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.

性別 및 年齡에 따른 體格과 體力의 特性과 變化에 關한 縱斷的 硏究Ⅱ : Emphasised on College Men of Department of Physical Education 體育專功 大學生을 中心으로

金尙國,姜東洹,張周鎬,金昇一,徐再均,金耕知,孫斗玉,鮮于攝,崔榮烈,尹宇相,金亨燉,方永鎭,朴英震,柳在忠 慶熙大學校 體育科學大學 1989 體育科學論叢 Vol.- No.2

The purpose of this study was to compare the characteristics, change in physique and physical function of college students majoring physical education and Taekwondo (454 males and 64 females of age groups ranging from 18 to 26). The results are as following: 1. The male group of 23yrs old in physical education showed highest values in 7 items(Weight, Chest Girth, Fore Arm Girth, Thigh Girth, Calf Girth, Scapular Skinfold Thickness and Suprailiac Skinfold Thickness). 2. In the Physical function, the male group of 18yrs old showed highest values in Power, Flexibility, and then 21yrs old at Back Strength, Vital Capacity, and 23yrs old at Grip Strength, and 25yrs old at Blood Pressure, respectively. 3. In the physique, the male group of 22yrs old showed highest values in Weight, Chest Girth, Thigh Girth, Calf Girth, and then 24yrs old Upper Arm Girth, Fore Arm Girth, and 19yrs old at Height, Upper Limb Length, respectively. 4. In Physical Function, the 22yrs old showed highest values in Back Strength, Vital Capacity, and then 23yrs old at Side Step, Trunk Extension, but 18yrs old showed lower Values in Grip Strength, Side Step, Vital Capacity and Blood Pressure. 5. The female group of 22yrs old showed highest values in 8 items(Height, Sitting Height, Waist Girth, Upper Limb Length, Lower Limb Length, Skinfold Thickness), and then 18yrs old at 5 items (Weight, Upper Arm Girth, Fore Arm Girth, Thigh Girth, Calf Girth), respectively. 6. In the physical function, the 22yrs old showed highest Values in Grip strength, Back Strength, Power, 5 Minute Run, and 18yrs old at flexibility, Harvard Step Test, respectively. 7. In the change of the physique for two years(1988-1989) in the male group, majoring Physical education the 22yrs old showed increase in 4 items, and the 20yrs old in 3 items, but 18yrs old showed decrease in 3 items. 8. In the change of the physical function for two years in the male group, the 20yrs old showed increase in 4 items, and the 21, 25, 26yrs old in 3 items, but the 19yrs old showed decrease in 6 items, and 18, 22 yrs old in 5 items, respectively. 9. The change of the physique for two years in all female group, of 18, 19, 20, 21yrs old showed increase in 11 items except Skinfold Thickness. 10. In the change of physical function for two years in female group, the 18yrs old showed increase in 3 items, and then 20yrs old in 5 items, but 19, 22yrs old decreased 12 items, respectively. 11. The highest significant difference in physique between male and female was found in weight(mean Value 17.5%), and the lowest difference was found Thigh Girth, Calf Girth(1,3%), Upper Limb Length, Lower Limb Length(2.5%). 12. The Highest difference in physical function was Strength (mean Value 40%), Vital Capacity (33%), Power(22%), but Lower Trunk Flexion, Foot Balance(3.4%). 13. In the difference of Physique and physical function between physical education major and taekwondo major, the physical education showed higher values in skinfold Thickines (mean Value 16.5%), Weight, Waist Girth(4.7%) and Strength(33%), Endurance(5.6%), but subjects majoring Taekwondo showed higher values in Flexibility and Foot Balance. 14. In all male groups, Waist Girth, Scapular Skinfold Thickness, Back Strength, Sargent Jump, Trunk Extension and Diastolic Blood Pressure were showed a significantly related at 0.001 level.

