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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.
재생에너지 수용 시 폐지 발전기의 동기조상기 전환에 대한 영향성 분석
전혜련,최동희 대한전기학회 2023 전기학회논문지 P Vol.72 No.3
As the penetration of inverter-based sources (IBR) based on variable-renewable energy (VRE), the stable operation of the power system is getting challenging since the operating synchronous generators (SGs) must be out-of-service for power balance between the generation and demand. In addition to the uncertainty and fluctuation of VRE-based IBR, the high penetration of the IBR reduces the system inertia because the portion of operating SGs must be decreased. However, the VRE-based IBR cannot provide the proper inertia which the SG can. As the result, the reduction of system inertia affect adversely with respect to the system frequency. Especially, the rate of changes of frequency (ROCOF) is also increasing because of the declination of system inertia. This could cause consecutive frequency stability problems since the IBR must be tripped in the high ROCOF condition due to the self protection scheme. Therefore, the possibility of the cascaded black-out will be increased in the lack of system inertia. Traditionally, the synchronous condenser is a synchronous machine who can provide reactive power only in a power system to deal with voltage stability problems. Nonetheless its previous applications, synchronous condenser (SC) could be an alternative the adequate system inertia due to stability problem for providing missing system inertia. This paper analyzes the effect of SC with respect to frequency stability. For reflecting practical problem, the conversion of disclosing SG into SC as well as the installation of SC were all considered. Moreover, the reinforcement with flywheel was also examined in converting SG into SC cases. These analyses were carried out with IEEE 39 Bus Benchmark System by considering the introduction of VRE-based IBRs.