• Journal of Veterinary Clinics
• /
• v.38 no.3
• /
• pp.143-146
• /
• 2021

A 2-year-old intact female Maltese dog was presented with generalized involuntary tremors and nystagmus without regular direction. The dog was conscious the whole time while it was trembling. Its involuntary tremors were alleviated at rest or during sleep. Magnetic resonance imaging (MRI) revealed asymmetric hydrocephalus and caudal occipital malformation. In cerebrospinal fluid (CSF) analysis, a trace of protein was found and total nucleated cell count (TNCC) was slightly increased. However, infectious pathogens were not found. In complete blood count, there was a mild leukocytosis. After the patient received anticonvulsants (midazolam, phenobarbital, KBr), diuretics (furosemide) with an anti-inflammatory drug (prednisolone, 0.5 mg/kg PO bid), and a proton-pump inhibitor (omeprazole), it showed no improvement. The patient was tentatively diagnosed with corticosteroid responsive tremor syndrome. So the anticonvulsants and diuretics were discontinued and the dose of prednisolone was increased to an immunosuppressive dose (1 mg/kg PO bid). After administering the immunosuppressive dose of prednisolone, the patient did not show nystagmus. Its tremors were much alleviated. However, they did not disappear. Five weeks later, the patient showed gradual improvement but still was trembling when moving around. Nine weeks later, its tremors were similar to before. So diazepam (0.3 mg/kg PO sid) was added to the treatment. After that, its tremors were alleviated more. Prednisolone and diazepam were maintained for about five months, with tapering of the dose of prednisolone (until 0.5 mg/kg PO sid). About 7 months later after the treatment was started, the dog was trembling rarely except when it was excited. Therefore, diazepam was discontinued. This case describes a refractory white dog shaker syndrome successfully managed with long-term administration of a steroid and diazepam.

• The Journal of Korean Medicine
• /
• v.42 no.4
• /
• pp.150-163
• /
• 2021

Objectives: The purpose of this study was to confirm the effects of Liriope platyphylla extract on relieving Gastroesophageal reflux disease (GERD) through regulation of acid secretion. Methods: 8-week-old ICR mice were divided into untreated control group (Ctrl), GERD elecitation group (GERDE), Omeprazole administrate group before GERD elicitation (OMA), and Liriope platyphylla extract administrate group before GERD elicitation (LPA). After inducing GERD, gross observation and histological examination were performed and ATP6V1B1 (ATPase H+ Transporting V1 Subunit B1), GRPR (Gastrin-releasing peptide receptor), COX-1 (Cyclooxygenase 1), 8-OHdG (8-hydroxy-2'-deoxyguanosine), Cathelicidin, p-JNK (phospho c-Jun N-terminal kinase) were observed to confirm the damage defense effect of the esophageal mucosa, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection, and apoptosis regulation Results: OMA and LPA showed lower levels of damage compared to GERDE in gross observation and histological examination. ATP6V1B1, GRPR, and 8-OHdG showed lower positive reactions in OMA and LPA than in GERDE. COX-1 were less positive in GERDE and OMA than in Ctrl, but showed higher secretion in LPA than in Ctrl. Cathelicidin showed a decreased positive reaction in GERDE, OMA and LPA compared to Ctrl, but the decrease in positive reaction was smaller in OMA and LPA compared to GERDE. p-JNK showed increased positive reaction in GERDE, OMA and LPA than in Ctrl, but the increase in the positive reaction was smaller in the OMA and LPA compared to GERDE. Conclusions: The effects of Liriope platyphylla extract on esophageal mucosal damage protection, acid secretion regulation, antioxidant, anti-inflammatory, mucosal protection and apoptosis regulation were confirmed.

• The Journal of Internal Korean Medicine
• /
• v.43 no.6
• /
• pp.1162-1185
• /
• 2022

