• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.75-82
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• 2017

The effects of acepromazine on human ether-$\grave{a}$-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an $IC_{50}$ value of $1.5{\mu}M$ and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV. Before and after application of acepromazine, the half activation potentials of hERG currents changed to hyperpolarizing direction. Acepromazine blocked both the steady-state hERG currents by depolarizing pulse and the peak tail currents by repolarizing pulse; however, the extent of blocking by acepromazine in the repolarizing pulse was more profound than that in the depolarizing pulse, indicating that acepromazine has a high affinity for the open state of the channels, with a relatively lower affinity for the closed state of hERG channels. A fast application of acepromazine during the tail currents inhibited the open state of hERG channels in a concentration-dependent. The steady-state inactivation of hERG currents shifted to the hyperpolarized direction by acepromazine. These results suggest that acepromazine inhibits the hERG channels probably by an open- and inactivated-channel blocking mechanism. Regarding to the fact that the hERG channels are the potential target of drug-induced long QT syndrome, our results suggest that acepromazine can possibly induce a cardiac arrhythmia through the inhibition of hERG channels.

• 디지털융복합연구
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• 제19권3호
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• pp.109-114
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• 2021

본 연구에서는 ERG의 하위요인들이 조직애착에 미치는 영향에서 자기효능감의 매개효과를 검증하는데 초점을 두었다. 이를 검증하기 위해 한국 내 기업에 근무하는 종업원을 대상으로 설문조사를 진행하여 실증분석을 진행하였으며, 연구결과 ERG의 하위요인들인 생존욕구, 관계욕구, 성장욕구가 모두 자기효능감에, 자기효능감도 조직애착에 유의한 정(+)의 영향을 미친다는 것이 밝혀졌다. 또한 자기효능감은 ERG 하위요인과 조직애착간의 관계에 있어서 모두 매개 역할을 한다는 것이 밝혀졌다. 이러한 연구결과를 바탕으로 실무적 시사점을 제시함과 동시에 향후의 연구 방향을 제시하였다.

• 디지털융복합연구
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• 제20권5호
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• pp.331-336
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• 2022

본 연구는 ERG의 구성요소들이 회복탄력성을 매개로 조직기반자긍심에 미치는 영향을 검증하는데 초점을 두었다. 특히 ERG와 조직구성원들의 심리적 요인 간의 관계를 규명함으로써 욕구와 태도 간의 영향관계를 살펴보았다. 이를 검증하기 위해 10여 개 기업에 종사하는 근로자를 대상으로 설문조사를 실시하였고, 그 자료를 토대로 실증분석을 실시하였다. 실증분석을 통해 ERG의 하위요인인 생존욕구, 관계욕구, 성장욕구는 모두 회복탄력성 및 조직기반자긍심을 향상시키는 것으로 밝혀졌다. 또한 회복탄력성은 ERG 하위요인과 조직기반자긍심간의 관계에 있어서 모두 매개 역할을 하는 것으로 나타났다. 결론에서 연구의 간략한 요약 및 실무적 시사점, 그리고 향후 연구 방향를 제시하였다.

• 대한한의학회지
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• 제42권3호
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• pp.44-55
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• 2021

