• The Journal of Korean Medicine
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• v.39 no.2
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• pp.92-105
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• 2018

Objectives: This aim of this study is to compare the reflux esophagitis improvement effects of Sepiae Os, Arcae Concha, Ostreae Concha, and Proton Pump Inhibitor(esomeprazole) through rat experiments. Methods: NO production inhibitory effect was measured by NO production amount and iNOS mRNA expression level in cell lines. iNOS, $TNF-{\alpha}$ and $p-I{\kappa}B$, and serotonin were compared using immunohistochemistry at the rat reflux esophagitis. Reflux esophagitis connection external form, lower esophageal sphincter, and gap were observed and an esophageal inflammatory indicator, IL-6 activity was also evaluated by immunohistochemistry. Results: NO production and iNOS mRNA expression was showed concentration dependent decrease in cell lines treated with Sepiae OS, Arcae Concha, and Ostreae Concha at the experiments of cell lines. In the suppression of iNOS and $p-I{\kappa}B$ at the rat reflux esophagitis, Sepiae Os treat group(SOT) and Ostreae Concha treat group(OCT) were more effective. In the increase of serotonin at the rat reflux esophagitis, ACT, MT and OCT were more effective. Damage of lower esophageal sphincter, and gap between esophageal keratin and mucosa were observed less at the SOT, ACT, OCT. In the suppression of IL-6 at the rat reflux esophagitis, SOT and OCT were more effective than GE and, SOT was more effective than MT significantly. Conclusions: The anti-inflammatory effect was the best in the SOT and lower esophageal sphincter muscle contraction was the best in the ACT at the rat reflux esophagitis. Sepiae OS was more effective than esomeprazole in the suppression of iNOS, $TNF-{\alpha}$, and IL-6.

• KSBB Journal
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• v.32 no.2
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• pp.108-116
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• 2017

Omeprazole, a benzimidazole derivative, suppresses gastric acid secretion by inhibiting $H^+/K^+$ ATPase in gastric parietals cells, and by reducing $H^+$ concentration. To improve stability of esomeprazole magnesium dihydrate (ESMD), enteric-coated preperation was composed of core tablet, subcoating and enteric coating layer. We were evaluated in vitro dissolution characteristics between test and reference ESMD preparation and stability. We could prepare enteric-coated formulation of ESMD by controlling disintegrating agent and coating ratio which could rapidly dissolved in neutral or alkali medium. The formulation D5 with crospovidone of 1.25% and coating ratio of 16.25% had a similar dissolution behavior compare to reference preparation. Difference factor ($f_1$) and similarity factor ($f_2$) were 0~15 and 50~100 and there was no significant difference in bioequivalence between formulations. The content and dissolution rate of formulation D5 were $96.54{\pm}0.21$ and $78.56{\pm}0.87%$ without change of color in accelerated condition ($40^{\circ}C$, RH 75%, high density polyethylene (HDPE) container) for 6 months. This study concluded that our enteric coated preparation of ESMD could be an useful method to improve stability of unstable drug without direct contact with coating material.

• The Journal of Korean Medicine
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• v.40 no.2
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• pp.17-34
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• 2019

