• Journal of Gastric Cancer
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• v.8 no.3
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• pp.160-165
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• 2008

Purpose: With the introduction of H. pylori eradication and proton pump inhibitor, the operative treatments for the acute or chronic complications of peptic ulcer, such as perforation, bleeding and stricture, have decreased. Also owing to the development of non-operative treatment such as interventional endoscopic treatment, the surgical approach to the acute complications, like perforation and bleeding, has diminished. The non-operative treatments for the stricture and obstruction of chronic peptic ulcer in part related to discontinuation of medication have not been satisfactory. We analyzed the clinical outcomes of the patients who underwent operative treatment for outlet obstruction with peptic ulcer. Materials of Methods: From January 1994 to December 2007, we reviewed 31 patients who had been operated on at the National Medical Center for peptic ulcer obstruction. We excluded the cases of adhesive obstructions that were caused by a former ulcer operation and also the cases of obstructions found during emergency operations for treating perforation and bleeding. We classified the surgical treatment group into the bypass operation group and the surgical resection group. We evaluated the effects of the operations by the Visick score. The recurrences were confirmed only by the endoscopic observation of peptic ulcer. Results: The number of patients in the bypass operation group was 6 (19.4%) and that of resection group was 25 (80.6%). The mean age was 57.5 (25~81) years. The number of male patients was 29 (93.5%) and the number of females was 2 (6.5%). The mean symptom duration was 29.6 months. There were 19 smokers (61.3%), 6 NSAID users (19.4%) and 7 H. pylori positive patients (22.6%). Two patients underwent endoscopic balloon dilatation with no success. The locations of lesion were the stomach, the duodenum and both in 9, 20 and 2 cases, respectively. There were operative complications in 13 cases (41.9%), recurrent ulcers in 2 cases (6.5%), and reoperations in 4 cases. The mean Visick score was 1.8 (1~4). There were no statistically significant clinicopathologic differences between the bypass operation group and the resection group. The two groups had 1 case each of recurrence. Although the bypass group had a greater complication rate (83.3%) than the resection group (32%), this was not statistically meaningful (P=0.175). The mean Visick score was 3.0 in the bypass group and 1.6 in the resection group, so the resection group was better (P=0.001). Conclusion: For a case of chronic peptic ulcer with outlet obstruction, even though it has been reported that endoscopic balloon dilatation worked well, surgery is still regarded as an important treatment. If you consider the patients' satisfaction and the difficulty of diagnosing malignant ulcers, surgical resection should be recommended more often than a bypass operation.

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.90-99
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• 2011

Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

• The Journal of Internal Korean Medicine
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• v.37 no.1
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• pp.90-108
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• 2016

Objectives: This study aimed to learn what should be considered in the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD) by analyzing the existing guidelines and clinical trials.Methods: The development committee searched the existing guidelines for herbal medicinal products or GERD. Then, clinical trials related to GERD using herbal medicine were selected. The chosen trials were analyzed in terms of their inclusion and exclusion of participants, intervention, comparators, outcome, and trial design. Then, we compared the results of the analysis according to the regulations and guidelines of the Ministry of Food and Drug Safety to suggest the issues that we will have to consider when developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).Results: As a result, few guidelines for GERD and clinical trials with herbal medicinal products were located in the national institution homepage. In addition, 8 articles were found using the following combination of search terms: “Gastroesophageal reflux disease”, “GERD”, “herbal medicine”, “herbal therapy”, “Korean Medicine”, “Traditional Chinese Medicine”, and “TCM”. Even though all trials had their own unique research questions, all studies were performed using a randomization method. Most trials included participants with reflux esophagitis, but two trials targeted proton pump inhibitor-refractory GERD. The type of intervention varied, such as decoction, granules, and capsules. Additionally, individualized herbal medicines were used in two studies. Comparators were diverse, such as placebo, Western medicine, and electro-acupuncture. The most frequently used outcome for efficacy was the effectiveness rate. In addition, the outcome for evaluating quality of life, esophageal mucosa and pressure, esophageal acid reflux, and recurrence rates were used. Safety was investigated by recording adverse events and carrying out laboratory tests.Conclusions: We identified some issues by reviewing the existing guidelines and comparing them with clinical trials for GERD and herbal medicinal products. These results will be utilized for developing the Guidelines of Clinical Trials with Herbal Medicinal Products for Gastroesophageal Reflux Disease (GERD).