Objectives: As the use of herbal medicinal products (HMPs) increases worldwide, systematic verification of the safety of HMPs is required. The induction of cardiotoxicity is one of the major factors in post-approval withdrawal of medicinal products, and drug-induced cardiotoxicity assessment is emerging as an important step in drug development. In the present study, we evaluated human ether-à-go-go-related gene (hERG) potassium channel-related cardiotoxicity to predict the risk of cardiac arrhythmia in thirteen herbal medicines known to have cardiac toxicity. Methods: We measured the inhibition rate of hERG potassium channel activity of 13 medicinal herbal extracts in hERG-expressing HEK 293 cells using an automated patch-clamping system. Quinidine was used as a positive control for inhibition of hERG activity. Results: Extracts of Evodiae Fructus, Strychni Semen, and Corydalis Tuber potently inhibited the activity of hERG, and IC₅₀ values were 3.158, 19.87, and 41.26 ㎍/mL, respectively. Cnidi Fructus, Ephedra Herba, Lithospermi Radix, Polygoni Multiflori Radix, Visci Ramulus et Folium, Asiasari Radix et Rhizoma, and Scolopendra weakly inhibited hERG activity, and the IC₅₀ value for each herbal medicine was more than 400 ㎍/mL. Aconiti Kusnezoffii Tuber and two types of Aconiti Lateralis Radix Preparata (Po and Yeom) had weak inhibitory activity against hERG, and the IC₅₀ values were more than 700 ㎍/mL. The IC₅₀ value of quinidine against hERG was 1.021 𝜇M. Conclusion: Evodiae Fructus, Strychni Semen, and Corydalis Tuber acted as potent inhibitors against hERG. These herbal medicines may cause cardiac arrhythmia through QT prolongation, so care should be taken when taking them.

• 디지털융복합연구
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• 제19권1호
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• pp.23-28
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• 2021

본 연구는 ERG 구성요소들인 생존욕구, 관계욕구, 성장욕구에 초점을 맞춰 그 중요성을 강조하였다. 그리고 ERG 구성요소들이 직무적합성을 매개로 조직애착에 미치는 영향을 검증하는데 초점을 두었다. 이러한 과정에 있어서 조직애착을 이끌어 낼 수 있는 핵심 변수로 직무적합성의 매개역할을 명확히 규명하였다. 본 연구는 이를 검증하기 위해 한국내 공기업, 서비스업, 제조업, 유통업 등에 종사하는 근로자를 대상으로 실증분석을 실시하였다. 실증분석을 통해 ERG 세 개 하위요인들은 생존욕구, 관계욕구, 성장욕구는 모두 직무적합성을 향상시키는 것으로 밝혀졌다. 또한 직무적 합성은 조직애착 수준을 높여주는 요소로 볼 수 있다는 것을 검증하였다. 더 나아가 개인직무적합성은 ERG 세 개 하위요인과 조직애착간의 관계에 있어서 모두 부분매개 역할을 하는 것으로 나타났다. 이와 같은 결과들을 통해 생존욕구, 관계욕구, 성장욕구 중에서 직무적합성에 가장 큰 영향력을 미치는 요소가 무엇인지를 밝혔다. 마지막으로 본 연구를 통한 실무적 시사점들을 제시하였고 향후 연구 방향에 대해 논의하였다.

• 대한한의학회지
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• 제43권1호
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• pp.33-41
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• 2022

Objectives: Drug-induced blockade of the human ether-à-go-go related gene (hERG) potassium ion channel causes acquired long QT syndrome, which is known to cause cardiac arrhythmias and be fatal. To establish safety evidence of herbal formulae, we evaluated the effects of 31 herbal formulae on hERG channel activity. Methods: The current through hERG channel was measured by changing the membrane voltage before and after treatment with 31 herbal formulae in HEK 293 cell overexpressing hERG channel using a whole-cell patch clamp system. The current-voltage curves and the activity curves were fitted, and the hERG activity and 50% inhibitory concentration (IC₅₀) according to each herbal formula were calculated. Results: Chokyungjongok-tang, Oncheong-eum, and Cheongsangbangpung-tang strongly inhibited the hERG activity, with IC₅₀ values of 67.67, 141.2, and 296.3 ㎍/mL, respectively. Yeonkyopaedok-san, Eunkyo-san, Ukgan-san gajinphibanha, Daegunjoong-tang (except Oryzae gluten), Insamyangyoung-tang, Banhahubak-tang, SokyungHwalhyul-tang, Jodeung-san, Hyeonggaeyeongyo-tang, and Bangkeehwangkee-tang weakly inhibited hERG activity, with IC₅₀ values ranging from 400 to 1000 ㎍/mL. The other 18 herbal formulae showed very weak hERG activity inhibition of less than 50% at the highest concentration (1000 ㎍/mL). Conclusion: This study provided safety information on cardiotoxicity by cardiac arrhythmia risk assessment of herbal formulae, and is expected to be a reference data for predicting the safety and risk of herbal formulae.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.215-220
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• 2009

