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전혜련,Gyu Chul Oh,석승혁,Hae-Young Lee 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.6
Background/Aims: Angiotensin II in the failing heart initially helps to maintain cardiac output and blood pressure, but ultimately accelerates its deterioration. In this study, we established a model of arrhythmia-induced heart failure (HF) in zebrafish and investigated the role of renin-angiotensin-aldosterone system (RAAS) modulation by using an angiotensin II type 1 receptor blocker, fimasartan, through the assessment of cellular and physiologic responses, morbidity, and mortality. Methods: HF was induced in zebrafish larvae by exposure to 20 μM terfenadine. Morphologic, physiologic, and functional parameters were assessed in the presence or absence of fimasartan treatment. Results: Zebrafish exposed to terfenadine showed marked dilatation of the ventricle and reduced systolic function. Treatment with terfenadine was associated with 10-fold higher expression of atrial natriuretic peptide (p < 0.001 vs. vehicle), increased p53 mRNA expression, and chromatin fragmentation in the TUNEL assay, all of which were significantly reduced by fimasartan treatment. Moreover, fimasartan improved fractional shortening (terfenadine + fimasartan 16.9% ± 3.1% vs. terfenadine + vehicle 11.4% ± 5.6%, p < 0.05) and blood flow (terfenadine + fimasartan 479.1 ± 124.1 nL/sec vs. terfenadine + vehicle 273.0 ± 109.0 nL/sec, p < 0.05). Finally, treatment with fimasartan remarkably reduced mortality (terfenadine + fimasartan 36.0% vs. terfenadine + vehicle 96.0%, p < 0.001). Conclusions: Fimasartan effectively protected against the progression of HF in zebrafish by improving hemodynamic indices, which improved survival. A reduction in apoptotic cell death and an improvement in hemodynamics may be the mechanisms behind these effects. Further human studies are warranted to evaluate the possible role of fimasartan in the treatment of HF.
Development of a Test Method for the Evaluation of DNA Damage in Mouse Spermatogonial Stem Cells
전혜련,이정선,김태성,오유경,이혜정,이민성,방진석,고기남,안일영,고경육,김주환,박혜경,이종권,손수정 한국독성학회 2017 Toxicological Research Vol.33 No.2
Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration (IC50) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.
Evaluation of Eye Irritation Potential for 30 Chemicals using Two Tiered Approaches
전혜련,조아랑,고경육,김주환,정미경,박교현,김배환,오원준,이종권,박기숙 한국동물실험대체법학회 2020 동물실험대체법학회지 Vol.14 No.1
Various alternative test methods are being developed to replace in vivo Draize rabbit test that evaluates eye irritation. However, a single alternative method has difficulty to be applied in safety evaluation on substances, because it cannot fully replace the in vivo test by simulating only part of the in vivo system. For this reason, different studies using several alternative test methods and test results of literatures have been under way. Our previous study suggested effective tiered approaches using three tests among Short Time Exposure (STE), Bovine Corneal Opacity and Permeability (BCOP), Hen’s Egg Test-Chorioallantoic Membrane (HET-CAM), re-constructed human cornea epitheliums (RhCE) tests. This study aimed to evaluate eye irritation potential for 30 new test chemicals using two tiered approaches. According to the data generated by direct test performance and literature survey, the accuracy, sensitivity and specificity of the two tiered approaches were 83.3%∼86.7%, 93.3%, 73.3%∼ 80%, respectively. Furthermore, the accuracy, sensitivity, and specificity of the two tiered approaches by applying combined data against 30 test chemicals in our present study and 47 test chemicals in previous study were 90.9%∼92.2%, 95.9%∼98.0%, 78.6%∼85.7%. Consequently, the two tiered approaches may be used to identify between irritants and non-irritants to replace in vivo test.
전력계통 내 관성확보를 위한 동기조상기 해외사례 검토 및 분석
전혜련,최동희,백승묵,이수형,이희진 한국정보기술학회 2023 한국정보기술학회논문지 Vol.21 No.1
기후 위기 등의 다양한 문제에 대처하기 위하여 신재생에너지원 기반 분산전원 계통의 수용율이 증가함에 따라 전통적인 계통의 구성 및 운영과 많은 다른 특성들을 가지게 되었다. 신재생에너지원 기반 분산전원의 출력변동은 동기발전기의 투입율이 줄어든 상황에서 전력계통에 관성저하 문제를 일으킬 수 있다. 전력계통의 관성이 낮을 경우, 급격한 주파수 변동은 계통 내의 기기들에 대하여 문제를 일으킬 수 있을 뿐만 아니라, 저주파수 부하 차단 등의 이벤트를 발생시켜 계통의 연속적인 사고를 야기할 수 있는 원인이 될 수 있다. 본 논문에서는 국내 전력계통 내 관성확보를 위한 동기조상기 설치를 위한 경제성 편익 분석을 위한 해외사례를 검토하였다. 아울러, 동기조상기의 신규설치 및 전환에 대한 단위 비용을 산정하여 국내 편익 분석을 위한 기초를 마련하고 그 비용을 해외사례와 비교 분석하였다.