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        Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury

        Kim, Kyeong Seok,Yang, Hun Yong,Song, Hosup,Kang, Ye Rim,Kwon, JiHoon,An, JiHye,Son, Ji Yeon,Kwack, Seung Jun,Kim, Young-Mi,Bae, Ok-Nam,Ahn, Mee-Young,Lee, Jaewon,Yoon, Sungpil,Lee, Byung μ,Kim, Hyung TAYLOR & FRANCIS 2017 Journal of Toxicology and Environmental Health Vol.80 No.9

        <P>Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.</P>

      • SSCISCIESCOPUS

        Associations of serotonergic genes with poststroke emotional incontinence

        Kim, Jae‐,Min,Stewart, Robert,Kang, Hee‐,Ju,Bae, Kyung‐,Yeol,Kim, Sung‐,Wan,Shin, Il‐,Seon,Kim, Joon‐,Tae,Park, Man‐,Seok,Cho, Ki‐,Hyun,Yoon, Jin‐ John Wiley Sons, Ltd 2012 INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Vol.27 No.8

        <P><B>Objectives</B></P><P>Poststroke emotional incontinence (PSEI) has been associated with serotonergic dysfunction. Polymorphisms of serotonin transporter (5‐HTT) and serotonin 2a receptor (5‐HTR2a) genes may regulate serotonergic signaling at brain synapses, and this study was to investigate associations with PSEI in an East Asian population.</P><P><B>Methods</B></P><P>In 276 stroke cases, PSEI was diagnosed by Kim's criteria. Covariates included age, gender, education, history of depression or stroke, current depression, and stroke severity and location. Genotypes were ascertained for 5‐HTT gene‐linked promoter region (5‐HTTLPR), serotonin transporter intron 2 variable number tandem repeat, 5‐HTR2a 1438A/G, and 5‐HTR2a 102 T/C. Associations with PSEI were estimated by using logistic regression models, and gene–gene interactions were investigated by using the generalized multifactor dimensionality reduction method.</P><P><B>Results</B></P><P>PSEI was present in 37 (13.4%) patients. The 5‐HTT gene‐linked promoter region <I>s</I>/<I>s</I> genotype was independently associated with PSEI. No associations with STin2 VNTR and 5‐HTR2a genes were found, and no significant gene–gene interactions were identified.</P><P><B>Conclusions</B></P><P>Stroke patients with 5‐HTTLPR <I>s</I> allele had higher susceptibility to PSEI, which underlines the potential role of serotonergic pathways in its etiology. Copyright © 2011 John Wiley & Sons, Ltd.</P>

      • KCI등재
      • C 의과대학에서 문제강의에 대한 학생들의 직접평가가 강의개선에 미친 영향

        김석용, 이상진, 최재운, 김승렬, 김용대, 배성은, 김영규 충북대학교 의과대학 충북대학교 의학연구소 2012 忠北醫大學術誌 Vol.22 No.1

        연구목적: 팀티칭에 근거한 통합강의는 최근 대부분의 의과대학에서 시행되는 강의형태이다. 그러나 기 존에 사용되고 있는 온라인 강의평가 방식은 이러한 강의 특성에서 나타나는 문제점을 파악하기 힘든 점이 있다. 본 대학에서는 팀티칭에 의한 통합강의에서 문제강의를 직접적으로 파악하는 ‘문제강의 직 접평가지’를 개발하였다. 본 연구의 목적은 새로이 개발된 문제강의 직접평가지가 강의개선에 끼친 영 향력을 알아보고자 하는 것이었다. 연구방법: 2007년 2학기부터 2009년 2학기까지 충북대학교 의과대학 1, 2학년을 대상으로 문제강의 직접평가지에 의한 강의평가를 실시하였다. 평가지 질문 중에서 두 가지 객관식 질문에 대한 답변을 분 석대상으로 선택하였다. 질문은 첫째, ‘가장 유익하고 도움이 많이 되었던 강의들은 무엇입니까?’와 둘 째, ‘가장 어렵거나 이해하기 힘들었던 강의들은 무엇입니까?’였다. 강의평가를 실시한 강좌들 중에서 2 년 이상 연속적으로 강좌구조와 평가지의 객관식 질문 형식이 변하지 않은 14개의 강좌를 분석대상으로 하였다. 각각 연도의 평균 긍정비율을 다른 연도의 것과 카이제곱 검정 방법을 사용하여 비교하였다. 결과: 14개의 강좌 중에서 시작연도와 마침 연도 간에 긍정비율이 증가된 경우는 13개 강좌였다. 그 러나 통계적으로 의미가 있는 경우는 5개 강좌에서 나타났다. 결론: 문제강의 직접평가지에 의한 문제강의를 판별해 내는 방법은 단기간에 통합강좌의 개선에 효과 적이다.

