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.

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.

성인형 T세포 백혈병 1례

김영곤,윤상준,장성종,이봉규,박유환,정춘해 조선대학교 부설 의학연구소 1999 The Medical Journal of Chosun University Vol.24 No.1

Adult T-cell leukemia(ATLL) is an endemic disease in southwestern Japan and the Caribbean, but occurs sporadically in most of the world. HTLV-1 is recognized as the etiologic agent of adult T-cell leukemia. ATLL is characterized by leukemia, lymphadenopathy tumor infiltration of the skin, hepatomegaly, hypercalcemia and lytic bone lesions. We report one case of ATLL, in Korea, which was confirmed by typical clinical findings and positive findings of HTLV-1. A 48 year old women, suffering from nausea and vomiting for 5 days, was admitted to hospital on June 1998. At admission, she had cervical lymphadenopathy. Her peripheral leukocytes count was 10.400/mm3 with 1-2% atypical lymphocytes containing pleomorphic and convoluted nucleus. In the bone marrow, a part of nucleated cells were leukemic cells. These abnormal cells had surface markers of helper T-cell(T4) and had positive finding of HTLV-1. Based on above mentioned findings, this case was diagnosed as ATLL. Despite of combined chemotherapy and intensive supportive care, she died of respiratory failure on 61 hospital days.

韓國 西北部 休戰線 近傍 및 서울 近郊에서의 自然農 벼 試驗耕作物 中 重金屬 檢出에 關한 硏究

金東俊,朴奉奎 梨花女子大學校 韓國生活科學硏究院 1976 韓國生活科學硏究院 論叢 Vol.17 No.-

30年間 人間千涉을 받지 않고 自然狀態로 放置되어 있던 西北部 體戰線近方 京畿道 坡州郡 郡內面 白蓮里 및 사람의 千涉이 頻繁한 서울 近郊 高陽郡 中面 白石里에서 農藥과 化學肥料를 施用하지 않고 有機肥料에 依存하는 自然農을 試驗耕作하였다. 이러한 自然農耕作에서 生産된 玄米, 7分搗米, 및 土壤에서 水銀을 檢出하였는데 水銀劑 撒布를 行한 一般農에서 生産된 것에 比하여 有意義한 差가 있었다. 土壤이 水銀에 依하여 汚染되어 있더라도 새로이 水銀劑를 撒布하지 않는 限 穀粒에는 極히 적은 量의 水銀이 含有된다. 穀粒에 含有되어 있는 水銀이나 鉛 같은 重金屬이 搗精過程에서 糠層의 脫落과 더불어 적어진다. 穀粒中의 鉛은 耕耘機나 車輛의 排氣, 灌漑水 等에 起因한 農産物의 重金屬汚染부터 離脫하는 手段으로 自然農을 勸奬한다. 또한 子然農 適格地로서 體戰線 近方 自然地를 推薦한다. The organic farming with compost without the use of chemical fertilizer and pesticide has been tried in Tong Ⅱ Chon near the North-western DMZ and Baik Ma in the suburb of Seoul. The mercury, lead, and cadmium in soil and crops during the farming have been analyzed with the Dithizone method for this study. The contents of heavy metals in soil and crops of the organic farming were found to be significantly less than those of the farming with the pesticides. In spite of the contamination with mercury in soil, the residual toxic mercury was scarcely traceable in the rice grain unless additional agricultural pesticide is applied. The mercury and lead in the rice grain were reduced in the process of milling of the rice-bran. The lead content in the rice was contaminated from the exhaust gas of motor vehicles, and the cadmium from the irrigation water. The organic farming should be considered as the tool of minimizing the contamination of heavy metals from the agricultural pesticides, the exhaust gas of motor vehicles and the irrigation water. The natural field near DMZ that has not been spoiled yet by the environmental pollution should be highly recommended for the organic farming.

난자의 회수시기, BSA, Cysteine 및 Myoinositol이 개 난자의 체외성숙에 미치는 영향

김상근,이봉구,이규승 충남대학교 농업과학연구소 2007 농업과학연구 Vol.34 No.1

This study was carried out to investigate the effects of ovarian estrus stage of oocytes and supplementation of medium with BSA, cysteine and myoinositol on in vitro maturation of canine oocytes. The in vitro maturation(IVM) rate to metaphase II (M II) stage of oocytes recovered from different stage of the reproductive cycle (inactive, follicular and luteal stage) cultured in TCM-199 media were 0.0±0.0%, 10.0±4.1% and 5.7±1.6%, respectively. The IVM rate of oocytes collected from follicular stage was significantly higher in inactive or luteal stage of oocytes. The IVM rates of oocytes recovered from different stage of the reproductive cycle cultured in TCM-199 media with 5% BSA and 0.1 mM cysteine were 0.0+0.0%, 15.8+4.7%, 5.6+1.5%, respectively. The IVM rates of oocytes recovered from different stage of the reproductive cycle cultured in TCM-199 media with 5% BSA and 10 mM myoinositol were 0.0±0.0%, 18.4±4.6% and 5.7±1.9%, respectively. The IVM rate of follicular stage oocytes was significantly higher in oocytes collected from follicular stage and with cultured 5% BSA and 0.1 mM cysteine or 5% BSA and 10 mM myoinositol compared to other experimental group.