• Journal of Preventive Medicine and Public Health
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• 제39권6호
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• pp.455-461
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• 2006

Objectives : Prolongation of the heart rate-corrected QT (QTc) interval has been reported to be associated with cardiovascular morbidity and mortality. However, few studies have examined the relationship between the QTc interval and cardiovascular risk factors in young healthy people, The aim of this study was to examine the associations between the QTc interval and cardiovascular risk factors in young healthy adults. Methods : This study was performed as part of the Kangwha study, which started in 1986, and is an on-going follow-up study on blood pressure and related cardiovascular risk factors. In follow-up examinations during 2005, cardiovascular risk factors, including anthropometrics, blood pressure, blood chemistry and carotid ultrasonography, were measured, and questionnaires on health behaviors completed by 127 men and 149 women aged 25 years. The QTc interval was measured on the resting 12-lead electrocardiogram using an automatic analysis program. Results : The mean QTc interval was significantly longer in women $(419{\pm}17ms)$ than in men $(405{\pm}17ms)$ (p<0.001). A significant positive correlation was found between the QTc interval and waist-hip ratio (p=0.030) in men. Women showed a positive correlation between the QTc interval and systolic blood pressure (p=0.017). On a multiple regression analysis, the QTc interval was positively associated with the waist-hip ratio in men (p=0.012) and with the systolic blood pressure (p=0.020) in women. Conclusions : In young healthy Korean adults, the QTc interval was independently associated with the waist-hip ratio in men and with the systolic blood pressure in women.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.448-453
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• 2010

Drug-induced long QT syndrome is known to be associated with the onset of torsades de pointes (TdP), resulting in a fatal ventricular arrhythmia. QT interval prolongation can result from blocking the human ether-a-go-go-related gene (hERG) channel, which is important for the repolarization of cardiac action potential. Nicardipine, a Ca-channel blocker and antihypertensive agent, has been reported to increase the risk of occasional serious ventricular arrhythmias. We studied the effects of nicardipine on hERG $K^+$ channels expressed in HEK293 cells and Xenopus oocytes. The cardiac electrophysiological effect of nicardipine was also investigated in this study. Our results revealed that nicardipine dose-dependently decreased the tail current of the hERG channel expressed in HEK293 cells with an $IC_{50}$ of 0.43 ${\mu}M$. On the other hand, nicardipine did not affect hERG channel trafficking. Taken together, nicardipine inhibits the hERG channel by the mechanism of short-term channel blocking. Two S6 domain mutations, Y652A and F656A, partially attenuated (Y652A) or abolished (F656A) the hERG current blockade, suggesting that nicardipine blocks the hERG channel at the pore of the channel.

• International Journal of Oral Biology
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• 제43권1호
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• pp.43-51
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• 2018

$K^+$ channels are key components of the primary and secondary basolateral $Cl^-$ pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human $K^+$ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier $K^+$ channel ($I_{Kr}$) in the heart. Mutations in hERG reduce $I_{Kr}$ and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at $36^{\circ}C$, treatment with $0.4{\mu}M$ paroxetine for 5 min decreased the action potential duration at 90% of repolarization ($APD_{90}$) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.

• Tuberculosis and Respiratory Diseases
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• 제69권6호
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• pp.474-479
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• 2010

Torsades de pointes associated with a prolonged QT interval is a life-threatening arrhythmia, which may be induced by any of the following: drugs, electrolyte imbalances, severe bradycardia and intracranial hemorrhage. Torsades de pointes is characterized by beat-to-beat variations in the QRS complexes in any ECG leads with rates of 200~250 per minute. Fluoroquinolones are widely used and well tolerated antibacterial agents. However, prolongation of the QT interval leads rarely to Torsades de pointes as a significant adverse effect. So, it should be used with caution in high-risk patients for developing Torsades de pointes. We report one case of 67-year old man with contact burns who experienced Torsades de pointes, which probably resulted from the use of levofloxacin, and no further episode occurred after its withdrawal.

• BMB Reports
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• 제53권10호
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• pp.545-550
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• 2020

Combination therapy using chloroquine (CQ) and azithromycin (AZM) has drawn great attention due to its potential anti-viral activity against SARS-CoV-2. However, clinical trials have revealed that the co-administration of CQ and AZM resulted in severe side effects, including cardiac arrhythmia, in patients with COVID-19. To elucidate the cardiotoxicity induced by CQ and AZM, we examined the effects of these drugs based on the electrophysiological properties of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using multi-electrode arrays. CQ treatment significantly increased the field potential duration, which corresponds to prolongation of the QT interval, and decreased the spike amplitude, spike slope, and conduction velocity of hESC-CMs. AZM had no significant effect on the field potentials of hESC-CMs. However, CQ in combination with AZM greatly increased the field potential duration and decreased the beat period and spike slope of hESC-CMs when compared with CQ monotherapy. In support of the clinical data suggesting the cardiovascular side effects of the combination therapy of CQ and AZM, our results suggest that AZM reinforces the cardiotoxicity induced by CQ in hESC-CMs.

