• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.246-253
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• 2007

Doxorubicin and daunorubicin are excellent chemotherapeutic agents utilized for several types of cancer but the irreversible cardiac damage is the major limitation for its use. The biochemical mechanisms of doxorubicin- and daunorubicin- induced cardiotoxicity remain unclear. There are many reports on toxicity of doxorubicin and doxorubicin in cardiomyocytes, but effects in cardiovascular system by these drugs are almost not reported. In this study, we investigated gene expression profiles in human umbilical vein endothelial cells (HUVECs) to better understand the causes of doxorubicin and doxorubicininduced cardiovascular toxicity and to identify differentially expressed genes (DEGs). Through the clustering analysis of gene expression profiles, we identified 124 up-regulated common genes and 298 down-regulated common genes changed by more than 1.5-fold by all two cardiac toxicants. HUVECs responded to doxorubicin and doxorubicin damage by increasing levels of apoptosis, oxidative stress, EGF and lipid metabolism related genes. By clustering analysis, we identified some genes as potential markers on apoptosis effects of doxorubicin and doxorubicin. Six genes of these, BBC3, APLP1, FAS, TP53INP, BIRC5 and DAPK were the most significantly affected by doxorubicin and doxorubicin. Thus, this study suggests that these differentially expressed genes may play an important role in the cardiovascular toxic effects and have significant potential as novel biomarkers to doxorubicin and doxorubicin exposure.

• 대한두개안면성형외과학회지
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• 제11권2호
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• pp.120-123
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• 2010

Purpose: Epinephrine itself exhibits some cardiotoxicity. However, it rarely induces cardiomyopathy when used in standard doses during surgery for local hemostasis. This paper reports a rare case of stress-induced cardiomyopathy in a young woman after the local infiltration of epinephrine. Methods: Corrective rhinoplasty was planned in a 20-year-old woman. Lidocaine mixed with epinephrine 1:100,000 was injected around the skin of the nose and nasal septum after inducing anesthesia, which resulted in sinus tachycardia and hypotension. Postoperative ECG showed a T wave inversion in the lead V2 and echocardiography revealed transient hypokinesia in the cardiac apex. Cardiac enzyme was mildly elevated. Results: Symptoms and laboratory findings improved considerably, and the patient was discharged from hospital without complications on the sixth day after surgery. Conclusion: The prognosis of catecholamine-induced cardiomyopathy is generally favorable. However, it is important to be aware of the possible adverse effects of local epinephrine infiltration. This case highlights the need for caution when using epinephrine.

• Biomolecules & Therapeutics
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• 제6권1호
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• pp.9-13
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• 1998

ln an attempt to define the effects of hyperbaric oxygen treatment on the lipid peroxidation and oxygen See radical reactions in rats exposed to carbon monoxide, we studied malondialdehyde(MDA) level and activities of catalase and superoxide dismutase in the heart of the rats exposed to carbon monoxide. Male Sprague-Dawley albino rats weighing 240 to 260gm were used. Experimental groups consist of Control group (=breathing with air), HBO group(=exposed to hyperbaric oxygen(HBO, 3ATA, 100%) after air breath), CO group(=exposed to CO(3,970 ppm) after air breath), CO-Air group(=exposed to CO after air breath followed by air breath) and CO-HBO group(=exposed to CO after ai. breath followed HBO treatment). The CO group showed significantly higher MDA level, catalase activity and SOD activity as compared to that of control group. The CO-HBO group showed significantly lower MDA level as compared to that of CO group, and did not show significantly lower catalase activity and SOD activity as compared to that of CO group. These results suggest that the excessive oxygen free radicals is an important determinant in pathogenesis of Co-induced cardiotoxicity and HBO inhibits the lipid peroxidation caused by excessive oxygen free radicals in the heart of the rats exposed to carbon monoxide.

• 동의생리병리학회지
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• 제16권6호
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• pp.1207-1210
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• 2002

To examine the cardiotoxic effect of adriamycin on cultured rat myocardial cells, cytotoxicity was measured by MTT assay after cultured myocardial cells were grown with various concentrations of adriamycin(ADA) for 48 hours. The protective effect of Benincasae Semen(BS) on ADR-induced cardiotoxicity was also examined in these cultures. ADR decreased cell viability of cultured rat myocardial cells remarkably in a dose- and time-dependent manners. In protective effect of BS, it was very effective in blocking ADR-induced cytotoxicity. From these results, it is suggested that ADR shows cardioxicity, and the herba extract, as is very effective in preventing ADR-induced cytotoxicity on cultured rat myocardial cells.

• 대한핵의학회지
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• 제38권5호
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• pp.331-337
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• 2004

Cardiac neurotransmission imaging allows in vivo assessment of presynaptic reuptake, neurotransmitter storage and postsynaptic receptors. Among the various neurotransmitter, I-123 MIBG is most available and relatively well-established. Metaiodobenzylguanidine (MIBG) is an analogue of the false neurotransmitter guanethidine. It is taken up to adrenergic neurons by uptake-1 mechanism as same as norepinephrine. As tagged with I-123, it can be used to image sympathetic function in various organs including heart with planar or SPECT techniques. I-123 MIBG imaging has a unique advantage to evaluate myocardial neuronal activity in which the heart has no significant structural abnormality or even no functional derangement measured with other conventional examination. In patients with cardiomyopathy and heart failure, this imaging has most sensitive technique to predict prognosis and treatment response of betablocker or ACE inhibitor. In diabetic patients, it allow very early detection of autonomic neuropathy. In patients with dangerous arrhythmia such as ventricular tachycardia or fibrillation, MIBG imaging may be only an abnormal result among various exams. In patients with ischemic heart disease, sympathetic derangement may be used as the method of risk stratification. In heart transplanted patients, sympathetic reinnervation is well evaluated. Adriamycin-induced cardiotoxicity is detected earlier than ventricular dysfunction with sympathetic dysfunction. Neurodegenerative disorder such as Parkinson's disease or dementia with Lewy bodies has also cardiac sympathetic dysfunction. Noninvasive assessment of cardiac sympathetic nerve activity with I-123 MIBG imaging nay be improve understanding of the pathophysiology of cardiac disease and make a contribution to predict survival and therapy efficacy.

