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>

만성 기관지염 및 재발성 급성 호흡기감염 치료에 있어서 경구용 Broncho-Vaxom에 대한 임상 연구

김세규,김병일,장준,김성규,이원영 최신의학사 1991 最新醫學 Vol.34 No.1

ON GENERALIZED WEIGHT NASH EQUILIBRIA FOR GENERALIZED MULTIOBJECTIVE GAMES

Kim, Won-Kyu,Ding, Xie-Ping Korean Mathematical Society 2003 대한수학회지 Vol.40 No.5

In this paper, we will introduce the general concepts of generalized multiobjective game, generalized weight Nash equilibria and generalized Pareto equilibria. Next using the fixed point theorems due to Idzik [5] and Kim-Tan [6] , we shall prove the existence theorems of generalized weight Nash equilibria under general hypotheses. And as applications of generalized weight Nash equilibria, we shall prove the existence of generalized Pareto equilibria in non-compact generalized multiobjective game.

재발 또는 불응성 비호즈킨 림프종 환자에서 CDME 구제항암화학요법 후 고용량 항암화학요법 및 자가말초혈액 조혈모세포이식의 효과

김세형,한강원,배상병,김찬규,이남수,이규택,박성규,원종호,홍대식,박희숙 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

Background and objectives : The long-term survival in patients with non-Hodgkin's lymphoma (NHL) after conventional dose chemotherapy is about 35% and the rest of the patients tend to have relapse. So, in relapsed or refractory NHL, we compared the outcome of patients undergoing high-dose chemotherapy with autologous peripheral blood stem cell transplantation(APBSCT) with only salvage chemotherapy of cisplatin, dexamethasone, mitoxantrone, and etoposide(CDME). Materials and methods : From June 1993 to December 1999, 25 patients with relapsed or resistant NHL were treated with CDME regimen as salvage chemotherapy. Twelve patients were received four cycles of CDME chemotherapy, and 13 patients were received high-dose chemotherapy with APBSCT following two cycles of CDME chemotherapy. Results : The median follow-up duration was 12.8 months(range:4-68). The overall response rate was 41.7% (complete response rate 25%, partial response rate 16.7%) in 12 patients with CDME only. Thirteen patients who were treated with high-dose chemotherapy with APBSCT achieved 61.5% complete response rate and 15.4% partial response rate, with an overall response rate of 76.9%. The estimated 3-year progression-free survival rate was significantly higher among patients who received high-dose therapy than patients who received CDME only(41.5% vs 20.0%, p<0.05). And, 3-year overall survival rate was significantly higher among patients who received high-dose therapy(51.3% vs 25.0%, p <0.05). Conclusions : In relapsed or refractory NHL, CDME chemotherapy is an effective salvage chemotherapy and allow peripheral blood stem cell collection. Also, high-dose chemotherapy with APBSCT following CDME is superior to CDME salvage chemotherapy only.

EXISTENCE OF NASH EQUILIBRIUM IN A NON-COMPACT ACYCLIC STRATEGIC GAME WITH INFINITE PLAYERS

Won Kyu Kim 충청수학회 2011 충청수학회지 Vol.24 No.2

In this paper, we will prove an equilibrium existence theorem of a non-compact acyclic strategic game with a±ne con-straint correspondences which is comparable with equilibrium exis- tence theorems due to Debreu, Nash, Kim-Kum, and Lu in several aspects.

간문부 담관암 환자에서 경피경관 양측성 금속 배액관의 효과

김금래,김주형,박원규,장재천,조재호,김태년,김준화,장병익 영남대학교 의과대학 2005 Yeungnam University Journal of Medicine Vol.22 No.2

Background: The purpose of this study was to determine the effectiveness of percutaneously place self-expanding metallic stent for the relief of biliary obstruction in patients with hilar cholangiocarcinoma. Materials and Methods: From November 2001 to December 2004, 48 patients with hilar cholangiocarcinoma were prospectively studied. After percutaneous placement of bilateral self-expanding, uncovered metallic stents, follow-up evaluation was carried out until July 2005. Results: There were 4 cased of Bismuth type Ⅱ,21 cases of Bismuth typeⅢa 8 cases of Bismuth type Ⅲb and 15 cases of Bismuth type Ⅳ. Stent placement was technically successful in all patients All patients had satisfactory biliary drainage, resulting in one week drainage rate of 72.8% and final drainage of 91.9% There were 12 cases (21.3%) of abdominal pain requiring analgesics and 1 case (7.1%) of cholangitis; both were successfully managed with conservative treatments. Late complications occurred in four patient (8.3%), including two patients with cholangitis, one patient with liver abscess, and one patient with biloma; all were appropriately managed by percutaneous drainage. The average length and median durations of stent patency and median survival time were 303 days (range, 60~815) and 338 days (range, 60 ~1175), respectively. Conclusion: Placement of a percutaneous metallic stent is an effective and safe method of palliation of patients with hilar cholangiocarcinoma.

