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>

측뇌실내 종괴의 감별진단 및 수술적 치료

김동규,김봉수,이상형,심기범,왕규창,정희원,김현집,조병규,최길수,한대희 대한신경외과학회 1993 Journal of Korean neurosurgical society Vol.22 No.2

We present a series of 42 patients with the lateral ventricular mass lesions who underwent operative removal between 1979 and 1992 at the Seoul National University Hospital. These lesions included 29 tumors, 10 benign cysts and 3 arteriovenous malformations. There were 20 lesions in the trigone, 14 in the frontal horn, 6 in the body, and 2 in the temporal horn. Together with the age of the patient, the location in the lateral ventricle and the CT or MR patterns, the range of the differential diagnosis of the lesions can be narrowed. The mass were removed by various surgical approaches ; 11 by the middle frontal gyrus, 10 by the superior parieto-occipital, 13 by the middle temporal gyrus, 4 by the anterior transcallosal, 2 by the posterior transcallosal and 3 by the combined approaches. The superior parieto-occipital approach left postoperative morbidities in 64% and other approaches in 20 to 25% of the cases. These morbidities included hemiparesis, hemianopsia, aphasia, memory distubance and seizure. Most hydrocephalus disappeared without the shunting procedure after removal of the lateral ventricular mass. The high frequency of postoperative complications in the superior parieto-occpital approach require meticulous consideration in the selection of this approach.

Palmes Tube를 이용한 지역별 NO₂농도와 직종별 NO₂개인 폭로량에 관한 연구

김준연,박순우,김동일,장봉기,정경동,김두희,홍대용,정갑열,김용규,이종섭,유일수,김정만 동아대학교 의과대학 부설 산업의학연구소 1992 산업의학연구소 논총 Vol.- No.1

Indoor air quality is important to human wellbeing because people their spend much of time indoors. Current efforts to reduce ventilation rates in building may conserve energy but may also passibly empair human health and welfare through increased levels of indoor contaminants. Nitrogn dioxide( NO₂)has been regarded as one of the important indoor air pollutants. This report updates the assessment of NO₂concentrations at indoor & vehicle road and personal NO₂exposure levels by job groups in four urban cities. NO₂concentrations were measured using the diffusion tube method on 671 subjects in four cities(Pusan, Taegu, Chinju. Iri) from Dec. 1988 to Feb, 1989 and from Dec. 1989 to Feb. 1990. The results of the study obtained were as follows. Ⅰ. Indoor & vehicle road NO₂levels 1. The mean NO₂level was 37.8±19.6(8∼189)ppb and the highest with 42.2±20.5ppb at Bus & Taxi. 2. The NO₂levels by area were as follows: Pusan city, 38.3±20.3ppb: Taegu city, 41.1±17.6ppb: Chinju city, 33.0±19.4ppb: Iri city, 35.8±20.6ppb. 3. The site of the highest NO₂level in Pusan, Taegu, Chinju and Iri city were as follows: Bus & Taxi, 45.4ppb: Vehicle road, 50.8ppb: Bus & Taxi, 37.5ppb: Bus & Taxi. 45.0ppb. Ⅱ. Personal NO₂exposure level 1. The mean level of personal NO₂exposure was 42.7 ±23.1(6∼145)ppb and the highest with 54.0±25.5ppb at office workers. 2. Personal NO₂exposure levels by area were as follows: Pusan city 44.8±20.2ppb: Taegu city, 50.6±24.3ppb: Chinju city, 47.1±23.2ppb: Iri city, 48.0±27.0ppb. 3. The job group of the highest personal NO₂exposure level in Pusan, Taegu, Chinju and Iri city were as follows: Office workers, 50.3ppb: Bus & Taxi drivers, 63.8ppb: Office workers, 59.8ppb: Office workers, 60.0ppb.

독성물질의 세포사 기전 및 세포사 유발물질의 검색법 개발에 관한 연구(Ⅰ) : 독성물질로 인한 파킨슨병 모델에서의 세포사 기전 연구 Study on the cell-death mechanisms of toxin-induced parkinsonism

강태석,김종민,서경원,김영옥,김준규,오재호,이윤동,김규봉,오정자,송연정,임종준,전범석,문전옥,최광식 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

