• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.207-213
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• 1999

To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was $2.35{\pm}1.93,$ that of 51 males was $2.30{\pm}2.26$ and 83 females was $2.37{\pm}1.85,$ respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was $2.30{\pm}2.06$ and that of 45 smokers was $3.62{\pm}3.19.$ This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; $r^2=0.28,$ p＜0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

• 한국환경성돌연변이발암원학회지
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• 제26권3호
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• pp.77-85
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• 2006

2,3,7,8-Tetrachlorodibenzo-$\rho$-dioxin(TCDD) displays high toxicity in animals and has been implicated in human carcinogenesis. Although TCDD is recognized as potent carcinogens, relatively little is known about their role in the tumor promotion and carcinogenesis. It is known that TCDD can increase of cancer risk from various types of tissue by a mechanism possibly involving the aryl hydrocarbon receptor (AhR) activation. In this study, effects of TCDD on cellular proliferation of normal human skin and lung fibroblasts, Detroit551 and WI38 cells were investigated. In addition, to enhance our understanding of TCDD-mediated carcinogenesis, we have investigated process in which expression of Erk1/2, cyclinD1, oncogene such as Ha-ras and c-myc, and their cognate signaling pathway. TCDD that are potent activators of AhR-mediated activity was found to induce significant increase of cytochrome P4501A1 mRNA expression, suggesting a presence of functional AhR. These results support that CYP1A1 enzyme may be involved in the generation of TCDD-induced toxicity. Moreover mitogen-activated protein kinases (MARKs) phosphorylation and cyclin D1 overexpression are induced by TCDD, which corresponded with the progression of cellular proliferation. However, TCDD did not affected Ha-ras and c-myc mRNA expression. Taken together, it seems that TCDD are could be a part of cellular proliferation in non-tumorigenic normal human cells such as Detroit551 and WI38 cells through the upregulation of MAPKs signaling pathway regulating growth of cell population. Therefore, AhR-activating TCDD could potentially contribute to tumor promotion and Detroit551 and WI38 cells have been used as a detection system of tumorigenic effects of TCDD.

• 대한기관식도과학회지
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• 제10권2호
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• pp.35-42
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• 2004

Background and objective : Rabeprazole is a new generation proton pump inhibitor, which has a rapid onset after first dose, predictable efficacy in all patients regardless of CYP2C19 genotype status, and less nocturnal acid breakthrough. The aim of the study is to investigate clinical efficacy and safety of rabeprazole sodium (Pariet 10mg qd)when administered once daily to patients with laryngopharyngeal reflux(LPR) disease. Methods : Among the patients who had visited the Department of Otolaryngology, those with LPR symptoms, had undergone laryngoscopy. Symptoms and endoscopic laryngeal sings were recorded initially, at 1 month, 2 months, 3 months, and more than 3 months, All patients were evaluated for clinical efficacy on the basis of symptom scores, reflux finding score(RFS), and side effects. Results : In general, most symptom scores and RFS improved over the time. Efficacy of the Pariet on LPR-related symptoms were $63.2\%,\;77.5\%,\;78.7\%,\;and\;90.9\%$ before 4 weeks, 4 to 8 weeks, 8 to 12 weeks, and after 12 weeks respectively. Efficacy on the RFS were $61.8\%,\;78.4\%,\;82.9\%,\;and\;85.5\%$ before 4 weeks, 4 to 8 weeks, 8 to 12 weeks, and after 12 weeks respectively. Pariet was well tolerated and was associated with few drug-related side effects. Conclusion Because of its efficacy and safety, Pariet may prove to be an alternative to currently available proton pump inhibitors.

