Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury

Kim, Kyeong Seok,Yang, Hun Yong,Song, Hosup,Kang, Ye Rim,Kwon, JiHoon,An, JiHye,Son, Ji Yeon,Kwack, Seung Jun,Kim, Young-Mi,Bae, Ok-Nam,Ahn, Mee-Young,Lee, Jaewon,Yoon, Sungpil,Lee, Byung μ,Kim, Hyung TAYLOR & FRANCIS 2017 Journal of Toxicology and Environmental Health Vol.80 No.9

<P>Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.</P>

당귀 추출물이 liposome 의 안정성 및 유동성에 미치는 영향

배송자,김경옥,노승배 신라대학교 자연과학연구소 1997 自然科學論文集 Vol.4 No.-

인지질 liposome의 안정성과 유동성에 대한 당귀 추출물의 영향을 알아보기 위해 여러 종류의 인지질을 만들어 실험한 결과 PC계 인지질 중 DPPC를 사용하여 인지질 liposome을 만들고, 막안 정성에 대한 영향을 calcein을 봉입한 liposome에 fluorescence self-quenching방법으로 측정하였으며, 막유동성에 대한 영향은 fluorescence polarization방법으로 P값을 측정하였고 그 결과를 다음과 같이 요약한다. 1. Phosphatidylcholine(PC)계 인지질 중 acyl chain의 C수가 14개인 dimyristoyl phosphatidylcholine(DMPC)과 C수가 16개인 dipalmitoyl phosphatidylcholine (DPPC) 및 여러 인지질의 혼합물인 egg phospatidylcholine(egg PC)을 사용하여 liposome 형성의 안정화와 막안정화에 대한 비교 실험을 하였다. 이중 liposome의 안정성이 가장 좋은 것은 egg PC였고, DPPC 그리고 DMPC의 순으로 calcein의 leakage %가 저하하였다. 2. 막 안정성에 미치는 당귀 추출물의 영향 : DPPC liposome에 당귀의 ethyl alcohol과 hexane 추출물을 가한 결과, DPPC만으로 만든 liposome보다 calcein leakage%가 감소하였으며, 추출용매에 다른 막안정화에 미치는 영향은 거의 유사하였다. 이와 같은 경향은 또한 인지질 liposome에 다른 약물을 첨가했을 경우 calcein의 leakage%정도보다 훨씬 그 영향이 탁월함을 보여주었다. 즉 당귀 추출물의 소수성 부분은 인지질 liposome의 상전이온도 이하(Tm. 41∼42℃)인 25℃에서 지질 이중 층의 rigid한 부분의 공간 속으로 깊숙히 들어가 막안정성 증가에 의한 인지질막의 condensing effect에 현저한 영향을 미침을 알 수 있었다. 3. 막 유동성에 미치는 당귀 추출물의 영향 : DPPC로 만든 liposome에 DPH로 labeling한 후 온도 증가에 따른 DPH의 fluorescence polarization값(P)의 측정에서 DPPC만으로 만든 liposome의 경우 상전이온도 이전의 gel 상태에서 상전이온도(phase transition temperature, Tm)로 되면서 P값이 현저히 저하하였으며, 당귀의 ethyl alcohol과 hexane추출물을 농도 별로 첨가했을 때는 35℃에서 시작하여 상전이온도 이전까지 현저히 P값의 저하가 일어남으로서 인지질 막의 유동성 증가를 알 수 있었으며 상전이온도 근처에서는 P값의 저하 경사가 완만해져서 온도의 증가에 따른 P값의 변화는 미미하였으나 상전이온도 이후에서는 DPPC liposome의 P값보다 당귀 추출물 첨가의 경우가 상대적으로 그 정도가 훨씬 증가된 상태였다. 이 결과에서 상전이온도 이전에서의 당귀 추출물의 막유동성 증가 효과를 읽을 수 있었고, 상전이를 전후해서 증가된 유동성은 상전이온도 이후에서는 온도 증가에 따라 미미하였으며, 오히려 상전이온도 이후에서는 DPPC만의 liposome보다 상대적으로 추출물의 농도 증가에 따른 P값의 변화가 미미하여 막유동성의 감소를 볼 수 있었다. 이상의 결과에서 당귀의 ethyl alcohol과 hexane 추출물의 소수성 부분은 DPPC의 상전이온도 이전에서는 인지질 liposome의 이중층으로 깊숙히 들어가서 막안정성과 막유동성을 증가 시키므로써 옛부터 보혈강장 및 정혈제로서 민간약제로 쓰이던 당귀 추출물이 인지질 세포막에 대한 생리적 활성을 일으킬 수 있는 촉진제로서의 가능성을 시사해 주었다고 볼 수 있다. We investigated the effects of the Angelica Radix extract on the physicochemical properties of biological membranes such as membrane stability and fluidity employing the phospholipid liposomal membranes as a biomembrane-mimetic system. The leakage of encapsulated calcein from the liposome and the fluorescence polarization of DPH labelled in the liposomal membrane were employed as the parameters of the stability and fluidity of the liposomal membrance. The results of the experiments showed that the addition of the Angelica Radix extract to the phospholipid exerted some effects stabilizing the barrier function of the membrane and increasing the fluidity of the membrane in proportion to the concentration of additive. These results suggest that the activities of the Angelica Radix extract to enhance stability and fluidity of the liposomal membrane might have implication in their biological activities.

