• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.603-607
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• 2011

The purpose of this study is to investigate the effects of Carthami Flos on interstitial cells of Cajal in the gastrointestinal tract. Many regions of the tunica muscularis of the gastrointestinal (GI) tract display spontaneous contraction. These spontaneous contractions are mediated by periodic generation of electrical slow waves. Recent studies have shown that the interstitial cells of Cajal (ICCs) act as pacemakers and conductors of electrical slow waves in gastrointestinal smooth muscles. We investigated the cytotoxicity activity, antioxidant activity, and pacemaking activity. The cytotoxicity activity was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Antioxidant activities were determined by DPPH (1.1-diphenyl-2-picrylhydrazyl) radical scavenging capacity assay and DCFH-DA (2,7-dichlorofluorescein diacetate) method. The effects of Carthami Flos on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by using whole-cell patch-clamp techniques at $30^{\circ}C$. The addition of Carthami Flos (5, 10, $30{\mu}g$/ml) depolarized the resting membrane potentials in a concentration dependent manner. These results suggest that the GI tract can be targets for Carthami Flos, and their interaction can affect intestinal motility.

• Journal of Sasang Constitutional Medicine
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• v.27 no.2
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• pp.254-269
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• 2015

Objectives This study aimed to observe the effect of Taeumjowi-tang on the cisplatin-induced gastrointestinal dysfunctions in rats. Methods Four groups, each of 8 rats per group, were used in this study. Saline and distilled water treated control rats were intact vehicle control group. Delayed gastrointestinal motility was induced by intraperitoneal treatment of cisplatin 2mg/kg, once a week for 5 weeks(Cisplatin control group). Taeumjowi-tang aqueous extracts(TJ) were orally administered in a volume of 5ml/kg, once a day for 14 days from 4th cisplatin treatment(TJ group). Ondansetron 1mg/kg was subcutaneously treated, in a volume of 1ml/kg, as same as TJ(ondansetron group). We measured the body weights, intestinal charcoal transit ratio, fecal parameters, fundus MDA(malondialdehyde), GSH(glutathione) contents and SOD(superoxide dismutase), CAT(catalase) activities, TPH(tryptophanhydroxylase) and MAO(monoamine oxidase) activities, pyloric gastrin and serotonin contents with their immunoreactive cells, colonic serotonin-immunoreactive cells, the histopathology of pylorus, fundus mucosa and colon. Results 1) The body weight gains, the small intestinal charcoal transfer rates, the fecal parameters(numbers, weights and water contents) were increased in TJ, ondansetron group. 2) The inhibit of fundus antioxidant defense systems by cisplatin were decreased in TJ, ondansetron group. 3) The pyloric TPH activities were increased and the pyloric MAO activities were decreased in TJ group. 4) The pyloric gastric contents and the gastrin-immunoreactive cells were increased and the pyloric serotonin contents and the pyloric and colonic serotonin-immunoreactive cells were decreased in TJ group. 5) The pylorus atrophic changes and the gastric surface erosive damage regions by cisplatin were favorably inhibited by treatment of TJ group. Conclusions The results obtained in this study suggest that TJ favorably retarded the cisplatin related GI(gastrointestinal) dysfunctions and constipation through modulations of GI enterochromaffin cells, serotonin and gastrin-producing cells and antioxidative systems.

• Journal of Korean Academy of Nursing
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• v.51 no.6
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• pp.732-745
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• 2021

