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Kim H.S.,Brain Korea 21 Project for Medical Science | Kim H.S.,Anesthesia and Pain Research Institute | Cho J.E.,Yonsei University | Hong S.W.,Kyungpook National University | And 5 more authors.
Physiological Research | Year: 2010

Remifentanil is a commonly used opioid in anesthesia with cardioprotective effect in ischemia-reperfused (I/R) heart. We evaluated the influence of remifentanil on myocardial infarct size and expressions of proteins involved in apoptosis in I/R rat heart following various time protocols of remifentanil administration. Artificially ventilated anesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Rats were randomly assigned to one of five groups; Sham, I/R only, remifentanil preconditioning, postconditioning and continuous infusion group. Myocardial infarct size, the phosphorylation of ERK1/2, Bcl2, Bax and cytochrome c and the expression of genes influencing Ca2+ homeostasis were assessed. In remifentanil-administered rat hearts, regardless of the timing and duration of administration, infarct size was consistently reduced compared to I/R only rats. Remifentanil improved expression of ERK 1/2 and anti-apoptotic protein Bcl2, and expression of sarcoplasmic reticulum genes which were significantly reduced in the I/R rats only. Remifentanil reduced expression of pro-apoptotic protein, Bax and cytochrome c. These suggested that remifentanil produced cardioprotective effect by preserving the expression of proteins involved in anti-apoptotic pathways, and the expression of sarcoplasmic reticulum genes in I/R rat heart, regardless of the timing of administration. © 2010 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic.


Baatarkhuu O.,Yonsei University | Kim D.Y.,Yonsei University | Nymadawa P.,Ulaanbaatar University | Kim S.U.,Ulaanbaatar University | And 8 more authors.
Hepatology International | Year: 2012

Purpose Hepatocellular carcinoma (HCC) is the most common cancer in Mongolia. We aimed to investigate the clinical features, therapeutic modalities, overall survival and prognostic factors for Mongolian patients with HCC. Method One hundred ninety-five patients with HCC were consecutively enroled in our study. Results The mean age was 61.7 years. The most common etiology for HCC was HCV infection (n = 89, 45.6%), followed by HBV infection (n = 67, 34.4%). The mean tumor diameter was 6.0 ± 2.6 cm. Only 29 (14.9%) patients had a single lesion, while 39 (20.2%) had[3 lesions. Extrahepatic metastasis to lung (n = 23), bone (n = 10) and lymph node (n = 3) were detected in 36 (18.5%) patients. Most patients had advanced HCC-88 (45.1%) in stage III and 57 (29.2%) in stage IV. Surgical resection was performed in 27 (13.8%) patients,RFAin 23 (11.8%) andTACEin 107 (54.9%).When all the patients were categorized as 'treated' (n = 156) and 'not treated' (n = 39), the 3-year survival was significantly lower in the 'not treated' group than in the 'treated' group (11 vs. 0%, P<0.001). Tumor diameter (≥3 cm vs. C3 cm), extrahepatic metastasis, TNM stage (I/II vs. III/IV) and treatment (or supportive care) were selected as independent predictors for survival. Conclusions High proportion of patients with HCC in Mongolia is diagnosed at an advanced stage and survival of these patients is lower compared to other countries. A surveillance system and referral policy for high-risk groups should be urgently established and implemented in Mongolia. © Asian Pacific Association for the Study of the Liver 2011.


Kim S.U.,Yonsei University | Kim D.Y.,Yonsei University | Park J.Y.,Yonsei University | Lee J.H.,Yonsei University | And 9 more authors.
Journal of Clinical Gastroenterology | Year: 2010

