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>

생체분해성 망막압정을 이용한 망막고정에 대한 실험적 연구

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

Biodegradable retinal fixation devices obtain mechnical fixation of the retina with desirable chorioretinal scarring and with the potential for local, sustained release of antimetabolites and steroids to inhibit proliferative vitreoretinopathy. We manufactured a biodegradable retinal tack with barb that was designed in order to prevent intrusion from implantation of retinal tacks. This study was carried to evaluate the efficacy for retinal fixation and the capability for sustained release of drugs with a newly designed biodegradable retinal tack Biodegradable retinal tacks were made of polymers of glycolic acids and were designed with barbs in a shape to prevent the disinsertion. Biodegradale retinal tacks are divided into 3 parts, a conical portion that is inserted into the sclera, a cylinder portion that remains in the vitreous, and a neck portion between the pin and the cylinder. The tapered conical end was manufactured to allow easy insertion through the retina and choroid into the sclera. A cylinder portion was manufactured with a tapered angle that fixes firmly into the orifice of 19 gauge spinal needle. A neck portion, 0.4 mm in diameter, was designed to prevent disinsertion from following implantation of retinal tack. The applicator was a 19 gauge spinal needle and its orifice was prepared to 15°angle to accept the tapered cylinder portion of the retinal tack. The retinal tacks, secured in the needles, were passed through the formed vitreous and inserted into the retina, choroid, and sclera and were released by pushing the internal needle, usually within 2-3mm of the medullary ray of the posterior rabbit retina A retinal tack was placed in each of 8 pigmented rabbit eyes. Slit-lamp biomicroscopy, indirect ophthalmoscopy and fundus photography were performed periodically from 1 day to 8 weeks after surgery. Eight eyes were enucleated and studied by light microscopy at 8 weeks. Biomicroscopic evaluation of the animals revealed edemas adjacent to the retinal surfaces immediately after insertion of the biodegradable retinal tacks in all the animals. These edemas disappeared after 1 week. The first noticeable change in the size of retinal tacks was shown after 2weeks. The size of the retinal tacks gradually got smaller, decreasing to about one-half at 4 weeks and about one-third at 8 weeks. All retinal tacks remained in inserted places without any movement for an 8 week period. On light microscopy, epiretinal proliferations were seen to extend into the vitreous cavity. Cellular capsules that lined the inner aspect of the scleral defect caused by tack insertion were found. However the adjacent retina had a normal cytologic appearance and architecture in all specimens. We manufactured a biodegradable retinal tack that is designed to prevent intrusion from implantation of retinal tacks. All biodegradable retinal tacks reduce in size with time, but no retinal tacks extruded from the inserted place. The newly designed biodegradable retinal tack can be used for retinal fixation and may be used as a vehicle for the introduction of pharmacologic agents to prevent the cellular events that promote proliferative vitreoretinopathy.

단기교육으로 시행가능한 심실기능평가법

김원,임경수,오병연,홍은석,김영식,김선만,이부수,현석천,김영득 대한응급의학회 2000 대한응급의학회지 Vol.11 No.4

Background: The initial history, physical examination, and ECG assessment should focus on identification of potentially serious noncardiac or cardiac disorders, including coronary artery disease, congestive heart failure, and electrical instability at the emergency room. additionally, it is essential to define disease severity, stability and need for emergency therapy. echocardiography is a useful tool for this purpose. especially Doppler echocardiography may be more sensitive and time-saving diagnostic tool for the evaluation of patients presenting with cardiogenic symptoms. So we evaluate the feasibility of the echocardiographic measurement by emergency physicain after short-term course. Method and Results: Twenty volunteers(10 male, 38.8±9.3 years) were included in the study for measurement of myocardial performance index and established parameters of ventricular function using conventional echo-Doppler methods. Myocardial performance index: (ICT+IRT)/ET, was obtained by subtracting ejection time(ET) from the interval between cessation and onset of the mitral inflow velocity to give the sum of isovolumic contraction time(ICT) and isovolumic relaxation time(IRT). The most of mean values of echocardiogrphic parameters were not significantly different between those of cardiologist and those of emergency physicians(p<0.01). The duration for measuring myocardial performance index was shortest among echocardiographic parameters. the validity of echocardiographic parameters measured by emergency physicians was proved relatively good. Conclusion: It is proved to be feasible for emergency physician to perform echocardiographic evaluation of ventricular function after short-term course

