• The Journal of Korean Medicine
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• v.26 no.2 s.62
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• pp.217-230
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• 2005

Objectives: Chungpaesagan-tang (CPSGT), which is frequently used for treating patients of cerebrovascular disease, has not been reported by clinical doctors concerning the effect of neuronal aptosis caused by brain ischemia. To study the effect of CPSGT on focal cerebral ischemia in normal and diabetic rats and SHR, focal cerebral ischemia was induced by transient MCAO, and after onset CPSGT was administrated. Methods: Rats (Sprague-Dawley) were divided into four groups: sham-operated group, MCA-occluded group, CPSGT­administrated group after MCA occlusion, and normal group. The MCA was occluded by intraluminal method. CPSGT was administrated orally twice (l and 4 hours) after middle cerebral artery occlusion. All groups were sacrificed at 24 hours after the surgery. The brain tissue Was stained with $2\%$ triphenyl tetrazolium chloride (TTC) or $1\%$ cresyl violet solution, to examine effect of CPSGT on ischemic brain tissue. The blood samples were obtained from the heart.~. Tumor necrosis $factor-\alpha$ level and interleukin-6 level of serum was measured from sera using enzyme-linked immunoabsorbent assay (ELISA). Then changes of immunohistochemical expression of $TNF-\alpha$ in ischemic damaged areas were observed. Results: In NC+MCAO+CP and DM+MCAO+CP, CPSGT significantly (p<0.01) decreased the number of neuron cells compared to the control group. CPSGT markedly reduced (p<0.01) the infarct size of the forebrain in distance from the interaural line on cerebral ischemia in diabetic rats. CPSGT significantly reduced the $TNF-\alpha$ expression in penumbra region of damaged hemisphere in diabetic rats. Conclusions: CPSGT had a protective effect on cerebral ischemia in SD rats, especially in diabetic rats compared with normal SD rats.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.86-95
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• 2020

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 10⁹ CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA_A receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.2
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• pp.147-157
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• 2021

Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 ㎛ microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.

• Journal of Ginseng Research
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• v.46 no.2
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• pp.255-265
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• 2022

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.27-33
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• 2005

Purpose : To determine incidence, characteristics and risk factors associated with intrauterine intraventricular hemorrhage(IU-IVH) among premature infants. Methods : The medical records of infants with intraventricular hemorrhage(IVH) admitted to the neonatal intensive care unit of Asan Medical Center from January 1999 to June 2003 were reviewed retrospectively. Infants whose IVH with cystic change were detected within five days of life were defined as the IU-IVH group. The control group included those without any IVH. Various maternal and neonatal factors were evaluated between the IU-IVH and control groups, and risk factors for IU-IVH were identified using multiple logistic regression analysis. Results : The incidence of IU-IVH was 49/1024(15.9%). Mothers who are younger, primiparous, use less antenatal steroid, and neonates with greater incidence of neonatal respiratory distress syndrome, had higher incidences of IU-IVH compared to neonates with normal neurosonography. Risk factors associated with IU-IVH included neonatal respiratory distress syndrome and placenta infarct by placenta biopsy. Most infants with IU-IVH were ${\geq}1,501g$, ${\geq}34$ weeks gestational age and had low grade IVH. The size of the cysts associated with IU-IVH remained the same or disappeared in 96 %. IU-IVH does not seem to affect short-term neurodevelopmental outcome although a longer period of follow-up is needed. Conculusion : IU-IVH occurred mostly in ${\geq}1,501g$, ${\geq}34$ weeks infants with grade I IVH without developmental delays. However, the high incidence of total IVH merits more attention in terms of awareness of its existence as an unusual IVH among premature infants.

• Journal of Chest Surgery
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• v.42 no.5
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• pp.576-587
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• 2009