김소월 「시혼」의 이기론적(理氣論的)고찰

김지혜 ( Ji Hye Kim ),권유성 ( Yu Seung Kwon ) 한국문학언어학회( 구- 경북어문학회) 2010 어문론총 Vol.52 No.-

This study aims at clarifying that Kim, So-Wol`s poetics is based on LiKi(理氣)philosophy. And this is to show the distinction between Western ideas like Romanticism which is accepted by Kim-uk and So-Wol`s traditional poetics. The results are as follows. First, So-Wol is realized paradoxical sense which can find out positive meaning from negative thing and overcome Western dichotomy by LiKijimyo(理氣之妙) principal means that Li(理) as Hyungisanja(形而上者: metaphysical thing) and Ki(氣) as Hyungihaja (形而下者: physical thing)are neither divided nor united. Second, So-Wol emphasizes that immutable character of Sihon(詩 魂) on his poetics because he wants to show Li`s character as inevitable cause and right. As he authorizes Sihon(詩魂) ontological and axiological character of Li, Sihon(詩魂) has Good truth and thereby has good effect for society. Unlike Kim-uk`s romanticism, to display subjectivity on So-Wol`s poetics is based on LiKi philosophy has a effect for society, because the subjectivity has a moral sensibility. Last, like Li and Ki, Sihon(詩魂) is manifested on poetry by Umyoung(陰影), so poetry is valuated by not Sihon but Umyoung. But So-Wol contradicted himself by asserting that Umyoung(陰影) isn`t discussed merits and demerits. This is explained by considering LiKijimyo(理氣之妙). Ki is a manifestation of Li, therefore when we see poetry as Ki with view is based on authenticity, Ki is not a thing of judgement. But when we poetry with view is based on substantiality, Ki is a thing of judgement. In conclusion, So-Wol intended to include not only eternal nature but also substantiality on modern poetry with LiKi(理氣) philosophy.

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Dahae Lee,Ki Sung Kang,Jae Sik Yu,Jung-Yoon Woo,Gwi Seo Hwang,Dae-Woon Eom,Seung-Hoon Baek,Hye Lim Lee,Ki Hyun Kim,Noriko Yamabe 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by 60mM FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with 60mM FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by 60mM FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Lee, Dahae,Kang, Ki Sung,Yu, Jae Sik,Woo, Jung-Yoon,Hwang, Gwi Seo,Eom, Dae-Woon,Baek, Seung-Hoon,Lee, Hye Lim,Kim, Ki Hyun,Yamabe, Noriko The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.3

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by $60{\mu}M$ FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with $60{\mu}M$ FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by $60{\mu}M$ FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

함암요법으로 골수기능이 억제된 악성종양환자에서 rhG-CSF의 임상적 효과

김원민,서영환,조경상,유병전,김상도,이승일,정춘해 朝鮮大學校 附設 醫學硏究所 1992 The Medical Journal of Chosun University Vol.17 No.2

We have studied the efficacy of rhG-CSF in patients with non-hodgkin's lymphoma, acute leukemia, and small cell lung cancer undergoing anticancer chemotherapy. These patients were below leukocyte count 3,000 cubic millimeter due to myelosuppression induced by the first cycle of intensive chemotherapy. Treatment with rhG-CSF (100㎍ per square meter of body surface area per day in a 30-minute intravenous infusion) was begun two days and for 14 consecutive days after the end of the second cycle of chemotherapy. The results were as follows. 1. The onset of myelosuppression was 6 days after chemotherapy, and the onset of recovery was 16.7 days after chemotherapy, and the duration of granulocytopenia was 10.7 days in patients with malignant tumor during contrast period. 2. The duration of granulocytopenia was shortened 5.2 days in patients administered rhG-CSF than without rhG-CSF, and we observed the shortest duration of granulocytopenia with increasing granulocyte in patients with small cell lung cancer. 3. Observing the differential count of leukocyte checked the highest level of leukocyte in contrast and rhG-CSF period, the persentage of neutrophil was increased in patients with acute leukemia and small cell lung cancer during rhG-CSF period, but not increased in patients with non-hodgkin's lymphoma. 4. rhG-CSF was not influenced on liver faction, renal fuction, uric acid, and glucose metabolism, also had no effect on recovery of platelet. In conclusion, rhG-CSF can be administered to patients with hematologic or nonhematologic malignant tumor that myelosuppression induced by anticancer chemotherapy result in shortening the duration of granulocytopenia and increasing the peripheral neutrophil, therefore full dose chemotherapy can be administered on time, and rhG-CSF may reduce the morbidity and mortality of patients with malignant tumor undergoing chemotherapy.

