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박희진 ( Hee Jin Park ),이숙환 ( Sook Hwan Lee ),차동현 ( Dong Hyun Cha ),김인현 ( In Hyun Kim ),전혜선 ( Hye Sun Jun ),이경진 ( Kyoung Jin Lee ),송송아 ( Song Ah Song ),박혜리 ( Hey Ri Park ),정창조 ( Chang Jo Chung ),이정노 ( Ch 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.10
Objective: To estimate the effect of maternal age on obstetric outcomes, a retrospective analysis was done. Methods: Twenty six hundred and forty six women who delivered a singleton baby at our hospital from January 1, to December 31, 2004 were enrolled in this study. Subjects were divided into 3 age groups; 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Chi-square test was used to assess the effect of age on obstetrics outcome. Then the odds ratio was calculated to represent clinically meaningful risk. Results: A total of 2646 women with complete data were available; 2245 (84.9%) less than 35 years of age; 350 (13.2%) 35-39 years; and 51 (1.9%) 40 years and older. Increasing age was significantly associated with chromosomal abnormalities (OR 3.9and 8.8 for ages 35-39 years and age 40 years and older, respectively), Preterm premature rupture of membranes (OR 1.3 and 3.2) and cesarean delivery (OR 2.0 and 5.5). Patients aged 35-39 years were at increased risk for placenta previa (OR 1.8) and congenital anomaly (OR 2.8) but these were not statistically significant. The rate of the preterm delivery was increased by age (OR 1.3 and 1.9 for ages 35-39 years and age 40 years and older, respectively) but it was not statistically significant (p=0.121). We did not find advanced maternal age to be associated with a statistically increased risk for preeclampsia, congenital anomaly, gestational diabetes, placenta abruption, low birth weight, macrosomia, neonatal morbidity (NICU admission), and perinatal loss. Conclusion: In conclusion, although the likelihood of adverse outcomes increases with maternal age, patients and obstetric care providers can be reassured that overall maternal and fetal outcomes are favorable in this patient population.
Kim, Young-Hoon,Bae, Young-Ji,Kim, Hyung Soo,Cha, Hey-Jin,Yun, Jae-Suk,Shin, Ji-Soon,Seong, Won-Keun,Lee, Yong-Moon,Han, Kyoung-Moon The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5
Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their interassay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
( Young-hoon Kim ),( Young-ji Bae ),( Hyung Soo Kim ),( Hey-jin Cha ),( Jae-suk Yun ),( Ji-soon Shin ),( Won-keun Seong ),( Yong-moon Lee ),( Kyoung-moon Han ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5
Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their interassay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
고환 특이적으로 발현되는 탈유비퀴틴효소 HIDE와 HSP90의 상호작용
성민우,김명선,김용수,이숙환,이혜진,차광열,백광현,Seong, Minu,Kim, Myung-Sun,Kim, Yong-Soo,Lee, Sook-Hwan,Lee, Hey-Jin,Cha, Kwang Yul,Baek, Kwang-Hyun The Korean Society for Reproductive Medicine 2005 Clinical and Experimental Reproductive Medicine Vol.32 No.3
연구목적: 본 연구는 아직 그 기능이 파악되지 않은 탈유비퀴틴효소 중 하나인 HIDE에 대한 기본적인 생화학적 특징과 고환에서의 발현 양상을 파악하고 있다. 연구재료 및 방법: 인간의 HIDE 유전자를 클로닝하여 효소활성이 있는지 세포 외 실험을 통해 확인하였고, 아미노산 서열을 분석하여 진화상 보존된 부분을 찾아 그 기능을 파악한 다음 HSP90과의 상호작용을 공동면역침전반응으로 확인하였다. HIDE의 조직별 발현양상을 파악하기 위해서 인간과 쥐의 RNA 블롯과 쥐의 단백질 블롯을 이용하여 각각 노던 블롯팅과 웨스턴 블롯팅을 수행하여 고환에서 많이 발현된다는 것을 알았고 이 사실을 바탕으로 쥐의 고환을 절개하여 면역조직화학반응으로써 고환 내의 HIDE 단백질의 발현양상을 파악하였다. 결 과: HIDE는 세포 외에서 유비퀴틴 잔기를 제거하는 탈유비퀴틴 활성이 있으나 세포 내에서 전체적인 유비퀴틴 복합체를 줄여주는 효과는 없었다. HIDE는 HSP90이라는 분자 샤페론과 상호작용한다. HIDE의 전사체는 고환에서 가장 많이 발현되며 다른 조직에서도 소량 발현된다. HIDE의 단백질은 웨스턴 블롯상에서 고환에서만 확인되었다. 고환 내에서의 HIDE의 발현양상은 왕성한 감수분열을 하는 정모세포에서 높았으며 지지세포나 정조세포에는 발현되지 않았다. 결 론: HIDE는 분자 샤페론 HSP90과 상호작용하며 고환 내의 감수분열 중인 세포에서 많이 발현되는 것으로 보아 감수분열이나 정자형성에 관여하는 것으로 보인다.
Cardiovascular Safety Pharmacology of Sibutramine
Yun, Jaesuk,Chung, Eunyong,Choi, Ki Hwan,Cho, Dae Hyun,Song, Yun Jeong,Han, Kyoung Moon,Cha, Hey Jin,Shin, Ji Soon,Seong, Won-Keun,Kim, Young-Hoon,Kim, Hyung Soo The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.4
Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an $IC_{50}$ of $3.92{\mu}M$ in patch clamp assay and increased the heart rate and blood pressure ($76{\Delta}bpm$ in heart rate and $51{\Delta}mmHg$ in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at $10{\mu}M$ and $30{\mu}M$, resulted in 15% and 29% decreases in $APD_{50}$, and 9% and 17% decreases in $APD_{90}$, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.
Cardiovascular Safety Pharmacology of Sibutramine
( Jae Suk Yun ),( Eun Yong Chung ),( Ki Hwan Choi ),( Dae Hyun Cho ),( Yun Jeong Song ),( Kyoung Moon Han ),( Hey Jin Cha ),( Ji Soon Shin ),( Won Keun Seong ),( Young Hoon Kim ),( Hyung Soo Kim ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.4
Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.