Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

Discordance in Spirometric Interpretations Based on Korean and Non-Korean Reference Equations

Nami Kim,Mi-Hee Park,Se-yeong Kim,Chunhui Suh,Sangyoon Lee,Kun-Hyung Kim,Chae-Kwan Lee,Dae-Hwan Kim,Jong-Tae Lee 대한직업환경의학회 2013 대한직업환경의학회지 Vol.25 No.-

Objectives: Korean regression models for spirometric reference values are different from those of other ethnic groups. The purpose of this study was to evaluate discordance in spirometric interpretations based on using Korean reference equations versus non-Korean reference equations. Methods: Spirometry was performed on 825 Korean male workers from April 2009 to November 2011. The spirometric patterns and disease severity were evaluated using two Korean equations (Choi’s and Lee’s) and three equations for Caucasians (NHANES III, Morris’s, and Knudson’s), and the results of Choi’s equation were compared with the non-Korean equations. The spirometric patterns were defined as normal, restrictive, and mild and moderate obstructive. Results: The mean differences in the FEV1% and FVC% between the two Korean equations were 2.0 ± 1.3% and 3.5 ± 2.2%, respectively. Morris’s equation had the greatest difference in the FEV1% from Choi’s equation: 32.9 ± 8.5%. Knudson’s equation had the greatest difference in the FVC% from Choi’s equation: 10.5 ± 6.5%. Conclusions: The two Korean equations shared similar characteristics of spirometric interpretation. The spirometric interpretations of Choi’s equation were significantly different from those of Morris’s equation and Knudson’s equation.

Medicinal Chemistry : EVALUATION OF CADMIUM-INDUCED NEPHROTOXICITY USING URINARY METABOLOMIC PROFILES IN SPRAGUE-DAWLEY MALE RATS

( Yu Kyung Lee ),( Eun Young Park ),( Shi Won Kim ),( Ji Yeon Son ),( Tae Hyung Kim ),( Won Gu Kang ),( Tae Chun Jeong ),( Kyu Bong Kim ),( Seung Jun Kwack ),( Jae Won Lee ),( Suh Mann Kim ),( Byung M 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-

The aim of this study was to investigate urinary metabolomics profiles associated with cadmium (Cd)-induced nephrotoxicity and their potential mechanisms. Metabolomic profiles were measured by high-resolution 1H-nuclear magnetic resonance (NMR) spectroscopy in the urine of rats after oral exposure to CdCl2 (1, 5, or 25 mg/kg) for 6 wk. The spectral data were further analyzed by a multivariate analysis to identify specific urinary metabolites. Urinary excretion levels of protein biomarkers were also measured and CdCl2 accumulated dose-dependently in the kidney. High-dose (25 mg/kg) CdCl2 exposure significantly increased serum blood urea nitrogen (BUN), but serum creatinine (sCr) levels were unchanged. High-dose CdCl2 (25 mg/kg) exposure also significantly elevated protein-based urinary biomarkers including osteopontin, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecules-1 (Kim-1), and selenium-bingding protein 1 (SBP1) in rat urine. Under these conditions, six urinary metabolites (citarate, serine, 3-hydroxyisovalerate, 4-hydroxyphentllactate, dimethylamine, and betaine) were involved in mitochondrial energy metabolism. In addition, a few number of amino acids such as glycine, glutamate, tyrosine, proline, or phentlalanine and carbohydrate (glucose) were altered in urine afrer CdCl2 exposure. In particular, the metabolites involved in the glutathione biosynthesis pathway, including cysteine, serine, methionine, and glutamate, were markedly decreased compared to the control. Thus, these metabolites are potential biomarkers for detection of Cd-induced nephrotoxicity. Our results further indicate that redox metabolomics pathways may be associated with Cd-mediated chronic kidney injury. These findings provide a biochemical pathway for better understanding of cellulat mechanism underlying Cd-induced renal injury in hunmans.

Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1

<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>

간 세포암에서 VEGF, TGF-β1, b-FGF 발현의 의의

김성용,남충현,주종우,채만규,백무준,이문수,김형철,안현철,김홍수,김창진,김창호 순천향의학연구소 2001 Journal of Soonchunhyang Medical Science Vol.7 No.1

