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.

최근 5년간 응급실을 내원한 구강악안면외과 환자에 대한 임상적 연구

김종렬,정인교,양동규,박봉욱 대한악안면성형재건외과학회 2001 Maxillofacial Plastic Reconstructive Surgery Vol.23 No.2

his is a clinical study on patients who had visitied the Emergency Room of Pusan National University Hospital and then been treated in the Department of Oral and Maxillofacial Surgery during recent 5 years, from 1992 to 1996. The results were as follow ; 1. The total number of patients was 2,680 and the ratio of male to female was 1.96:1, The highest monthly incidence was shown in September(12.1%) and October(10.5%) and the age distribution peaks was the third decade(24.3%) , followed by the first(23.1%) and the fourth decade(17.2%). 2. Soft tissue injury group(29. 1%) was the most prevalent, followed by tooth injury group(16. 1%), facial bone injury group (16.0%), toothache group(11.2%), socket bleeding group(11.1%), infection group(9.8%) and TMJ dislocation group(5.9%). 3. The percentage of in-patients and out-patient were 21.6% and 78.4%, respectively. The frequent causes of admission were facial bone fracture(73.8%) , infection(20.8%) and soft tissue injury(4.8%) in order. However, soft tissue injury was the most frequent cause in out-patient, followed by tooth injury(20.5%), toothache(14.3%), socket bleeding(14.2%) and TMJ dislocation(7.6%). 4. In the facial bone injury group, the mandibular fractures(70.6%) showed the highest incidence, followed by zygomatic bone and arch fractures(7.5%), maxillary bone fractures(4.0%) and nasal bone fractures(4.0%). 5. In the mandibular bone fracture, the most common location was symphysis(36.7%), followed by the mandibular angles(33.1%) and the condyles(21.8%) 6. The common causes of facial bone fractures were violence, fall and traffic accident in order. 7. The common causes of soft tissue injury were fall down, fight and traffic accident in order and the highest incidence was observed in infants before the age of 10 years(44.0%). 8. In the group of tooth injury, tooth luxation(38.5%) showed the highest incidence followed by tooth fracture(33.2%) and tooth loss(17.1%). The common causes of tooth injury were fall, fight and traffic accident in order. 9. In infected patients group, the ratio of in-patients to out-patients was 1 : 1.28, Buccal(24,7%) and infraorbital space abscess(23.3%) showed the highest incidence. 10. The pain caused by dental caries(39.0%) and pericoronitis(26.6%) showed high incidence in the toothache group. 11. The high incidence was observed during third(34.0%) and fourth (24.5%) decades in TMJ dislocation group. 12. In the group of socket bleeding patients, 92% was post-operative hemorrhage and 8% was accompanied with other systemic hemorrhagic diseases.

흰쥐에서 에스트로젠 결핍이 하악골 골밀도에 미치는 영향

김기현,신상훈,김욱규,박봉수,정인교 대한악안면성형재건외과학회 2002 Maxillofacial Plastic Reconstructive Surgery Vol.24 No.2

The relationship between systemic bone loss(osteopenia) and loss of oral bone has been of considerable recent interest. In dentistry, some investigators have studied using human subjects, but no firm conclusion due to many obstacles have yet been obtained. From these obstacles in the assessment of human subjects, the significance of investigations with overiectomized rats has been proposed recently. Also, in ovariectomized rats, quantitative data on changes in the alveolar bone of mandible and basal bone of mandible using dual-energy x-ray absorptiometry(DEXA) were far fewer. The purposes of this study were to certify systemic estrogen deficiency-induced osteopenia by biochemical markers(serum osteocalcin(OC) & urinary deoxypyridinoline(DPD)) and bone mimeral density(BMD) of femur by DEXA and examine changes in BMD of the rat mandible by DEXA with 24-week-old female Sprague-Dawley rats. Forty eight rats were used in this study and twenty four rats were ovariectomized bilaterally(OVX) to induce systemic osteopenia and remainders were subjected to sham surgery(Sham). The experimental rats were killed at different time interval(1st, 2nd, 3rd, 4th, 6th, 8th, 12th and 16th week) for histologic examination, biochemistry analysis and BMD measurement. The results obtained from this study were as follows: On histological examination, in mandible, early degeneration of periodontal ligament, early bone resorption in alveolar bone and late bone resorption in basal bone were observed. On biochemical analysis, OC and DPD were observed statistically no significancy to predict systemic osteopenia. On DEXA measurement, in OVX group, we observed statistically significant decrease from 3rd week in distal metaphysis, statistically non-significant decrease from 2nd week in alveolar bone of mandible, and statistically significant decrease at 16th week in total mandible. From these results, it could be stated that systemic osteopenia by ovariectomy was early affected in the trabecular bone of femur and alveolar bone of the mandible whereas the total mandible was affected later.

酸性過망간酸鹽法에 의한 化學的 酸素要求量의 比色定量

金奉圭 東亞大學校 大學院 1981 大學院論文集 Vol.5 No.-

Absoption photometric methos have applied to the determinantion of COD substances in the sample solution quickly and accurately in measurement of chemical oxygen demand (COD) by redox titration method. This study is that the reaction is accelerated by heating the solution of 1/100-1/1000N potassium permanganate and is measured the absorbance (As) at the 525nm, for another way, have used the oxalic acid on the standard mateial for the COD of JIS method in the range of 8~80 mg 1 , and is calculated the COD by following equation. COD=1000/V×f×N×a×8 Absorbance and COD were obtained from these experiments were plotted and obtained the calibration curve. In this method, the COD have measured after by adding and mixing 5ml of the solution of sulfric acid(1:3) and 1/100-1/1000N potassium permangate in the sample solution and have made dilute on the fixed volume and have heated, and measured the absorvance decreasign and the COD have been calculated by COD=As/S. The determination of COD in the sample solution proceeded by this method and the COD pbtained through the measured As comparing to the claibration curve. The calivration curve showed the linearity against the volume of COD at the 0~32mg 1 and the lowest limiting of detection was the COD value at the 8.0mg 1 . This COD values are agreed with in the range of ±0.6-20% error comparing the COD values by JIS method.

금강 및 만경강 상류의 식물플랑크톤 군집구조와 동태

김백호,최민규,정연태,이종빈,위인선,길봉섭 원광대학교 환경과학연구소 1997 環境科學硏究誌 Vol.6 No.1