• Journal of Veterinary Science
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• v.22 no.4
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• pp.54.1-54.13
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• 2021

Background: Hypoxia causes oxidative stress and affects cardiovascular function and the programming of cardiovascular disease. Melatonin promotes antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase. Objectives: This study aims to investigate the correlation between melatonin and hypoxia induction in cardiomyocytes differentiation. Methods: Mouse embryonic stem cells (mESCs) were induced to myocardial differentiation. To demonstrate the influence of melatonin under hypoxia, mESC was pretreated with melatonin and then cultured in hypoxic condition. The cardiac beating ratio of the mESC-derived cardiomyocytes, mRNA and protein expression levels were investigated. Results: Under hypoxic condition, the mRNA expression of cardiac-lineage markers (Brachyury, Tbx20, and cTn1) and melatonin receptor (Mtnr1a) was reduced. The mRNA expression of cTn1 and the beating ratio of mESCs increased when melatonin was treated simultaneously with hypoxia, compared to when only exposed to hypoxia. Hypoxia-inducible factor (HIF)-1α protein decreased with melatonin treatment under hypoxia, and Mtnr1a mRNA expression increased. When the cells were exposed to hypoxia with melatonin treatment, the protein expressions of phospho-extracellular signal-related kinase (p-ERK) and Bcl-2-associated X proteins (Bax) decreased, however, the levels of phospho-protein kinase B (p-Akt), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (Bcl-2) proteins, and antioxidant enzymes including Cu/Zn-SOD, Mn-SOD, and catalase were increased. Competitive melatonin receptor antagonist luzindole blocked the melatonin-induced effects. Conclusions: This study demonstrates that hypoxia inhibits cardiomyocytes differentiation and melatonin partially mitigates the adverse effect of hypoxia in myocardial differentiation by regulating apoptosis and oxidative stress through the p-AKT and PI3K pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5849-5855
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• 2012

Objective: The purpose of this study was to determine pretreatment effects of moderate-term endurance training before the various dosages (10 and $20{_{mg.kg}}^{-1}$) of DOX on a heat shock protein ($HSP_{70kda}$) and cardiotoxicity in heart tissue. Methods: Forty-eight male rats were randomly assigned to nontraining (NT) and training (T) groups and three subgroups; $DOX{_{10mg.kg}}^{-1}$ and $DOX{_{20mg.kg}}^{-1}$ and saline treatment. The training program included treadmill running between 25-39 min/day and 15-17 m/min, 5 days/wk for 3 wk. Result: DOX administration, in particularly with $20{_{mg.kg}}^{-1}$, caused up-regulation of oxidants and cardiac damage (MDA, CK, CPK-MB and CK/CPK-MB) and down-regulation of cardioprotection ($HSP_{70}$, SOD) markers, as compared to NT+saline group. Pretreatment effect of treadmill running endurance exercise in the presence of DOX with $10{_{mg.kg}}^{-1}$ caused a significant increase in $HSP_{70}$, SOD and a significant decrease in MDA and insignificant decrease in CK, CPK-MB and CK/CPK-MB, in comparison $T+DOX_{10}$ with $NT+DOX_{10}$ group. However, there was no significant difference between $T+DOX{_{10mg.kg}}^{-1}$ and $T+DOX{_{20mg.kg}}^{-1}$ in the aforesaid markers. Conclusion: Dox-induced cardiotoxicity is related to oxidative stress. Our study suggests that pretreatment with endurance exercise may be considered as a potentially useful strategy to improve myocardial tolerance against single dose DOX-induced oxidative damage.

• Journal of KIISE:Software and Applications
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• v.33 no.3
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• pp.335-343
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• 2006

This paper proposes a novel technique of marker-based 2D-3D registration to combine 3D information obtained from preoperative CT images into 2D image obtained from intraoperative x-ray fluoroscopy image. Our method is divided into preoperative and intraoperative procedures. In preoperative procedure, we generate CT-derived DRRs using graphics hardware and detect markers automatically. In intraoperative procedure, we propose a hierarchical two- step registration to reduce a degree of freedom from 6-DOP to 2-DOF which is composed of in-plane registration using principal axis method and out-plane registration using minimal error searching method in spherical coordinate. For experimentation, we use cardiac phantom datasets with confirmation markers and evaluate our method in the aspects of visual inspection, accuracy and processing time. As experimental results, our method keeps accuracy and aligns very fast by reducing real-time computations.