막걸리 농축액의 투여가 흰쥐의 혈중 지질 함량에 미치는 영향

김미향,김원희,배송자 가톨릭대학교 자연과학연구소 2001 自然科學論文集 Vol.9 No.-

동동주, 청맥 농축물의 투여가 흰쥐의 성장률, 혈청 효소활성 혈청 지질에 미치는 영향을 조사하였다. 실험동물의 체중 증가량은 동동주, 청맥 농축물의 농도별 투여가 대조군과 비슷한 경향을 나타내었으므로, 동동주, 청맥의 투여가 성장률에 지장을 주기 않음을 알 수 있었다. 총 콜레스테롤 함량, 중성지질 함향은 DD1군과 CM1군에서 대조군 보다 낮은 경향을 나타냈고, LDL함량은 DD1군에서 대조군 보다 낮은 경향을 나타냈다. 이러한 결과로부터 동동주 8g/kg 투여는 25%(v/v) 에탄올 5g/kg/day 경구 투여가 만성중독을 일으킬 수 있는데 반해 혈중 지질 함량을 감소시키므로 혈중 중성지질 농도 증가로 인한 심질환 예방에 기여 할 것으로 사료된다. Makkoli is a traditional and general alcoholic beverage in Korea. It's brewed from rice, shows an alcohol concentration of about 16%, has a characteristic fragrance, is slightly acidic, and has a sweet taste. Recently, taking these tradition alcoholic beverages are decreased. We examined the effect of Dongdongju and Cheongmaek kinds of Makkoli on serum enzyme activity and lipid concentration in rats. Sparague-Dawley rats were randomly assigned to groups as follows: control group, Dongdongju 8g/kg administered group(DD1), Dongdongju 1.6gkg administered group(DD2), Dongdongju 0.8g/kg administered group(DD3) and Cheongmaek 8g/kg administered group(CM1), Cheongmaek 1.6g/kg administered group(CM2), Cheongmaek 0.8g/kg administered group(CM3). Experimental diets were fed for 6 weeks. The body weight gain, seram enzyme activity and serum lipid values of all groups were compared with control group. There were no differences in growth. Alkaline phosphatase and GPT activities of DD3 and CM2 were lower than control group, but no significant differences. The total cholesterol concentrations of DD1 and CM1 were lower than that of control group. The triglyceride concentration of DD1 and CM1 was the same as results of total cholesterol concentration. These results suggest that Dongdongju and Cheongmaek positively influenced on serum lipid concentration.

炭素纖維板으로 補强한 鐵筋콘크리트보의 構造的擧動에 관한 實驗的 硏究

김하진,고송균,박영배,조창호,김정섭 朝鮮大學校 建設技術硏究所 1998 建設技術硏究 Vol.18 No.1

This study is a part of research to improve the yield strength of concrete structure with a structural damage and conducts the experiment with the variables such as the period of restrengthening of specimen, restrengthening length (1.9m, 1.5m, 1.0m) and restrengthening effect according to restrengthening mehthod of restrengthening materials (nonrestrengthening, Anchor, Angle) to test bending behavior and yield strength performance of reinforced concrete beams restrengthened with carbon fiber laminate. As a result of experiment, in the restrengthening effects by the period of restrengthening, specimen restrengthened before loading, during reloading and after loading show 1.9m, 1.5m and 1.0m respectively, in the restrengthening effects according to restrengthening length, specimen restrengthened with 1.9m, 1.5m and 1.0m show 113.7%, 122.4% and 112.7% and in restrengthening effects according to restrengthening method of restrengthening materials, non-restrengthening and restrengthening in anchor and angle show 113.7%, 115.9% and 184.4% of increase in yield strength respectively. Accordingly, the specimen restrengthened during loading, the specimen with 1.5m of restrengthening and the specimen restrengthened with angle show high restrengthening effects respectively. With the above results, a crack is closed by elastic behavior in the case of test materials, but since in the actual concrete strucutre, a crack is not closed like the specimen during loading, the influence of it on restrengthening should be considered. It is found that although restrengthening effect by the restrengthening length secures a sufficient length, the increase of yield strength by restrengthening cannot be expected when bonded performance is not secured and in deciding restrengthening method of restrengthening materials, the method which have not damage to restrengthening materials and can be integrated with restrengthening materials and structure is effective.