국민건강보험의 의약품 가격전략: 산업과 보험의 공존

김원식 ( Won Shik Kim ),이규식 ( Kyu Sik Lee ) 한국사회보장학회 2008 社會 保障 硏究 Vol.24 No.4

化卉의 消費形態에 관한 硏究

崔圭晧,裵相源,金昶佑 全北大學校 1995 論文集 Vol.39 No.-

The purpose of this survey is to investigate and analize the status of flower consumption by city households so that it can provide basic materials for the development of horticulture industry. For this purpose, one thousand housewives were questioned living in six large cities : Seoul, Pusan, Taegu, Inchon, Kwangju and Taejon. The results of the analysis are as follows; 1. The most favorite cut flowers by season were rose, carnation and freesias in spring: roses and gypsophila paniculate in summer : chrysanthermum in autumn : gypsophila paniculate, roses chrysanthemums and lilies in winter. 2. The uses of cut flowers was mostly for gifts(58.4%), and that of pot flowers was mostly for home decoration. 3. flower shops were the most popular place for buying cut flowers(59.5%), followed by wholesale markets(22.5%) and street stalls(16.2%). In the case of pot flower, wholesale markets were the most favorite place(32.4%), street stalls(27.9%), flower shops(24.8%), and farm houses(11.9%). The survey showed that consumers frequent a shopping place because of 'easy accessibility', and 'various varieties in stock' in the case of cut flowers and, in that of pot flowers, 'easy accessibility' and 'low price' were the main resons in the case of pot flowers. 4. The purchase frequency rate by seson for cut flowers was that 'regardless of season' was 58.1% and 'spring', 28.9%. For pot flowers, 'spring' 58.9% and 'regardless of season' 33.6%. For the day of the week cut flowers were bought most open, Saturday came first with 34.2%, Monday and Sunday followed with 27.0% and 15.5% respectively. On the other hand, Sunday came first with 42.3%, Saturday(32.5%) and Monday(8.3%) took the second and third place respectively for pot flowers When it came to the purchase time of the day for cut flowers, 31.8% of the respondents bought then between ten and noon and 21.8% between four and six in the afternoon. 5. concerning the average amount of money spent at one time for cut flowers, 33.3% of the respondents said 3,000won to 5,000won and 23.2% replied 5,000won to 10,000won. While 36.8% answered that they paid 5,000won to 10,000won and 23.5% said 3,000won to 5,000won for a pot flowers. 6. Relating to the demand of flower stores, 28.8% wanted 'low price' : 27.9%. requested 'clear markings of the prices' : and 26.4%, wanted 'abundant commodities'

Effects of epigallocatechin gallate on CoCl_(2)-induced apoptosis in PC12 cells

Yang, Kyu-Ho,Mo, Hyun-Chul,Choi, Nam-Ki,Kim, Seon-Mi,Kim,Won-Jae 大韓小兒齒科學會 2006 大韓小兒齒科學會誌 Vol.33 No.1