      • S-542 Indomethacin aggravates the renal injury by inhibition of adenosine-medited renal protection in AKI

        ( Hyejung Kim ),( Sun-hee Kim ),( Mi Seon Kang ),( Park Seok Ju ),( Min Sung An ),( Ki Beom Bae ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

        Background: Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. AKI emerges in various clinical settings and is complex with outcome linking oxidative stress, inflammation, and cell death. Therefore protection of AKI is still an unsolved problem. Indomethacin is generally known that it inhibits the production of prostaglandins through the inhibition both cyclooxygenase (COX) 1 and 2. Prostaglandins have a wide variety of effect such as regulation of vasodilation, inflammation, regeneration, pain, fever. Therefore effect of indomethacin in AKI is different according to injury model. We investigated whether indomethacin which inhibits the production of prostaglandins aggravate the renal injury in AKI mouse model. Methods: Male C57/BL6 mice (8-10 weeks old, weight 20~25 g) were used. Acute kidney injury is induced by bilateral kidneys pedicle clamping which were subjected to 20 min or 30 min at both kidneys. Mice were treated with indomethacin at before and after injury. Blood and kidney samples were collected at 24 hr after IRI. The expression level of creatinine, N-gal & Kim-1 were detected in serum. And the expression level of PGE2, cAMP and adenosine were detected in kidney. Kidney Injury score were measured by HE staining and TUNEL. Results: In bilateral AKI model, Serum NGAL level and creatinine level were significantly highest in indomethacin treated group compared to non-treated group (NGAL, p<0.05; creatinine, p<0.01). Indomethacin treated group showed significantly more necrosis and apoptosis compared to non-treated group. Furthermore, Indomethacine inhibited the production of prostaglandins, cAMP and adenosine. Conclusions: Indomethacin inhibits adenosine-mediated renal protection by inhibition of prostaglandin production in AKI. Therefore Indomethacin worsened renal injury by inhibition of prostaglandin production in AKI. * This research was supported by a grant of the Korea Health Technology R&D Project through the KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (grant number :H15C2212)

      • Uric acid-lowering effect and intestinal permeability of Kampo medicine, Hachimijiogan, Yokuininto and Goshakusan

        Lee, Seung Hoon,Park, Gunhyuk,Kim, Sung Bae,Oh, Dal-Seok Elsevier 2018 EUROPEAN JOURNAL OF INTEGRATIVE MEDICINE Vol.20 No.-

        <P><B>Abstract</B></P> <P><B>Introduction</B></P> <P>The aim of the present study was to investigate the uric acid-lowering effect of several Kampo (Japanese) herbal medicines (Hachimijiogan, Hangekobokuto, Yokuininto, Keishibukuryogan, Rikunshito, Kakkonto and Goshakusan), in a drug-permeability mimicked model using human intestinal epithelial Caco-2 cells.</P> <P><B>Methods</B></P> <P>Caco-2 cells pretreated with potassium oxonate (PO) were treated with each medicine. The protein levels of xanthine oxidase (XO), glucose transporter 9 (GLUT9), and organic anion transporter 3 (OAT3) were determined via immunoblot analysis and ELISA. Caco-2 cell protein expression was additionally analyzed via immunofluorescence staining. OAT3 transporter uptake assays were measured by HEK293 cells overexpressing system. The levels of renal injury biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were measured.</P> <P><B>Results</B></P> <P>The results indicated that Hachimijiogan, Yokuininto and Goshakusan upregulated OAT3 protein levels (18%, 35% and 34%, respectively) and downregulated GLUT9 protein levels (69%, 49% and 63%, respectively), reversing the effects of PO. In addition, they remarkably inhibited XO activity (40%, 45% and 36%, respectively) as well as inflammatory renal injury biomarkers, NGAL (32%, 51% and 52%, respectively) and KIM-1 protein levels (55%, 41% and 41%, respectively). The nominated herbal medicines can modulate the expression of OATs involved in uric acid uptake, and may have anti-inflammatory actions via the suppression of acute kidney injury biomarkers.</P> <P><B>Conclusion</B></P> <P>Kampo medicines, Hachimijiogan, Yokuininto and Goshakusan were demonstrated to have anti-hyperuricemic effects by suppression of XO activity and regulation of uric acid transport proteins. Furthermore, Hachimijiogan, Yokuininto and Goshakusan were found to reduce the activities of NGAL and KIM-1.</P>

      • KCI등재
      • Mo 화학기상증착에 있어서 불순물 농도에 미치는 증착조건의 영향

        배상석,서성교,홍은식,김승모,조미정,한혜정,이두성,김세훈,민석홍 국립7개대학공동논문집간행위원회 2001 공업기술연구 Vol.1 No.-

        The thermal decomposition process of Mo(CO)_6 on chemical vapor deposition was investigated by analyzing the effects of deposition temperature, pressure, and reaction gas on the phase change of deposited films. Mo_2C was deposited at or below 350℃ due to the incompleteness of thermal decomposition of Mo(CO)_6, but Mo films was successfully deposited at 400℃ or higher temperatures. The variation of deposition pressure did not change the dependence of decomposition process on deposition temperature. The activation energy of surface reaction was 5.8 ㎉/mole.

      • OSI-Internet 관리를 위한 응용 게이트웨이에서의 보안

        배석찬,김태연 群山大學校 1997 論文集 Vol.25 No.-

        As the scale and importance of open distributed system increase, efficient network management has faced difficulties to cope with them. To manage the network efficiently, quite a few network management architectures are proposed and the standardizations are progressed in parallel. So, new paradigms are needed to integrate heterogeneous network management systems and to manage network efficiently. In this thesis, we design and implement the application gateway which transforms the management functions as well as the powerful and flexible services of CMIP. And it supports the delegation of management functions to agent by the manager according to the time-constrained critical situations. We propose the algorithm which transforms the management services. And we also suggest the role based access control policy which controls the accesses to the managed objects between the two domains using different security policies.

      • KCI등재

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