• Journal of Oral Medicine and Pain
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• v.38 no.3
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• pp.221-233
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• 2013

Bile acids are polar derivatives of cholesterol essential for the absorption of dietary lipids and regulate the transcription of genes that control cholesterol homeostasis. Recently it have been identified the synthetic chenodeoxycholic acid (CDCA) derivatives HS-1200 and cisplatin showed apoptisis-inducing activity on various cancer cells in vivo and in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with HS-1200 and cisplatin on human tongue squamous cell carcinoma cells (SCC25 cells). To investigate whether the co-treatment with HS-1200 and cisplatin compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis DNA hypoploidy. Westen blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, co-treatment with HS-1200 and cisplatin on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, reduction of MMP and proteasome activity, the increase of Bax and the decrease of Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated SCC25 cells did not show these patterns. Although the single treatment of $25{\mu}M$ HS-1200 and $4{\mu}g/ml$ cisplatin for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that the combination therapy with HS-1200 and cisplatin could be considered as a novel therapeutic strategy for human squamous cell carcinoma.

• Journal of the korean academy of Pediatric Dentistry
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• v.47 no.1
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• pp.53-61
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• 2020

Midazolam is a short-acting benzodiazepine that is widely used in pediatric dental sedation. However, its clinical effectiveness as an intravenous sedative agent in children has not been widely documented. A retrospective study was conducted to evaluate the efficacy and safety of intravenous midazolam and nitrous oxide inhalation sedation in pediatric dental treatment. The subjects were 115 patients (118 cases) who received dental treatment under intravenous midazolam and nitrous oxide inhalation sedation. Demographic factors, general health status, sedation time, midazolam and nitrous oxide dosage, and success rate of sedation were evaluated from electronic medical records. Behavioral management was the main reason of choosing sedation. Mean duration of sedation was 56.7 minutes for surgical treatment, and 74.4 minutes for restorative treatment. The initial dosage of intravenous midazolam was 0.051 ± 0.019 mg/kg. In 34 cases (28.8%), additional midazolam of 0.036 ± 0.057 mg/kg was delivered during the treatment. The concentration of nitrous oxide was maintained between 40% and 50%. The success rate of sedation was 99% (n = 117). In 1 case, laryngospasm occurred and the patient was reversed with benzodiazepine antagonist, flumazenil. Intravenous midazolam sedation with nitrous oxide was shown to be clinically effective for the dental treatment in children, if administered by trained personnel and patients are carefully selected in accordance with guidelines.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.1
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• pp.79-86
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• 2012

This study was performed to investigate the physiochemical properties and anti-diabetic effect of yacon vinegar by two-step fermentation. Yacon was matured at room temperature for 20 days. The sugar content of yacon juice prepared from mature yacon was approximately $14^{\circ}Brix$. In the first stage, yacon wine was produced from the juice at $28^{\circ}C$ for 6 days. In the second stage, acetic acid fermentation was conducted at $30^{\circ}C$ and 200 rpm for 6 days to produce yacon vinegar with 4.75% acidity. The major free sugars of yacon vinegar were glucose and fructose at 2,072.12 mg% and 463.95 mg%, respectively. The acetic acid content was the highest of the major organic acids at 3,881.44 mg%. The total free amino acid content was 62.88 mg% with the main free amino acids being proline, ${\gamma}$-amino-n-butyric acid and ornithine. The major minerals of yacon vinegar were Ca, K and Mg. The in vivo anti-diabetic activity of yacon vinegar was investigated in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. Diabetic mice were administered orally with 10% yacon juice and two yacon vinegars (5% and 10%) at a dose of 7 mL/kg body weight once per day for 4 weeks. Five% yacon vinegar improved the fasting blood glucose levels and glucose tolerance test significantly compared to the diabetic control group (p<0.05). Yacon vinegar increased the pancreatic C-peptide concentration in a dose-dependent manner. These results show that 5% yacon vinegar has a more potent effect on ameliorating hyperglycemia than 10% yacon juice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.9
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• pp.1243-1252
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• 2009