Chlorpheniramine is a potent first-generation histamine $H_1$ receptor antagonist that can increase action potential duration and induce QT prolongation in several animal models. Since block of cardiac human ether-a-go-go-related gene (hERG) channels is one of leading causes of acquired long QT syndrome, we investigated the acute effects of chlorpheniramine on hERG channels to determine the electrophysiological basis for its proarrhythmic potential. We examined the effects of chlorpheniramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Chlorpheniramine induced a concentration-dependent decrease of the current amplitude at the end of the voltage steps and hERG tail currents. The $IC_{50}$ of chlorpheniramine-dependent hERG block in Xenopus oocytes decreased progressively relative to the degree of depolarization. Chlorpheniramine affected the channels in the activated and inactivated states but not in the closed states. The S6 domain mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) the hERG current block. These results suggest that the $H_1$ antihistamine, chlorpheniramine is a blocker of the hERG channels, providing a molecular mechanism for the drug-induced arrhythmogenic side effects.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7875-7882
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• 2015

Background: The objectives of this study were to evaluate the expression of brain and acute leukemia, cytoplasmic (BAALC) gene and erythroblast transformation-specific related gene (ERG) in de novo cases of acute myeloid leukemia (AML) and identify roles in disease progression and outcome. Materials and Methods: This study included 50 newly diagnosed AML patients, along with 10 apparently healthy normal controls. BAALC and ERG expression was detected in the bone marrow of both patients and controls using real-time RT-PCR. Results: BAALC and ERG expression was detected in 52% of cases but not in any controls. There was a statistically significant correlation between BAALC and ERG gene expression and age (p-value=0.004 and 0.019, respectively). No statistical significance was noted for sex, lymphadenopathy, hepatomegaly, splenomegaly, other hematological findings, immunophenotyping and FAB sub-classification except for ERG gene and FAB (p-value=0.058). A statistical significant correlation was found between response to treatment with ERG expression (p-value=0.028) and age (p-value=0.014). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value=<0.001, 0.045, 0.041, <0.008 and 0.025 respectively). Conclusions: Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.

• 대한전자공학회:학술대회논문집
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• 대한전자공학회 2000년도 ITC-CSCC -2
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• pp.637-640
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• 2000

ERG signal represents the responses of the each layer of retina for the visual stimulus and accumulated responses according to the signal processing occurring in the retina. By investigating the reaction types of each wave of the ERG, various kinds of information for the diagnosis and the signal processing mechanisms in the retina can be obtained. In this paper, the ERG signal is generated by simulating of the volume conductor field of response of each retina layer and summing of them algebraically. The retina model used for simulation is Shah’s Computer Retina model which is one of the most reliable models recently developed. The generated ERG is compared with the typical ERG and shows a very close similarity. By changing the parameters of the retina model, the diagnostic investigation is performed with the variation of the ERG waveform.

• 대한한의학회지
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• 제40권2호
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• pp.94-105
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• 2019

Objectives: The correlation between medicinal herbal formulas and a risk of cardiotoxicity has been controversial. Thus, this study investigated cardiac safety assessment of 52 most commonly used medicinal herbal formulas. Methods: We evaluated the in vitro effects of medicinal herbal formulas on recombinant human embryonic kidney 293 (HEK 293) cell line expressing human ether-a-go-go-related gene (hERG) potassium channel. Results and Conclusion: Our results demonstrated that all of 52 medicinal herbal formulas did not show inhibition of hERG current in hERG-HEK 293 recombinant cells. In conclusion, these safety data suggest that 52 medicinal herbal formulas were not associated with an increased risk of cardiotoxicity in hERG-HEK 293 recombinant cells.