• 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 Society of Food Science and Nutrition
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• v.38 no.12
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• pp.1656-1663
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• 2009

The antioxidant activities of water extracts from wild vegetables such as Ligularia fischeri (GC), Capsicum annuum L. (GCY), Aster scaber (CNM), Petasites japonicus S. et Z. Max (MYD), Ipomoea batatas L. (Lam) (GGM) were evaluated and compared with water extracts from freeze dried block. The antioxidant properties of water extracts from wild vegetables and their freeze dried block were evaluated using different antioxidant tests; 2.2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging, hydroxyl radical scavenging and nitrite scavenging activities. The water extracts from wild vegetables were found to have a higher total phenolic content than water extracts from freeze dried block. Total phenolic contents of water extracts from GC, GCY, CNM, MYD, and GGM were $471.66{\pm}3.52\;{\mu}g/mg,\;141.33{\pm}2.51\;{\mu}g/mg,\;177.33{\pm}2.88\;{\mu}g/mg,\;238.66{\pm}9.50\;{\mu}g/mg\;and\;122.67{\pm}3.51\;{\mu}g/mg$, respectively. At the concentrations of 1000 ppm, water extracts from GC, GCY, CNM, and GGM showed higher activities than water extracts from their freeze dried block on DPPH radical scavenger activity. The activity of water extracts from CNM, GC, GCY, MYD, and GGM were 90.9%, 89.9%, 76.6%, 71.1%, and 57.4%, respectively. When 10000 ppm of GC, GCY, CNM, MYD, and GGM water extracts tested for hydroxyl radical scavenging activity, activities were increased by 38.8%, 33.4%, 35.9%, 34.3%, and 33.8%, respectively and a similar effect was found with water extracts from GCY, CNM, and GGM freeze dried block at 10000 ppm concentration. However, the water extracts from GC and MYD was slightly more effective than freeze dried block extracts. The water extracts from wild vegetables and their freeze dried block had effective DPPH radical scavenger activity and hydroxyl radical scavenging activity at all tested concentrations. Nitrite scavenging activity of GC water extract significantly increased in a dose-dependent manner and the extract had higher nitrite scavenging activity than extracts freeze dried block extracts. We found that freeze dried block maintained antioxidant activities of the wild vegetables.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1552-1559
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• 2013

Rubus coreanus Miquel (RCM) has been used as one of the Korean traditional medicines for prostate health. In addition, recent studies have reported that RCM reduced chronic inflammatory diseases such as cancer, and rheumatoid arthritis. Therefore, in this study, we investigated the effects of unripe and ripe RCM on inflammationrelated gene expressions in LPS-stimulated mouse peritoneal macrophages. Mice were fed with 2% unripe RCM (U2), 10% unripe RCM (U10), 2% ripe RCM (R2), and 10% ripe RCM (R10) for 8 weeks. Peritoneal macrophages were isolated and stimulated with LPS then proinflammatory mediators (TNF-${\alpha}$, IL-$1{\beta}$, and IL-6), and prostaglandin E2 ($PGE_2$) productions were assessed. Moreover, gene expression profiles were analyzed by cDNA microarray method. Unripe and ripe RCM significantly reduced TNF-${\alpha}$ production but only unripe RCM decreased IL-$1{\beta}$ and IL-6 production. RCM intake significantly reduced inflammatory-related gene expressions such as arachidonate 5-lipoxygenase, interleukin 11, and nitric oxide synthase 2. Furthermore, unripe and ripe RCM significantly decreased ceruloplasmin, tissue plasminogen activator, thrombospondin 1, and vascular endothelial growth factor A expression which modulates symptoms of chronic inflammatory diseases. RCM intake also significantly increased hypoxia inducible factor 3, alpha which is the negative regulators of hypoxia-inducible gene expression. Furthermore, only unripe RCM reduced chemokine (C-C motif) ligand 8, chemokine (C-X-C motif) ligand 14, and phospholipase A2 expression. In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions and may reduce chronic inflammatory disease progress through regulation of gene expressions. These findings suggest that RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• Tuberculosis and Respiratory Diseases
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• v.40 no.3
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• pp.223-235
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• 1993