MPTP 독성물질이 도파민성 신경세포에 선택적으로 작용하여 산화성 손상에 의한 신경세포사를 일으키는 것을 이용하여 파킨슨병의 동물모델을 만들고, 이를 통해서 아폼토시스를 비롯한 포사의 기전에 대한 연구 및 너코틴의 신경세포 보호효과 여부를 판정하는 실험을 병행하고자 하였다. 파킨슨꾐의 동물모델을 MPTf 독성 물질을 이용하여 확립하였으며, MPTP(30mgag, i.p.)를 투여한 후 1, 2,3, 4, 5일째 흑질 조직을 채춰하여 tarm로 박걸하여 tyrosine hydroxylase 면역조직화학염색을 수행하여 cell countif우한 결과, control은 57.635ce11s, 1일째 친.OfDells,2일째 57.9±6cells,3일릴 없.3±죠ells, 4일째 49.0츠3cells, 5일째 39.4±Scells료 4, 3일째 뚜렷한 신경세포 수의 감소를 보였다. 신경세포사 기전 규명을 위한 아폼토시스 분걱에서는 벼PTP 투여 후 1, 2, 3, 4, 5일째 조직을 채취하여 Hoechst staining, TUNEL staining을 수곡하였는데 양성 반응을 보인 신경세포는 관찰되지 않아. 아폼토시스로 인한 세포사가 관찰되지 않았다. bIPTP 파킨슨병 동물모델에서 nicotine 보호효과 탐색에 관한 실험은 nicat푸e 0.2mgAg을 5일 퐁안 투여 후 리『fP(30mgag)를 CS7Bt/6 마은스에 복강 내주사로 nicotine과 병용 투여한 후 1, 2, 3, 4, 5일째 뇌를 적출하땄다. 신경세포사가 뚜렷이 관찰되기 시작하는 4, 5일째의 신경세포 수의 감소 정도를 20. 30% 정도 약화시키는 경향을 보였으나, nicotine 보호효과에 대한 추가 실헝이 현재 수행 중에 있다. The cause of Parkinson's disease (PD) is largely unknown. However, free radical toxicit? may plaf a role ip. the degeneration of substantia nigra, which is the Hajorfocus of pathological damages in PD. Recently, a neuroprotective effect of nicotine in PD has been suggested. Therefore, the mechanism of neurodegenerafion and protective potential o( nicotine in PD were investigated in the experimental modeB of Pll using a neurotoxin, C57BL/6mice were administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg,j.p.). The degree of neurodegenerafion was determined by immunohistochemical stainiHB oftyrosine hydroxylase (TH). TH-positive cells on nigral sections were found 56.0 ±4, 57.9 ±6,52.315ce11s, 49.0±3cells, and 39,4±Scells at days 1, 2, 3, 4, 5, respectively (controls : 57.6±Scells). Hoechst and TUNEL staining showed no evidence of apoptosis. The exandnation on themice co-adrunistered with nicotine(0.2mgAg) and MPTP(30mgag) revealed a tendency ofnicotine protective effects. At days 4 and 5, the degree of TH-positive cells was decreased by20-30%, In corclusiffn, the role of apoptosis was not evidenced in this MPTP modeB of PB.The possible proteccon by nicotine should be elucidated with further studies.

老齡者의 建康을 위한 生活習慣 實態調査

申東敏,長鳳愚,李揆文,金賢俊,金昌範,崔宗洙,崔鍾晥,李鍾珏,金圭碩,趙庚旭,金鍾聲,朴鍾振 平生體育硏究所 論文集 1987 平生體育硏究所 論文集 Vol.2 No.-

With a view to examining the habit and method in which old people maintain and improve their health, we consulted 551 men and 444 women who were over 65 years old, and concluded as follows: 1. Habit of eating It's been revealed that most of the old people keep a regular eating hour, control the quantity of meal or eat a little food, and prefer vegetables to meat. 2. Mental health Old people feel the necessity for mental health and most of them (about 80%) keep good mental health without becoming pessimistic. Their chief concenrs have turned out to be about their sons and daughters and their own health and finance. 3. Managing Good Health It has been revelaed that old people do not possess any special kind of secret to keep good health but taking plenty of rest, regular meal, and proper exercise, and many of them (about 60%) have been shown to eat invigorant food that they can easily get around their living area. 4. Physical Functions It has been revealed that many old people are conscious of some symptoms about their parts of body and about to percent of them suffers from neuralgia. Some measures like medical aid especially for old people need to be taken as soon as possible. As we have found that the health-keeping method of old people consists plenty of rest, proper exercise, and appropriate nutrition, we can conclude that the recreatonal and culture facilities and programs for keeping old people in good health should be developed. It is also necessary to study food that contribute to their health and develop ways to get rid of the stresses to which they are exposed in their daily life. Presides, it is natural that government found an administrative department to deal with these matters effectively.

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.