Background: The up-regulation of the nitric oxide (NO)-cGMP pathway might be involved in the change of vascular reactivity in rats 3 days after they suffer acute myocardial infarction. However, the underlying mechanism for this has not been clarified. Material and Method: Acute myocardial infarction (AMI) was induced by occluding the left anterior descending coronary artery (LAD) for 30 min (Group AMI), whereas the sham-operated control rats were treated similarly without LAD occlusion (Group SHAM), The concentration-response relationships for phenylephrine (PE), KCl, acetylcholine (Ach) and sodium nitroprusside (SNP) were determined in the endothelium intact E(+) and endothelium denuded E(-) thoracic aortic rings from the rats 3 days after AMI or a SHAM operation. The concentration-response relationships of PE in the E(+) rings from the AMI rats were compared with those relationships in the rings pretreated with nitric oxide synthase (NOS) inhibitor $N{\omega}$-nitro-L-arginine methyl ester (L-NAME) or the cyclooxygenase inhibitor indomethacin. The plasma nitrite/nitrate concentrations were checked via a Griess reaction. The cyclic GMP content in the thoracic aortic rings was measured by radioimmunoassay and the endothelial nitric oxide synthase (eNOS) mRNA expression was assessed by real time PCR. Result: The mean infarct size (%) in the rats with AMI was $21.3{\pm}0.62%$. The heart rate and the systolic and diastolic blood pressure were not significantly changed in the AMI rats. The sensitivity of the contractile response to PE and KCl was significantly decreased in both the E(+) and E(-) aortic rings of the AMI group (p<0.05). L-NAME completely reversed these contractile responses whereas indomethacin did not (p<0.05). Moreover, the sensitivity of the relaxation response to Ach was also significantly decreased in the AMI group (p<0.05). The plasma nitrite and nitrate content (p<0.05), the basal cGMP content (p<0.05) and the eNOS mRNA expression (p=0.056) in the AMI rats were increased as compared with the SHAM group. Conclusion: Our findings indicate that the increased eNOS activity and the up-regulation of the NO-cGMP pathway can be attributed to the decreased contractile or relaxation response in the rat thoracic aorta 3 days after AMI.

• The Korean Journal of Nuclear Medicine
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• v.30 no.1
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• pp.104-111
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• 1996

We did Tc-99m sestamibi myocardial perfusion SPECT in 36 patients with acute myocardial infarction when they arrived at the emergency room. And we compared myocardial perfusion images with ECG findings. Then we obtained the follows. The myocardial infarction by the obstruction of left coronary descending artery and right coronary artery showed a good concordance in the diagnosis and infarction site between myocardial perfusion images and ECG findings. The 7 patients with myocardial infarction by a left circumflex coronary artery showed a perfusion defect in the lateral wall in myocardial perfusion SPECT images. But 4 patients of them showed ST segment elevation, 2 patients showed ST depression and 1 patient showed normal ECG findings. The diagnostic sensitivity of Tc-99m sestamibi myocardial perfusion SPECT was 100% by a qualified analysis. The perfusion defect site in the myocardial perfusion SPECT were corresponded with the infarct related coronary artery in 31 patients which was diagnosed by coronary angiograpy. The size of perfusion defect in the po1ar map was $31{\pm}18%(M{\pm}SD)$, in the myocardial infarction with left anterior descending coronary arery obstruction, $31{\pm}13% (M{\pm}SD)$ in the myocardial infarction with right coronary artery obstruction and $25{\pm}5.9%(M{\pm}SD)$ in the myocardial infarction with left circumflex coronary artery obstruction. We concluded that emergency myocardial perfusion SPECT images are useful in the diagnose of myocardial infarction and it's very useful when we are difficult to diagnose with ECG like as lateral wall infarction or left bundle branch block.

• Journal of the Korean Society of Radiology
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• v.81 no.3
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• pp.665-675
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• 2020

Purpose This study aimed to identify independent predictors of favorable outcomes associated with emergent carotid artery stenting (CAS) in patients with acute anterior circulation stroke. Materials and Methods This study included 93 patients with acute stroke who underwent emergent CAS to treat stenoocclusive lesions in the cervical internal carotid artery (ICA) within 6 hours of the onset of the associated symptoms. Data were compared between patients with and without favorable outcomes. The independent predictors of a favorable outcome were determined via logistic regression analysis (modified Rankin Scale 0-2 at 90 days). Results Intracranial tandem occlusion was noted in 81.7% of patients (76/93) among which (76/93), 55 of whom underwent intracranial recanalization therapy. Intracranial reperfusion was successful in 74.2% (69/93) and favorable outcomes were noted in 51.6% of patients (48/93). The mortality rate was 6.5% (6/93). In logistic regression analysis, diffusion-weighted imaging-Alberta Stroke Program Early CT Score [odds ratio (OR), 1.487; 95% confidence interval (CI), 1.018-2.173, p = 0.04], successful reperfusion (OR, 5.199; 95% CI, 1.566-17.265, p = 0.007), and parenchymal hemorrhage (OR, 0.042; 95% CI, 0.003-0.522, p = 0.014) were independently associated with a favorable outcome. Conclusion Baseline infarct size, reperfusion status, and parenchymal hemorrhage were independent predictors of favorable outcomes after emergent CAS to treat stenoocclusive lesions in the cervical ICA in patients with acute anterior circulation stroke.