• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.1.1-1.14
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• 2018

DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

• The Korean Journal of Pharmacology
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• v.9 no.1
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• pp.23-37
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• 1973

This paper presents the effect of chronic administration of psychotropic drugs on rats. The experimental animals were litter mates (average initial body weight $47{\pm}1.1g$) whose mother were bred at our laboratory. Each litter mate was treated as one group. Control animals were treated with tap water and each experimental group was treated with caffeine citrate 0.1%, nialamide 0.1%, ethyl alcohol 2.5%, phenobarbital sod. 0.1%, diphenylhydantoin 0.1%, chlorpromazine 0.1%, reserpine 0.005%, diazepam 0.01%, chlorpheniramine 0.01% solutions respectively in drinking water over a period of ten weeks. All rats were allowed food and drinking water ad libitum. The mortality rate and the per cent increase of body weight were recorded weekly throughout the course of the experiment. The effects of above agents on the pentobarbital sleeping time, gastric secretion, and brain and liver weights were studied at the end of ten weeks treatment. The obtained results are summarized as follows: 1. Mortality rate was highest in the groups treated with phenobarbital and chlorpromazine respectively. Through the experimental period (ten weeks), the mortality rate was higher in earlier stage than in the later period. 2. During the period of prolonged administration of psychotropic drugs, only diazepam treated group showed remarkable difference in per cent increase of body weight from the control group of rats. 3. Acute treatment with psychotropic drugs delayed the onset of pentobarbital sleeping time. In contrast, the sleeping time was significantly shortened (p<0.001) when the rats were treated chronically with those agents. 4. The effects of chronic treatment with phenobarbital or diphenylhydantoin on the gastric secretion are as follows: the total acidity was remarkably decreased while the pH was increased. 5. The brain weight was significantly decreased in the ethyl alchol and in the chlorpheniramine treated groups, in the mean time, there was no change in liver weight treated with any psychotropic drugs.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.18 no.2
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• pp.108-112
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• 2007

Otolaryngological manifestations of acid reflux include a wide range of pharyngeal and laryngeal symptoms ; and the constellation of symptoms has been called laryngopharyngeal reflux (LPR). In the absence of definite diagnostic criteria, LPR disease remains a subjective entity. A diagnosis of LPR is usually based on response of symptoms to empirical treatment. Investigative modalities such as pH monitoring and, more recently, impedance studies are generally reserved for treatment failures. LPR usually requires more aggressive and prolonged treatment to achieve regression of both symptoms and laryngeal findings. The suppression of gastric acid and secretion with anti-secretary agents has been the mainstay of medical treatment for patients with acid-related disorders. The suppression of gastric acid secretion achieved with Hz-receptor antagonist $(H_2RA)$ has proved suboptimal for relief of reflux symptoms. The rapid development of tolerance and rebound acid hypersecretion after the with-drawal of $H_2RA$ limit their clinical use. Proton pump inhibitors (PPI) have been proved to be very effective for suppressing intragastric acidity, but the optimal dose and duration is unknown. Current evidence indicates that pharmacologic intervention should include, at a minimum, a 3 month trial of twice daily PPI. Symptoms of LPR improve over 2 months of therapy. The physical findings of LPR resolve more slowly than the symptoms and this continues through out at least 6 months of treatment. For most patients with LPR, twice daily dosing with a PPI is usually recommended for an initial treatment for a period of no less than 6 months treatment, and lifetime treatment may be required.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.35-42
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• 2018

Ascorbic acid is one of the most well-known nutritional supplement and antioxidant found in fruits and vegetables. Calcium ascorbate has been developed to mitigate the gastric irritation caused by the acidity of ascorbic acid. The aim of this study was to compare calcium ascorbate and ascorbic acid, focusing on their antioxidant activity and effects on gastric juice pH, total acid output, and pepsin secretion in an in vivo rat model, as well as pharmacokinetic parameters. Calcium ascorbate and ascorbic acid had similar antioxidant activity. However, the gastric fluid pH was increased by calcium ascorbate, whereas total acid output was increased by ascorbic acid. In the rat pylorus ligation-induced ulcer model, calcium ascorbate increased the gastric fluid pH without changing the total acid output. Administration of calcium ascorbate to rats given a single oral dose of 100 mg/kg as ascorbic acid resulted in higher plasma concentrations than that from ascorbic acid alone. The area under the curve (AUC) values of calcium ascorbate were 1.5-fold higher than those of ascorbic acid, and the $C_{max}$ value of calcium ascorbate (91.0 ng/ml) was higher than that of ascorbic acid (74.8 ng/ml). However, their $T_{max}$ values were similar. Thus, although calcium ascorbate showed equivalent antioxidant activity to ascorbic acid, it could attenuate the gastric high acidity caused by ascorbic acid, making it suitable for consideration of use to improve the side effects of ascorbic acid. Furthermore, calcium ascorbate could be an appropriate antioxidant substrate, with increased oral bioavailability, for patients with gastrointestinal disorders.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.179-204
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• 1998