• 한국약용작물학회지
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• 제4권1호
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• pp.78-85
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• 1996

강활(羌活)(Angelic koreana Max.)의 캘러스 배양(培養)과 식물체(植物體) 재분화(再分化)에 필요한 배양(培養) 조건(條件)을 구명(究明)하기 위하여 유엽(幼葉) 및 미숙화(未熟花)의 화경(花梗) 배양(培養)에 미치는 생장조절제(生長調節劑), sucrose 및 배지(培地) 응고제(凝固劑) 등의 영향(影響)을 조사(調査)한 결과(結果)는 다음과 같다. 1. 유엽(幼葉) 유래(由來) 캘러스 생장은 1 mg/l 2,4-D를 첨가한 MS배지에서 왕성하여, 생체중(生體重) 및 건물중(乾物重)이 가장 높았다. 2. 캘러스 생장을 위한 적정 sucrose농도는 2% 였으며, sucrose 농도가 증가함에 따라 캘러스 생장이 억제되는 경향이었다. 3. 배지(培地) 응고제(凝固劑)에 따른 캘러스 생장은 1.2% agar, 0.4% Gelrite에서 생체중(生體重) 및 건물중(乾物重)이 가장 높았다. 4. 배지내 10mg/l ABA와 $5{\sim}10mg/l\;AgNO_3$ 첨가는 유엽(幼葉) 유래(由來) 캘러스의 갈변화(褐變化)를 현저히 억제하였으며, 무처리(無處理)보다 캘러스 활력도 높았다. 5. 미숙(未熟) 화(花)의 화경(花梗) 배양(培養)에서 캘러스 형성율은 NAA보다 2,4-D가 효과적이었으며, 2mg/l 2,4-D를 첨가한 배지에서 81.7%로 가장 높았고, 캘러스 생장도 왕성하였다. 6. 유엽(幼葉) 유래(由來) 캘러스로부터는 식물체(植物體)가 재분화(再分化)되지 않았으나, 미숙(未熟) 화(花)의 화경(花梗) 유래(由來) 캘러스는 0.5 mg/l 2,4-D, 1 mg/l kinetin, 5 mg/l ABA와 5 mg/l $AgNO_3$ 첨가배지에서 체세포(體細胞) 배(胚)가 형성되었으며, 이들 체세포(體細胞) 배(胚)로부터 식물체(植物體)가 발생(發生)되었다. 무처리(無處理) 229.1kg보다 63.3kg 더 무거운 28%의 증수(增收) 효과(效果)를 나타냈으며 60배(倍), 80배(倍), 처리시(處理時)에도 각각(各各) 6%, 3% 증수(增收)되었다.로 42% 소득(所得)이 증대(增大)되었다.7. 3%였고 개분함량(漑粉含量)은 10월(月), 11월(月) 각각 30. 8%, 27, 7%로서 수확시기별(收穫時期別) 함량(含量)에는 변이폭(變移幅)이 크지 않았다. 이를 종합하면 유효성분(有效成分)의 함량(含量)이 높은 11월(月) 30일(日) 수확(收穫)이 10월(月) 30일(日) 수확(收穫)보다 유리(有利)할 것으로 판단된다. 4. 구경(球莖) 크기별 약효성분(藥效成分)의 함량변이도 커서 10월(月), 30일(日) 경우 S가 0. 53%로 가장 높고 M, L 순(順)으로 구경(球莖)이 커지면서 함량(含量)이 감소(感少)하였다. 5. 정식(定植)깊이 $0{\sim}1cm$가 다른 정식(定植)깊이에 비교하여 수량(收量)이 206kg/10a로 가장 많았으며 유효성분(有效成分) 변이(變移)는 $0. 33{\sim}0. 39%$로서 정식(定植)깊이에 따라 크지않은 것을 고려하면 택사(澤瀉) 재배시(栽培時) 정식(定植)깊이는 $0{\sim}1cm$가 가장 유리(有利)할 것으로 판단된다.군에서 18.8% 갑상선기능항진증 환자군에서 16.6%으로 나타났으며 이러한 slow acetylator의 빈도는 통계적으로 유의하지 않았다(chi-square, p= 0.83 표 3.). 결 론: Metoprolol을 표지 약물로 측정한 CYP2D6 poor metabolizer는 정상인과 갑상선기능항진증 환자군 모두에서 관찰할 수 없었다. N-acetyltransferase의 활성도는 갑상선기능항진증 환자군과 정상 대조군 사이에 유의한 차이를 보이지