• Korean Circulation Journal
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• v.48 no.11
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• pp.1014-1024
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• 2018

Background and Objectives: Intense exercise (IE) induced myocardial fibrosis (MF) showed contradictory findings in human studies, making the relationship between IE and the development of MF unclear. This study aims to demonstrate exercise induced MF is associated with cardiac damage, and inflammation is essential to the development of exercise induced MF. Methods: Sprague-Dawley rats were submitted to daily 60-minutes treadmill exercise sessions at vigorous or moderate intensity, with 8-, 12-, and 16-week durations; time-matched sedentary rats served as controls. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum cardiac troponin I (cTnI) concentration. After completion of the exercise protocol rats were euthanized. Biventricular morphology, ultrastructure, and collagen deposition were then examined. Protein expression of interleukin $(IL)-1{\beta}$ and monocyte chemotactic protein (MCP)-1 was evaluated in both ventricles. Results: After IE, right but not left ventricle (LV) MF occurred. Serum cTnI levels increased and right ventricular damage was observed at the ultrastructure level in rats that were subjected to long-term IE. Leukocyte infiltration into the right ventricle (RV) rather than LV was observed after long-term IE. Long-term IE also increased protein expression of proinflammation factors including $IL-1{\beta}$ and MCP-1 in the RV. Conclusions: Right ventricular damage induced by long-term IE is pathological and the following inflammatory response is essential to the development of exercise induced MF.

• Journal of Life Science
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• v.20 no.10
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• pp.1458-1467
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• 2010

The present study was retrospectively designed to define whether preoperative levels of leukocytes and D-dimer are potentially useful factors in predicting perioperative outcomes of coronary heart disease (CHD). There was no relationship between preoperative leukocyte counts (Pre-OP leukocyte) and preoperative D-dimer levels (Pre-OP D-dimer). Pre-OP leukocyte counts each had positive correlation with cardiac troponin-I, creatine kinase-MB or C-reactive protein (cardiac markers) levels at preoperative and postoperative periods. Pre-OP D-dimer levels were positively associated with each cardiac marker at the same periods. Pre-OP leukocyte counts positively related with aspartate aminotransferase and alanine aminotransferase (liver markers), whereas Pre-OP D-dimer level positively or negatively correlated with bilirubin (liver marker), creatinine (renal marker) or glucose levels at preoperative and/or postoperative periods. Pre-OP leukocyte and Pre-OP D-dimer were inversely associated with Pre-OP high density lipoprotein cholesterol levels or left ventricular ejection fraction. Pre-OP leukocyte counts each had positive correlation operation duration and postoperative mechanical ventilation-time (PMVT), whereas Pre-OP D-dimer levels had positive relationship with PMVT, intensive care unit-staying period and hospitalization. The retrospective data suggest that Pre-OP leukocyte and Pre-OP D-dimer levels may be clinically useful factors for predicting perioperative outcomes in patients with CHD.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.493-501
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• 2018

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.283-289
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• 2013

This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/$dt_{max}$) and maximal rate of relaxation (-dP/$dt_{max}$). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

• Clinical and Experimental Reproductive Medicine
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• v.29 no.2
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• pp.139-147
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• 2002

