gallbladder contraction, whereas acid-instability led to rapid layering of fat in the gastric lumen with accelerated gastric emptying, lower CCK levels, and reduced gallbladder contraction. Manipulation of the acid stability of fat emulsion added to preprocessed foods could maximize satiety signaling and, in turn, help to reduce overconsumption of calories.     

Expression of FHL1 in gastric cancer tissue and its correlation with the invasion and metastasis of gastric cancer

This study was performed to analyze the expression of four and a half LIM domains 1 (FHL1) in gastric carcinoma tissue and its correlation with the clinicopathological characteristics of gastric cancer. In addition, the role of FHL1 in the invasion and metastasis of gastric cancer cells was investigated to provide an experimental basis for future treatments of gastric cancer. FHL1 mRNA and protein expression in gastric carcinoma and the adjacent normal gastric mucosa tissue were determined using RT-PCR and western blots. Correlations of FHL1 expression with the incidence, progression, and clinicopathological characteristics of gastric cancer were analyzed. Changes in the invasion and metastatic potential of MKN45 human gastric cancer cells were observed after the transient transfection with an eukaryotic expression vector containing full-length FHL1. Expression of FHL1 mRNA in gastric carcinoma tissue was significantly lower than that in the adjacent normal tissue (P < 0.05). FHL1 expression in gastric carcinoma tissue from patients who were positive for lymph node metastasis was significantly lower than those in patients who were negative for lymph node metastasis (P < 0.05). Lower FHL1 expression was correlated with lower degrees of differentiation, higher TNM stages, and greater invasive potential of the gastric cancer (P < 0.05). The FHL1 mRNA and protein expression patterns were similar in gastric cancer. FHL1 protein expression in gastric carcinoma tissue was significantly lower than that in the surrounding normal tissue (P < 0.05). FHL1 protein expression was significantly lower in gastric carcinoma tissue from patients who were positive for lymph node metastasis than that detected in patients with no lymph node metastasis (P < 0.05). Lower FHL1 protein expression was correlated with lower degrees of differentiation, higher TNM stages, and greater invasive potential in gastric cancer (P < 0.05). However, the expression of FHL1 was independent of the patient's gender, age, and tumor size (P > 0.05). Overexpression of FHL1 in the MKN45 human gastric cancer cell line using an eukaryotic expression vector resulted in a significant reduction in the invasiveness and metastatic ability of these cells as determined using the Transwell chamber invasion assay (P < 0.05). The decrease in or loss of FHL1 expression may be related to the incidence, progression, invasiveness, and metastatic potential of gastric cancer.     

Gastric emptying in response to IAPP and CCK in rats with subdiaphragmatic afferent vagotomy

In the subdiaphragmatic vagal deafferentation procedure (SDA), the afferent fibers of the vagus are surgically severed unilaterally where they enter the brain stem. The technique includes a subdiaphragmal truncal vagotomy performed on the contralateral side. This procedure has been used to study the control of food intake, but it has not been used previously to investigate the role of vagal afferent fibers in the control of gastric emptying (GE). The current experiment studied the effect of SDA on the inhibition of GE by islet amyloid polypeptide (IAPP or amylin) and cholecystokinin (CCK) in awake, unrestrained rats with gastric cannulas. The experimental group underwent subdiaphragmatic vagal deafferentation; the control group had sham operations. All rats received 20-min intravenous infusions of IAPP (1, 3, 9, 27, and 81 pmol/kg/min), CCK (3, 30 and 90 pmol/kg/min), and normal saline in random order. Gastric emptying of saline was measured by the phenol red method during the last 5 min of each infusion period. CCK dose-dependently inhibited gastric emptying in both the control and SDA animals. The inhibition of GE by CCK was significantly attenuated by SDA (p<0.01). IAPP also inhibited gastric emptying dose-dependently, but the difference between the SDA and control groups was not significant. The current experiment, which used a different methodology than previous studies, provides support for the hypothesis that the inhibition of gastric emptying by CCK, but not by IAPP, is mediated partly by afferent vagal fibers.     

