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사염화탄소와 에탄올로 유발된 간손상에 대한 GODEX<SUP>Ⓡ</SUP>의 치료효과 및 투여 중단에 따른 효소 역전 현상의 비교 평가
신지순(Ji Soon Sin),정은용(Eun Yong Jung),채희열(Hee-Youl Chai),권운(Woon Kwon),최은경(Ehn Kyoung Choi),조영민(Young Min Cho),황석연(Seok-Yeon Hwang),이민호(Min Ho Lee),김윤배(Yun-Bae Kim),강종구(Jong-Koo Kang) 한국실험동물학회 2003 Laboratory Animal Research Vol.19 No.4
Cephalosporin계 항생제 IDC7181에 대한 항원성시험
신지순(Ji Soon Sin),장호송(Hu-Song Zhang),최은경(Ehn-Kyoung Choi),권운(Woon Kwon),채희열(Hee-Youl Chai),조영민(Young Min Cho),김윤배(Yun-Bae Kim),강종구(Jong-Koo Kang) 한국독성학회 2003 Toxicological Research Vol.19 No.4
Antigenic potential of a novel cephalosporin, IDC7181 was examined a active systemic anaphylaxis (ASA) and passive cutaneous anaphylaxis (PCA) test, in guinea pig and mouse-rat models, respectively. In ASA test, IDC7181 induced the signs of restlessness in a few animals immunized with a high dose (100 mg/kg) of IDC7181 alone or in combination with Freund's complete adjuvant (FCA). In PCA test, only one of ten sera from the animals immunized with a high dose (100 mg/kg) of IDC7181 in the absence or presence of FCA showed positive reaction. The positive reaction,<br/> induced by IDC7181, which may be due to β-lactam ring, in ASA and PCA tests were negligible in comparison with those of traditional cephalosporins. Taken together, it is suggested that IDC7181 do<br/> not cause immunological problems in clinical dosage.
Antitumor Activity of K6, an Allylthiopyridazine Derivative, in Hep-G2 Cells-transplanted Nude Mice
채희열,신지순,김태명,권운,조영민,최은경,황석연,김윤배,강종구 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.1
In vitro cytotoxicity and in vivo growth-inhibitory effect of 3-methoxy-6-allylthiopyridazine (K6), an allylthiopyridazine derivative, were evaluated in human hepatocellular carcinoma Hep-G2 cell line and in nude mouse xenograft model, respectively, in comparison with doxorubicin. In vitro cytotoxicity, K6 (5-2,000 μM) and doxorubicin (0.05-10 μM) decreased tetrazolium conversion by viable cells to formazan in a dose-dependent manner. From a mechanistic study, the Hep-G2 cells exposed to K6 or doxorubicin underwent morphological changes, displaying elongation with filamentous protrusions. In addition, the cells showed chromatin condensation and fragmentation, producing apoptotic bodies. In vivo solid tumor xenograft model, the growth rate of tumor mass was significantly suppressed to the half level by daily oral administration of K6 (20-100 ㎎/㎏), which is comparable to the effect of intravenous treatment with doxorubicin (2 ㎎/㎏), resulting in the decrease in final tumor weights to 0.78 and 0.50 g by K6 (100 ㎎/㎏) and doxorubicin, respectively, compared with 1.32 g of control. Also, mean survival time of mice of control group (14.4 days) was doubled by treatment with K6 (27.2-29.4 days) or doxorubicin (28.8 days), leading to 100% increase in life span. Interestingly, daily oral treatment with a high dose (100 ㎎/㎏) of K6 did not induce testicular toxicity, in contrast to full degenerations of germ cells in atrophic testes intravenously exposed to doxorubicin at 4-6-day intervals, in addition to the emaciation and decrease in body weights of the animals. Taken together, K6, an allylthiopyridazine derivative originated from dially sulfide in garlic oil, could be a promising candidate for chemotherapy of hepatocellular carcinomas as an oral regimen. 키워드
HepaRG 세포를 이용한 Bosentan 약물의 CYP450 효소활성 측정
한경문,정정아,신지순,차혜진,배영지,김현욱,김영훈,성원근,강호일 대한약학회 2014 약학회지 Vol.58 No.4
Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metab- olism 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 sev-eral 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 µM omeprazole, 2C9 and 2C19: 10 µM rifampin, 3A4: 10, 25, 50 µM rifampin) at 37 o C, 5 % CO2 in a humidified atmosphere. This study was to eval-uate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction abil-ity 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 Cmax (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.