Purpose: Angiogenesis is important for the proliferation and the metastasis of solid tumors. The growth of a solid tumor is widely recognized to depend on the process of neovascularrozation. Without angiogenesis, tumors cease to grow beyond even a few milimeters in diameter. It has been shown that tumor vascular density is an independent prognostic marker in several types of human tumors and is known to correlate with poor prognosis. To date, many angiogenic factors have been identified, such as transforming growth factor-α(TGF-α), transforming growth factor-β(TGF-β), fibroblast growth factor family(FGF), vascular endothelial growth factor(VEGF), platelet derived endothelial cell growth factor(PD-ECGF), tumor necrosis factor-α(TNF-α), and angiogenin. Hepatocellular carcinoma(HCC) is the second most common tumor in Korean males and is known as a typical hypervascular tumor with frequent portal vein invastion. The authors identified the expreesion of VEGF, TGF-β1, and b-FGF in HCC specimens and evaluated the relationship between these growth factors and the clinicopathologic characteristics of HCC. Method: We reviewed the medical records of 30 patients who were diagnosed as hepatocellular carinoma treated with hepatic resection between January 1994 and December 1998 in Soonchunhyang University Chunan Hospital. The selection of the cases was decided according to the condition of paraffin block fixation. The prognostic factors such as age, sex, tumor size, concentration of serum α-fetoprotein, presence of liver cirrhosis, presence of tumor emboli in portal vein, TMN stage, amount of transfusion during the operation, hepatitis B virus(HBV) infection, and Edmonson-Steiner(E-S) grade were investigated. Relationship between the prognostic factors and the immunopathologic expression of the TGF-β1, b-FGF, and VEGF was examined. Result: Thirty patients (24 males, 6 females) were included in the current study. The patient's mean age was 50.6 years and the age ranged from 36 to 65 years. The mean size of the tumor was found to be 5.2cm. All the patients were follewed up for 7 to 63 months. Child's classification A patients were 23(76.7%)cases, B patients were 7(23.3%)cases, and C was none. Immunohistochemical staining of HCC tumor mass in VEGF expression patients were 17(56.7%), b-FGF expression patients were 10(33.3%), and TGF-β1 expression patients were 10(33.3%). VEGF expression or more than one positive expression among the three factors correlated with tumor size and the stage of HCC but did not correlated with other clinicopathological characteristics. TGF-β1 and b-FGF did not correlate with any clinicopathological characteristics. Conclusion: The results suggest that the expression of VEGF or more than one positive expression among the three factors in HCC cells may be a significant prognostic factor of HCC.

관상동맥 질환에서 SDF-1α의 농도

김보영,박용규,박형서,노상필,정승현,이유선,이정우,이재환,최시완,정진옥,성인환 충남대학교 의과대학 의학연구소 2003 충남의대잡지 Vol.30 No.1

Atherosclerosis is now viewed as an inflammatory disease of the vascular system. Expression of several chemokines, including monocyte chemoattractant protein(MCP)-1, MCP-4, RANTES(regulated on activation normal T-cell expressed and secreted), and interleukin-8(IL-8) are increased in human atherosclerotic plaques compared with normal vessels. They are involved in the pathogenesis of atherosclerosis and plaque rupture by activating and directing leukocytes into the atherosclerotic lesions. However, some are involved in homeostatic functions such as normal leukocyte traffic and growth regulation. SDF-la is a multi-functional cytokine that is involved in myelogenesis, hematopoiesis, angiogenesis and injured gastric mucosal regeneration in the gastric ulcer patient. SDF-la is recently shown to be highly expressed in atherosclerotic plaques and a potent platelet agonist. At least in high concentrations, SDF-la may mediate antiinflammatory and matrix stabilizing effects in unstable angina. Many studies are going on to know the function of SDF-la in coronary artery diseases. I investigated the difference of the plasma level of SDF-la between control group and coronary artery disease group. Total 75 subjects were enrolled. The diagnosis of coronary artery disease was confirmed in all patients by coronary angiography. Control subjects in this study were confirmed normal by coronary angiography. Clinical profile and risk factors were also reviewed. Control subjects in this study were 27 (M=10, F=17). Plasma for the study was collected before the angiography and centrifuged. SDF-la analysis was performed by ELISA. Plasma level of SDF-la is significantly increased in patients with stable angina(n=20) and unstable angina group(n=28) compared with healthy control group(n=27). the risk factors do not influence the plasma level of SDF-la in coronary artery diseases. In this study, plasma level of SDF-la is increased in patients with stable angina and unstable angina groups compared with healthy control group(P<0.05). the risk factors do not influence the plasma level of SDF-la in coronary artery diseases.

상완골 간부 골절 불유합의 금속판과 자가골 이식에 의한 치료 결과

이광현,이성필,김형종,이봉근,김주학 대한골절학회 2004 대한골절학회지 Vol.17 No.2

폐내 기관지 낭종

이석열,이숭진,박형주,이철세,이길노,김윤정,나주옥 순천향의학연구소;Soonchunhyang Medical Research Institute 2004 Journal of Soonchunhyang Medical Science Vol.10 No.2

A 33-year-old female was admitted to our hospital due to removal of lung mass which indicentally detected Chest radiography. Chest computerized tomography revealed lung parenchymal cystic lesion. Open thoracotomy was done for diagnosis and therapy. Cystic lesion was communicated to bronchus and wedge resection including cystic lesion was done. Bronchogenic cyst is congenital disease and mainly locate in mediastinum. It is rare in lung parenchyme. Herein we report a case of intrapulmonary bronchogenic cyst.