The purpose of this research was to investigate the efficacy of Goiwhasan extract powder on the gastric injuries, antiulcer, gastrointestinal tract and blood hemostasis. Animals were used through this studies mice and rats. All animals were divided into 3 groups, contol group(no treatment), sample Ⅰ group(375mg/kg administration), sample Ⅱ group(750mg/kg administration). The gastric injuries and ulcer have been made by using pyloric ligation, indomethacin, HCI-ethanol, acetic acid and then The histological observation was followed. In the gastrointestinal tract, gastric juice secretion, gastric acidity, pepsin output, blood gastrin and secretin level, transport potentials in the small and large intestine were checked. And studies on blood hemostasis were performed on normal hemostatic activities and plasma prothrombin time, plasma recalcification time, plasma fibrinogen levels in the hypoprothrombinemic mice induced by warfarin. The results were as follows: 1. The antigastric ulcer effects on the pyloric ligation, indomethacin, HCl-ethanol, acetic acid induced gastric injuries were shown in Sample Ⅱ group(p<0.05). 2. Through the morphologic examination on the acetic acid induced ulcer, Sample Ⅰ group showed mild regeneration of epithelium and slight decrease of periulcer edema then that of Control group, while Sample Ⅱ group showed more retraction of round ulcer site, remarkable loss of swelling and edema then that of Control group, and revealing the regenerated epithelium in the surrounding ulcer site. Thus it was noted that both Sample groups have antigastriculcer effects on the experimentally induced gastric ulcer. 3. The inhibitory effects on gastric juice were noted in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.01). However, only Sample Ⅱ group showed the inhibitory effects on total acidity and pepsin output(p<0.05). 4. The significant inhibition of blood gastrin level showed at 30 min.(P<0.05) and 90 min.(P<0.05) after starting medication in only Sample Ⅱ group, but significance of blood secretin level in both groups was not recognized. 5. Any significant changes in barium sulfate transport in the small intestine of mice was not recognized in both groups, but the significantly inhibitory effect in large intestine was recognized in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.001). 6. In hemostatic effect on both normal mice and hypoprothrombinemic mice induced by warfarin, the significantly shortening effect on coagulation time was seen in only Sample Ⅱ group(p<0.01). 7. On plasma prothrombin time in hypoprothrombinemic rat induced by warfarin, Sample Ⅱ group have shortened the prothrombin time significantly(p<0.001). 8. On plasma reclcification time in hypoprothrombinemic rat induced by warfarin, the recalcification time have been shortened significantly in both Sample Ⅰ group(p<0.05) and Sample Ⅱ group(p<0.01). 9. On plasma fibrinogen levels in hypoprothrombinemic rat induced by warfarin, the fibrinogen contents in Sample Ⅱ have been decreased significantly(p<0.01). Overall the above results suggest that Goiwhasan has an therapeutic efficacy on antigastric ulcer and blood hemostasis. Further studies would be needed on the interaction of its herbal medicine and its mechanism in the future.

• Korean Journal of Pharmacognosy
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• v.15 no.3
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• pp.121-127
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• 1984

Attempts were to investigate the effects of 'Bojungikgi-tang' on the digestive system, blood pressure and diuresis. The results showed that relaxing action was shown on the isolated ileum in mice and that strong antagonistic actions were seen on $BaCl_2$, acetylcholine and histamine-induced contraction of the ileum in mice and guinea-pigs that the relaxing effect of the intestinal smooth muscle was recognized. Inhibitory effects on transport rate in the small intestine of mice and castor oil-induced catharsis in mice were noted. Inhibitory action on the secretion of gastric juice, pH ascending effect and decreasing effect of the free acidity and total acidity were recognized. Continuous hypotensive action was seen, but when the vagus nerve was cut, hypotensive action was remarkably decreased. The diuretic effect was also recognized.