• Biomedical Science Letters
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• v.13 no.3
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• pp.197-206
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• 2007

P2X receptors are membrane-bound ion channels that conduct $Na^+,\;K^+$, and $Ca^{2+}$ in response to ATP and its analogs. There are seven subunits identified so far ($P2X_1-P2X_7$). $P2X_2$ receptors are known to be expressed in a wide range of organs including brains and adrenal grands. PC12 cells are originated from adrenal grand and differentiated by nerve growth factor or pituitary adenylate cyclase activating poly peptide (PACAP). Previous studies indicate that $P2X_2$ receptor activation in PC12 cells couples to $Ca^{2+}-dependent$ release of catecholamine and ATP. It is known that acidic pH potentiates ATP currents at $P2X_2$ receptors. This leads to a hypothesis that $P2X_2$ receptors may play an important role in PC12 cell differentiation, one of the characteristics of which is neurite outgrowth, induced by the hormones under lower pH. In the present study, we isolated several clones which potentiate neurite outgrowth by PACAP in acidic pH (6.8), but not in alkaline pH (7.6). RT-PCR and electrophysiology data indicate that these clones express only functional $P2X_2$ receptors in the absence or presence of PACAP for 3 days. Potentiation of neurite outgrowth resulted from PACAP (100 nM) in acidic pH is inhibited by the two P2X receptor antagonists, suramin and PPADS ($100\;{\mu}M)$ each), and exogenous exprerssion of ATP-binding mutant $P2X_2$ receptor subunit ($P2X_2[K69A]$). However, acid sensing ion channels (ASICs) are not involved in PACAP-induced neurite outgrowth potentiation in lower pH since treatments of an inhibitor of ASICs, amyloride ($10\;{\mu}M$), did not give any effects to neurite extension. The vesicular proton pump ($H^+-ATPase$) inhibitor, bafilomycin (100 nM), reduced neurite extension indicating that ATP release resulted from $P2X_2$ receptor activation in PC12 cells is needed for neurite outgrowth. These were confirmed by activation of mitogen activated protein kinases, such as ERKs and p38. These results suggest roles of ATP and $P2X_2$ receptors in hormone-induced cell differentiation or neuronal synaptogenesis in local acidic environments.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.23 no.1
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• pp.43-47
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• 2012

Background and Objectives : Laryngopharyngeal reflux disease (LPRD) originates from regurgitation of gastric contents to the laryngopharynx, and it is relatively common disease in otolaryngology. Proton-pump inhibitor (PPI) medication is frequently using treatment method in present time, but controversies exist regarding treatment for it. High-resolution manometry (HRM) system is a newly developed device that using 36 channels and pressure topography plotting program, checking the function and status of esophagus. The aim of this study was to evaluate clinical usefulness of HRM in LPRD patients who do not response to PPI medication. Materials and Method : From July 2009 to July 2010, a total of 99 patients who were suspected LPRD according to symptoms (Reflux Symptom Index >13) and laryngoscopic findings (Reflux Finding Score >7) were retrospectively enrolled in this study. Patients were consisted of 31 men and 68 women, the mean age was 51.8 years, the mean BMI was 22.46. Patients have taken PPI medication for 2 months, after medication, they performed HRM. Comparative analysis was performed with results of the difference in symptoms. Results : In 99 patients, 37 patients (37.4%) show not improvement of LPRD symptoms after PPI medication. Among them, 18 patients (48.6%) showed abnormal findings that were classified as Peristaltic dysfunction (38.9%), Diffuse esophageal spasm (11.1%), Relaxation impairment of LES (11.1%), Achalasia (5.6%), Hypotensive LES (11.1%), Relaxation impairment of UES (11.1%), Nutcracker esophagus (5.6%), Decreased resting pressure (5.6%). Other 62 patients (62.6%) show improvement of LPRD symptoms, 23 patients (37.1%) showed abnormal findings. Most common finding was Peristaltic dysfunction (43.4%) More prevalent abnormal findings of HRM were found in patients who revealed no response to PPI medication (48.6% vs. 37.1%), but it does not reach the statistical significance. Conclusion : Although statistical significances is not showed, the difference observed in the frequency of HRM abnormal finding between response and no response for PPI medication. It has been estimated that HRM may be used to determine differential diagnosis in patients with LPRD. Further studies in lager population containing normal controls will be needed to prove clinical usefulness.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.22 no.2
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• pp.151-155
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• 2011