Purpose: This study aimed to assess combined effects of early oral feeding after Cesarean section (C/S) under regional anesthesia on bowel function, gastrointestinal complications and surgical recovery. Methods: A systematic literature search was conducted using KISS, RISS, PubMed, CINAHL, EMBASE, CENTRAL and Google Scholar to identify randomized clinical trials comparing early oral feeding (EOF) with delayed oral feeding (DOF) after C/S. Outcome variables were bowel function and gastrointestinal complications and surgical recovery. Effect size was calculated using weighted mean differences (WMDs) and relative risks (RRs), with 95% confidence intervals (CIs). Results: Seven studies involving 1,911 patients from 568 studies, 7 studies were included in meta-analysis. EOF was significantly associated with shorter time to recover bowel movement compared with DOF (WMD, - 2.50; CI, - 3.50~- 1.50). EOF was not associated with nausea (RR, 1.15; CI, 0.87~1.53) and vomiting (RR, 0.96; CI, 0.65~1.42), but lower incidence of abdominal distension (RR, 0.70; CI, 0.50~0.98). EOF was significantly associated with shorter time to discontinuation of intravenous fluids (WMD, - 8.88; 95% CI, - 16.65~- 1.11) and removal of urinary catheter (WMD, - 15.23; CI, - 25.62~- 4.85). Conclusion: This meta-analysis provides evidence that EOF after C/S under regional anesthesia not only accelerates return of bowel function and surgical recovery but also reduces gastrointestinal complications. These results suggest that EOF should be offered to women who have undergone C/S to improve the recovery experience and reduce overall medical costs.

• Advances in pediatric surgery
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• v.8 no.2
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• pp.113-118
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• 2002

The etiology of several motility disorders, including persistent megacolon after definitive surgery for Hirschsprung's disease, meconium ileus which is not associated with cystic fibrosis and idiopathic megacolon, is still unclear. Interstitial cells of Cajal (ICC) are thought to modulate gut motility as gastrointestinal pace maker cells. The aim of this study was to evaluate the role of ICC in the bowel walls of the patients (n=15) who had variable motility disorders. The ICC were identified by immunohistochemical staining using an anti-C-Kit antibody and the results were compared with control specimens (n=2). The control group (G1) showed evenly distributed ICC in their bowel walls. The second group (G2, n=5) who had normal bowel movements after Duhamel procedures and the third group (G3, n=4) who had persistent megacolon after Duhamel procedures showed absent or scarcely distributed ICC in their aganglionic bowels. The ICC were immunohistochemical staining using an anti-C-Kit antibody and the results were compared with control specimens (n=2). The control group (G1) showed evenly distributed ICC in their bowel walls. The second group (G2, n=5) who had normal bowel movements after Duhamel procedures and the third group (G3, n=4) who had persistent megacolon after Duhamel procedures showed absent or scarcely distributed ICC in their aganglionic bowels. Whereas ICC were evenly distributed in the ganglionic bowels of G2, they were not seen or scarecely distributed in the ganglionic bowels of G3. Two patients (G4) who suffered from idiopathic megacolon showed absence or decrease of ICC in spite of presence of ganglion cells in their colons. Four neonates (G5) who underwent ileostomy because of meconium obstruction showed absent or markedly decreased ICC in the the colon at the time of ileostomy and the distribution of ICC was changed to a normal pattern at the time of ileostomy closure between 39-104 days of age and their bowel motility were restored after that. The results suggest that lack of ICC caused reduce motility in the ganglionic colons and it may be responsible for the development of various motility disorders. Delayed maturity of ICC may also playa role in the meconium obstruction of neinates.

• Korean Journal of Veterinary Research
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• v.38 no.3
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• pp.614-628
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• 1998

The effects of electroacupuncture(EA) on blood concentration of endocrine substances were investigated in 6 horses. Three acupuncture points ; Guan Yuan Shu(BL-26), Wei Shu(BL-21) and Da Chang Shu(BL-25) were stimulated for 20 minutes by EA at separate occasions under varying condition ; 2V-1Hz, 2V-5Hz, 2V-30Hz, 4V-1Hz, 4V-5Hz and 4V-30Hz. Plasma levels of adrenocorticotropic hormone(ACTH), ${\beta}$-endorphin, epinephrine, norepinephrine and serum levels of gastrin were analysed. Blood samplings were carried out before, 0, 20 and 40 minutes after the EA stimulation. The serum gastrin levels were increased by 2V-5Hz stimulation on the Wei Shu. Plasma ACTH levels were decreased by 2V-1Hz stimulation on the Wei Shu, but largely increased by 4V-30Hz stimulation on the Guan Yuan Shu. Plasma ${\beta}$-endorphin levels were slightly increased or decreased by 2V-1Hz stimulation, but largely increased by 4V-30Hz stimulation on the Guan Yuan Shu. Plasma levels of epinephrine and norepinephrine were not so much changed by 2V-1Hz or 5Hz stimulation, but tended to increase by 4V-30Hz stimulation on Guan Yuan Shu. These results suggest that the low voltage-low frequence EA stimulation increased blood concentration of gastrin, but decreased ACTH, ${\beta}$-endorphin, epinephrine and norepinephrine, whereas high voltage-high frequence EA stimulation induced opposite results. Accordingly, there appears to be a close relationship between the changes of gastrointestinal motility and the changes of blood concentration of endocrine substances by EA stimulation.

