The Prokinetic Face of Ghrelin

This review evaluated published data regarding the effects of ghrelin on GI motility using the PubMed database for English articles from 1999 to September 2009. Our strategy was to combine all available information from previous literature, in order to provide a complete structured review on the prokinetic properties of exogenous ghrelin and its potential use for treatment of various GI dysmotility ailments. We classified the literature into two major groups, depending on whether studies were done in health or in disease. We sub-classified the studies into stomach, small intestinal and colon studies, and broke them down further into studies done in vitro, in vivo (animals) and in humans. Further more, the reviewed studies were presented in a chronological order to guide the readers across the scientific advances in the field. The review shows evidences that ghrelin and its (receptor) agonists possess a strong prokinetic potential to serve in the treatment of diabetic, neurogenic or idiopathic gastroparesis and possibly, chemotherapy-associated dyspepsia, postoperative, septic or post-burn ileus, opiate-induced bowel dysfunction and chronic idiopathic constipation. Further research is necessary to close the gap in knowledge about the effect of ghrelin on the human intestines in health and disease

Effects of Transcutaneous Electrical Acustimulation on Refractory Gastroesophageal Reflux Disease

Objective. To investigate effects and possible mechanisms of transcutaneous electrical acustimulation (TEA) performed by a wearable watch-size stimulator for refractory gastroesophageal reflux disease (RGERD). Methods. Twenty patients diagnosed as RGERD were enrolled in the study and randomly divided into four groups: esomeprazole group (Group A), esomeprazole combined with TEA group (Group B), esomeprazole combined with sham-TEA group (Group C), and esomeprazole combined with domperidone group (Group D). HRM and 24 h pH-impedance monitoring and GerdQ score were used to measure related indexes before and after treatment. Results. (1) TEA significantly increased LESP, compared with PPI treatment only or PPI plus sham-TEA. After pairwise comparison, LESP of Group B was increased more than Group A (P=0.008) or Group C (P=0.021). (2) PPI plus TEA decreased not only the number of acid reflux episodes but also the number of weak acid reflux episodes (P=0.005). (3) Heartburn and reflux symptoms were improved more with PPI + TEA than with PPI treatment only or PPI plus sham-TEA (GerdQ scores, P=0.001). Conclusion. TEA can improve symptoms in RGERD patients by increasing LESP and decreasing events of weak acid reflux and acid reflux; addition of TEA to esomeprazole significantly enhances the effect of TEA

Effects and Mechanisms of Transcutaneous Electroacupuncture on Chemotherapy-Induced Nausea and Vomiting

Nausea and vomiting are one of the major complications of chemotherapy for cancers. The aim of this study is to investigate the emetic effects and mechanisms involving serotonin and dopamine of needleless transcutaneous electroacupuncture (TEA) at Neiguan (PC6) and Jianshi (PC5) on chemotherapy-induced nausea and vomiting in patients with cancers. Seventy-two patients with chemotherapy were randomly divided into sham-TEA group (sham-TEA, n=34) and TEA group (n=38). TEA was performed at PC 6 and PC 5 (1 h, bid) in combination with granisetron. Sham-TEA was delivered at nonacupoints using the same parameters. We found the following. (1) In the acute phase, the conventional antiemetic therapy using Ondansetron effectively reduced nausea and vomiting; the addition of TEA did not show any additive effects. In the delayed phase, however, TEA significantly increased the rate of complete control (P<0.01) and reduced the nausea score (P<0.05), compared with sham-TEA. (2) TEA significantly reduced serum levels of 5-HT and dopamine in comparison with sham-TEA. Those results demonstrate that needleless transcutaneous electroacupuncture at PC6 using a watch-size digital stimulator improves emesis and reduces nausea in the delayed phase of chemotherapy in patients with cancers. This antiemetic effect is possibly mediated via mechanisms involving serotonin and dopamine

1

1H NMR-based metabolic profiling combined with multivariate data analysis was used to explore the metabolic phenotype of functional dyspepsia (FD) in stressed rats and evaluate the intervention effects of the Chinese medicine Weikangning (WKN). After a 7-day period of model establishment, a 14-day drug administration schedule was conducted in a WKN-treated group of rats, with the model and normal control groups serving as negative controls. Based on 1H NMR spectra of urine and serum from rats, PCA, PLS-DA, and OPLS-DA were performed to identify changing metabolic profiles. According to the key metabolites determined by OPLS-DA, alterations in energy metabolism, stress-related metabolism, and gut microbiota were found in FD model rats after stress stimulation, and these alterations were restored to normal after WKN administration. This study may provide new insights into the relationship between FD and psychological stress and assist in research into the metabolic mechanisms involved in Chinese medicine