Objectives: This study was carried out to observe and compare the effects of Pinellia ternata, Zingiber officinale and Sobanhatang on the reflux esophagitis induced by gastric fundus and pylorus ligation in mice with esomeprazole. Methods: Antioxidant effects were measured by DPPH radical scavenging activity at four different concentration of 0.125, 0.25, 0.5 and $1.0mg/102{\mu}{\ell}$. Zingiber officinale water extract(ZE), Pinellia ternata water extract(PE) and Sobanhatang water extract(SBE) and esomeprazole were treated orally for 14 days before gatric fundus and pylorus ligation. In the histochemistry, changes in suface mucous cells, muscle tissue and connective tissue in gastro esophageal junction(GEJ) and mast cell on the esophageal mucosa were observed. The change of Hemo oxygenase(HO)-1, ghrelin, gastrin and substance P in gastric body tissue were measured by immunohistochemistry. Results: DPPH radical scavenging activity exhibited concentration dependently increases in ZE, PE, SBE. ZE was significantly higher at all concentrations than PE. The gastric surface mucous cells were more in the treated group than in the reflux esophagitis elicited group(GE) in the order of PE, SBE, ZE and esomeprazole treateded group(PT, SBT, ZT, ET). Lower esophageal sphincter muscle damage and intercellular space in the GEJ were less in the treated group than GE. In the esophageal mucosa, the mast cell distribution and the migration of inflammatory cells were lower in the treateded troup than GE in order to ZT, SBT, PT and ET. The antioxidative enzyme, HO-1 was more in the order of ZT, SBT, control group, PT, ET than in GE. ZT was significantly higher than the other groups and SBT was significantly higher than ET. Ghrelin was found to be higher in ZT, ET, SBT and PT than in GE, and ZT was significantly higher than all other groups except ET. Gastrin showed the highest positivity in GE, and was lower in the order of ET, ZT, SBT, PT, and control group. Substance P was the highest in GE, and was lower in the order of ET, ZT, SBT, PT and control group, and PT were significantly lower than ET. Conclusion: ZT, PT and SBT showed superior antioxidative, anti-inflammatory and mucosal protective effects on mouse reflux esophagitis as compared with ET. In particular, ZE was more effective in antioxidant and gastric motility enhancement, while PE was more effective in mucosal protection and anti-inflammatory effects. Sobanhatang is expected to be effective treatment because it has advantages of both drugs and reduces toxicity.

• Bulletin of the Korean Chemical Society
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• v.29 no.10
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• pp.1879-1880
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• 2008

• The Korean journal of helicobacter and upper gastrointestinal research
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• v.18 no.4
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• pp.277-279
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• 2018

전 세계적으로 Helicobacter pylori의 항생제 내성률은 지속적으로 증가하고 있으며, 기존의 제균 치료에 실패한 H. pylori 감염 환자들에 대한 효과적인 구제요법(rescue therapy)의 필요성 역시 증가하고 있다. 이 연구는 두 개 기관, 공개, 평행 그룹, 무작위 배정 연구로서 불응성 H. pylori 감염 환자들의 구제요법으로 유전자형 내성을 기반한 치료(genotype resistance-guided therapy)와 경험적 치료(empirical therapy) 중 어느 것이 보다 효과적인지를 비교하고자 하였다. 2012년 10월부터 2017년 9월까지 20세 이상의 불응성 H. pylori 감염 환자들을 대상으로 하였으며, 불응성 H. pylori 감염은 과거 두 종류 이상의 H. pylori 제균 치료를 받았음에도 불구하고 H. pylori 제균에 실패한 환자들로 정의하였다. 이들에게서 한 군은 14일간의 유전자형 내성을 기반한 순차 치료(n=21 in trial 1, n=205 in trial 2)를, 다른 한 군은 환자들의 과거 제균 치료 종류를 감안한 14일간의 경험적 순차 치료(n=20 in trial 1, n=205 in trial 2)를 시행하였다. 순차 치료법은 첫 7일은 esomeprazole 40 mg과 amoxicillin 1 g을 하루 두 번 복용한 다음, 나머지 7일은 esomeprazole 40 mg과 metronidazole 500 mg, 그리고 1) levofloxacin 250 mg 또는 2) clarithromycin 500 mg 또는 3) tetracycline 500 mg을 하루 두 번 복용하는 것으로 구성하였다. 23S ribosomal RNA (rRNA)나 gyrase A에 대한 내성 관련 돌연변이 여부는 direct sequencing을 통한 중합효소연쇄반응(polymerase chain reaction, PCR) 검사를 이용하였고, 제균 성공 여부는 요소호기검사를 통해 확인하였다. 일차 결과 지표는 치료 방법에 따른 제균율로 정하였다. Trial 1에서는 tetracycline 대신 doxycycline 100 mg을 사용하였는데, 제균 성공률이 유전자형 내성을 기반한 치료군에서는 17명(81%), 경험적 치료군에서는 12명(60%)으로 나타났다(P=0.181). 하지만, 다른 순차 치료군들과 비교하였을 때, doxycycline을 포함한 순차 치료군의 제균율이 현저히 낮은 것으로 나타나서(15/26, 57.7%) doxycycline을 포함한 순차 치료법은 종결하기로 하고, trial 2부터는 doxycycline 대신 tetracycline으로 교체하여 연구를 지속하였다. Trial 2의 intention-to-treat (ITT) 분석 결과, 유전자형 내성을 기반한 치료군에서는 160/205명(78%), 경험적 치료군에서는 148/205명(72.2%)으로 두 그룹 간의 통계적인 제균율의 차이는 보여주지 못하였다(P=0.170). 부작용 및 환자 순응도에서도 양 군 간의 의미 있는 차이는 없었다. 따라서, 두 종류 이상 H. pylori 제균 치료에 실패한 환자들이라고 할지라도 기존의 제균 치료력을 바탕으로 적절한 경험적 치료를 시행하는 것은 유전자형 내성을 기반한 치료 정도의 효과는 있으며 접근성, 비용, 환자들의 선호도 등의 여러 가지 부가적인 사항들을 고려할 때, 제균 치료력을 고려한 경험적 치료는 간단한 수준의 유전자형 내성을 기반한 치료의 대안으로 받아들여질 수 있을 것으로 제안하였다.