Neuronal apoptotic events, consequently resulting in neuronal cell death, are occurred in hypoxic/ischemic condition. This cell death has been shown to be accompanied with the production of reactive oxygen species (ROS), which can attack cellular components such as nucleic acids, proteins and phospholipid. However, the underlying mechanisms of apoptosis induced in hypoxic/ischemic condition and its treatment methods are unsettled. Cobalt chloride (CoCl_(2)) has been known to mimic hypoxic condition including the production of ROS. Epigallocatechin gallate (EGCG). a green tea polyphenol, has diverse pharmacologial activities in cell growth and death. This study was aimed to investigate the apoptotic mechanism by CoCl_(2) and effects of EGCG on CoCl_(2)-induced apoptosis in PC12 cells. Administration of CoCl_(2) decreased cell survival in dose- and time-dependent manners and induced genomic DNA fragmentation. Treatment with 100 µM EGCG for 30 min before PC12 cells were exposed to 150 µM CoCl_(2), being resulted in the cell viability and DNA fragmentation being rescued. CoCl_(2) caused morphologic changes such as cell swelling and condensed nuclei, whereas EGCG attenuated morphologic changes by CoCl_(2). EGCG suppressed the apoptotic peak and a loss of Δψ_(m) induced by CoCl_(2). CoCl_(2) decreased Bcl-2 expression but Bax expression was not changed in CoCl_(2)-treated cells. EGCG attenuated the Bcl-2 underexpression by CoCl_(2). CoCl_(2) augumented the cytochrome c release from mitochondria into cytoplasm and increased caspase-8, -9 and caspase-3 activity, a marker of the apoptotic executing stage. EGCG ameliorated the incruement in caspase-8, -9 and -3 activity, and cytochrome c release by CoCl_(2). NAC (N-acetyl-cysteine), a scavenger of ROS, attenuated CoCl_(2)-induced apoptosis in consistent with those of EGCG. These results suggest, that CoCl_(2) induces apoptotic cell death through both mitochondria- and death receptor-dependent pathway and EGCG has neuroprotective effects against CoCl_(2)-induced apoptosis in PC12 cells. 신경세포자멸사는 저산소 및 허혈환경에서 일어나며 이러한 세포죽은 reactive oxidant species (ROS) 생성을 동반함이 알려져있다. 그러나, 저산소 및 허혈환경에서 일어나는 세포자멸사의 기전 및 그 치료방법은 아직 정립되어 있지 않다. CoCl_(2)는 ROS를 생성하는 등 저산소환경과 유사한 조건을 초래하는 것으로 알려져 있다. Epigallocatechin gallate (EGCG)는 녹차의 polyphenol 성분으로서 세포성장과 죽음에 다양한 약리학적 효과를 나타냄이 알려져 있다. 본 연구는 PC12 세포에서 CoCl_(2)에 의한 세포자멸사기전을 밝히고 이에 미치는 EGCG의 효과를 조사하는데 목적이 있다. Cell viability는 MTT 측정으로 조사되었고, DNA fragmentation은 DNA laddering으로 조사되었다. Bcl-2와 Bax발현 정도는 RT-PCR로, caspase-3와 -9의 활성은 spectrophotometer, caspase-8의 활성은 flow cytometry에 의해 측정되었다. 미토콘드리아에서 세포질로 분비된 cytochrome c는 western blot으로, 분해된 DNA 양과 미토콘드리아 세포막전위 (Δψ_(m))는 FACScan으로 조사되었다. CoCl_(2)투여로 PC12 세포수는 용량 및 시간 의존형태로 감소하였고, genomic DNA fragmentation이 발생하였다. CoCl_(2)투여로 야기된 cell viability의 감소와 DNA fragmentation은 EGCG 전처치에 의해 억제되었다. CoCl_(2)은 세포용적팽창과 condensed nuclei 같은 형태적 변화를 일으켰으며, apoptotic peak, Δψ_(m)감소 및 cytochrome c 유리를 야기하였다. EGCG는 CoCl_(2)에 의한 세포형태변화, apoptotic peak, Δψ_(m)소실 및 cytochrome c 유리를 억제시켰다. CoCl_(2)는 Bcl-2 발현을 감소시켰지만, Bax 발현에는 영향을 미치지 않았다. EGCG는 CoCl_(2)에 의해 야기된 Bcl-2 발현 감소를 억제시켰다. CoCl_(2)는 caspase-3, -8, 그리고 -9의 활성을 증가시켰으며, EGCG는 CoCl_(2)에 의한 세포자멸사를 억제시켰다. 본 실험결과는 PC12 세포에서 CoCl_(2)가 미토콘드리아 의존 및 death receptor의존 기전으로 세포자멸사를 일으키며, EGCG는 세포자멸사기전을 억세지킴으로 신경보호기능을 가짐을 시사하였다.

흉선종 제거후에 발생한 재생 불량성 빈혈 : 증례보고

전원선,이상철,김현정,배상병,김찬규,이남수,박노진,이규택,박성규,홍대식,박희숙,원종호 순천향의학연구소 2007 Journal of Soonchunhyang Medical Science Vol.13 No.2

Thymoma is associated with myasthenia gravis, Pure red cell aplasia, and autoimmune diseases such as autoimmune hemolytic anemia, aplastic anemia, and hypogammaglobulinemia. It's association with aplastic anemia is rare and aplastic anemia appearing after surgical removal of thymoma is especially rare. The authors hereby report a case of aplastic anemia occuring in a patient who was diagnosed with thymoma and myasthenia gravis and had the tumor surgically removed. The patient was treated with anti-thymocyte globulin, cyclosporin, and prednisolone, and showed partial remission with hematologic improvements after 12 months.