Terfenadine과 Ketoconazole 복용 후 발생된 Torsades de pointes 심실 빈맥증의 치험 1례

김세경,이기중,유승진,박일영,박승현,임근우,이원재,강동헌 대한응급의학회 1995 대한응급의학회지 Vol.6 No.1

Torsades de pointes is a form of polymorphic ventricular tachycardia that is associated with prolongation of the QT interval, characterized by QRS complexes of progressively changing amplitude and contour that seem to revolve around the isoelectric line. The most common cause of Torsades de pointes induced by antiarrhythmic agents, occupying in certain drugs or toxin, electrolyte disturbance, congenital QT prolongation syndrome. Cardiotoxicity terfenadine, in overdose a widely used, nonsedating antihistamine, has been reported. Case after administration of terfenadine and ketoconazole causing syncope and torsades de pointes have been reported in recommended dose. We report a case of QT prolongation with torsades de pointes after therapeutic administration of terfenadine, a long acting histamine H1 receptor antagonist, together with ketoconazole, an antifungal preparation. The patient is a 43-year-old female, who experienced palpitation, dizziness and syncopal episoders after coadministration of terfenadine and ketoconazole, for a fungal infection of the skin. The ECG showing typical episodes of torsades de pointes with QT prolongation. Magnesium sulfate was given, torsades de pointes did not recur. The patient was discharged with improved condition.

조직내 컴퓨터 사용 및 태도와 조직, 개인 및 과업 특성들과의 관계

김명언,홍유승 서울大學校 社會科學大學 心理科學硏究所 1996 心理科學 Vol.5 No.1

조직 내에 컴퓨터 시스템이 도입되어 사용되는 목적은 업무수행의 효율성을 증진시키기 위한 것이다. 막대한 예산이 투입되는 조직업무의 컴퓨터 시스템의 효과는 주로 경제적 또는 시간적 측면에서 평가되어 왔다. 그러나, 컴퓨터 시스템의 효과적인 활용은 도입결정 주체인 조직, 사용자인 개인, 그리고 담당업무의 복합적 결과이다. 본 연구에서는 조직, 개인, 그리고 직무특성 변인들이 컴퓨터의 사용량, 사용용도, 태도와 어떠한 관련이 있는지를 살펴보고자 하였다.조직변인으로는 사전교육, 작업환경, 분위기 조성, 제도화의 4가지 변인들을, 개인특성변인으로는 컴퓨터에 대한 사전지식과 친숙도, 내-외 통제형 성격, 모호성에 대한 인내성을 고려하였다. 과업특성변인으로는 과업다양성, 분석 가능성과 Hackman과 Oldham(1980)의 다섯가지 직무특성 차원을 조사하였다. 24명에게 실시된 예비조사를 통해 확정된 설문지조사에 국내 4개 대기업의 사무직 직원 190명이 참여하였다.주요연구결과는 다음과 같다. 첫째, 국내 대기업 사무직 직원들의 컴퓨터 활용수준은 초보적인 수준에 머무르고 있고, 컴퓨터의 사용용도도 문서작성이나 도표그리기 등에 치중되어 있다. 둘째, 컴퓨터의 사용시간에는 (컴퓨터 지향적) 분위기 조성이나 제도화(보상제도와의 연계화)의 영향력이 가장 중요한 것으로 나타났다. 셋째, 컴퓨터 시스템에 대한 태도와는 개인특성 변인이 조직변인들보다 밀접한 관련성을 가졌고, 내-외 통제형 성격변인은 컴퓨터의 고난도 활용에 중요한 역할을 하고 있다. 넷째, 직무특성변인들 중 과업다양성, 과업정체성, 피드백 등의 과업특성 변인들은 컴퓨터 사용시간과 밀접한 관계를 보이고 있다. 다섯째, 사용용도에 기초한 군집분석결과 전체응답자들은 수동집단, 보통집단, 전문집단으로 분류되었고, 이들 집단 간에는 컴퓨터 사용시간 및 태도, 사전교육, 분위기 조성, 제도화 등의 조직변인에서 차이를 보였다. 이상의 연구결과들은 조직 내의 효과적인 컴퓨터 활용을 위해서는 단순한 기계 장치 도입 이상의 체계적이고 종합적 추진계획이 필요함을 밝혀주고 있다.ABSTRACTThe purpose of introduction and use of computer system in organization is to increase work efficiency. Although effective implementation and use of computer system are influenced by various variables, the aspects of financial and time saving have been mainly considered. However, the effective application of computer system in an organization relies on the interactive results of the organization which is a sole decision maker of the system implementation, the organization member as a user, and the work. The present study was conducted to investigate the relations of computer use and attitude toward computer with three areas of related variables including the characteristics of organization, individuals, and jobs. Organizational variables included computer training, physical work setting, work atmosphere, institutionalization of computer system. Individual difference variables included preknowledge about computer, familiarity with computer, internal-external locus of control, tolerance of ambiguity. Task variety, task analyzability, and Hackman and Oldham' s(1980) 5 core job characteristics were examined as task characteristic variables. 190 white collar workers of 4 large companies participated in this study. The main results of this study were as follows: (1) as a whole, white collar workers of large companies were novices in computer use, who tend to mainly use computer for basic purposes(for example, word processing and spread-sheet work). (2) Both the creation of pro-computer atmosphere and the connection of computer system to reward system were the most important variables in determining the frequency of computer use. (3) Attitude toward computer was more influenced by individual difference variables than by organizational variables. Especially, internal-external locus of control played an important role in adapting new applications. (4) Task variety, task identity, feedback from the job had close relations to computer use. (5) There exist significant differences among three groups, which were obtained via a cluster analysis based on the computer application, in not only organizational variables but also individual variables. These results indicate that more systematic and comprehensive plans are critical for effectively implementing computer systems into organizations.