Background: Superoxide anion which was produced by macrophage and neutrophil has a defensive role to kill invasive microorganisms and also an injurious role to produce self lung damage. Production of oxygen free radicals including superoxide is a main mechanism of acute lung injury caused by bacterial endotoxin. Endotoxin is known to activate alveolar macrophage to produce increased oxygen free radicals after the stimulation with various biological materials (priming effect). Calcium is a very important intracellular messenger in that cellular process of superoxide production. Method: This experiment was performed to elucidate the effects of endotoxin and calcium on superoxide production by phorbol myristate acetate-stimulated alveolar macrophage and the effect of verapamil on priming effect of endotoxin. Results: 1) Preincubation of macrophages with endotoxin (E. coli 055-B5) primed the cells to respond with increased superoxide production after the stimulation with PMA. Priming with endotoxin ($10^{-1}$ug/ml) produced a maximal enhancement of superoxide production (43%). 2) Verapamil could inhibit the superoxide production by PMA stimulated macrophage regardless of the presence of extracellular calcium. This means that the inhibitory effect of verapamil is caused by a mechanism independent of blocking calcium influx. 3) Verapamil could inhibit the priming effect of endotoxin on alveolar macrophage (from 30% increment to 13% increment) and could inhibit the superoxide production by PMA-stimulated macrophage preincubated with endotoxin. Conclusion: We concluded that verapamil could inhibit the superoxide production by PMA-stimulated rat alveolar macrophage and also inhibit the priming effect of endotoxin on alveolar macrophage. These inhibitory effects of verapamil could be one of the mechanisms of verapamil effects on endotoxin induced lung injury.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.650-659
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• 1999

Background/Aims: It is well recognized that all aerobic cells have the protective mechanisms in order to minimize the tissue damage induced by various reactive oxygen species(ROS). Thioredoxin peroxidase(TPX) which has been recently identified and characterized functions to convert peroxide to water. The protein is also found in various subtypes(TPX-A & B, MER5, HS22 and HORF-06) and is known to be ubiquitous in most human cells. Especially, ischemic brain injuries, partial hepatectomy and radiation induced DNA damages. In treating lung cancer, radiation therapy has a major place in the local control and the relief of symptoms, but radiation induced free radical injury and resulting pulmonary fibrosis has been the major drawback of the therapy. However, little is known about the protective mechanisms and biologic modulations against radiation-induced tissue damages. Methods: Eighteen mice were divided into six groups, 3 in each group, and fifteen had received 900cGy of radiation. The mice were sacrificed according to the pre determined time schedule; immediate, 1, 2, 3 and 6 weeks after irradiation. Extracts were made from the lungs of each mice, Western blot analysis of various subtypes of TPX were done after SDS-P AGE. Examination of H & E stained slides from the same irradiated specimens and the control specimens were also performed. Results: No difference in the intensity of the immunoreactive bands in the irradiated lung samples of the mice compared to the unirradiated control was observed regardless of the time intervals, although H & E examination of the sample specimens demonstrated progressive fibrotic changes of the irradiated lung samples. Conclusion: In conclusion, according to our data, it is suggested that various thioredoxin peroxidase subtypes and catalase which are known to be increased in many repair processes may not be involved in the repair of the radiation injury to the lung and subsequent fibrosis.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.364-372
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• 2001

Background : To observe the immediate and long-term results of bronchial artery embolization(BAE) for hemoptysis and the factors influencing the recurrences. Methods : This study involved 75 patients with massive, or moderate and recurrent hemoptysis, who underwent bronchial artery embolization(BAE) from 1994 to 1999. The underlying diseases included pulmonary tuberculosis in 35, bronchiectasis in 22, aspergilloma in 12, lung cancer in 3, and 3 with other diseases. Results : After BAE, bleeding was controlled immediately in 61 patients(82.7%). One patient died of another medical problem, 3 patients were referred to surgery and 5 patients could not be followed-up. In the remaining 66 patients who were followed for more than one-year after BAE, 37(56.1%) patients had another hemorrhage (26 hemoptysis, 11 minor hemosputa). Among the recurred 37 subjects, 19(51.4%) experienced hemorrhage within 1 month after BAE, 31(83.8%) within 1 year, and 36(94.1%) within 3 years. The underlying lung diseases, the amount of bleeding and the extent of the involved lungs were factors affecting the outcome, especially blood loss >500cc was an important factor affecting the recurrence rate. BAE for two cases with lung malignancy was ineffective. Long-term control of bleeding (3-year cumulative non-recurrence) was achieved in 30 subjects(45.5%). Conclusion : Bronchial artery embolization(BAE) is effective as an initial treatment for moderate to massive hemoptysis. Because most of the recurrences occurred within 3 years, it is important to follow-up such patients for at least 3 years after BAE and the most significant factor affecting the prognosis was amount of blood loss.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.334-345
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• 2001