학생청소년의 불안성향과 문제행동 유형간의 상관분석

김헌수,이재우,나철,김영돈,김민호,김은희,권지란,박광식,이길홍,민병근 중앙대학교 의과대학 의과학연구소 1987 中央醫大誌 Vol.12 No.4

The purpose of the present study was to examine the relationship between their problem behavioral pattern and anxious trends among Korean student adolescent. Zung's measurement of anxiety level undergone through used of the self-rating anxiety scale. the data were collected through the questionaire survey which was conducted on Dec.1, 1983. Subjects served for this atudy consisted of 1,404 syudents in Korea, randomly sampled from Korean student population by means of census method. The data were analysed by CDC-174 computer of KAIST, using SPSS pogram. Statistical methods empoyed were χ^2 test and Eta measures. the results of this study were as follows. 1. It showed that students psychological anxious trends had greatest significant correlation with adolescent student's problem brhavioral pattern, but the cardiovascular, respiratory, gastrointestional and genitourinary anxious trends has not significantly related with student's problem behavioral pattern. 2. Students group with undersocialized aggressive, undersocialized nonaggressive,undersocialized school-norm avoidant, or socialized nonaggressive behavioral patterns were less anxious, whereas those with socialized latent aggressive, socialized sexual, or socialized modellong behavioral patterns were higher anxious.

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.

위절제술 환자의 표준진료지침 개발 및 적용 효과

김은희,김철규,이순교,김순덕,이혜옥,권정순,이경미,이민미,심순미,유용만,신종식,강은희,이상일,김병식,오성태,육정환,박수길 한국의료QA학회 2003 한국의료질향상학회지 Vol.10 No.2

Background : Gastric cancer is the most common malignant tumor in Korea. surgical operation is one of the major treatment modalities for gastric cancer patients. Therefore, gastrectomy is one of the most common procedures in General Surgery. There were variation in length of hospital stay and medical treatment for gastrectomy between three surgeons at Asan Medical Center. Clinical pathways have received considerable attention as a tool for recucing the medical practice variation, increasing the efficiency of care process, and improving the quality of care. The aim of this study was to evaluate the effect of a clinical pathway for gastrectomy in gastric cancer patients. Methods : The clinical pathway for gastrectomy was developed and implemented by a multidisciplinary group in Asan Medical Center. A computerized clinical pathway program was developed and revised after a pilot test. A total of 145 patients underwent gastrectomy by three surgeons at Asan Medical Center. We compared the length of hospital stay, patient satisfaction, and unplanned readmission rate between the pre-pathway group(n=67) and the post-pathway group(n=78). We also investigated the degree of satisfaction among the physicians and nurses who were main end-users of the clinical pathway. Results : The clinical pathway was applied to all target patients. The average length of hospital stay was shortened from 12.7days to 10.6days(p<0.01). The degree of patient satisfaction with the care process changed from 90.3% to 89.2% after the implementation of the clinical pathway, but the difference was of satistically significant(p=0.761). Unplanned readmission rate was 2.9% in the pre-pathway group. More than 90% of physicians and nurses answered that the clinical pathway had been a useful tool in their medical practice. Conclusions : The findings of the study demonstrated that implementation of the clinical pathway for gastrectomy produced substantial reduction in the length of hospital stay while improving the quality of patient outcomes. The computerized clinical pathway program can be used as one of the powerful patient management tools for reducing the practice variations and increasing the efficiency of care process in Korea hospital settings.