각종 암세포주에 대한 Sb-31^(?)의 항암효과

김삼용,김송배 忠南大學校 癌共同硏究所 1998 癌共同硏究所 硏究誌 Vol.2 No.1

Extracts of P. koreana(SB-Sl_(?)) has been tried as an antitumor agent by traditional medicine practitioner in Korea for the past 30 years. It is a specially prepared extract of P. koreana whose fractions lose efficacy compared to the original mixture. Lee observed substantial antitumor effects and minimal toxicity of SB-31 in sarcoma 180 animal tumor model(unpublished data). For the past 5 ears, there has been dramatic though anecdotal therapeutic outcomes with SB-31 in some advanced stage cancer patients. We evaluated the in vitro antitumor effects of SB-31 against 3 kinds of gastric cancer cells, A549, HeLa and Caski, MCF7, HepG2 and Hep3B and normal mononuclear cells. Cytotoxicity ws evaluated with the Tetrazolium-based colori-metric assay(MTT) after incubation of cancer cells with SB-31. Results; in 3 gastric cancer cells, ID_(50), of SB-31 were 0.16, 0.34 and 0.53mg/ml. Most effective tumor cell kill was achieved after 96 hrs of incubation with SB-31. The ID_(50) values of SB-31 on various cancer cell lines ranged from 0.14 mg/ml to 0.27 mg/ml. Keeping SB-31 ampul in room temperature up to 4 days did not affect the efficacy but the activity decreased after more than 4 days in the ambient temperature. It is concluded that SB-31 is an active antitumor agent without significanct toxicity. The mechanism of action of SB-31 and its toxicity and efficacy should be further evaluated. ◁표 삽입▷ (원문을 참조하세요)

쑥 추출성분의 암세포 증식억제와 Quinone reductase 유도 활성 효과

배송자,박윤자,김미향 가톨릭대학교 자연과학연구소 2001 自然科學論文集 Vol.9 No.-

In this study, Artemisia princeps var. orientalis(AP), the Compositae species, were extracted using methanol(APM) and the extracts was fractionated to five different types which are hexane(APMH), ethylether(APMEE), ethylacetate(APMEA), butanol(APMB) and aqueous(APMA) partition layers. The various partition layers were screened far the cytotoxic effects on HepG2, MCF-7 and C6 cells by MTT assay and for their ability induce quinone reductase(QR) in HepG2 cells. Compared with the other partition layers of AP, the APMEE showed the strongest cytotoxic effects on HepG2, MCF-7 and C6 cells. The quinone reductase(QR) induced activity in HepG2 cells, grown in the presence of APMEE and APMH, were 5.08 and 2.99 times more effective compared with the control value of 1.0 respectively. Therefore, based on these results, the ethylether partition layer(APMEE) of the Artemisia princeps var. orientalis may have that potentially useful cancer chemoprevention effect on the human cancer cells, HepG2, MCF-7 and C6. Key word : Artemisia princeps var. orientalis, MTT assay, quinone reductase(QR)

도라지가 난소를 절제한 흰쥐의 혈 중 지질 함량 변화에 미치는 영향

김미향,김원희,박미라,한희선,배송자 신라대학교 자연과학연구소 2003 自然科學論文集 Vol.11 No.-

This study was designed to observe the effects of the feeding Platycodon grandiflorum A.DC(PG) extract on the improvement of the lipids on serum in ovariectomized rats. To investigate the effects of ethanol extract, Sprague-Dawley female rats were randomly assigned to groups as follows: Sham, OVX-control and ovariectomized rats supplemented with PG at 50㎎/㎏ bw/day. Body weight gain was not significantly different in groups. The levels of total cholestcrol was higher in ovaiectornized control rats than Sham-operated rats, but supplementation of PG ethanol extracts at 50mg/kg bw/day decreased the level of cholesterol in surum. These results might be expected that ethanol extract of PG is believed to be possible protective effects for the fatty serum increasing serum lipid.