We investigated a method to improve anticancer activities of Acer mono by ultra high pressure extraction process. The extract yields by ultra high pressure were 9.49% and 9.87% for 5 min and 15 min processing time, respectively, which were relatively higher than 3$\sim$4% of conventional extraction processes due to their resid bark structure. The extract for 15 minutes extraction (HPE15) showed higher potent scavenging effect as 94.56% than the control, BHA as 93.24%. On SOD-like test, HPE15 also showed the highest activity as 38.6% at 1.0 mg/mL concentration. The cytotoxicity of HPE15 on normal human lung and kidney cell were below 23.54% in adding 1.0 mg/mL. Generally, human cancer cell growth stomach adenocarcinoma (AGS), lung adenocarcinoma (A549), breast adenocarcinoma (MCF-7), colon adenocarcinoma (Caco-2) and liver adenocarcinoma (Hep3B) were inhibited up to 75% with higher selectivity of above 4.0. High antioxidant activity of HPE15 resulted in high anticancer activity, and its activity was also due to higher yields of Acer mono by ultra high pressure extraction process. It was also proved by HPLC comparison analysis.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.354-363
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• 2001

Background : Although lung involvement has been reported in 5 to 46% of dermatomyositis/polymyositis(DM/PM) patients, reports of the condition in Korea are rare. This study evaluated the clinical features of lung involvement in DM/PM patients. Methods : The medical records, laboratory results and radiologic findings of 79 DM/pM patients, who attended the Seoul National University Hospital (SNUH) between 1989 and 1999, were reviewed retrospectively. Results : A total 79 patients of whom 24 patients(33%) showed lung involvement, were enrolled in this study. More patients with lung involvement were female(F:M=11:1), and older compared with those without lung involvement. Patients with lung involvement presented with dyspnea(79%), coughing(67%), an elevated ESR, and CK/LD. Anti-Jo 1 antibody test was positive in 30%, which is significantly higher in patients with lung involvement. A simple chest X-ray of the patients with lung involvement exhibited reticular opacity(50%), reticulonodular opacity(30%), patchy opacity(29%), nodular opacity(13%) and linear opacity(4%). HRCT(n=24) showed ground glass opacity(75%), linear or septal thickening(50%), patchy consolidation(42%), honey-combing(33%) and nodular opacity(17%). The pulmonary function test showed a restrictive ventilatory pattern(77%) and a lower diffusing capacity(62%). The patients were followed up during a mean duration of $30{\pm}28$ months. They were treated with steroid only(50%) or a combination of steroids and cytotoxic agents(46%). Muscle symptoms were improved in 89% with treatment, but an improvement in the respiratory symptoms or in the pulmonary function test was rare. Patients with lung involvement had a higher mortality rate(21%) than those without lung involvement(10%) during the follow-up periods. Conclusion : DM/PM patients with lung involvement were mostly female, older and had a higher positive rate Anti-Jo 1 antibodies, but there was no significant difference in prognosis.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.257-264
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• 2004

Background : There are many combinations of treatment for locally advanced non-small cell lung cancer (NSCLC). Recent studies have showed the efficacy of concurrent chemoradiotherapy (CCRT) in NSCLC. At present, however, there is no consensus about the optimal dosages and timing of radiation and chemotherapeutic agents. The aims of study were to determine the feasibility, toxicity, response rate, and survival rate in locally advanced NSCLC patients treated with doxetaxel and cisplatin based CCRT. Method : Sixteen patients with unresectable stage III NSCLC were evaluated from May 2000 until September 2001. Induction chemoradiotherapy consisted of 3 cycles of docetaxel (75 $mg/m^2/IV$ on day 1) and cisplatin (60 $mg/m^2/IV$ on day 1) chemotherapy every 3 weeks and concomitant hyperfractionated chest irradiation (1.15 Gy/BID, total dose of 69 Gy) in 6 weeks. Patient who had complete or partial response, and stable disease were applied consolidation chemotherapy of docetaxel and cisplatin. Results : All patients showed response to CCRT. Four patients achieved complete response (25%), partial responses in 12 patients (75%). The major common toxicities were grade III or more of neutropenia (87.3%), grade III esophagitis (68.8%), pneumonia (18.8%) and grade III radiation pneumonitis (12.5%). Thirteen patients were ceased during follow-up period. Median survival time was 19.9 months (95% CI; 4.3-39.7 months). The survival rates in one, two, and three years are 68.7%, 43.7%, and 29.1%, respectively. Local recurrence was found in 11 patients (66.8%), bone metastasis in 2, and brain metastasis in 1 patient. Conclusion : The response rate and survival time of CCRT with docetaxel/cisplatin in locally advanced NSCLC were encouraging, but treatment related toxicities were high. Further modification of therapy seems to be warranted.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.480-489
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• 2005