Background and Objectives : Laryngopharyngeal reflux disease (LPRD) originates from regurgitation of gastric contents to the laryngopharynx, and it is relatively common disease in otolaryngology. Proton-pump inhibitor (PPI) medication is frequently using treatment method in present time, but controversies exist regarding treatment for it. High-resolution manometry (HRM) system is a newly developed device that using 36 channels and pressure topography plotting program, checking the function and status of esophagus. The aim of this study was to evaluate clinical usefulness of HRM in LPRD patients who do not response to PPI medication. Subjects and Method : From July 2009 to July 2010, a total of 99 patients who were suspected LPRD according to symptoms (Reflux Symptom Index >13) and laryngoscopic findings (Reflux Finding Score >7) were retrospectively enrolled in this study. Patients were consisted of 31 men and 68 women, the mean age was 51.8 years, the mean BMI was 22.46. Patients have taken PPI medication for 2 months, after medication, they performed HRM. Comparative analysis was performed with results of the difference in symptoms. Results : In 99 patients, 37 patients (37.4%) show not improvement of LPRD symptoms after PPI medication. Among them, 18 patients (48.6%) showed abnormal findings that were classified as Peristaltic dysfunction (38.9%), Diffuse esophageal spasm (11.1%), Relaxation impairment of LES (11.1%), Achalasia (5.6%), Hypotensive LES (11.1%), Relaxation impairment of UES (11.1%), Nutcracker esophagus (5.6%), Decreased resting pressure (5.6%). Other 62 patients (62.6%) show improvement of LPRD symptoms, 23 patients (37.1%) showed abnormal findings. Most common finding was Peristaltic dysfunction (43.4%) More prevalent abnormal findings of HRM were found in patients who revealed no response to PPI medication (48.6% vs. 37.1%), but it does not reach the statistical significance. Conclusion : Although statistical significances is not showed, the difference observed in the frequency of HRM abnormal finding between response and no response for PPI medication. It has been estimated that HRM may be used to determine differential diagnosis in patients with LPRD. Further studies in lager population containing normal controls will be needed to prove clinical usefulness.

• Korean Journal of Environmental Agriculture
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• v.21 no.2
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• pp.102-108
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• 2002