산성 과망간산염법에 의한 화학적 산소 요구량의 측정에 있어서 시료량과 적정액량과의 관계

金奉圭 東亞大學校 大學院 1980 大學院論文集 Vol.4 No.1

JIS K 0102 13의 산성 과망간산염법에 의한 화학적 산소 요구량(COD)의 측정에서 시료량(V)과 과망간산염의 표준용액의 적정액량(a)과의 사이에 경험식(실험식)으로 표시되는 두 대수직선 관계식 log a = log k + n log V …………(1) 이 적정액량(2∼7)㎖의 범위내에서 도시 하수 및 표준물질에 대하여 성립한다는 것이 보고되었다. 이 관계를 실험실에서 행해지고 있는 산화환원적정에 적용하여 보았다. COD를 측정할 때 적정액량 5㎖에 대응하는 시료용액의 부피 V( )를 결정한다는 것은 매우 어려운 일이었다. 본 연구에서는 식(1)에서 유도되는 식 log V( ) = log V + {log(5/a) × log(V'/V)} / log(a'/a)을 이용하여 일정량의 시료량(V)과 적정액량(a)을 2회 측정함으로써 COD( )를 산출하는 데 필요하 시료량(V( ))을 간단하게 산출할 수가 있었다. 그리하여 그 결과를 보고한다. The experimental equation, linearty relationship of two logarithm, log a = log k + n log V that show between the sample volume (V) and the titrant volume (a) of standard solution of potassium permanganate in measurement of Chemical Oxygen Demand (COD) by acidic permanganate method of JIS K 0102 (The examination method of industrial wastewater), is known to correspond to urban sewage and standard solution. This relationship turned to account for the experiment oxidation and reduction titration. .

分娩中 母體 및 臍帶血漿의 β-endorphin 및 Prolactin 値의 變動에 關한 硏究

金鍾洹,李揆玩,姜宰成,洪性鳳 고려대학교 의과대학 1987 고려대 의대 잡지 Vol.24 No.1

β-endorphin is derived from proopiomelanocortin (POMC) and has been implicated as the modulators of pain during labor. Prolactin secretion is increased during pregnancy more than tenfold compared to the non-pregnant levels, but decreased following delivery. This study was undertaken to determine the levels of β-endorphin and prolactin in healthy term pregnant women during the labor, after delivery and their neonates. β-endorphin and prolactin were measured by radioimmunoassay in 22 spontaneous labors and 14 elective cesarean sections during early and late stages of labor, and after delivery. The results obtained are as follows: 1. In cases of spontaneous vaginal delivery, the maternal plasma β-endorphin levels were significantly increased during the first postpartum hour. The maternal plasma prolactin levels were significantly decreased during the late labor than early labor and increased during the first postpartum hour. 2. In cases of elective cesarean sections, the maternal mean plasma level of β-endorphin was significantly lower than spontaneous veginal delivery But there was no difference in maternal mean plasma levels of prolactin between cesarean sections and spontaneous veginal delivery. 3. There was negative correlation between the maternal plasma β-endorphin and prolactin during the late labor. 4. Umbilical arterial β-endorphin levels in newborn infants after spontaneous veginal deliveries were significantly higher than levels in infants born by elective cesarean section. Umbilical arterial prolactin levels in newborn infants after spontaneous vaginal deliveries showed higher than infants born by elective cesarean sections, though there was no statistical significance between them. 5. There was no relationship between the maternal and the umbilical plasma β-endorphin and prolactin level. There was no significant correlation between levels of β-endorphin and prolactin in the cord plasma, fetal weight and placental weight. Present studies suggest that β-endorphin is significantly increased during late labor, but significantly decreased in prolactin during labor due to stress and pain.

데이터 신뢰성을 높이기 위한 CRC BLOCK을 갖는 DSP INTERFACE 설계

김인규,하주영,김주현,강봉순 東亞大學校附設 情報技術硏究所 2005 情報技術硏究所論文誌 Vol.13 No.1

This paper presents the design and implementation of a DSP interface between a rotary machine encoder and DSP The data transfer process has unique data format for harmonious communication between DSP and encoder. In DSP Interface confirm data format that transferred from DSP to encoder and received data. Also it detected occurrence of the error. In order to data detect, As DSP interface has CRC Block that generate promised data and it is possible to more stable communication and we get high data integrity.

玉胚芽油 사용시 小型디젤機關의 運轉性能에 關한 硏究

金泰圭,鄭鳳守,黃光性,金明奎,鄭泰相,愼英喆 진주산업대학교 농업기술연구소 1991 農業技術硏究所報 Vol.4 No.-

The purpose of this study is to figure out the engine performance of corn oil as a diesel engine fuels. corn oil-diesel fuel mixtures in 3 type proportions were tested in a single cylinder diesel test engine. The automatic and successive data for engine performance obtained by microcomputer-measuring system. The results of experiment summarized as follows 1. The viscosity reduction ratio of corn oil was approximately 80% when the temperature raised from 10℃ to 60℃. 2. The maximum torque and maximum power out were decreased with increasing of the amount of corn oil in the mixture, it was considered of the lower specific heat value of corn oil comparative to diesel fuel. 3. In view of fuel consumption and thermal efficiency tested engine with corn oil-diesel fuel blends showed better performance at heavy loads and at high speeds.