• Korean Journal of Pharmacognosy
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• v.20 no.3
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• pp.188-195
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• 1989

Hyangsayangwee-Tang, a combined preparation of crude drugs, which has been used for stomach and intestinal disorder, was examined for anti-spasmodic, anti-ulcerative and anti-emetive effects. Spontaneous motility of isolated ileum was strongly suppressed and inhibitory effects against contraction of isolated ileum induced by acetylcholine and barium chloride were shown in mice. And, contraction of isolated guinea-pig ileum by histamine was inhibited. In rats fundus preparations, Hyangsayangwee-Tang elicited strong relaxation and had antagonist effects against the spasm induced by acetylcholine and barium chloride. A significant inhibitory effect on the intestinal propulsion of barium sulfate in mice was shown. In pylorus-ligated rats, Hyangsangwee-Tang inhibited gastric secretion and showed a strong anti-peptic activity. Protective effects against gastric ulceration induced by pyloric ligation, water-immersion stress, histamine and aspirin were significantly recognized in mice and rats. Hyangsayangwee-Tang decreased cupric sulfate-induced vomitting in frogs.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.100-100
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• 1997

To treat peptic ulcer diseases, many potent proton pump inhibitors have been developed for suppressing the gastric acid secretion in clinical patients. However, most of these agents have common irreversible mechanisms against H$\^$+/, K$\^$+/-ATPase which might be the cause of hypergastrinemia and ECL cell hyperplasia. Therefore, the development of new reversible inhibitors is prompted. In this study, we investigated the inhibitory mechanism of a newly synthesized proton pump inhibitor, YJA20379-8 using lyophilized hog gastric microsomes. YJA20379-8 inhibited K$\^$+/-stimulated H$\^$+/K$\^$+/-ATPase activity uncompetitively with respect to K$\^$+/, and in the other hand, showed competitive inhibitory pattern with ATP, respectively. From these data, we suggest that YJA20379-8 may be a proton pump inhibitor with a new inhibitory mechanism.

• The Journal of Korean Medicine
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• v.44 no.2
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• pp.70-105
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• 2023

This study was conducted to examine the current status of traditional korean medicine studies on gastroesophageal reflux disease in Korea, identify deficiencies, and suggest the direction of future medicine research methods to lay the foundation for traditional korean medicine treatment. All domestic papers on the korean traditional treatment of gastroesophageal reflux disease were selected among the literature published until August 2022 in six domestic databases. A total of 52 selected research data were classified into experimental research papers, clinical research papers, and review papers. In experimental papers, to evaluate the effectiveness of treatment, improvement of esophageal mucosal lesions, anti-inflammatory mechanisms, antioxidant mechanisms, esophageal mucosal protection mechanisms, gastric peristalsis control, and gastric acid secretion inhibition mechanisms were used as evaluation measures. In the clinical research paper, the basis for diagnosis of cases was clinical symptoms through medical history listening and diagnosis through visits to hospitals in the past. The average treatment period was 40.7 days, and the duration of treatment was not significantly affected by the duration of the disease. The most widely used Korean medicine treatment intervention was herbal medicine. There were 3 literature review studies, 3 systematic literature review and meta-analysis studies, 1 comparative review study for clinical trial guideline development, all using Chinese papers. This study included all domestic papers on gastroesophageal reflux disease to identify the research trend of the Korean oriental medicine community, and based on this, it is meaningful to confirm areas that need to be supplemented in future research plans.

• Journal of Food Hygiene and Safety
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• v.9 no.3
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• pp.175-184
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• 1994

This was performed to investigate the antiulcer effects of Aloe vera on the stomach ulcer induced by restraint and water-immersion stress in rats. For this experiment, 60 male Sprague-Dawley strain were used. The experimental groups were divided into five: a control(CA) and 4 aloe treatment groups. Each dose of aloe was 50 mg/kg BW(AA), 100mg/kg BW(AB), 200 mg/kg BW(AC), and 400 mg/kg BW(AD). The rats were allocated to each group by 12 and observed for 4 weeks. The results are as following. 1. The stomach surface pH in each group showed no significant difference, byt the values of aloe treatment groups were higher than the value of the control group. 2. The gastric wall mucus was significantly increased in all aloe treatment groups(p<0.05) compared with the control group. Especially in AC and AD group the differences were higher(p<0.01). 3. At shear rate rate 11.25, 45.0, 90.0, 225.0 sec-1, whole blood viscosity and plasma viscosity were measured. Most of the values of aloe treatment groups were significantly low compared with those of the control group(P<0.05). 4. The ulcer index of aloe treatment groups were significantly low campared with control group(p<0.05). Especially in AC and AD group the differences were more significant(p<0.01). 5. Less severe ulcers were observed in AA and AB group than in the control group. Tissues of AC and AD group had only slight ulcers and necrosis of tissue was not observed in these groups. Especially in AD group, there was more mucus than other groups and it seemed that alove vera stimulated the epithelial regeneration. From the results of this study, it can be concluded that the oral administration of Alove vera results in protection of stomach ulcer by stimulating the secretion of gastric mucus and the circulation of blood.