• Molecules and Cells
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• v.27 no.3
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• pp.307-312
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• 2009

The interstitial cells of Cajal (ICC) are pacemaking cells required for gastrointestinal motility. The possibility of whether DA-9701, a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber, modulates pacemaker activities in the ICC was tested using the whole cell patch clamp technique. DA-9701 produced membrane depolarization and increased tonic inward pacemaker currents in the voltage-clamp mode. The application of flufenamic acid, a non-selective cation channel blocker, but not niflumic acid, abolished the generation of pacemaker currents induced by DA-9701. Pretreatment with a $Ca^{2+}$-free solution and thapsigargin, a $Ca^{2+}$-ATPase inhibitor in the endoplasmic reticulum, abolished the generation of pacemaker currents. In addition, the tonic inward currents were inhibited by U-73122, an active phospholipase C inhibitor, but not by $GDP-{\beta}-S$, which permanently binds G-binding proteins. Furthermore, the protein kinase C inhibitors, chelerythrine and calphostin C, did not block the DA-9701-induced pacemaker currents. These results suggest that DA-9701 might affect gastrointestinal motility by the modulation of pacemaker activity in the ICC, and the activation is associated with the non-selective cationic channels via external $Ca^{2+}$ influx, phospholipase C activation, and $Ca^{2+}$ release from internal storage in a G protein-independent and protein kinase C-independent manner.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.512-527
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• 2018

This review provides a comprehensive overview of brain imaging studies of the brain-gut interaction in functional gastrointestinal disorders (FGIDs). Functional neuroimaging studies during gut stimulation have shown enhanced brain responses in regions related to sensory processing of the homeostatic condition of the gut (homeostatic afferent) and responses to salience stimuli (salience network), as well as increased and decreased brain activity in the emotional response areas and reduced activation in areas associated with the top-down modulation of visceral afferent signals. Altered central regulation of the endocrine and autonomic nervous responses, the key mediators of the brain-gut axis, has been demonstrated. Studies using resting-state functional magnetic resonance imaging reported abnormal local and global connectivity in the areas related to pain processing and the default mode network (a physiological baseline of brain activity at rest associated with self-awareness and memory) in FGIDs. Structural imaging with brain morphometry and diffusion imaging demonstrated altered gray- and white-matter structures in areas that also showed changes in functional imaging studies, although this requires replication. Molecular imaging by magnetic resonance spectroscopy and positron emission tomography in FGIDs remains relatively sparse. Progress using analytical methods such as machine learning algorithms may shift neuroimaging studies from brain mapping to predicting clinical outcomes. Because several factors contribute to the pathophysiology of FGIDs and because its population is quite heterogeneous, a new model is needed in future studies to assess the importance of the factors and brain functions that are responsible for an optimal homeostatic state.

• Integrative Medicine Research
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• v.6 no.2
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• pp.149-155
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• 2017