Mirizzi 증후군의 변형된 분류와 치료

김형철,강길호,채만규,김성용,백무준,이문수,박상흠,이문호,김창호,송옥평,조무식,박희주 순천향의학연구소;Soonchunhyang Medical Research Institute 2000 Journal of Soonchunhyang Medical Science Vol.6 No.1

Purpose : The Mirizzi syndrome is relatively rare and preoperative diagnosis of this disease is difficult. In 1978, Morelli suggested the subclassification of the Mirizzi syndrome into acute or chronic form. We experienced 5 cases of acute form. We analysed clinical features, preoperative radiologic findings and operative findings of 18 cases including acute forms which were diagnosed as Mirizzi syndrome and should suggest the modified classification of Mirizzi syndrome for choice of appropriate treatment. Method : From January 1995 to December 1998, 18 cases, of which 8 cases were diagnosed at Soonchunhyang University Chunan Hospital, and 10 cases were reported in the Korean Journal were retrospectively analysed with regard to clinical features, preoperative radiologic findings and operative findings. According to the clinical features, whole cases were divided into type Ⅰ(acute form) and type Ⅱ(chronic form) and then each type of cases were subclassified according to preoperative radiologic findings and operative findings. Results : Of 18 cases there were 5 cases in type Ⅰ(27.8%), 13 cases in type Ⅱ(72.2%). Type Ⅱb was most common. Type Ⅰa cases were treated only with cholecystectomy. We applied cholecystectomy, T-tube choledochostomy and patch technique in type Ⅰb and thpe Ⅰc cases. Cholectystectomies including removal of gallstones and internal drainage procedures were done in type Ⅱ chronic forms. Conclusion : The acute form(Type Ⅰ) of Mirizzi syndrome was suggested by Morelli might be subclassified into typeⅠa,Ⅰb and Ⅰc following the presence of the necrotic defect in common hepatic duct. Through the modified classification of Mirizzi syndrome based on clinical feature, preoperative radiologic findings and operative findings, we can choice appropriate treatment.

부산지역 수돗물과 지하수의 중금속 농도

김준연,손지언,김형수,김두희,원미숙,김인식,이혜령 동아대학교 산업의학연구소 2000 산업의학연구소 논총 Vol.- No.5

This study investigated mean airborne CO concention of 15 workplaces, suspected of CO exposure and conducted self-reported questionnaire completion and indirect COHb concentration measure using Micro II Smokerlyzer to healthy 702 adult subjects from 1999 May to 1999 September in order to find a relation of CO exposure and occupational factors, socioeconomic factors, and health related behaviors and confirm the related conditions in the screening test for CO exposure. The results of this study were summarized as follows : 1. In the CO exposed and non exposed group, COHb concentrations of the smokers were 2.55±0.96% and 2.21±0.97% and that got a statistically significant difference, There were not statistically significant differences in the age and total smoking index. Passed times after the last smoking, Working time/day, and working duration were statistically significant difference (p〈0.05). 2. In the CO exposed and non exposed group, COHb concentrations of non-smoking group were 0.94±0.35% and 0.68±0.47% and that got a statistically significant difference. There were not statistically significant differences in the age and working duration but Working time/day was a statistically significant difference(p〈0.05). 3. In the CO exposed group, r-square of multiple regression of the smokers was 38.5 % and passed time after the last smoking, working time/day, and job category were statistically significant differences (p〈0.05). And r-square in the CO non-exposed group was 38.3 % and age, passed time after the last smoking, and total smoking index were statistically significant difference. 4. In the CO exposed group, r-square of multiple repression of the non-smokers was 66.3% and job category and airborne CO concentration were statistically significant differences(p〈0.05). But r-square of non-smokers in the CO non-exposed group was 1.0% and there was not a statistically significant difference(p〈0.05). 5. In the smokers of CO exposed and non exposed groups, relation of COHb concentration and passed time after the last smoking was expressed as exponential function, Y = 2.9182e-0.0083x and r-square of this function was 37.4%. Therefore it was more than 150 minutes that passed time after the last smoking was when COHb concentrations were measured as less than 1%. In conclusion, variable, that was statistically significant to COHb concentraion in the both CO exposed and non-exposed smokers, was a passed time after the last smoking. We suggest that you have to restrict the smoking of smokers at least 150 minutes in the exposed and non exposed group before COHb concentration measure in order to exclude smoking effects