Purpose: We examined the effects of Dansam (Salvia miltiorrhiza Bunge, SM) and Dansam-eum (DSE) on gastroesophageal reflux disease (GERD) and reflux esophagitis by comparing the inhibitory effects of SM and DSE with the representative treatment of PPI Omeprazole to determine if the effects of the prescription DSE based on Korean medicine are better than those of a single-use of SM. Methods: We performed experiments using both animal models and cancer cells. Results: Comparison of SM and DSE with PPI in the animal model tests revealed that the effects were superior for SM and DSE than for PPI in all categories (8-OHdG, p-IκB, PAR2, COX-1, cathelicidin, p-JNK, Caspase 3, ATP6V1B1, GRPR, serotonin, and NPY). In three categories (COX-1, serotonin, and NPY), SM and DSE showed superior results over the Controls. In the animal model tests, DSE was superior to SM in all categories except for serotonin. The anti-cancer effects observed in cancer cell tests revealed that SM and DSE had meaningful results in terms of cytotoxicity and cell movement rate, as well as in cancer cell apoptosis. Conclusions: We confirmed that SM and DSE can have effects on reflux esophagitis through the regulation of oxidative stress, inflammation, mucosal protection, apoptosis, proton pumping, and the enteroendocrine system in the stomach and esophagus. We also confirmed that SM and DSE have superior effects to those of PPI on all aspects, especially gastric mucosa protection and enteroendocrine system control. We also confirmed that SM and DSE have anti-cancer effects. Above all, we confirmed that DSE has superior effects on almost all aspects compared to using SM alone.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.7 no.2
• /
• pp.153-162
• /
• 2004

Purpose: The Helicobacter pylori stool antigen (HpSA) enzyme immunoassay is a non-invasive test for the diagnosis and monitoring of H. pylori infection. But, there are few validation studies on the HpSA test after eradication in children. The aim of this study was to assess the diagnostic accuracy of HpSA enzyme immunoassay for the detection of H. pylori to confirm eradication in children. Methods: From January 2001 to October 2003, 164 tests were performed in 146 children aged 1 to 17.5 years (mean $9.3{\pm}4.3$ years). H. pylori infection was confirmed by endoscopy-based tests (rapid urease test, histology, and culture). All H. pylori infected children were treated with quadruple regimens (Omeprazole, amoxicillin, metronidazole and bismuth subcitrate for 7 days). Stool specimens were collected from all patients for the HpSA enzyme immunoassay (Primier platinum HpSA). The results of HpSA tests were interpreted as positive for $OD{\geq}0.160$, unresolved for $$0.140{\leq_-}OD$$<0.160, and negative for OD<0.140 at 450 nm on spectrophotometer. Results: 1) One hundred thirty-one HpSA tests were performed before treatment. The result of HpSA enzyme immunoassay showed three false positive cases and one false negative case. The sensitivity, specificity, positive predictive value, and negative predictive value of HpSA enzyme immunoassay before treatment were 96.4%, 97.1%, 90%, and 99%, respectively. 2) Thirty-three HpSA enzyme immunoassay were performed at least 4 weeks after eradication therapy. The results of HpSA enzyme immunoassay showed two false positive cases and one false negative case. The sensitivity, specificity, positive predictive value, and negative predictive value after treatment were 88.9%, 91.7%, 80%, and 95.7%, respectively. Conclusion: Diagnostic accuracy of the HpSA enzyme immunoassay after eradication therapy was as high as that of the HpSA test before eradication therapy. The HpSA enzyme immunoassay was found to be a useful non-invasive method to confirm H. pylori eradication in children.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.32 no.8
• /
• pp.1357-1363
• /
• 2003

This study was conducted to investigate the effect of chicken egg containing IgY against H. pylori in patients with gastritis. Sixty three H. pylori-infected volunteers (20∼43 year, Male Female=49 : 14) were randomized into four groups which were treated with one chicken egg containing IgY b.i.d. (IgY group; n=17) or omeprazole 20 mg b.i.d., amoxicillin 1.0 g b.i.d. and clarithromycin 500 mg b.i.d. (OAC group; n=17) or omeprazole 20 mg b.i.d., amoxicillin 1.0 g b.i.d., clarithromycin 500 mg b.i.d. and one chicken egg containing IgY b.i.d. (OAC with IgY group; n=16) for 2 weeks or lyophilized IgY 1 g b.i.d (lyophilized IgY group) for 1 month. $\Delta$$^{13}$ $CO_2$ before and after treatment, the eradication rate of H. pylori and histologic change including H. pylori density, acute and chronic inflammation activity, intestinal metaplasia and glandular atrophy by updated sydney system were evaluated. Eradication rate of OAC with IgY group (94%) was higher than IgY group (0%), lyophilized IgY group (0%) and OAC group (88%). $\Delta$$^{13}$ $CO_2$at 2 weeks after treatment in one patient of IgY group was decreased. But that was not changed in the other patients. $\Delta$$^{13}$ $CO_2$ at 1 week after treatment in 15 patients of OAC with IgY group was significantly lower than pretreatment level (p<0.05), and $\Delta$$^{13}$ $CO_2$ at 1 week and 2 week after treatment was decreased in the other patient. Acute inflammation activity at antrum was significantly decreased after treatment in IgY and lyophilized IgY group (p<0.01), H. pylori density at antrum was significantly decreased after treatment in IgY and lyophilized IgY group (p<0.05). Chronic inflammation activity at body was decreased after treatment in lyophilized IgY group. Intestinal metaplasia and glandular atrophy at antrum and body were not changed after treatment in IgY group. Mild intestinal metaplasia in one patient of lyophilized IgY group changed to normal after 1 month treatment. Gandular atrophy at antrum and body were not changed after treatment in lyophilized IgY group.