Objective : This study was to establish a reproducible differentiation system from the parthenogenetic mouse embryonic stem (P-mES02) cells into functional cardiomyocytes like as in vitro fertilization mouse embryonic stem (mES01) cells. Materials and Methods: To induce differentiation, P-mES02 cells were dissociated and aggregated in suspension culture environment for embryoid body (EB) formation. For differentiation into cardiomyocytes, day 4 EBs were treated with 0.75% dimethyl sulfoxide (DMSO) for another 4 days (4-/4+) and then were plated onto gelatin-coated dish. Cultured cells were observed daily using an inverted light microscope to determine the day of contraction onset and total duration of continuous contractile activity for each contracting focus. This frequency was compared with the results of DMSO not treated P-mES02 group (4-/4-) and mES01 groups (4-/4+ or 4-/4-). For confirm the generation of cardiomyocytes, beating cell masses were treated with trypsin-EDTA, dispersed cells were plated onto glass coverslips and incubated for 48 h. Attached cells were fixed using 4% paraformaldehyde and incubated with specific antibodies (Abs) to detect cardiomyocytes (anti-sarcomeric ? -actinin Ab, 1 : 100; anti-cardiac troponin I Ab, 1 : 2000) for 1 h. And the cells were finally treated with FITC or TRITC labelled 2nd Abs, respectively, then they were examined under fluorescence microscopy. Results: Rhythmically contracting areas in mES01 or P-mES02 cells were firstly appeared at 9 or 10 days after EBs plating, respectively. The highest cumulative frequency of beating EBs was not different in both treatment groups (mES01 and P-mES02, 4-/4+) with the results of 61.3 % at 13 days and 69.8% at 15 days, respectively. Also, the contracting duration of individual beating EBs was different from minimal 7 days to maximal 53 days. However, DMSO not treated groups (mES01 and P-mES02, 4-/4-) also had contracting characteristics although their frequency was a few compared to those of DMSO treated groups (6.0% and 4.0%). Cells recovered from the spontaneously contracting areas within EBs in both treated groups were stained positively with muscle specific anti-sarcomeric ? -actinin Ab and cardiac specific anti-cardiac troponin I Ab. Conclusion: This study demonstrated that the P-mES02 cell-derived cardiomyocytes displayed similarly structural properties to mES01 cell-derived cardiomyocytes and that the DMSO treatment enhanced the cardiomyocytes differentiation in vitro.

• Journal of Chest Surgery
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• v.31 no.1
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• pp.20-27
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• 1998

It is well known that troponin T(below TnT) is present in the myocardial cells and released during myocardial damage, so it`s very specific enzyme to myocardium. Availability of cardiac specific TnT in assessing perioperatively myocardial damage was evaluated from 34 open heart surgery patients. They consisted of 11 ischemic heart, 13 acquired valvular heart and 10 congenital heart cases. Patients were divided into two groups, group A(patients with myocardial damage) and group B(patients without myocardial damage), according to the symptom of chest pain suspecting angina and the ECG findings of ST segment and T wave changes which show myocardial ischemia and injury. Serum TnT levels were measured by enzyme immunoassay method preoperatively, immediately postoperatively, postoperative day 1, day 2, day 3, and day 7. We observed and analyzed the changes of serum TnT levels in two groups and compared the serum TnT levels with CK-MB levels measured at the same time. In group A, serum TnT levels showed 1.37$\pm$0.26$\mu$g/L, 3.16$\pm$0.66$\mu$g/L, 2.39$\pm$0.74$\mu$g/L, 2.49$\pm$0.76$\mu$g/L, and 1.23$\pm$0.60$\mu$g/L, immediate postoperatively, postoperatively day1, day2, day3, and day7, respectively. It was observed there were significant differences compared with those of group B(0.38$\pm$0.04$\mu$g/L, 0.34$\pm$0.05$\mu$g/L, 0.25$\pm$0.03$\mu$g/L, 0.24$\pm$0.04$\mu$g/L, and 0.11$\pm$0.03$\mu$g/L) during identical periods(P<0.01). Serum CK-MB level in group A significantly elevated to 145.04$\pm$35.08 IU/L on the postoperative day 1 compared to group B(31.28$\pm$5.87 IU/L, P<0.05), However, it stiffly decreased from day 2 and returned to preoperative level at day 3. When serum TnT level more than 1.0$\mu$g/L is thought to reflect myocardial damage, serum TnT had 100% of sensitivity and 87% of specificity in diagnosing the postoperative myocardial damage(p<0.01). I conclusion, serum TnT levels increased significantly at very early stage of myocardial damage and persisted much longer period than CK-MB. This suggests that serum TnT has more advantage and availability in assessing the perioperatively myocardial damage than any other tests.

• Korean Journal of Plant Resources
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• v.25 no.6
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• pp.693-699
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• 2012

