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>

Curcumin ameliorates cadmium-induced nephrotoxicity in Sprague-Dawley rats

Kim, Kyeong Seok,Lim, Hyun-Jung,Lim, Jong Seung,Son, Ji Yeon,Lee, Jaewon,Lee, Byung Mu,Chang, Seung-Cheol,Kim, Hyung Sik Elsevier 2018 Food and chemical toxicology Vol.114 No.-

<P><B>Abstract</B></P> <P>Chronic exposure to cadmium (Cd) causes remarkable damage to the kidneys, a target organ of accumulated Cd after oral administration. The aim of the present study was to investigate the protective effect of curcumin against Cd-induced nephrotoxicity. Sprague–Dawley male rats were divided into the following four treatment groups: control, curcumin (50 mg/kg, oral), CdCl<SUB>2</SUB>, (25 mg/kg, oral), and pre-treatment with curcumin (50 mg/kg) 1 h prior to the administration of CdCl<SUB>2</SUB> (25 mg/kg, oral) for 7 days. At 24 h after the final treatment, the animals were killed, and the biomarkers associated with nephrotoxicity were measured. Our data indicated that blood urea nitrogen (BUN) and serum creatinine (sCr) levels were significantly reduced by curcumin pre-treatment in CdCl<SUB>2</SUB>-treated animals. Histopathological studies showed hydropic swelling and hypertrophy of the proximal tubular cells in the renal cortex after Cd treatment. Pretreatment with curcumin ameliorated the histological alterations induced by Cd. The urinary excretion of kidney injury molecule-1 (Kim-1), osteopontin (OPN), tissue inhibitor of metalloproteinases 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL), and netrin-1 significantly reduced by curcumin treatment compared to that in the CdCl<SUB>2</SUB>-treated group. The administration of curcumin provided a significant protective effect against Cd-induced nephrotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Curcumin protects against cadmium-induced renal injury. </LI> <LI> Curcumin reduces urinary excretion of AKI biomarkers. </LI> <LI> Curcumin protects against cadmium-induced apoptosis in the kidney. </LI> </UL> </P>

부산지역 수돗물과 지하수의 중금속 농도

김준연,손지언,김형수,김두희,원미숙,김인식,이혜령 동아대학교 산업의학연구소 2000 산업의학연구소 논총 Vol.- No.5

This study investigated mean airborne CO concention of 15 workplaces, suspected of CO exposure and conducted self-reported questionnaire completion and indirect COHb concentration measure using Micro II Smokerlyzer to healthy 702 adult subjects from 1999 May to 1999 September in order to find a relation of CO exposure and occupational factors, socioeconomic factors, and health related behaviors and confirm the related conditions in the screening test for CO exposure. The results of this study were summarized as follows : 1. In the CO exposed and non exposed group, COHb concentrations of the smokers were 2.55±0.96% and 2.21±0.97% and that got a statistically significant difference, There were not statistically significant differences in the age and total smoking index. Passed times after the last smoking, Working time/day, and working duration were statistically significant difference (p〈0.05). 2. In the CO exposed and non exposed group, COHb concentrations of non-smoking group were 0.94±0.35% and 0.68±0.47% and that got a statistically significant difference. There were not statistically significant differences in the age and working duration but Working time/day was a statistically significant difference(p〈0.05). 3. In the CO exposed group, r-square of multiple regression of the smokers was 38.5 % and passed time after the last smoking, working time/day, and job category were statistically significant differences (p〈0.05). And r-square in the CO non-exposed group was 38.3 % and age, passed time after the last smoking, and total smoking index were statistically significant difference. 4. In the CO exposed group, r-square of multiple repression of the non-smokers was 66.3% and job category and airborne CO concentration were statistically significant differences(p〈0.05). But r-square of non-smokers in the CO non-exposed group was 1.0% and there was not a statistically significant difference(p〈0.05). 5. In the smokers of CO exposed and non exposed groups, relation of COHb concentration and passed time after the last smoking was expressed as exponential function, Y = 2.9182e-0.0083x and r-square of this function was 37.4%. Therefore it was more than 150 minutes that passed time after the last smoking was when COHb concentrations were measured as less than 1%. In conclusion, variable, that was statistically significant to COHb concentraion in the both CO exposed and non-exposed smokers, was a passed time after the last smoking. We suggest that you have to restrict the smoking of smokers at least 150 minutes in the exposed and non exposed group before COHb concentration measure in order to exclude smoking effects