胃食管反流病患者餐后近端胃内酸分布及与食管酸暴露的关系

目的:探讨餐后胃食管反流病(GERD)病人近端胃内酸度的分布状态及其和食管酸暴露的相关性。方法:抽选我院12例GERD患者,应用3级锑电极对定位于LES上缘近侧5 cm(食管)和LES上缘远侧5 cm的贲门下(近端胃内)、LES上缘远侧10cm的近端胃远侧(近端胃内)进行pH监测,监测时间为空腹1 h和餐后4 h,同期抽选健康志愿者12例为对照组,计算两组患者食管酸暴露以及胃内整合酸度(IA)。结果:两组空腹时近端胃内IA和食管酸暴露比较无显著性差异(P0.05);对照组中,试检者餐后1、2、3、4 h贲门下IA均显著低于近端胃远侧部位(P0.05),但GERD组中IA部位差异不明显(P0.05);餐后2 h,两组近端胃内IA均有所回升,但是对照组未超过基线(P0.05),而GERD组明显高于基线水平(P0.05);两组食管酸暴露均主要在餐后2h发生,并且两组比较差异显著(P0.05);在餐后各时段,两组中食管酸暴露与IA均无显著相关性。结论:GERD餐后晚期近端胃酸分泌增高,扩大了酸性近端胃池,可部分解释GERD进食后食管过度酸暴露。     

Chronic tachygastrial electrical stimulation reduces food intake in dogs

Objective: Tachygastria is known to be associated with gastric hypomotility. This study investigated the effect of tachygastrial electrical stimulation (TES) on food intake and its effects on gastric motility. Research Methods and Procedures: Five experiments were performed to study the effects of TES on gastric slow waves, gastric tone, accommodation, and antral contractions, gastric emptying, acute food intake, and chronic food intake in dogs. Results: TES at tachygastrial frequencies induced tachygastria and reduced normal slow waves. TES significantly reduced gastric tone or induced gastric distention, impaired gastric accommodation, and inhibited antral contractions. TES significantly delayed gastric emptying. Acute TES reduced food intake but did not induce any noticeable symptoms. Chronic TES resulted in a 20% reduction in food intake, and the effect of TES was found to be related to specific parameters. Discussion: TES at the distal antrum results in a significant reduction in food intake in dogs, and this inhibitory effect is probably attributed to TES‐induced reduction in proximal gastric tone, gastric accommodation, antral contractility, and gastric emptying. These data suggest a therapeutic potential of the specific method of TES for obesity.     

Peripheral mechanisms of sibutramine involving proximal gastric motility in dogs

Objective: Sibutramine, a serotonin‐norepinephrine uptake inhibitor, has been used for treating obesity. However, its possible mechanisms involving gastric motility have not been reported. The aim of this study was to evaluate the effects of sibutramine on gastric accommodation and antral motility. Research Methods and Procedures: The study was performed in seven dogs with a stomach cannula and composed of two separate experiments: antral contractions and gastric tone. Each experiment included two sessions on 2 separate days in a randomized order: a control session and a treatment session with sibutramine (5 mg/kg per os) administrated 2 hours before the study. Results: Sibutramine significantly increased fasting gastric tone; the gastric volume in the fasting state at baseline was 103.8 ± 12.3 mL and significantly decreased to 35.3 ± 16.0 mL with sibutramine (p = 0.0075). Sibutramine also impaired gastric accommodation. The average postprandial gastric volume was 472.1 ± 16.7 mL in the control session and reduced to 302.2 ± 53.6 mL with sibutramine (p = 0.013). The average postprandial increase in gastric volume during the 60‐minute postprandial period with sibutramine was significantly lower than the corresponding values in the control session: 266.8 ± 46.1 vs. 393.9 ± 15.3 mL (p = 0.03). Sibutramine had no effects on postprandial antral contractions. Discussion: Sibutramine increases gastric tone and impairs gastric accommodation to an orally ingested meal. The inhibitory effect of sibutramine on gastric accommodation may partially explain the reduced food intake with sibutramine in patients with obesity.