• Journal of Chest Surgery
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• v.36 no.8
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• pp.576-582
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• 2003

During the Off-Pump Coronary Arterial Bypass surgery (OPCAB), the manipulation of the heart can depress cardiac contractility and cause hemodynamic instability. In this study, hemodynamic parameters were measured during operation and the laboratory and clinical data were investigated to evaluate their effects on postoperative outcome. Material and Method: From March 2001 to August 2002, 50 consecutive patients who underwent OPCAB were included in this study. During the same period, total number of CABG was 71 The blood pressure, pulmonary artery pressure, mixed venous oxygen saturation, and cardiac index were measured before manipulation, after application of stabilizer, and at the end of anastomosis. Postoperatively, we measured the cardiac enzymes such as CK-MB, troponin 1 and checked the amount of inotropes required, chest tube drainage, the amount of transfusion, duration of ventilator support, and duration of ICU stay. Result: The number of mean distal anastomoses was 2.8$\pm$0.9 per patient. On elevation and stabilization of the heart, systolic blood pressure was depressed and pulmonary artery pressure was elevated significantly, but during each anastomosis no significant changes were detected. The peak level of cardiac markers was 29.2$\pm$46.7 for CK-MB, 0.69$\pm$0.86 for troponin 1 on postoperative day f. Among the intraoperative hemodynamic parameters, the ischemic change of EKG and bolus injection of inotropes significantly affected the posteroperative cardiac enzymes. But, no difference other than the level of cardiac enzymes between the two groups with or without the ischemic change of EKG and bolus injection of inotropes was noticed. Conclusion: The significant hemodynamic changes occurred when the heart was elevated and stabilized, however during anastomoses there were no significant changes. Serum cardiac enzymes rose significantly in the group that showed the ischemic charge of EKG or needed the bolus injection of inotropes for maintaining hemodynamic stability intraoperatively, but it did not affect the postoperative outcome. In conclusion, the ischemic change of EKG and the need for bolus injection of intropes during operation may be very indicative for probable ischemia.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.278-283
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• 2004

The incidence of a pulmonary leiomyosarcoma as a primary lung tumor is quite rare. We report a case of primary leiomyosarcoma with a cardiac invasion in a 76 year old man. He was admitted due to left anterior chest wall pain for one month. Chest computed tomography showed a $9{\times}8{\times}10cm$ sized, large round mass in the left upper and lower lobes, and an amorphous low density lesion within the left atrium. Chest magnetic resonance imaging showed a large round mass in the left upper and lower lobes with growth into the left atrium. A diagnosis of leiomyosarcoma with prominent osteoclast-like giant cells was made based on the microscopic and immunohistochemical findings of a permanent specimen by explothoracotomy. The pathologic features of the tumor showed round mononuclear hyperchromatic cells and multinucleated giant cells that resembled osteoclasts. The immunohistochemical staining showed that the giant cells are positive for CD68 but negative for the muscle markers while the round cells were positive for the muscle marker. The patient refused further treatment and died after two months.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.278-287
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• 2010

The present study was undertaken to evaluate the protective effect of ethanol (EtAS), ethyl acetate (EAAS) and aqueous (AQAS) extracts of Argyreia speciosa (AS) roots against Isoproterenol (ISO)-induced myocardial infarction in rats. The animals were exposed to isoproterenol (200 mg/kg. s.c) twice at an interval of 24 hrs. Cardioprotective effect was assessed by observing ECG parameters, serum marker enzymes and histopathology of the heart. Pretreatment of EAAS, and EtAS (200 mg/kg) resulted in a significant (P < 0.001) increase in P wave, QRS complex and R-R interval, whereas heart rate, QT interval and cardiac cycle were maintained near to normal values. EtAS and EAAS showed significant (P < 0.05; P < 0.001) reduction in all the tested diagnostic markers compared to ISO treated group. Histological studies on the structural changes of heart tissue supported the protective activity of AS. The result suggest that treatment of AS prior to ISO has a significant role in protecting the animals from ISO induced myocardial infarction.

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.1-11
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• 2009

Since the Committee for Proprietary Medicinal Products (CPMP) of the European Union issued in 1997 a "points to consider" document for the assessment of the potential for QT interval prolongation by non-cardiovascular agents to predict drug-induced torsades de pointes (TdP), the QT liability has become the critical safety issue in the development of pharmaceuticals. As TdP is usually linked to delayed cardiac repolarization, international guideline (ICH S7B) has advocated the standard repolarization assays such as in vitro IKr (hERG current) and in vivo QT interval, or in vitro APD (as a follow up) as the best biomarkers for predicting the TdP risk. However, the recent increasing evidence suggests that the currently used above biomarkers and/or assays are not fully predictive for TdP, but also does not address potential new druginduced TdP due to the selective disruption of hERG protein trafficking to the cell membrane or VT and/or VF with QT shortening. There is, therefore, an urgent need for other surrogate markers or assays that can predict the proarrhythmic potential of drug candidate. In this review, we provide an ideal pre-clinical strategy to predict the potentials of QT liability and lethal arrhythmia of the drug candidates with recent issues in this field in mind, not at the expense of discarding therapeutically innovative drugs.