Effect of Aurantii Fructus Immaturus Flavonoid on the Contraction of Isolated Gastric Smooth Muscle Strips in Rats

This study was designed to investigate the effect of Aurantii fructus immaturus flavonoid (AFIF) on the contraction of isolated gastric smooth muscle in rats and explore its underlying mechanisms. Isolated antral longitudinal smooth muscle strip (ALSMS) and pyloric circular smooth muscle strip (PCSMS) of rats were suspended in tissue chambers. The responses of ALSMS and PCSMS to administration of AFIF were observed. Cyclic guanosine monophosphate (cGMP) and protein kinase G (PKG) levels of PCSMS were measured by ELISA kits. In this study, AFIF showed no significant effect on ALSMS contraction, but it dose-dependently reduced the mean contraction amplitude of PCSMS. When the concentration of AFIF reached 3000 g/mL, 6000 g/mL, and 10000 g/mL, its inhibitory effect on PCSMS contraction was significant. This effect of AFIF was weakened in Ca 2+ -rich environment. And N -nitro-L-arginine methyl (L-NAME), the inhibitor of nitric oxide synthase (NOS), significantly inhibited AFIF&apos;s action in comparison with control ( &lt; 0.05). After incubation with AFIF for 30 min, levels of cGMP and PKG in PCSMS were significantly increased compared with control ( &lt; 0.05). Our results suggest that AFIF has a dose-dependent diastolic effect on PCSMS in rats, which may be related to the regulatory pathway of NO/cGMP/PKG/Ca 2+

Effects and mechanisms of auricular electroacupuncture on gastric hypersensitivity in a rodent model of functional dyspepsia

Background Functional dyspepsia (FD) is a common functional gastrointestinal disease, and abdominal pain is one of the main symptoms. The aim of this study was to explore the effects and mechanisms of auricular electro-acupuncture (AEA) on gastric hypersensitivity in a rodent model of FD. Methods Ten-day-old pups were gavaged with 0.2 ml of 0.1% iodoacetamide daily for 6 days. AEA at the “stomach” point with different parameters or sham-EA was performed on 8-week-old animals. Gastric sensitivity to gastric distention was measured under different conditions. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. Naloxone was injected intraperitoneally before AEA to explore the opioid mechanism. Gastric emptying was measured at the end of the study. Results 1) Gastric sensitivity to gastric distention was higher in the FD rats. AEA with parameters of 0.1s on, 0.4s off, 100Hz, 0.3ms and 0.4–0.5mA, but not other parameters or sham-EA, decreased gastric hypersensitivity in the FD rats. Naloxone did not block the effect of AEA. 2) Lower vagal activity and higher sympathovagal ratio were noted in the FD rats, compared with the controls. AEA increased vagal activity and improved sympathovagal imbalance. Conclusions AEA ameliorates gastric hypersensitivity in FD rats and this effect may be attributed to the improvement of sympathovagal balance.Yeshttp://www.plosone.org/static/editorial#pee

Cellular effects of gastric electrical stimulation on antral smooth muscle cells in rats

The cellular effects of gastric electrical stimulation (GES), which has recently been introduced as a potential therapy for the treatment of gastroparesis and obesity, were investigated in rat antrum smooth muscle cells (SMCs). Effects on cell membrane potentials of single electrical current pulses (pulse width from 0.1 ms to 200 ms) and 2-s pulse train stimuli with different pulse widths (0.1–4 ms), different frequencies (20–200 Hz), and different intensities were studied: 1) the stimulus amplitude had an exponential relationship to the pulse width from 2 ms to 200 ms, along with a rapidly rising strength-duration curve at pulse widths less than 5 ms, and a relatively flat curve at pulse widths greater than 50 ms; 2) when the pulse frequency was at 80 Hz or above, pulse train electrical stimulation, with a pulse width of 2 ms or above but not ≤1 ms, was able to depolarize cell membrane potentials to above −30 mV and/or generate action potentials. Electrical stimulation with a single long pulse and a width of 50 ms or greater is effective in depolarizing cell membrane potentials of SMCs with low amplitude. Pulse train electrical stimulation with a pulse width of ≤1 ms fails to generate action potentials in SMCs, whereas pulse train electrical stimulation with a pulse width of 2–4 ms and a sufficiently high pulse frequency is able to generate action potentials. These cellular findings may be useful in optimizing stimulation parameters of GES. </jats:p