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>

Rat의 복강에 삽입한 Fluorouracil-Polyglycolic acid 제형의 Fluorouracil 용출에 관한 연구

노승무,정경수,오정연,김진향,양준묵,강대영,송규상,최정목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 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

A common form of relapse in adenocarcinoma of the stomach is intraperitoneal dissemination, in fact, among gastric adenocarcinoma patients who have undergone surgery intended to cure, approximately 50% of the patients develope initial recurrence in the peritoneal cavity regardless of the anatomic site of the primary tumor within the stomach. The efficacy of systemic postoperative chemotherapy to prevent peritoneal recurrence of gastrric adcnocarcinoma is not satisfactory. There is still a great need for improved therapeutic strategies on the disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface or lymphatics after operation. The authers have made fluorouracil-polyglycolic acid composite disks(Fu-PGA disks) with fluorouracil and biodegradable polymer: polyglycolic acid for more effective intraperitoneal chemotherapy. We inserted the Fu-PGA disk(s) in the peritoneal cavity of rat and pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at 24 hour, 72 hour and 168 hour after insertion of Fu-PGA disk(s). Myelosuppressive action of this composite also was determined following its administration. The data of this study suggested that Fu-PGA composite will be a new device releasing drugs in a controlled manner and having targetability to peritoneum, and this device will be improving the efficacy of intraperitoneal chemotherapy for gastric adenocarcinoma.

위암 환자의 복강내 투여를 위한 Activated Charcoal-Alginate Bead 제형으로부터 Mitomycin C의 용출 거동

이진호,최선웅,서중기,김동민,정경수,오정연,김진향,노승무,민병무,김용백,김창식,박근성,강대영,송규상,양준묵,조준식,정현용,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

Locoregional recurrence is the most common type of recurrence in surgical operation of gastric adenocarcinoma, and peritoneal dissemination is one of the most difficult problems in advanced gastric adenocarcinoma treatment. Because the peritoneal cavity is the most common site of the first recurrence after gastric cancer resection, intraperitoneal chemotherapy seems a logical choice for cancer chemotherapy. In this study, Mitomycin C (MMC)-activated charcoal (CH)-alginate (ALG) beads were prepared by the mixtures of CH particles adsorbed with MMC as an anti-cancer drug and aqueous alginate solution. The alginate is recognized as biodegradable, nontoxic, and biocompatible. The release of MMC from the beads in 0.1 M Tris buffer was stable and continuous until about 1 week. The MMC-CH-ALG beads can be applied in the peritoneal cavity for intraperitoneal chemotherapy since they provide a good adhesiveness on the tissue and controlled release pattern of the drugs.

Rat의 복강에 삽입한 Filorouracil-Polyglycolic acid제형의 Fluorouracil용출에 관한 연구

노승무,정경수,오정연,김진향,양준묵,강대영,송규상,최정목,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

A common form of relapse in adenocarcinoma of the stomach is intraperitioneal dissemination, in fact, among gastric adenocarcinoma patients who have undergone surgery intended to cure, approximately 50% of the patients develope initial recurrence in the peritoneal cavity regardless of the anatomic site of the primary tumor within the stomach. The efficacy of systemic postoperative chemotherapy to prevent peritoneal recurrence of gastrric adenocarcinoma is not satisfactory. There is still a great need for improved therapeutic strategies on the disseminated microscopic disease and small miliary nodules remaining on the peritoneal surface or lymphatics after operation. The authers have made fluorouracil-polyglycolic acid composite disks(Fu-PGA disks) with fluorouracil and biodegradable polymer: polyglycolic acid for more effective intraperitoneal chemotherapy. We inserted the Fu-PGA disk(s) in the peritoneal cavity of rat and pharmacokinetic study was performed to measure fluorouracil concentration in the peritoneal fluid, plasma, liver, kidney and heart tissue at 24 hour, 72 hour and 168 hour after insertion of Fu-PGA disk(s). Myelosuppressive action of this composite also was determined following its administration. The data of this study suggested that Fu-PGA composite will be a new device releasing drugs in a controlled manner and having targetability to peritoneum, and this device will be improving the efficacy of intraperitoneal chemotherapy for gastric adenocarcinoma.

배달 미니 게임 개발:"최고의 웨이터를 꿈꾸며"

김정훈,정한교,김영옥,김중곤,박정윤,윤진성,김경식 호서대학교 반도체제조장비국산화연구센터 2001 반도체장비학술심포지움 Vol.2001 No.-

본 미니 게임은 웨이터라는 직업을 모티브로 하여서 남녀노소 누구나 재미를 느낌과 동시에 기억력 향상시켜 주는 게임제작이라는 목적아래 제작되었다.본 논문에서는 이 게임의 제작과정을 기술하고자 한다.이 게임은 제3회 AGC(한국 아마추어 게임제작 공모전)에서 우수 작으로 선정되었다.