• Tuberculosis and Respiratory Diseases
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• v.58 no.6
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• pp.562-569
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• 2005

Background : The severity scoring system is useful for predicting the outcome of critically ill patients. However, the system is quite complicated and cost-ineffective. Simple serologic markers have been proposed to predict the outcome, which include troponin-I, lactate and C-reactive protein(CRP). The aim of this study was to evaluate the prognostic values of troponin-I, lactate and CRP in critically ill non-cardiac patients. Methods : From September 2003 to June 2004, 139 patients(Age: $63.3{\pm}14.7$, M:F = 88:51), who were admitted to the MICU with non-cardiac critical illness at Gyeongsang National University Hospital, were enrolled in this study. This study evaluated the severity of the illness and the multi-organ failure score (Acute Physiologic and Chronic Health EvaluationII, Simplified Acute Physiologic ScoreII and Sequential Organ Failure Assessment) and measured the troponin-I, lactate and CRP within 24 hours after admission in the MICU. Each value in the survivors and non-survivors was compared at the 10th and 30th day after ICU admission. The mortality rate was compared at 10th and 30th day in normal and abnormal group. In addition, the correlations between each value and the severity score were assessed. Results : There were significantly higher troponin-I and CRP levels, not lactate, in the non-survivors than in the survivors at 10th day($1.018{\pm}2.58ng/ml$, $98.48{\pm}69.24mg/L$ vs. $4.208{\pm}10.23ng/ml$, $137.69{\pm}70.18mg/L$) (p<0.05). There were significantly higher troponin-I, lactate and CRP levels in the non-survivors than in the survivors on the 30th day ($0.99{\pm}2.66ng/ml$, $8.02{\pm}9.54ng/dl$, $96.87{\pm}68.83mg/L$ vs. $3.36{\pm}8.74ng/ml$, $15.42{\pm}20.57ng/dl$, $131.28{\pm}71.23mg/L$) (p<0.05). The mortality rate was significantly higher in the abnormal group of troponin-I, lactate and CRP than in the normal group of troponin-I, lactate and CRP at 10th day(28.1%, 31.6%, 18.9% vs. 11.0%, 15.8 %, 0%) and 30th day(38.6%, 47.4%, 25.8% vs. 15.9%, 21.7%, 14.3%) (p<0.05). Troponin-I and lactate were significantly correlated with the SAPS II score($r^2=0.254$, 0.365, p<0.05). Conclusion : Measuring the troponin-I, lactate and CRP levels upon admission may be useful for predicting the outcome of critically ill non-cardiac patients.

• Pediatric Infection and Vaccine
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• v.28 no.3
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• pp.173-180
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• 2021

After initial reports of multisystem inflammatory syndrome in children (MIS-C) in April 2020 in Europe, this disease has been known to occur in children with recent history of coronavirus disease 2019 (COVID-19) and most cases have been reported in Europe and the Unites States of America. We report a case of a 14-year-old girl who was diagnosed with MIS-C with acute myocarditis and successfully treated with intravenous immunoglobulin (IVIG), methylprednisolone, and anakinra. At initial presentation, she had persistent high fever, generalized rash, generalized swelling, abdominal pain, and low blood pressure. She showed a remarkably elevated level of inflammation and cardiac enzyme markers and had a previous history of COVID-19 5 weeks before the initial presentation. After extensive work up, other infectious and non-infectious causes were excluded. She was diagnosed with MIS-C and initially treated with IVIG and high-dose methylprednisolone; however, despite treatment, her heart function deteriorated and coronary artery dilatation progressed. Therefore, anakinra, an interleukin-1 receptor antagonist, was administered on hospital day 6, after which her cardiac function exhibited improvement. She was discharged on hospital day 19 without any symptoms, and follow-up echocardiography after 1 month revealed fully recovered heart function with normal coronary arteries.

• Journal of Nutrition and Health
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• v.56 no.4
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• pp.361-376
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• 2023

Purpose: This study evaluates the potential protective effects of hemp (Cannabis sativa L.) seed oil supplementation in rats fed a high-cholesterol diet. Methods: Rats were fed a 1.25% cholesterol diet for 8 weeks, followed by oral administration of either of the two doses of hemp seed oil (HO) (0.5 mL/kg (HOL group) or 1 mL/kg (HOH group) body weight/day) or simvastatin at 10 mg/kg body weight/day. Oxidative stress, lipids, liver enzymes, and renal markers were measured in the serum. Western blot analysis was applied for evaluating the expressions of inflammatory makers. Results: Except for HDL-cholesterol, the altered levels of lipoproteins, aminotransferases, urea, and creatine kinases in hypercholesterolemic rats were significantly corrected by HO administration. Especially, compared to the HOH group, HOL treatment further reduced AST, ALT, creatinine, TC, and LDL-cholesterol levels. Moreover, both the atherogenic index and cardiac risk factor (CRF) in the HOL group were more restrained compared to the HOH group. Increased levels of p-AMPK coincided with the inhibition of SREBP-2 activation which subsequently suppressed the expression of HMGCR. Nuclear factor (NF)-κB activation coincided with the PI3K/Akt pathway activation and the increased phosphorylation of p38; these levels were significantly suppressed by HO treatment. In addition, HO treatment markedly reversed the changes in chemokines such as ICAM-1, VCAM-1, and MCP-1. Histological alterations induced by cholesterol overload in cardiac and hepatic tissues were ameliorated by HO supplementation. Conclusion: Taken together, our results indicate a low concentration of HO demonstrates improved dysfunctions caused by a high-cholesterol diet via inhibition of the PI3K/Akt/NF-κB signaling pathway.