• 대한임상독성학회지
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• 제18권2호
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• pp.130-135
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• 2020

Purpose: Taking large amounts of glyphosate is life-threatening, but the amounts of glyphosate taken by patients for suicide are not known precisely. The purpose of this study was to find the predictors of large amounts of glyphosate ingestion. Methods: This retrospective study analyzed patients presenting to an emergency department with glyphosate intoxication between 2010 and 2019, in a single tertiary hospital. The variables associated with the intake amounts were investigated. The parameters were analyzed by multivariate variate logistic regression analyses and the receiver operating characteristic (ROC) curve. Results: Of the 28 patients with glyphosate intoxication, 15 (53.6%) were in the large amounts group. Univariate analysis showed that metabolic acidosis, lactic acid, and corrected QT (QTc) interval were significant factors. In contrast, multivariate analysis presented the QTc interval as the only independent factor with intoxication from large amounts of glyphosate. (odds ratio, 95% confidence interval: 1.073, 1.011-1.139; p=0.020) The area under the ROC curve of the QTc interval was 0.838. Conclusion: The QTc interval is associated significantly with patients who visit the emergency department after being intoxicated by large amounts of glyphosate. These conclusions will help in the initial triage of patients with glyphosate intoxication.

• 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.

• Annals of Occupational and Environmental Medicine
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• 제35권
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• pp.34.1-34.8
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• 2023

Background: Hydrogen sulfide is a toxic substance that humans can be exposed to occupationally, and cases of hydrogen sulfide poisoning of workers in industrial sites are commonly reported. However, there have been no cases of poisoning of the public due to an unauthorized discharge of wastewater, so it is important to describe this incident. Case presentation: In a small village in Jeollanam-do, Republic of Korea, accounts of a terrible stench had been reported. A 26-year-old man who lived and worked in a foul-smelling area was taken to the emergency room with a headache, dizziness, nausea, and repeated syncope. A subsequent police and Ministry of Environment investigation determined that the cause of the stench was the unauthorized discharge of 9 tons of wastewater containing hydrogen sulfide through a stormwater pipe while the villagers were sleeping. The patient had no previous medical history or experience of symptoms. Leukocytes and cardiac markers were elevated, an electrocardiogram indicated biatrial enlargement, left ventricular hypertrophy, and corrected QT interval prolongation. Myocardial hypertrophy was detected on a chest computed tomography scan, and hypertrophic cardiomyopathy was confirmed on echocardiography. After hospitalization, cardiac marker concentrations declined, symptoms improved, and the patient was discharged after 7 days of hospitalization. There was no recurrence of symptoms after discharge. Conclusions: We suspect that previously unrecognized heart disease manifested or was aggravated in this patient due to exposure to hydrogen sulfide. Attention should be paid to the possibility of unauthorized discharge of hydrogen sulfide, etc., in occasional local incidents and damage to public health. In the event of such an accident, it is necessary to have government guidelines in place to investigate health impact and follow-up clinical management of exposed residents.

• Journal of Korean Neurosurgical Society
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• 제47권4호
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• pp.252-257
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• 2010

Objective : Barbiturate coma therapy (BCT) is a useful method to control increased intracranial pressure (IICP) patients. However, the complications such as hypotension and hypokalemia have caused conditions that stopped BCT early. The complications of low dose BCT with $Bispectral^{TM}$ index (BIS) monitoring and those of high dose BCT without BIS monitoring have been compared to evaluate the efficacy of low dose BCT with BIS monitoring. Methods : We analyzed 39 patients with high dose BCT group (21 patients) and low dose BCT group (18 patients). Because BIS value of 40-60 is general anesthesia score, we have adjusted the target dose of thiopental to maintain the BIS score of 40-60. Therefore, dose of thiopental was kept 1.3 to 2.6 mg/kg/hour during low dose BCT. However, high dose BCT consisted of 5 mg/kg/hour without BIS monitoing. Results : The protocol of BCT was successful in 72.2% and 38.1% of low dose and high dose BCT groups, respectively. The complications such as QT prolongation, hypotension and cardiac arrest have caused conditions that stopped BCT early. Hypokalemia showed the highest incidence rate in complications of both BCT. The descent in potassium level were $0.63{\pm}0.26$ in low dose group, and $1.31{\pm}0.48$ in high dose group. The treatment durations were $4.89{\pm}1.68$ days and $3.38{\pm}1.24$ days in low dose BCT and high dose BCT, respectively. Conclusion : It was proved that low dose BCT showed less severe complications than high dose BCT. Low dose BCT with BIS monitoring provided enough duration of BCT possible to control ICP.

• Clinical and Experimental Pediatrics
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• 제51권11호
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• pp.1232-1235
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• 2008

삼환계 항우울제의 하나인 이미프라민은 우울장애와 야뇨증, 불안장애, 신경성 통증에 쓰인다. 그러나 이미프라민을 포함한 삼환계 항우울제는 많은 부작용이 관찰되는 데, 항콜린성 작용으로 초기에 입이 마르고 동공산대, 소변 정체, 동성빈맥을 보인다. 또한 중추신경계에 작용하여 섬망, 불안, 초조, 환각, 경련, 혼수를 야기할 수 있다. 그러나 앞에서 말한 부작용 보다도 치명적인 것인 삼환계 항우울제에 의해 소디움 채널 차단으로 인한 부정맥이다. QRS파의 연장과 QTc 연장, 넓은 QRS파 빈맥, Brugada 심전도 양상이 나타나며 이런 현상은 중탄산 나트륨을 통해 나트륨을 대량으로 공급하여 회복시킬 수 있다. 이미프라민을 포함한 삼환계 항우울제에는 아직도 널리 쓰이고 있지만 지금까지 소아에서 부정맥이 부작용으로 나타난 증례에 대한 보고가 없었다. 따라서 저자들은 이미프라민 과량복용 후 경련, 넓은 QRS파를 보이는 빈맥, Brugada 심전도 양상, 무뇨를 보인 환아를 경험, 치료하여 이를 보고한다.