Assessment of In Vitro Assay System for Thyroid HormoneDisruptors Using Rat Pituitary GH3 Cells

Hee Jin Kim1,Hae Young Park1,Jeonga Kim1,Il Hyun Kang2,Tae Sung Kim2,Soon Young Han2,Tae Seok Kang2,Kui Lea Park2,Hyung Sik Kim1 한국독성학회 2006 Toxicological Research Vol.22 No.4

The development of in vitro assays has been recommended to screening and test-ing the potential endocrine disruptors (EDs). These assay systems focus only on identifying thethe thyroid hormone (TH) disruptors. The aim of this study was to evaluate a test system to detectTH disruptors using rat pituitary tumor GH3 cells. The test system is based on the TH-dependentincrease in growth rate. As expected, L-3,5,3-triiodothyronine (T3) markedly induced a morphologicalchange in GH 3 cells from flattened fibroblastic types to rounded or spindle-shaped types. T3 stimu-lated GH3 cell growth in a dose-dependent manner with the maximum growth-stimulating effect9 M. In addition, T3 increased the release of growth hor-mone and prolactin into the medium of the GH3 cells culture. Using this assay system, the TH-dis-rupting activities of bisphenol A (BPA) and its related compounds were examined. BPA,dimethylbisphenol A (DMBPA), and TCI-EP significantly enhanced the growth of GH3 cells in therange of 1 × 10-5M to 1 × 10-6M concentrations. In conclusion, this in vitro assay system might bestandardization before it can be used as a broad-based screening tool.

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

Son, Ji Yeon,Kang, Yoon Jong,Kim, Kyeong Seok,Kim, Tae Hyung,Lim, Sung Kwang,Lim, Hyun Jung,Jeong, Tae Cheon,Choi, Dal Woong,Chung, Kyu Hyuck,Lee, Byung Mu,Kim, Hyung Sik Korean Society of ToxicologyKorea Environmental Mu 2014 Toxicological Research Vol.30 No.2

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

딤플을 적용한 평판에 대한 항력 감소 연구

백부근(Bu-Geun Paik),편영식(Young-Sik Pyun),김준형(Jun-Hyung Kim),김경열(Kyung-Youl Kim),김기섭(Kim1 ?Ki-Sup),정철민(Chul-Min Jung),김찬기(Chan-Ki Kim) 대한조선학회 2012 大韓造船學會 論文集 Vol.49 No.4

한의진단명과 진단요건의 표준화 연구 III : 3차년도 연구결과 보고

최선미,양기상,최승훈,박경모,박종현,심범상,김성우,노석선,이인선,정진홍,이진용,김달래,임형호,김윤범,박성식,송태원,김종우,이승기,최윤정,신순식 한국한의학연구원 1997 한국한의학연구원논문집 Vol.3 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the third year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows : - analyzing and differentiating of epidemic febrile disease - analyzing and differentiating in accordance with the Sasang constitution medicine based on four-type recognition - differentiation of disease according to pathological changes of Chong and Ren channels - standards for diagnosis of women's disease - standards for diagnosis of children's disease - standards for diagnosis of motor and sensor disturbance (-muscle. born, joint, etc.) - standards for diagnosis of neuropsychiatric disease - standards for diagnosis of five sense organ disease - standards for diagnosis of external disease The indivisual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name, notion of diagnosis pattern, index of differentiation of symptoms and signs, the main point of diagnosis, analysis of diagnosis pattern, discrimination of diagnosis pattern, prognosis, a way of curing a disease, prescription, herbs in common use, disease appearing the diagnosis pattern, documents. The standards for diagnosis of each disease was arranged by the diagnostic requirements in the following order : another name, notion of disease, the main point of diagnosis, analyzing and differentiating of disease, analysis of disease, discrimination of disease, prognosis, a way of curing and prescription of disease, disease in western medicine appearing the disease in oriental medicine, documents.