Goal: This study aimed to enhance the diagnostic accuracy by defining different cutoff liver stiffness measurement (LSM) values according to alanine aminotransferase (ALT) level and combining LSM with noninvasive models in patients with chronic hepatitis B (CHB). Background: Several studies have indicated that ALT influences LSM using FibroScan. Study: The study prospectively enrolled 200 patients (143 men, mean age 45.4y) between June 2007 and November 2008 who had been diagnosed with CHB and underwent both liver biopsy and LSM on the same day. Results: The area under the receiver operating characteristic curves (AUROC) of LSM for predicting cirrhosis in patients with ALT ≤upper limit of normal (ULN) was higher than that of all patients or those with ALT >ULN and ≤2× ULN (AUROC=0.884 vs. 0.849 and 0.867). The cutoff LSM values for ≥F2, ≥F3, and F4 were 6.0, 7.5, and 10.1kPa, respectively, in patients with ALT ≤ULN, whereas they were 8.9, 11.0, and 15.5kPa, respectively, in those with ALT >ULN and ≤2× ULN. The combination of LSM and the age-spleen-platelet ratio index performed the best at predicting cirrhosis, regardless of ALT level (AUROC=0.917 in patients with ALT ≤ULN, 0.909 in those with ALT ≤2× ULN, and 0.894 in all patients). Conclusions: Different cutoff LSM values according to ALT level and combination with age-spleen-platelet ratio index can enhance the performance of LSM in CHB, regardless of ALT level. Copyright © 2009 by Lippincott Williams & Wilkins.


Chung S.,Brain Korea 21 Project for Medical Science | Chung S.,Yonsei University | Ahn D.-S.,Brain Korea 21 Project for Medical Science | Ahn D.-S.,Yonsei University | And 8 more authors.
Experimental Physiology | Year: 2010

Presynaptic imidazoline receptors (Ri-pre) are found in the sympathetic axon terminals of animal and human cardiovascular systems, and they regulate blood pressure by modulating the release of peripheral noradrenaline (NA). The cellular mechanism of Ri-pre-induced inhibition of NA release is unknown. We, therefore, investigated the effect of Ri-pre activation on voltage-dependent Ca2+ channels in rat superior cervical ganglion (SCG) neurons, using the conventional whole-cell patch-clamp method. Cirazoline (30 μm), an Ri-pre agonist as well as an α-adrenoceptor (Rα) agonist, decreased Ca2+ currents (ICa) by about 50% in a voltage-dependent manner with prepulse facilitation. In the presence of low-dose rauwolscine (3 μm), which blocks the α2-adrenoceptor (Rα2), cirazoline still inhibited ICa by about 30%, but prepulse facilitation was significantly attenuated. This inhibitory action of cirazoline was almost completely prevented by high-dose rauwolscine (30 μm), which blocks R i-pre as well as Rα2. In addition, pretreatment with LY320135 (10 μm), another Ri-pre antagonist, in combination with low-dose rauwolscine (3 μm), also blocked the Rα2-resistant effect of cirazoline. Addition of guanosine-5′-O-(2-thiodiphosphate) (2 mm) to the internal solutions significantly attenuated the action of cirazoline. However, pertussis toxin (500 ng ml-1) did not significantly influence the inhibitory effect of cirazoline. Moreover, cirazoline (30 μm) suppressed M current in SCG neurons cultured overnight. Finally, ω-conotoxin (ω-CgTx) GVIA (1 μm) obstructed cirazoline-induced current inhibition, and cirazoline (30 μm) significantly decreased the frequency of action potential firing in a partly reversible manner. This cirazoline-induced inhibition of action potential firing was almost completely occluded in the presence of ω-CgTx. Taken together, our results suggest that activation of Ri-pre in SCG neurons reduced N-type I Ca in a pertussis toxin- and voltage-insensitive pathway, and this inhibition attenuated repetitive action potential firing in SCG neurons. © 2010 The Physiological Society.