Background : Dysregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. X-linked inhibitor of apoptosis (XIAP) is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. This study was designed to assess the pattern of expression and the prognostic value of XIAP in radically resected non-small cell lung carcinoma (NSCLC) patients. Method : The expression of XIAP and its relationship with clinicopathologic parameters (patient age, TNM stage, TNM-pT, TNM-pN, histologic type, VEGF expression, microvessel density, PCNA index) and overall survival were analysed with formalin-fixed, paraffin-embedded blocks from eighty cases of NSCLC. In addition, the apoptotic index (AI) was also assessed. Results : In a regard to histologic type, squamous cell carcinoma (SCC) showed XIAP expression in 91.3%(42/46) and adenocarcinoma (AC) in 61.8%(21/34). The difference was significant(p=0.001). There was no correlation between XIAP expression and other parameters. In the group of AC, XIAP expression showed the signifcant correlation with older age group ${\geq}58years$ and VEGF expression(p=0.028, p=0.014, respectively). The AI in the group with or without XIAP expression were $2.5{\pm}4.9%$ and $18.5{\pm}28.9%$, respectively(p=0.001). Both groups just aforementioned showed no significant difference in median survival time (42.5 months, 29.8 months, respectively). Conclusion : This study suggests that the XIAP expression in NSCLCs could have relation to inhibition of apoptosis, and show differential expression according to histologic type. However, its prognostic role during the progression of NSCLC needs to be further defined.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.473-479
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• 2005

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.404-411
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• 2006

Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

• Tuberculosis and Respiratory Diseases
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• v.66 no.5
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• pp.358-364
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• 2009

Background: The appropriate empirical antimicrobial choice in the treatment of community-acquired pneumonia (CAP) should be advocated by community-based information on the etiologic pathogens, their susceptibility to antimicrobials, clinical characteristics and outcomes. Jeju is a geographically isolated and identical region in Korea. However, there is no regional reference on adult CAP available. This study investigated the etiologic agents and clinical outcomes of adult patients diagnosed with CAP in Jeju, Korea, to help guide the empirical antimicrobial choice. Methods: A prospective observational study for one year in a referral hospital in Jeju, Korea. Patients diagnosed with CAP were enrolled with their clinical characteristics. Microbiological evaluations to identify the etiologic agents in the adult patients with CAP were performed with blood culture, expectorated sputum smear and culture, antibody tests for mycoplasma, chlamydophila, and antigen tests for legionella and pneumococcus. The clinical outcomes of the initial empirical treatment were analyzed. Results: Two hundred and three patients with mean age of 64 and 79 females were enrolled. Ten microbials from 90 cases (44.3%) were isolated and multiple isolates were confirmed in 30. Among the microbial isolates, S. pneumoniae (36.3%) was the most common, followed by M. pneumoniae (23.0%), C. pneumoniae (17.0%), S. aureus (9.6%) and P. aeruginosa (5.9%). The initial treatment failure (23.8%) was related to the isolation of polymicrobial pathogens, elevated inflammatory markers, and the presence of pleural effusion. Among the 30 isolates of S. pneumoniae, 16 (53.3%) were not susceptible to penicillin, and 19 isolates (63.3%) to erythromycin and clarithromycin. However, 29 isolates (96.7%) were susceptible to levofloxacin and ceftriaxone. Conclusion: S. pneumoniae, M. pneumoniae, S. aureus, and P. aeruginosa are frequent etiologic agents of adult CAP in Jeju, Korea. The clinical characteristics and antibiotic resistance should be considered when determining the initial empirical antimicrobial choice. Respiratory quinolone or ceftriaxone is recommended as an empirical antimicrobiotic in the treatment of adult CAP in Jeju, Korea.