This study was conducted to investigate the effects of Woohwangcheungsimweun (ox bezoar), deer antlers, and wild ginseng on induction of cardiomyocyte differentiation using the established mouse embryonic stem (ES) cells. The expression of atrial natriuretic peptide (ANP) was highest in Woohwangcheungsimweun treatment group. The expression of rabbit anti-GATA-4(GATA-4) and troponin (TnI) were highest in wild ginseng and Woohwangcheungsimweun treatment groups, respectively. Fluorescence activated cell sorting (FACS) analysis showed that the expression of ANP was highest in Dimethyl sulfoxide(DMSO) and Woohwangcheungsimweun treatment groups. The expression of GATA-4 was relatively high in wild ginseng treatment group. The expression of TnI was highest in Woohwangcheungsimweun treatment group. In the gene expression analysis, DMSO greatly inhibited GATA-4 expression to 25% of control. Woohwangcheungsimweun treatment caused to increase cTnI and cardiac ANP expression significantly. Wild ginseng extract upregulated GATA-4 gene expression. In conclusion, DMSO widely used as cardiomyocyte differentiation inducer did not show significant effects on the expression of ANP, GATA-4 and TnI in this study. Woohwangcheungsimweun showed upregulation of ANP and TnI expression. Wild ginseng extract showed greater effects than DMSO on GATA-4 expression. These results might suggest that the combination of Woohwangcheungsimweun and wild ginseng extract treatment can be expected to increase expressions of all three genes.

• Biomedical Science Letters
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• v.22 no.1
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• pp.9-17
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• 2016

Unfortunately, the five-year survival rate of lung cancer is relatively low compared with other cancers. Therefore, better predictors are need for prognosis, therapeutic strategy, risk stratification and predicting long-term mortality of lung cancer. Recently, increasing data suggest that Glasgow Prognostic Score (GPS) and procalcitonin levels are useful predictor cancer prognosis. In this study, we retrospectively investigated the correlation of GPS or procalcitonin to clinical variables in patients with pretreatment lung cancer. In 135 patients with pretreatment lung cancer, GPS, procalcitonin, demographic characteristics, hematological, coagulation, biochemical, inflammatory and cardiac markers were measured. Monocyte, eosinophil, basophil, neutrophil to lymphocyte ratio, red cell distribution width (RDW), platelet to lymphocyte ratio, mean platelet volume to platecrit ratio, D-dimer and prothrombin time (PT) levels were higher, whereas mean platelet volume was lower than their normal ranges. Glucose and sodium levels were low, whereas gamma glutamyl transferase (GGT), total bilirubin, creatinine and inorganic phosphorus concentrations were increase compared their normal ranges. Procalcitonin, high sensitivity C-reactive protein and troponin-I concentrations were elevated compared with their normal ranges. GPS had significantly positive or negative relations to cancer stage, hematological, coagulation, biochemical, inflammatory and troponin-I. Based on the data, we suggest that GPS may be a potent and useful predictor for prognosis, therapeutic strategy, risk stratification and predicting long-term mortality of lung cancer.

• Biomedical Science Letters
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• v.16 no.4
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• pp.247-258
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• 2010

The objective of this research was to evaluate the relationships of preoperative (Pre-OP) levels of hematological and biochemical indices to perioperative variables in patients that underwent coronary artery bypass graft surgery (CABG). Pre-OP levels of hematological factors [total white blood cells (T-WBC), erythrocytes, hemoglobin, hematocrit, glycohemoglobin A1c (HbA1c), or platelet] were negatively or positively related with biochemical indices [alanine aminotransferase (ALT), bilirubin, glucose, fructosamine, triglyceride, and high density lipoprotein cholesterol (HDL)]. Pre-OP levels of hematological factors and biochemical indices were negatively or positively correlated with echocardiographic variables. Pre-OP level of HbA1c had a relationship with C-reactive protein. Pre-OP levels of aspartate aminotransferase (AST), ALT, HDL, glucose, fructosamine, or blood urea nitrogen (BUN) were positively or negatively associated with Pre-OP levels of cardiac markers (brain natriuretic peptide, troponin-I, creatine kinase isoenzyme 2, or CRP). Pre-OP levels of hematological factors (excepting T-WBC) related with operation time (OPT), postoperative mechanical ventilation time (POMVT), intensive care unit-period (ICU-period) or hospitalization. Pre-OP levels of AST, ALT, bilirubin, triglyceride, HDL, low dwensity lipoprotein, fructosamine, or BUN were positively or negatively correlated with OPT, graft numbers, POMVT, ICU-period or hospitalization. Retrospective this study reveals that Pre-OP levels of hematological and biochemical markers are associated with echocardiographic variables, several cardiac markers and postoperative outcomes, suggesting that Pre-OP levels of hematological and biochemical markers may be useful predictors for the diagnosis and prognosis of coronary artery disease.

• Biomedical Science Letters
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• v.12 no.3
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• pp.289-301
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• 2006

Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.