생체분해성 고분자를 이용한 사시수술용 제형개발 및 효용성에 대한 연구

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

A new device, muscle clamping system was developed to facilitate exact quatifying technique A strabismus surgery, and reduce the risk of complications. The device is composed of a lower fixing body with three jaws and an upper supporting body. They are used to clip an extraocular muscle and fix it to the sclera with a single bite. Superior rectus recession on 16 rabbit eyes were performed with this new device. Conjunctival injection, muscle adhesion strength, and light microscopic findings were examined at 1, 2, 4 and 8 weeks postoperatively. The Conjunctival injection were minimal, adhesion power ranged from 420 to 600 gram gravity, which is sufficient in withstand the normal pull of human extraocular muscle. In microscopic exam, some Inflammatory cells and fibrosis were found. The new device was technically easy, fast, and accurate, so it may be useful in stabismus surgery.

방향성 응고된 이상형 스테인레스강에서 질소첨가가 미세조직에 미치는 영향

최병학,정병길,김진우,고석민,이재현,김상식,김성준 국립7개대학공동논문집간행위원회 2001 공업기술연구 Vol.1 No.-

Microstructures in the directionally solidified duplex stainless steels were investigated in order to understand the effect of nitrogen addition. It was found that the addition of nitrogen causes formation of fine precipitates in a matrix and segregation phases of nitrogen in the α/γ interface. Both the fine precipitates and the segregation phases were identified CrN(fcc, a=4.16A˚), which has the coherent phase relationship with bcc α matrix of (200) CrN // (0 1￣ 1) α and (1￣1￣ 1) CrN // ( 3￣ 2￣ 1) α.

내시경적 점막절제술로 치험한 식도 과립상 세포종 1례

강혁주,김성욱,최석진,이중현,장재식,서영범,윤병구,박건욱,김성자,김용섭,강승완,이구,양창헌,이창우,김욱년,이광헌,서정일 동국대학교 의학연구소 2000 東國醫學 Vol.7 No.-

과립상 세포종은 Schwann 세포 기원으로 생각되며 인체에 비교적 드물게 발생한다. 과립상 세포종은 전신 어느 곳에서나 발견될 수 있으나 주로 혀, 구강, 피부 혹은 유방 등에서 호발하며 드물게 위장관에서 발견된다. 위장관에서는 식도에서 가장 호발하며 다음으로 위, 대장 순이다. 과립상 세포종은 대부분, 특히 위장관에서는 양성이며 소수의 악성 병변이 보고되었다. 이러한 이유와 함께 수술 전의 진단이 어렵기 때문에 과립상 세포종에 대한 근본적인 치료는 현재까지 외과적 절제술이다. 최근에 시도되는 치료방법들로는 내시경적 레이저 치료, 용종절제술, 내시경적 점막 절제술 등이 있다. 저자들은 상부 소화관 내시경검사를 시행하여 식도 과립상 세포종을 진단하고 내시경적 점막 절제술을 시행하여 합병증 없이 퇴원하여 현재 재발없이 경과 관찰중인 1례를 경험하였기에 보고하는 바이다. Granular cell tumors, which occur infrequently, are probably of Schwann cell origin. They can occur almost anywhere in the body but usually affect the tongue, oral cavity, skin, or breasts and are rarely found in the gastrointestinal tracts. The esophagus is the most frequent gastrointestinal site, followed by the stomach and the colon. Granular cell tumors are generally benign, especially in the gastrointestinal tract, some malignant lesions have been reported. For this reason, and also because preoperative diagnosis is difficult, the standard treatment for granular cell tumor has until now been surgical excision. In recent years, other therapeutic methods is endoscopic laser therapy (ELT), polypectiomy, endoscopic mucosal resection (EMR). We report a case of esophageal granular cell tumor which was diagnosed by an endoscopy and managed using an endoscopic mucosal resection without complication.