人 諸臟器 Alkaline Phosphatase Isoenzyme의 電氣泳動 및 定量

金在植,金京善,金重明,金榮泰,蔣卓仙,李鉉基 慶北大學校 醫科大學 1980 慶北醫大誌 Vol.21 No.2

著者들은 家兎와 人體로부터 採取한 血淸과 諸臟器組織을 使用하여 ALPI 電氣泳動像을 觀察하고 生化學的 定量法을 利用하여 ALP의 活性度를 測定試圖하였으며 臟器特異性 沮害因子에 對한 影響을 觀察하였다. 家兎 血淸 및 諸臟器組織 ALPI電氣泳動에서 血淸은 ±의 活性度를 가진 α2와 α2/β分劃을 나타내었으며 肝組纖은 血淸보다 빠른 移動度를 가진 ??의 α_1과 α_2分劃을 나타내었다. 그리고 肝, 骨, 腎 淋巴腺, 脾臟 및 腸組織에서는 顯著하게 높은 活性度를 나타내는 各各 서로 相異한 分劃을 볼 수 있었으며 人體諸 臟器와大體로 類似하였으나 家兎 血淸의 ALP는 사람에서 와는 다르게 肝組織의 分劃과 一致하지 않고 오히려 骨組織과 더 잘 一致되는 것 같았다. ALPI 活性度에 있어서 家兎의 諸臟器는 生化學的 定量法으로 腎 ALP의 活性度가 49.5B.L. units로 다른 臟器組織에 비하여 顯著하게 높았으며, 그 다음은 脾臟, 脊椎骨, 肝, 肺淋巴腺 및 脾 順으로 높은 活性度를 나타내었으며 人體에 있어서는 胎盤, 骨, 小賜, 脾臟, 肝 및 腎臟의 順으로 높았다. 臟器 特異性 沮害因子에 對한 影響에 있어서 胎盤分劃은 特有하게 耐熱性을 나타내었고 보다 urea低抗性이며 肝分劃은 neuraminidase에 對하여 移動度의 遲延을 招來하였다. The studies upon cellulose acetate microzone electrophoretic patterns, quantitative estimation and effects of organspecific inhibitor on ALP isoenzyme of rabbit and human sera and various organ tissues were performed. On electrophoretic pattern the tissue ALP from the liver bone kidney lymph node spleen and intestine showed the characteristic fraction of high activities. The electrophoretic mobility of rabbit serum ALP was not correspond to the liver ALP as observed in human serum and it appeared to be rather corresponded to the bone ALP, which seemed to be the origin of ALP in serum of rabbit. In the quantitative measurement of tissue ALP activity the kidney ALP showed the highest level and the activity of the skeletal muscle ALP was the lowest(1.5 B. L. units), while higher activities were observable in placenta, bone, intestine, spleen, liver and kidney in order. On the effect of organ specific physico chemical agents the placental ALPI was highly stable to the heat and relatively resistant to urea while other organ ALPI were on the contrary. The neuraminidase seemed to effect to the motility of liver fraction.

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>

하지 분절 각도에 따른 수의 등척성 수축(MVIC)시 근전도 비교

김정자,이민형,김연정,채원식,한윤수,권선옥 한국운동역학회 2005 한국운동역학회지 Vol.15 No.1

J. J. KIM, M. H. LEE, Y. J. KIM, W. S. CHAE, Y. S. HAN, O. KWON. Comparison of the maximum EMG levels recorded in maximum effort isometric contractions at five different knee flexion angles. Korean Journal of Sport Biomechanics, Vol. 15, No. 1, pp. 197-206, 2005. The purpose of this study was to quantify the maximum EMG levels and determine if there are differences in these EMG levels with respect to different knee flexion angles. Eight university students with no known musculoskeletal disorders were recruited as the participants. The maximum voluntary isometric knee extensions and flexions were taken from each participant sat on the isokinetic exercise machine (Cybex 340) at five different knee flexion angles (10?30?50?70? 90?. After surface electrodes were attached to rectus femoris, vastus medialis, vastus laterlis, biceps femoris, and semitendinosus, maximum EMG levels at five different knee flexion angles were measured. The results showed that there was no significant difference in maximum EMG levels among five different knee flexion angles. Although there was no significant difference in EMG levels and were some variations among different knee flexion angles, the EMG signals of quadriceps in extension and biceps femoris in flexion were the greatest at 30? It seems that different joint angles or relative locations of body segments might affect the magnitude of EMG levels. Because the maximum EMG levels could change with a different knee flexion angle, an attempt should be made to more accurately measure these values. If then, %MVIC measure provides more reliable data and is most appropriate for EMG normalization.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic, 24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12 days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting, diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large, prospective, and randomized comparative studies are warranted for aspergillosis.

파종시기가 다른 일미찰의 등숙 중 호화 특성 비교

김미정, 박효진, 이유영, 김선림, 김정태, 우관식, 권영업, 정일민 忠北大學校 農業科學硏究所 2014 農業科學硏究 Vol.30 No.2

This study was conducted to investigate the pasting properties of waxy corn ‘Ilmichal’ during ripening with different sowing date. Starch content of Ilmichal was increased as matured (p<0.05). Analysis of pasting properties with waxy corn starch using a rapid visco analyser (RVA) showed linear changes in peak viscosity, trough viscosity, final viscosity, breakdown and consistency according to ripening. There were significantly positive correlation between starch content of Ilmichal and peak viscosity (0.39*), trough viscosity (0.58***), final viscosity (0.58***), and consistency (0.57**). Differential scanning calorimerty (DSC). The enthalpy of gelatinization was increased as ripening. But onset and peak temperature were decreased. There were significantly positive correlation between starch content of Ilmichal and onset temperature (0.44*), peak temperature (0.38*), and completion temperature (0.59***), on the other hand, crude protein content presented significantly negative correlation between completion temperature (-0.41*).