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>

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.

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.

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.

2-[(4-Cyanophenyl)amino]-3-chloro-1,4-naphthalenedione(NQ-Y15)의 돌연변이원성

김봉희,정기화,유충규,창동신,이기선,전선덕,소동수,채상호,문창규 한국환경독성학회 2000 환경독성보건학회지 Vol.15 No.4

2-[(4-Cyanophenyl)amino]-3-chloro-1, 4-naphthalenedione (NQ-Y15) was asssayed for its genotoxic potential by using Salmonella typhimurium reversion assay and in vitro chromosome aberration test on Chinese hamster lung cells. In the Ames test, NQ-Y 15 induced his+ revertants of Salmonella typhimurium TA 98 and TA1537, reaching levels twice the negative control values. But, NQ-Y15 induced only his^(+) revertants of Salmonella typhimurium TA1537 more than twice the control values under the condition with metabolic activation system. In the cytogenetic test on chinese hamster lung cells, NQ-Y15 showed significant chromosomal aberrations, but the incidence was significantly reduced in the presence of metabolic activation.

農家所得增大를 위한 土地利用改善에 關한 調査硏究 : -中間地帶를 中心으로-

金文植,朱奉圭 서울大學校 農科大學 1977 서울대농학연구지 Vol.2 No.2

A study on land utilization characteristics has been made chiefly on general description of farming scale, type of farming, land productivity and cropping patterns and so on. However, a study on land utilization related to family labor earnings and economic land rent has not been undertaken. From this point, attempt was made on comparative study between family labor earnings and economic land rent on land utilization. In short, the comparative research result between family labor earnings and economic land rent on land utilization can be summarized as follows. 1) A final goal on land utilization in semi-plain crop region depend upon family labor earning than economic land rent. This means that land utilization is related to subsistence rather than commercial type. 2) There are the differential economic returns by crops. This means that the differential economic returns by crops depend upon the adequate or non-adequate crop choice based on same soil fertility condition. Therefore, it is very important subject on crop choice. 3) As size of farm increase, economic land rent per tanbo is higher than family labor earnings per tanbo. This means that the larger size of farm was adopted in farm machinery. 4) In comparing with family labor earning and economic land rent between single cropping system and double cropping system. However, family labor earnings on double cropping system is higher than single cropping system. 5) It appears thar a larger proportion of semi-plain crop fields is allocated for food crop and single cropping systems, while a smaller proportion of semi-plain crop field is utilized for cash crop and double cropping system. To suggest the further research on land utilization characteristics technical coefficient should be studied and over-all allocation models related to land resource allocation should be developed near future.

忠北大學校 附設 平生體育硏究所

金泰完,金昌範,張鳳愚,金奎鎭 忠北大學校 平生體育硏究所 1985 平生體育硏究所 論文集 Vol.1 No.-

This study is based on the written inquiry about STAI as a measuring tool, which spielberger developed as a anxiety measure to examine what relationship is between the ability in athletic sports and anxiety. The female or male 153 players 918 to 21 years old) became the subject of this written inquire. Trait anxiety was measured by Form x-2 of STAI (State-Trait Anxiety Inventory) while state anxiety was measured by Form x-1. And then, we compared the records in everyday practices with those in games, and used these records as an ability in games. We tried to clarify the relationship between the ability in games and the anxiety. The subjects for the measurement is divided in the three groups of the athletics track sports; a short, a middle, a long-distance race, and the three groups of the athletics field sports; running, jumping and throw. Analysis-the correlation with the state-trait anxiety we measured the records of athletic sports, examined the influence that anxiety exerts on the ability in game, and compared and analyzed the level of anxiety in each event. We have received these results as the following. 1. The influence that anxiety exerts on the athletics records. The events of athletic sports the relation between the anxiety in everday life and the records in that time shows its correlation(r=-0.374, r=-0.361) only in 100m running, but this is not connected with the other events. But except the midium distance events all of the women and men players are connected with the relation detween the anxiety in game and the records. So, because the level of anxiety in the game affects the records in the game, the players need to practice the psychological control of themselves and a little anxiety is needed as a stimulant in everyday practices. 2. Anxiety and records in usual time and game. In events of athletic track sports there was a deep relation, except the event of women distance running (r=0.365), between the anxieties in normal times and in game; (0.50,r<0.70). And the event of men 100M running practicing records in normal times and those in games was not considered here. Therefore, the higher anxiety one has in normal times, the higher his anxiety tends to go up in games; the records in practicing times generally corespond to those in games though such relation is not always applied to the event of 100M running. 3. Anxiety in track and field athletic sports. There was no difference of anxiety in the events of track and field athletic sports between men and women players. Anxiety in games showed the difference in the mean value in all games and their players.

韓國에 있어서의 自然農 調査 硏究

金東俊,朴奉奎 梨花女子大學校 醫科大學 醫科學硏究所 1979 EMJ (Ewha medical journal) Vol.2 No.1

The organic farming has recently been introduced into Korea by the mass media mainly through news papers, TV, and the farmers who are interested in the organic farming abroad. The organic farmers wish to avoid the use of chemical fertilizers and pesticides that demage soil and create toxic effects in the wild life and human body. They are also very much concerned about the adding humus and other organic matters to soil in order to improve fertility, energy conservation, and proper nutrition. The organic farming has been costly conducted in Korea in the workshop of Korea Association of Agricultural Specialists. With the ecological studies, we have learned that there are much differences of the divergence, number of species appearance among perennial and annual herbs, species population fluctuation, and entrophication between the organic and conventional farming. In conventional farming, we found that the mercury and cadmium in the soil of An Yang River area are over 0.2ppm and 2ppm respectively, and the cadmium in the rice over 1ppm, although the heavy metal contents in the irrigation water of rice fields are below the control limit of Korean Government. Even in the organic farming, the cadmium contents in the soil of the sea side are over 1ppm. This shows the cadmium are widely distributed through this country. With the advent of the energy crisis, farmers have been facing at present the shortage of fertilizers and pesticides that require petroleum as a source of both the raw materials and the heat in the process of the manufacture. The organic which the present world has to confront.