한열성향에 따른 위전도 특성 연구

하성룡 ( Song-yong Haa ),김민용 ( Min-yong Kim ),박영재 ( Young-jae Park ),박영배 ( Young-bae Park ) 대한한의진단학회 2008 大韓韓醫診斷學會誌 Vol.12 No.1

Background : In relation to a diagnosis of Korean Medicine, heat-cold is one of the most important indicators for evaluation. In spite of this importance, there has not been the study that tries to examine the change of indicators in an electrogastrography (EGG) according to the heat-cold patternization. Objective: The objective of this study is to establish the correlation between the heat-cold patternization and indicators of EGG by means of Standardized Questionnaire for Heat-Cold Patternization. Method: To conduct this study, we used the method as follows: Before conducting EGG, subjects were requested to give answers to the questionnaire which was developed by Kim. Before EGG, subjects were demanded to fast for more than 8 hours and then eat the test meal. Before eating the test meal(test meal: two slices of bread, 4oz of apple juice), EGG signals were detected for 30 minutes, and then subjects could eat the test meal for 10 minutes. After eating the test meal, EGG signals were detected for 30 minutes. Results: 1. There was a negative correlation between heat score and the power ratio of channel 1 and channel 2 of EGG. There was a positive correlation between cold score and the power ratio of channel 1 of EGG. 2. There was a positive correlation between heat score and pre-prandial gastric arrhythmia in the channel 1, 2 and 4 of EGG. There was a negative correlation between cold score and post-prandial gastric arrhythmia in the channel 1, 2 and 3 of EGG. 3. There was a negative correlation between heat score and normal pre-prandial gastric slow wave in the channel 1, 2 and 4 of EGG. There was a positive correlation between cold score and normal post-prandial gastric slow wave in the channel 3 of EGG. Conclusions: From the results above, we could conclude as follows: Indicators of EGG and cold score presented a positive correlation, and heat score displayed a negative correlation. As a result, to apply EGG to a diagnosis of functional indigestion, the application of EGG to subjects who have heat patternization would increase the reliability of a diagnosis.

절수에 의한 mongolian gerbil의 체중 변화에 관한 연구

이경열,송치원,김무강,조성환,류시윤,김상근,박배근 충남대학교 수의과대학 동물의과학연구소 1996 動物醫科學硏究誌 Vol.4 No.-

Recently, the mongolian gerbils have been used in neurology and the study of water metabolism because of their easy onset of epileptic seizure and typical resistance to water deprivation. The sebaceous glands which are under the control of the gonadal hrmones are differently developed from the other laboratory animals. However the physiological data on the changes of body weight following water deprivation in mongolian gerbils is not available until now. In order to investigate the effect of the water deprivation on the body weight, the animals were deprived of water for 15 days. The body weights were measured daily by the torsion balance. The mean, the standard deviation, the standard error and the coefficient of variance of the body weights were calculated. The correlation was examined. The potential regression equation was y = 61.5458 - 2.0533 * x + 0.0487 * x^2. The regression coefficient was 0.993. The results obtained were as follows : 1. The body weights of the mongolian gerbils were continuously decrased from the 1st day to the 15th day after the water deprivation. 2. The mean body weight on the water deprivation was 63.0±7.00g and that at the 15th day was 41.4 ± 5.42g. 3. The coefficients of the variance showed the highest (13.09) at the 15th day and the lowest (10.10) at the 10th day. the coefficients of the variance kept decreasing until the 10th day and thereafter gradually increased until the 15th day. 4. The changing rate of the body weight kept continuously decreasing from the 1st day to the 15th day showing the daily loss of 1.0 - 3.3%. 5.The deviations (M - QBW) between the measured values (m) and the theorical values (QBW) using the regression equation showed the highest (1.494) at the 1st day and the lowest (0.053) at the 13th day. 6. The sum of the devitions was 0.179 and that of the deviation square was 1.15. The sum of the deviation rates between the mesaured body weights and the theorical ones was 0.484. 7. The daily body weight loss showed the highest at the 1st day by 2.053g and the lowest at the 15th day by 0.591g. 8. The specific body weight changing rates which were the rate of the body weight changing velocity to the changed body weight were decreased from 0.033% at the 1st day to 0.014% at the 15th day.

고콜레스테롤혈증 토끼에서의 지질강하효과와 독립적인 Naringin의 항동맥경화 효과

최성준,김효수,정태숙,복성해,박영배 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.11