In order to investigate the mechanism of growth inhibition by salt stress, lettuces were grown hydroponically in three different nutrient solutions, normal and 30 mM or 50 mM $KNO_3$-added nutrient solutions, and the electrical conductivities of these solutions were 1.0, 4.5, and 6.5 dS/m, respectively. The activities of plasma and vacuolar $H^+$-ATPases in the root tissue of lettuce were measured by specific inhibitors, 100 ${\mu}M$ vanadate and 50 mM $NO_3^-$, respectively. Microsomal ATPase activity of lettuce grown in the normal nutrient solution was $356\pm1.5$ nmol/min/mg protein. When lettuces were grown in 30 mM and 50 mM $KNO_3$-added nutrient solutions, total activities of microsomal ATPases were increased by 1.6 and 1.9 times, respectively, and the increases were mainly mediated by vacuolar $H^+$-ATPase. These results show that lettuces adapt themselves to salt-stressed condition by increasing the activities of $H^+$-ATPases. Effects of various heavy metal ions were investigated on the microsomal ATPases and various metal ions at 100 $\mu M$ inhibited the activities by 10$\sim$25%. $Cu^{2+}$ showed the highest inhibitory effect on the vacuolar $H^+$-ATPase. These results suggest that lettuce increases the activities of root ATPases, specially that of vacuolar $H^+$-ATPase, in salt-stressed growth conditions and $Cu^{2+}$ could be a useful tool to control the activity of vacuolar $H^+$-ATPase.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.19 no.2
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• pp.128-132
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• 2008

Background: Laryngeal contact granuloma is an inflammatory hypertrophic granulation tissue arising at around the vocal process of arytenoid cartilage. Various approaches are currently used for the treatment, but a solid guideline has not been established. Objectives: We aimed to compare the each treatment modality in the hope of suggesting a guideline for the successful management of laryngeal contact granuloma. Method: Eighty-seven treatment cases of 56 patients were analyzed. Cases having recent intubation history were excluded from the study. All patients received vocal hygiene education. Proton pump inhibitors (PPI, N = 33) or H2 receptor antagonists ($H_{2}RA$, N =26) were used as a first-line treatment. Among the non-responders to $H_{2}RA$, 11 cases received PPI as a second-line therapy. Eight cases received botulinum toxin injection and 9 cases had laryngomicrosurgical removal. Results: As an initial therapy, response rate to PPI and $H_{2}RA$ was 60.6% and 38.5% respectively, which was not statistically different (p=0.091). Response rate of PPI as the second-line therapy was 36.3% (p=0.162 when compared to that of first-line PPI therapy). Response rate of Botulinum toxin injection was 75%. All cases of surgical removal recurred in a relatively short period (mean 1.9months). Conclusion: In patients having laryngeal contact granuloma, combined therapy with vocal hygiene education and PPI medication would provide more than 60% of therapeutic response. Botulinum toxin injection is highly effective even in non-responders to antireflux therapy. The only indications of surgery are to resolve diagnostic doubt or to treat acute airway compromise.

• Food Science and Preservation
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• v.24 no.7
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• pp.1017-1024
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• 2017

The objective of this study was to investigate the inhibitory effects of Litsea japonica fruit flesh extract (LJF-HE) on gastritis in an indomethacin-induced SD rat model. Rats were randomly divided into six groups: G1 (normal group), G2 (control group, indomethacin-induced gastritis), G3 (positive group, indomethacin-induced gastritis and ranitidine 50 mg/kg), G4 (LJF-HE-L group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 30 mg/kg), G5 (LJF-HE-M group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 60 mg/kg), G6 (LJF-HE-H group, indomethacin-induced gastritis and L. japonica fruit flesh extract at 120 mg/kg). In the group treated with LJF-HE (G4, G5, and G6), gastric mucosal damage, gastric juice secretion and pepsin activity were significantly decreased compared to the control group. Additionally, there were decreases in the expression of cholecystokinin 2 receptor (CCK-2r), histamine receptor H2 (H2r) and H+/K+ ATPase in the gastric lesions. The plasma levels of TNF-${\alpha}$ and IL-$1{\beta}$ significantly decreased in LJF-HE (G4, G5, and G6) treated groups compared with control. The plasma level of PGE2 was also significantly increased by LJF-HE (G5 and G6). These results suggest that LJF-HE (G4, G5, and G6) has the ability to inhibit on indomethacin-induced gastritis.

• Molecules and Cells
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• v.40 no.8
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• pp.567-576
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• 2017

The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.