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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.
문성채(Sung Chae Moon),김병수(Byung Soo Kim),김동민(Dong Min Kim),최필선(Phil Sun Choi),한경문(Kyeong Moon Han),이성욱(Sung Ook Lee),이혜정(Hye Jung Lee),천종철(Jong Chul Chun),선병호(Byung Ho Sun),김혜숙(Hye Suk Kim) 대한소화기학회 1997 대한소화기학회지 Vol.29 No.1
Enteric duplications are rare congenital anomalies. These are eharacterized by finn attachment to at least one point of the alirnentary tract and a well-developed coat of smooth muscle, and the epithelial lining always resembles some part of the alinentaty tract. Stomach is the least frequent location for these anomalies. The vast majority of patients with gastric duplication presented in infancy have an abdominal mass causing pain, upper gastrointestinal obstruetion, and failure to thrive. However, some cases have not been diagnosed until later in childhood. To date, fewer than 20 eases of gastric duplication have been diagnosed in adults. The present case is a 51 year-old male presenting with mild upper abdominal discomfort for a few years. A gastroscopy revealed an about 1.5 * 1.5 cm sized round protruding rnass with smooth surface of normal mucosa at the lesser curvature of gastric antrum, which was removed by surgical operation. Postoperative pathologic examination disclosed a gastric duplication which was a muscle-coated, cystic and tubular structure invested with a common musculature on gross finding, and was lined with a gastric mucosa on microscopie finding. (Korean J Gastroenterol 1997; 29:118 - 121)
한경문,김진호,조수열,심선보,이진희,이지현,황인선,김성일,조양하,채갑용,권순재,이준호 한국식품위생안전성학회 2011 한국식품위생안전성학회지 Vol.26 No.2
Melamine has raised international concerns for its catastrophic health effects from tainted infant formula. This report concerns the developmental validation of a sensitive HPLC/MS/MS and GC/MS methods about melamine and cyanuric acid in human urine and serum. Analytical detection ranges of LC/MS was from 0.2 to 5.0 ng/mL and 2.0 to 60.0 ng/mL about melamine and cyanuric acid, respectively. The limits of quantification and confirmation are 0.2 ng/mL for both analytes in human urine and serum by LC/MS/MS. The range of recovery was 91.6%, and 107.6% for cyanuric acid and melamine in urine, respectively. The range of precision coefficient variation was from 2.0%, to 11.8% for cyanuric acid and melamine in urine. The range of recovery was from 94.9%, to 119.0% about cyanuric acid and melamine in serum, respectively. The range of precision coefficient variation from was 3.7%, and 13.5% about cyanuric acid and melamine in serum. Analytical detection ranges of GC/MS were 5.0 to 100.0 ng/mL about melamine and cyanuric acid, respectively. The limits of quantification and confirmation are 5.0 ng/mL for both analytes in human urine and serum by GC/MS. The range of recovery was from 83.7%, to 114.5% for cyanuric acid and melamine in urine, respectively. The range of precision coefficient variation was 3.5%, and 10.7% for cyanuric acid and melamine in urine. The range of recovery was 94.4%, and 110.7% for cyanuric acid and melamine in serum,respectively. The range of precision coefficient variation from was 3.9%, and 13.8% for cyanuric acid and melamine in serum. Several changes were taken to optimize performance by this method.
한경문,안순영,서혜원,윤재석,차혜진,신지순,김영훈,김형수,박혜경,이용문 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3
The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with 20 μM bosentan+200 μM rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.
Linux 플랫폼 상에서의 대용량 로그 처리 기법에 대한 연구
문세광(Moon, Sae-Kwang),윤한경(Yun, Han-Kyung) 한국정보전자통신기술학회 2008 한국정보전자통신기술학회논문지 Vol.1 No.3
네트워크 보안 장비에서 발생되는 대용량 로그를 syslog-ng을 이용하여 파일로 저장하도록 구현하고, 파일로 저장된 로그 메시지를 데이터베이스로 저장하기 위해 gcc를 이용하여 쓰레드 프로그램을 개발하였으며, 이것을 서버스크립트 언어인 PHP를 이용해 로그의 내용을 파악하는 웹기반 뷰어를 개발하였다. 또한 방화벽에서 발생되는 로그 메시지를 처리하는 패키지 상품과의 비교를 통해 성능을 분석하였다. In the course of research, the program that is able to process files through gcc and imput them into the database has been developed, using Syslog-ng based Unix system. PostgreSQL and PHP are used for database and Web-based server side script respectively.