Background: Naringenin (NRG) is a common dietary polyphenolic constituent of fruits. NRG has diverse pharmacological activities, and is used in traditional medicine to treat various diseases including gastrointestinal (GI) disorders. Interstitial cells of Cajal (ICCs) are pacemaker cells of the GI tract. In this study, the authors investigated the effects of NRG on ICCs and on GI motility in vitro and in vivo. Methods: ICCs were dissociated from mouse small intestines by enzymatic digestion. The whole-cell patch clamp configuration was used to record pacemaker potentials in cultured ICC clusters. The effects of NRG on GI motility were investigated by calculating percent intestinal transit rates (ITR) using Evans blue in normal mice. Results: NRG inhibited ICC pacemaker potentials in a dose-dependent manner. In the presence of tetraethylammonium chloride or iberiotoxin, NRG had no effect on pacemaker potentials, but it continued to block pacemaker potentials in the presence of glibenclamide. Preincubation with SQ-22536 had no effect on pacemaker potentials or on their inhibition by NRG. However, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one blocked pacemaker potential inhibition by NRG. In addition, L-NG-nitroarginine methyl ester blocked pacemaker potential inhibition by NRG. Furthermore, NRG significantly suppressed murine ITR enhancement by neostigmine in vivo. Conclusion: This study shows NRG dose-dependently inhibits ICC pacemaker potentials via a cyclic guanosine monophosphate/nitric oxide-dependent pathway and $Ca^{2+}$-activated $K^+$ channels in vitro. In addition, NRG suppressed neostigmine enhancement of ITR in vivo.

• Molecules and Cells
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• v.42 no.6
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• pp.470-479
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• 2019

Interstitial cells of Cajal (ICCs) are pacemaker cells that exhibit periodic spontaneous depolarization in the gastrointestinal (GI) tract and generate pacemaker potentials. In this study, we investigated the effects of ghrelin and motilin on the pacemaker potentials of ICCs isolated from the mouse small intestine. Using the whole-cell patch-clamp configuration, we demonstrated that ghrelin depolarized pacemaker potentials of cultured ICCs in a dose-dependent manner. The ghrelin receptor antagonist [D-Lys] GHRP-6 completely inhibited this ghrelin-induced depolarization. Intracellular guanosine 5'-diphosphate-${\beta}$-S and pre-treatment with $Ca^{2+}$-free solution or thapsigargin also blocked the ghrelin-induced depolarization. To investigate the involvement of inositol triphosphate ($IP_3$), Rho kinase, and protein kinase C (PKC) in ghrelin-mediated pacemaker potential depolarization of ICCs, we used the $IP_3$ receptor inhibitors 2-aminoethoxydiphenyl borate and xestospongin C, the Rho kinase inhibitor Y-27632, and the PKC inhibitors staurosporine, Go6976, and rottlerin. All inhibitors except rottlerin blocked the ghrelin-induced pacemaker potential depolarization of ICCs. In addition, motilin depolarized the pacemaker potentials of ICCs in a similar dose-dependent manner as ghrelin, and this was also completely inhibited by [D-Lys] GHRP-6. These results suggest that ghrelin induced the pacemaker potential depolarization through the ghrelin receptor in a G protein-, $IP_3$-, Rho kinase-, and PKC-dependent manner via intracellular and extracellular $Ca^{2+}$ regulation. In addition, motilin was able to depolarize the pacemaker potentials of ICCs through the ghrelin receptor. Therefore, ghrelin and its receptor may modulate GI motility by acting on ICCs in the murine small intestine.

• Biotechnology and Bioprocess Engineering:BBE
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• v.11 no.3
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• pp.240-244
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• 2006

To develop a health-aid preparation of Chinese yam (Dioscorea batatas Decne), lactic acid fermentation was attempted using a mixed starter comprising of Lactobacillus acidophilus, Streptococcus thermophilus, and Bifidobacterium bifidus. The anaerobic fermentation of a 5% Chinese yam flour suspension gave a uniform suspension of pH 4.35, containing $7.76{\times}10^6 CFU/mL$ lactic acid bacteria (LAB), and which was found to be acceptable to the panel from a sensory assessment. During the administration of the lactic acid fermented (LAF) Chinese yam to Sprague Dawley rats for 6 weeks, a smaller body weight gain, but greater excretion of feces were observed, implying the creation of a healthy gastrointestine on the administration of LAF Chinese yam, which was also confirmed by the gastrointestinal motility of the feed in rats fed on LAF Chinese yam. The constipation induced by loperamide was further suppressed in a rat group fed on a LAF Chinese yam diet, which was qualified from healthy gastrointestinal flora established by LAB. A serochemical analysis revealed a slight improvement in the blood glucose, neutral lipid and total cholesterol concentrations on administration of LAF Chinese yam, suggesting LAF Chinese yam could be served as a healthy-aid preparation, even for hyperglycemia or hyperlipidemia patients.