Wang H.J.,Brain Korea 21 Project for Medical Science | Lee E.Y.,Yonsei University | Han S.J.,Ajou University | Kim S.H.,Yonsei University | And 7 more authors.
Metabolism: Clinical and Experimental | Year: 2012

Reactive oxygen species (ROS), driven by excessive levels of glucose and free fatty acids, appears to induce cell apoptosis. However, the underlying molecular mechanism of this process remains unclear in cardiac myocytes. We investigated the glucolipotoxicity effects of high glucose and palmitic acid (C16:0) on the rat cardiomyoblast cell line (H9c2) focusing on tumor suppressor p53. Cultured H9c2 rat cardiomyoblasts were exposed to palmitate and /or to an elevated glucose concentration for 18 hours. Only the glucolipotoxic condition of 30 mM glucose in combination with 250μM palmitate resulted in significant generation of ROS and upregulation of p53 which caused to an increased cleavage of caspase-3. On the other hand, the expression of NF-E2-related factor 2 (Nrf2) showed increased tendency while the expression of NAD(P)H: quinone oxidoreductase-1 (NQO1) was decreased. N-acetyl L cysteins and pifithrin-α, an inhibitor of p53 abrogated glucolipotoxicity-induced ROS generation and p53 expression. Chromatin immunoprecipitation analysis revealed that p53 interacted antioxidant responsive elements (ARE)-containing promoter of NQO1. Upregulated p53 counteracted the Nrf2-induced transcription of ARE-containing promoter of NQO1 gene and leaded to decrease in NQO1 expression. We demonstrated that the elevated p53 mediated glucolipotoxicity-induced apoptosis of rat cardiomyoblast cell through dual pathways: stimulating pro-apoptosis signaling as well as suppressing anti-apoptosis pathway of Nrf2-NQO1 signaling. © 2012 Elsevier Inc. All rights reserved.


Lee J.Y.,Brain Korea 21 Project for Medical Science | Moon J.H.,Yonsei University | Park J.S.,Yonsei University | Lee B.-W.,Yonsei University | And 5 more authors.
Diabetes and Metabolism Journal | Year: 2011

Background: Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a major cause of liver-related morbidity and mortality. The underlying mechanisms of disease progression remain poorly understood, and primary therapy of NAFLD is not yet established. We investigated the effects of dietary oleate on the development and progression of NAFLD in a methionine- and choline-deficient (MCD) diet-fed animal model. Methods: A total of 30 C57BL/6J mice were randomly divided into three groups (n=10 in each group) and fed various experimental diets for four weeks: chow, MCD diet, or OMCD (MCD diet with oleate, 0.5 mg/g/day). Liver samples were examined for steatohepatitis and fibrosis parameters and associated genes. Results: Additional dietary oleate dramatically reduced MCD diet-induced hepatic steatosis. Hepatic carbohydrate responsive element-binding protein was overexpressed in MCD diet-fed mice, and dietary oleate prevented this overexpression (P<0.001). Dietary oleate partially prevented MCD diet-induced serum level increases in aspartate aminotransferase and alanine aminotransferase (P<0.001, respectively). The mRNA expressions of hepatic monocyte chemoattractant protein 1, tumor necrosis factor-α and matrix metalloproteinase-9 were increased in MCD diet-fed mice, and this overexpression of inflammatory molecules was prevented by dietary oleate (P<0.001). Hepatic pericellular fibrosis was observed in MCD diet-fed mice, and dietary oleate prevented this fibrosis. Altogether, dietary oleate prevented MCD diet-induced hepatic steatosis, inflammation and fibrosis. Conclusion: Dietary oleate has beneficial effects in every step of NAFLD development and progression and could be a nutritional option for NAFLD prevention and treatment. © 2011 Korean Diabetes Association.


PubMed | Brain Korea 21 Project for Medical Science
Type: Journal Article | Journal: Experimental physiology | Year: 2010