• Journal of Veterinary Clinics
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• v.38 no.5
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• pp.231-234
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• 2021

A 14-month-old, intact female Maltese (case 1) and a 26-month-old, spayed female Dachshund (case 2) had persistent regurgitation over 1 year and 2 years, respectively. In both cases, there were not specific findings in blood examination. Diagnostic imaging and fluoroscopy revealed that gastroesophageal reflux (GER) occurred when the patients ate a barium meal without abdominal contraction. They were treated with proton-pump inhibitor (esomeprazole), sucralfate and prokinetics (cisapride) while in a standing position for an hour after every meal, according to the gastroesophageal disease (GERD) suggested treatment. The case 1 dog was discharged with improved clinical signs, and the case 2 dog also had been improved clinical signs; however, aspiration pneumonia occurred in case 2, which was thought to be a complication from GERD. After receiving treatment for aspiration pneumonia, the case 2 dog was discharged from the hospital. Since there was no further improvement in symptoms after discharge, the case 1 dog was euthanized by owner's request, and the case 2 is alive, having only mild clinical signs upon the writing of this paper.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4885-4890
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• 2015

Background: Helicobacter pylori plays an important role in gastric cancer and typical eradication regimens are no longer effective in many countries, including Thailand. The aim of our study was to compare the effect of Lactobacillus delbrueckii and Streptococcus thermophillus on tailored triple therapy for Helicobacter pylori eradication. Materials and Methods: This prospective single-center study was conducted in Thailand. Helicobacter pylori associated gastritis patients were randomized to 2 groups: group 1 (n=100) was tailored triple therapy with placebo (esomeprazole 20 mg bid, clarithromycin 500 mg bid or metronidazole 400 mg tid if clarithromycin resistance and amoxicillin 1000 mg bid), and group 2 was tailored triple therapy plus pretreatment with probiotic containing yogurt. Successful eradication was defined as both negative histology and negative rapid urease test at four weeks after treatment. Results: A total of 200 infected patients were enrolled. PP analysis involved 194 patients: 96 in the tailored triple therapy with placebo group (group 1) and 98 the in tailored triple therapy plus pretreatment with probiotic containing yogurt group (group 2). Successful eradication was observed in 170 (87.6%) patients; by PP analysis, the eradication rate was significantly higher in group 2 (P = 0.04, 95%CI; 0.02-0.13) than in group 1. ITT analysis also showed that the value was significantly higher in the tailored triple threapy plus pretreatment with probiotic containing yogurt group (group 2) (89/100; 89%) than in the tailored triple therapy with placebo group (group 1) (P= 0.01, 95%CI; 0.04-0.15). In terms of adverse events, there was no significant difference between the two groups. Conclusions: Pretreatment with probiotic containing yogurt can improve Helicobacter pylori eradication rates with tailored triple therapy. Adding probiotics does not reduce adverse effects of the medication.