• YAKHAK HOEJI
• /
• v.58 no.4
• /
• pp.255-261
• /
• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• Journal of Pharmaceutical Investigation
• /
• v.39 no.1
• /
• pp.73-78
• /
• 2009

A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.14 no.1
• /
• pp.45-51
• /
• 2011

Purpose: The antimicrobial resistance of Helicobacter pylori is one of the critical factors in failure of eradication therapy. The purpose of this study was to evaluate antimicrobial resistance of H. pylori in Korean children. Methods: Gastric mucosal specimens for H. pylori were obtained from children with dyspepsia who were cared for at Asan Medical Center Children's Hospital in Seoul, Korea between 2003 and 2009. Antimicrobial resistance tests were performed using the disk diffusion method for clarithromycin and amoxicillin and the E-test for metronidazole and tetracycline. Most children with H. pylori infections were treated using triple therapies. Results: Thirty-three children had positive H. pylori cultures, although a resistance test was only performed in 28 patients. Resistant strains were found in 9 children (32.1%). The resistance rates to clarithromycin and metronidazole were 25% and 17.8%, respectively. There was no resistance to amoxicillin or tetracycline. The resistance rates decreased from 44.4% (2003~2006) to 26.3% (2006~2009) during the study period. Conclusion: Korean children demonstrated relatively high antimicrobial resistance to H. pylori in this study. However, there was a temporarily decreasing trend during the study period. A larger multi-regional study may be needed to determine the optimal antimicrobial treatment for pediatric patients infected with H. pylori.

• Korean Journal of Clinical Pharmacy
• /
• v.10 no.3
• /
• pp.111-119
• /
• 2000

The objective of this study was to evaluate the efficacy and the pattern of regimens prescribed for the treatment of peptic ulcer disease in a regional community hospital. 226 patients were treated as an outpatient and followed for one year. 88 patients $(38.9\%)$ had gastric ulcer (GU) alone, 6 patients $(2.7\%)$ had duodenal ulcer (DV) alone, 5 patients $(2.2\%)$ had gastroesophageal reflux disease (GERD) alone, 25 patients $(11.1\%)$ had both GU and DU, 88 patients $(38.9\%)$ had both GU and GERD, and 14 patients $(6.2\%)$ had both DU and GERD. During this study period no one was treated for Zollinger-Ellison Syndrome. The disease showed higher occurrence in male population (139 patients, $61.5\%$) and among the ages of 30 and 40 $(62.4\%)$. The average age of these patients was 41.3 years and there was no difference between the genders. $81.4\%$ of these patients underwent CLO test to check for the existence of Helicobacter and $66.3\%$ of these Patients showed the positive response. $65.6\%$ of patients with GU and $80\%$ of patients with DU showed the positive response and there was no difference between the genders $(65.4\%\;vs.\;67.6\%)$. 184 patients $(81.4\%)$ were deemed to be cured based on the disappearance of their symptoms after completing the regimens. Compliance rate did not differ for gender or different diseases, while showing a difference in age. Patients between the ages of 20 to 30 years old showed the worst compliance rate. In addition, the compliance was lower among the patients who had previous occurrence of the disease, and this was more evident among female patients. Although 184 patients out of the total 226 patients were deemed to be cured, 36 patients $(20.65\%)$ of these returned to the hospital for relapsed diseases within one year. The factors that affected for patients to relapse were the diseases accompanied by ulcer and social environments, such as smoking, alcohol consumption, and previous history of the diseases (smoking P<0.001, alcohol consumption P<0.02, previous history of disease P<0.05). The regimen using $H_2$ receptor antagonists+tripotassium dicitrato bismuthate+clarithromycin showed the lower rate of relapse, and the regimens of omeprazole (OMP)+amoxicillin+tripotassium dicitrato bismuthate and OMP+amoxicillin+metronidazole showed better compliance rate. Patient education by pharmacists on the importance of compliance to regimens and the risk factors fer relapse can provide a better patient care. This would ultimately result in more cost-effective treatments by preventing additional cost for treating relapsed symptoms in approximately $20\%$ of patients.

• Journal of Microbiology and Biotechnology
• /
• v.22 no.12
• /
• pp.1659-1664
• /
• 2012

TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.