Presynaptic imidazoline receptors (R(i-pre)) are found in the sympathetic axon terminals of animal and human cardiovascular systems, and they regulate blood pressure by modulating the release of peripheral noradrenaline (NA). The cellular mechanism of R(i-pre)-induced inhibition of NA release is unknown. We, therefore, investigated the effect of R(i-pre) activation on voltage-dependent Ca(2+) channels in rat superior cervical ganglion (SCG) neurons, using the conventional whole-cell patch-clamp method. Cirazoline (30 M), an R(i-pre) agonist as well as an -adrenoceptor (R()) agonist, decreased Ca(2+) currents (I(Ca)) by about 50% in a voltage-dependent manner with prepulse facilitation. In the presence of low-dose rauwolscine (3 M), which blocks the (2)-adrenoceptor (R(2)), cirazoline still inhibited I(Ca) by about 30%, but prepulse facilitation was significantly attenuated. This inhibitory action of cirazoline was almost completely prevented by high-dose rauwolscine (30 M), which blocks R(i-pre) as well as R(2). In addition, pretreatment with LY320135 (10 M), another R(i-pre) antagonist, in combination with low-dose rauwolscine (3 M), also blocked the R(2)-resistant effect of cirazoline. Addition of guanosine-5-O-(2-thiodiphosphate) (2 mm) to the internal solutions significantly attenuated the action of cirazoline. However, pertussis toxin (500 ng ml(1)) did not significantly influence the inhibitory effect of cirazoline. Moreover, cirazoline (30 M) suppressed M current in SCG neurons cultured overnight. Finally, omega-conotoxin (omega-CgTx) GVIA (1 M) obstructed cirazoline-induced current inhibition, and cirazoline (30 M) significantly decreased the frequency of action potential firing in a partly reversible manner. This cirazoline-induced inhibition of action potential firing was almost completely occluded in the presence of omega-CgTx. Taken together, our results suggest that activation of R(i-pre) in SCG neurons reduced N-type I(Ca) in a pertussis toxin- and voltage-insensitive pathway, and this inhibition attenuated repetitive action potential firing in SCG neurons.


PubMed | Brain Korea 21 Project for Medical Science
Type: Journal Article | Journal: Knee surgery & related research | Year: 2012

The purpose of this study is to evaluate the effect of change in tibial posterior slope on contact force and ligament stress using finite element analysis.A 3-dimensional finite element model for total knee arthroplasty was developed by using a computed tomography scan. For validation, the tibial translations were compared with previous studies. The finite element analysis was conducted under the standard gait cycle, and contact force on ultra-high molecular weight polyethylene (UHMWPE) and stresses on lateral and medial collateral ligaments were evaluated.The tibial translations showed similarity with previous studies. As the tibial posterior slope angle increases, the contact stress area increased and was well distributed, and the contact force on UHMWPE decreased overall. However, the maximum contact force in the case for 10 case was greater than those for others. The stresses on ligaments were the greatest and smallest in 0 and 10 cases, respectively.The higher tibial posterior slope angle leads to the lower contact stress and more extensive stress distribution overall in posterior-stabilized total knee arthroscopy. However, it does not absolutely mean the smallest contact force. The stresses on ligaments increased with respect to the smaller tibial posterior slope angle.


PubMed | Brain Korea 21 Project for Medical science
Type: Journal Article | Journal: Digestive diseases and sciences | Year: 2010

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. The genetic differences of H. pylori isolates play a role in the clinical outcome of the infection. Inflammatory genes including cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in H. pylori gastritis. Transcription factor AP-1 is composed of c-Fos and c-Jun and mediates inflammation and carcinogenesis. Ras acts as a regulator for AP-1 activation in various cells. We investigated whether H. pylori in a Korean isolate (HP99), a cagA ( + ), vacA ( + ) strain, induces the expression of c-Fos and c-Jun for AP-1 activation to induce COX-2 and iNOS and whether HP99-induced expressions of COX-2 and iNOS are mediated by Ras and AP-1, determined by the expressions of c-Fos and c-Jun, in gastric epithelial AGS cells, using transfection with mutant genes for Ras (ras N-17) and c-Jun (TAM-67). As a result, HP99 induced the expression of c-Fos and c-Jun and the expressions of COX-2 and iNOS in AGS cells. Transfection with mutant genes for Ras or c-Jun suppressed HP99-induced expressions of COX-2 and iNOS in AGS cells. In conclusion, H. pylori in a Korean isolate induces the expression of COX-2 and iNOS via AP-1 activation, which may be mediated by Ras and the expression of c-Fos and c-Jun in gastric epithelial cells.

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