Background : Pulmonary tuberculosis(TB) is still prevalent and remains a significant clinical problem for the elderly. However, the disease presents in many ways, and there are frequent adverse drug reactions that may prevent the early diagnosis and treatment of elderly TB patients compared to the young. The purpose of this study was to determine whether or not there are any differences in the clinical feature of pulmonary tuberculosis(TB) in both the diagnosis and treatment between the young (less than 64 years) and the elderly (65 years and more). Methods : The medical records of 125 young and 70 elderly pulmonary TB patients, who were diagnosed with and treated for pulmonary TB at the Seoul Municipal Boramae Hospital from November 1991 to January 1997, were analyzed retrospectively. Results : Anorexia(12% vs. 31.4%), general weakness (20.0% vs. 54.3%), dyspnea(21.6% vs. 37.1%) and an abnormal mentality (0.8% vs. 15.7%) were more frequent presenting symptoms in elderly TB patients, whereas hemoptysis (32.8% vs. 10.0%) and fever (BT > $37^{\circ}C$, 58.4% vs. 35.7%) were more frequent in the young. The elderly had a higher number of cardiovascular and chronic obstructive pulmonary diseases as underlying illnesses. In chest PA, there were no differences in the location of the TB lesion, but the appearances were initially diagnosed more frequently as pneumonia or lung cancer (8.8% vs. 30.0%, p<0.05) in the elderly. There was no difference in the detection rate of acid fast bacilli(AFB) in the sputum between the two groups. There were no differences in the treatment response and follow-up loss. However, adverse drug reactions (13.6% vs. 45.7%, p<0.05), and changes in medication (4.9% vs. 25.7%, p<0.05) during treatment occurred more frequently in the elderly. One among the 125 young patients died from tuberculosis whereas 6 among the 70 elderly patients died from the disease. Conclusion : Because the clinical and radiological presentations were more atypical, a sputum AFB smear and culture should be done immediately in the elderly who are TB. The elderly experienced more frequent adverse drug reactions and mortality during treatment, but the response to treatment was good and rapid.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.337-341
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• 2006

Objectives : Endobronchial anthracofibrotic pigmentation, which presents as dark black or brown pigmentation mucosal changes of multiple bronchi combined with bronchial fibrosis and obstruction, is not a rare finding when performing diagnostic bronchoscopy for Koreans. This study was performed to define the clinical characteristics and to determine the association of these finding with the Korean life style and such other diseases as coal workers, pneumoconiosis or tuberculosis in the patients with anthracofibrotic pigmentation. Methods : This retrospective analysis was conducted on 70 (5.2%) patients with endobronchial anthracofibrotic pigmentation, among a total of 1340 patients who underwent bronchoscopy. The distinctive clinical features, the personal life style, the past medical history, the histology and microbiology, the radiologic finding and the natures of the bronchoscopic lesions were analyzed. Results : This mean age of the patients with anthracofibrotic pigmentation was $60.6{\pm}9.2$ year old and the male to female ratio was 1:1.7. The common respiratory symptoms of these patients were coughing and sputum (81%, 57/70), and this was followed in order by dyspnea and hemoptysisir. The symptoms were not related with smoking and an occupational history such as being a coal worker and so on. Pneumonia was most common finding on the radiologic studies. On bronchoscopy, the right middle lobe bronchus was most commonly involved. The most common associated disease was tuberculosis, and 40 cases (57.1%) were diagnosed by AFB staining, TB PCR, bronchoscopic guided tissue biopsy and a past history of tuberculosis. Other diseases related with anthracotic pigmentation were hypertension, diabetes, COPD, lung cancer, pneumoconiosis and asthma. Conclusion : These results suggest that endobronchial anthracofibrotic pigmentation was mostly related with pulmonary tuberculosis rather than with coal- related disease. Endobronchial anthracofibrotic pigmentation was more prevalent in older age females in Korea.

• Tuberculosis and Respiratory Diseases
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• v.79 no.1
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• pp.14-21
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• 2016

Cough is one of the most common symptom of many respiratory diseases. The Korean Academy of Tuberculosis and Respiratory Diseases organized cough guideline committee and cough guideline was developed by this committee. The purpose of this guideline is to help clinicians to diagnose correctly and treat efficiently patients with cough. In this article, we have stated recommendation and summary of Korean cough guideline. We also provided algorithm for acute, subacute, and chronic cough. For chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered. If UACS is suspicious, first generation anti-histamine and nasal decongestant can be used empirically. In CVA, inhaled corticosteroid is recommended in order to improve cough. In GERD, proton pump inhibitor is recommended in order to improve cough. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, angiotensin converting enzyme inhibitor, habit, psychogenic cough, interstitial lung disease, environmental and occupational factor, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and idiopathic cough can be also considered as cause of chronic cough. Level of evidence for treatment is mostly low. Thus, in this guideline, many recommendations are based on expert opinion. Further study regarding treatment for cough is mandatory.