• BMB Reports
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• 제39권6호
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• pp.759-765
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• 2006

In this study, we investigate Nitric oxide synthase (NOS) expressions in adriamycin (ADR)-induced cadiomyopathy in rats. Sixty male Wistar rats were randomly divided into two main groups: control and ADR groups. Myocardial histopathological observation was performed; Expressions of 3 isoforms of NOS genes were examined by RT-PCR analysis; Expressions of 3 isoforms of NOS protein was assessed by Western blot analysis. Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment. The expression levels of inducible NOS (iNOS) gene and protein were significantly increased in ADR-treated rats after 8 weeks of treatment and then slightly increased at weeks 9 and 10. No significantly difference of neuronal NOS (nNOS) or endothelial NOS (eNOS) gene and protein were observed in the myocardium obtained from the control rats and ADR-injected rats at any time point. iNOS gene expression is selectively induced by ADR in heart. The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR.

• 대한한방내과학회지
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• 제36권4호
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• pp.458-469
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• 2015

Objectives: Buja and Cheono, containing aconitine known for its cardiotoxicity, are not commonly prescribed, but they are necessary for some clinical conditions. Hence, consequences for electrocardiography (EKG) after short- and long-term dosage of herbal medicine including Buja and Cheono are here reported.Methods: From September 2014 to April 2015, 36 patients belonging to the sixth internal medicine department of the Dong Eui Oriental Medicine Hospital took herbal medicine including Buja and Cheono, and after these doses, they underwent an EKG. Thirty-one patients who took the medicine for 7-8 days comprised the short-term group, and 18 patients taking the medicine for 17-106 days comprised the long-term group. The results of the EKGs for each group, before and after dosage with herbal medicine, are compared.Results: No significant changes in EKG appeared in either the short- or the long-term group after taking herbal medicine including Buja and Cheono.Conclusions: If Buja or Cheono are prescribed along with other suitable herbs by a doctor of Korean medicine, no cardiac trouble will occur on an EKG regardless of the term of the dosage.

• 대한임상독성학회지
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• 제2권1호
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• pp.63-66
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• 2004

Hydrofluoric acid (HF), one of the strongest inorganic acids, is used mainly for industrial purpose. Hydrofluoric acid injuries has a potential for both systemic as well as severe local tissue destruction. One of the most serious consequences of severe exposure to HF by any route is marked lowering of serum calcium (hypocalcemia) and other metabolic changes, such as hypomagnesemia and which may result in a fatal outcome if not recognized and treated. promptly cardiotoxicity is not well known except arrhythmias, which are a primary cause of death. We report a case of myopericarditis by ingestion of hydrofluoric acid.

• The Korean Journal of Physiology and Pharmacology
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• 제23권5호
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• pp.295-303
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• 2019

A heart simulator, UT-Heart, is a finite element model of the human heart that can reproduce all the fundamental activities of the working heart, including propagation of excitation, contraction, and relaxation and generation of blood pressure and blood flow, based on the molecular aspects of the cardiac electrophysiology and excitation-contraction coupling. In this paper, we present a brief review of the practical use of UT-Heart. As an example, we focus on its application for predicting the effect of cardiac resynchronization therapy (CRT) and evaluating the proarrhythmic risk of drugs. Patient-specific, multiscale heart simulation successfully predicted the response to CRT by reproducing the complex pathophysiology of the heart. A proarrhythmic risk assessment system combining in vitro channel assays and in silico simulation of cardiac electrophysiology using UT-Heart successfully predicted drug-induced arrhythmogenic risk. The assessment system was found to be reliable and efficient. We also developed a comprehensive hazard map on the various combinations of ion channel inhibitors. This in silico electrocardiogram database (now freely available at http://ut-heart.com/) can facilitate proarrhythmic risk assessment without the need to perform computationally expensive heart simulation. Based on these results, we conclude that the heart simulator, UT-Heart, could be a useful tool in clinical medicine and drug discovery.

• 센서학회지
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• 제31권1호
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• pp.6-11
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• 2022

To date, various techniques have been utilized to assess the contractility of cardiomyocytes and their response to drug-induced toxicity. However, these techniques are either invasive or involve complex fabrication methods and expertise. Here, we introduce the use of video-based analysis software to track the motion of cardiomyocytes and assess their contractility. The software, called "Tracker", is freely available and this is the first attempt at using it for cardiac contractility measurement. We used the software to measure the contractile properties of cells cultured on a rigid substrate and two flexible polydimethylsiloxane (PDMS) substrates having different elastic moduli day-wise up to eight days. Contractility was found to be highest in the most flexible substrate. Subsequently, the cardiotoxicity response of the cells on three different substrates was analyzed with verapamil. It was observed that the cells on rigid substrate were primarily affected by drug-induced toxicity, while the drug had a lesser impact on cells on the more flexible PDMS substrate. Evidently, the flexible substrate aided the maturation of cells and had lower drug toxicity, while the cells on PS could not fully mature. The assessment of cardiomyocytes using "Tracker" proved to be simple and reliable.