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

Ji Yeon Son,Yoon Jong Kang,Kyeong Seok Kim,Tae Hyung Kim,Sung Kwang Lim,Hyun Jung Lim,Tae Cheon Jeong,Dal Woong Choi,Kyu Hyuck Chung,Byung Mu Lee,Hyung Sik Kim 한국독성학회 2014 Toxicological Research Vol.30 No.2

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

Original Article : Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

( Ji Yeon Son ),( Yoon Jong Kang ),( Kyeong Seok Kim ),( Tae Hyung Kim ),( Sung Kwang Lim ),( Hyun Jung Lim ),( Tae Cheon Jeong ),( Dal Woong Choi ),( Kyu Hyuck Chung ),( Byung Mu Lee ),( Hyung Sik Ki 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

우리나라 文書管理制度에 關한 一般的 考察 : Filing System의 問題意識을 中心으로

金馨植 이화여자대학교 법정대학 비서학과 1982 비서학연구 Vol.- No.2

The purpose of this paper is to study the practice and performance of filing systems exercised currently by business corporations in Korea with reference to the problems of efficiency, organization and paperwork which is essential for effective management operations in the office. To this aim, questionnaires were given to 400 business corporations covering domestic and foreign firms in Seoul. A random sampling of 365 was evaluated. A brief summary of the results is as follows: 1. With rapid economic growth in the past decade. today's business corporations are playing a vital role in the rapid transition to industrialization, and in the process of which our corporations appear to have grown enough to stand up against international competition in the world market. However, it used to be true, even only a decade ago, that large companies' executives as a whole wuold certainly not have thought of any problems arising out of filing and records management. Today, as our corporations grow in the form of modern businesses, the filing system has become an important management operation throughout the country, and executives have to deal with a variety of information, most of which is generated outside the company. Many of our corporations have turned out to be modern establishments to the extent that they have installed the latest large-scale plants and equipment so as to enable them to take advantage of the merits of volume production. Nevertheless, it is a widely accepted fact that despite the progress made on physical expansion, the administrative and management side has not been able to keep pace with the physical progress and has lagged behind owing to a lack of operating experience and managerial techniques in modern management. As a result, the organized filing system in our business society has not been improved. 2. According to the survey, it was revealed that as the problem of communication within business corporations is recognized to be one of the major problems in a highly sophisticated society, great emphasis has been placed on the improvement of the filing system by organizing and controlling files and records managemengt as an integral part of overall rationalization of management operations. The survey also indicates that most corporations, both domestic and foreign alike expressed the urgent need for improvement, of which the bigger the firm the more serious the expression was made, especially in the case of domestic companies. Domestic companies as a whole pointed out a number difficulties such as a lack of systematic filing systems and procedures, ignorance of the basic knowledge of practices, propensity to hoard and not destroy invalid records, shortage of filing cabinets, narrow space in the office room, etc. However, it should be noted at this juncture that there are certain differences between domestic and foreign firms in their expression of difficulties. For example, the former stresses the shortage of cabinets wheras the latter is concerned about not destroying invalid records. 3. The survey shows that, in the case of domestic firms, the importance of systematic filing and records management is widely recognized and accepted in some degree by the executives of most large firms, but they are reluctant to take necessary action, as insisted by clerical workers, because it would incur additional expenses and be a tedious, time consuming task. Therefore, it was concluded that unless an executive makes up his mind to solve the communications problem completely and to confirm whether or not the present system is suitable for the job, the company would have to gamble on guess work without useful information at hand. The time alone that is lost by looking for improperly stored records may cost a company much money. Regardless of the size of company, a standardized filing system should be introduced, (if necessary, step by step) and practices shuld be based on research and be suited to meet the needs of the company in consultation with a professional consultant, because the practice of copying another company's filing system for similar records in their own company is not suitable in some cases and many other technical factors should be taken into account. 4. According to the survey, standardized paper sizes and uniform writing patterns in the business community as a whole, including government groups, should be made as a first step toward the social goal of efficient management throughout our society. In orther to do this, it is desirous for the government to take the initiative to provide the business community with uniform paper sizes and writing patterns similar to those of western countries in collaboration with research institutes, business circles and others. Furthermore, one factor hindering our filing system as pointed out in the survey is the multi-staged approval system, a system peculiar to our business community. This system implies that documents are subject to interim officers review, which often means that it most pass more than half a dozen checkers before they get the final approval of the top manager. This system is time-consuming, and unnecessary paperwork is generated which stems from not delegating responsibilities to subordinates. Finally, it should be kept in mind that even though a filing system is installed it can not be managed without trained personnel. Therefore, the system must be led by a competent administrator and be staffed with trained clerks who understand the full importance of records management. And the community as a whole should cooperate to improve our present filing system and to provide more opportunities to train clerical workers for the betterment of our business society.