국제 인적자원관리 전략의 결정요인과 성과 : 한국내 외국인기업을 중심으로

유승훈,윤영득,김종관,김영근 대한경영학회 2003 大韓經營學會誌 Vol.16 No.7

This study explores how the tension between global integration and local responsiveness affects the dimensions and determinants of international human resource strategy. The effects of interorganizational interdependencies, competitive strategies and cultural differences, ownership on the two different dimensions of IHR strategy were studied using a sample of 53 MNCs subsidiaries operating in Korea. The findings for global integration suggest that when a subsidiary is highly dependent on the parent to provide crucial resources. And the findings for local responsiveness suggest that when a subsidiary is highly dependent on the host to provide crucial resources and institution. As for the hypothesized interaction shows a negative, significant relationship between a subsidiary's dependence on host institution and ownership and its localization(b=0.0211, p=0.05). Also between a subsidiary's dependence on host resource and ownership and its localization(b=-0.0113, p=0.1). Accordingly, these insights should prove to be useful to researchers and international human resource managers interested in the formulation and implementation of international human resource strategies.

Umbilicaria esculenta가 생산하는 Depside계 화합물의 구조 및 Phospholipase A₂ 저해활성

김진우,송경식,장현욱,유승헌,유익동 영남대학교 약품개발연구소 1996 영남대학교 약품개발연구소 연구업적집 Vol.6 No.-

Phospholipase A₂(PLA₂) is lipolytic enzyme that has known to be involved in inflammation. In the course of our screening for antiinflammatory compounds from natural products, a compound having PLA₂ inhibitory activities was isolated from the methanol extract of Umbilicaria esculenta. The compound was identified as lecanoric acid based on various NMR studies including DEPT, HETERO-COSY and HMBC experiments. Lecanoric acid inhibited human rheumatoid synovial PLA₂ activity with IC_(50) of 0.17 mM and also exhibited antitumor activity (ED_(50)=2.7μg/ml) against skin tumor cell line (LOX-IMVI).