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>

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.

한국국제회계기준(K-IFRS)의 도입과 이익조정

김진규, 이택란, 김규빈, 김민식 가톨릭대학교 산업경영연구소 2012 産業經營硏究 Vol.- No.20

위발성 위장관 악성림프종 환자에서 항암치료의 효과

김찬규,신영록,김현정,배상병,이남수,이규택,박성규,원종호,홍대식,박희숙 순천향대학교 2006 Journal of Soonchunhyang Medical Science Vol.12 No.1

Purpose: The gastrointestinal (GI) tract is the most common site of extranodal non-Hodgkin's lymphoma (NHL), which is increasing in incidence, but there is no established optimal treatment modality. Thus, this study was investigated the clinicohistologic feature, the therapeutic modalities, and the prognosis for GI-NHL, as well as the factors affecting it. Methods: We retrospectively analyzed 45 patients who had been diagnosed as having GI-NHL and had been followed up from July 1994 to February 2005 at Soonchunhyang University Hospital. The patients were divided into groups according to the site of origin and to various other features, and the survivals of the various groups were compared. The modified Ann Arbor system and WHO classification were adopted for staging and histopathologic classification, respectively. Results: GI-NHL of the stomach, small bowel, ileocecal region, and colon occurred in 28 patients (62.2%), 5 patients (11.1%), 3 patients (6.7%), and 8 patients (17.8%), respectively, In one patient, the entire gastrointestinal tract was diffusely involved. The median age of patients was b5 years (25~78 years), and male-to-female ratio was 1:1.1. Fourteen patients were in stage Ⅰ, 24 in stage Ⅱ, 4 in stage Ⅲ, and 3 in stage Ⅳ. Surgical resection was performed in 19 patients, and combination chemotherapy was performed in 43 patients. Surgical resection only was performed in 4 patients, Chemotherapy only was performed in 26 patients. The expected overall 5 year survival of 45 patients was 39.6%, and there was a significant survival difference between the stages, but between sites of origin (p=0.842). The most important factors influencing the survival was the stage and other factors were not significant. Conclusion: The stomach was the most common site of GI-NHL. Most GI-NHL were localized Stage was the most important prognostic factor. However, Prospective randomized studies are needed to approve the therapeutic modality.

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.

Fabrication and High-Temperature Compressive Behavior of Unique Multi-Sheet Stacked Block Ni–Cr–Al Metallic Foam

Kyu‑Sik Kim,Tae‑Hoon Kang,박만호,Kee‑Ahn Lee 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.5

Large unique block Ni–Cr–Al superalloy foam was fabricated using a combination method of powder-alloying, multi-sheetstacking, and hot compression processes. Subsequently, the compressive properties and deformation behaviors of multi-sheetstacked block metallic foam were investigated from room temperature to 1073 K. The analysis of the resulting structuralcharacteristics of the block foam showed that the interfaces between the sheets have complex strut interactions, such ascontacted (deformed) and intersected struts. The relative density was measured as 2.93% for sheet foam and 4.90% for blockfoam. The compressive deformation of sheet and block Ni–Cr–Al foams showed the typical compressive stress–strain curvesof plastically deformable metallic foams regardless of foam type. However, different deformation behaviors in the plateauregions were detected based on the type of foam. It is noteworthy that the yield strength of block foam showed a relativelylower value than that of sheet foam, even though the block foam had higher relative density. The existence of unique interfacesin the multi-sheet stacked block foam may have affected strength and plastic deformation. Finally, distinct compressivebehaviors related to the structural and microstructural characteristics of block Ni–Cr–Al foam are discussed.

Antiadhesive effect and safety of oxidized regenerated cellulose after thyroidectomy

Kyoung Sik Park,Kyu Eun Lee,Do Hoon Ku,Su-Jin Kim,Won Seo Park2,Hoon Yub Kim3,,Mi Ra Kwon1,Yeo-Kyu Youn1 대한외과학회 2013 Annals of Surgical Treatment and Research(ASRT) Vol.84 No.6

Purpose: To evaluate the antiadhesive effects and safety of an oxidized regenerated cellulose (Interceed) after thyroidectomy. Methods: Seventy-six thyroidectomized patients were prospectively randomized into two groups with regard to the use of Interceed. We evaluated each group for their adhesive symptoms using four subjective and four objective items at the 2nd week, 3rd and 6th month after thyroidectomy. All patients were examined for vocal cord motility by indirect laryngoscope at each period. Results: Total adhesion scores at each postoperative follow-up period decreased with time, but were not significantly different in each group. The median score for swallowing discomfort for liquid was significantly lower in the Interceed group than in the control group 2 weeks after surgery. In addition, the severity of skin adhesion to the trachea was reduced in the Interceed group compared with the control group 6 months after surgery. During the study, there were no adverse effects or significant differences in postoperative complications between the groups. Conclusion: Interceed appeared to be safe and effective in improving neck discomfort at early postoperative periods and preventing skin adhesion to the trachea 6 months after thyroidectomy.

백서의 복강내에 투여한 Mitomycin-C-Polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

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

To evaluate the in-vivo effects of mitomycin-C-polyglycolic acid composite(MMC-PGA) the disk: shaped composite were implanted into the peritoneal cavity of the Sprague-Dawley rats. The pathologic changes were examined at various time points up to 12 weeks. Initially the soft tissue around the inserted disks showed capillary congestion at 3 days. Inflammatory infiltrates with foreign body giant cells appeared from the 2nd week and reached peak response at 6-8 weeks. These reaction diminished prominently at 12 weeks. No specific pathologic change was found in the liver, the kidneys, and the heart. The above results suggest that the MMC-PGA composite can serve as a new device for intraperitoneal chemotherapy of various types of cancers.

폐흡충증으로 확진된 고립성 폐결절 1예

유영권,김규식,김윤현,나국주,김경수,임성철,김영철,박경옥 全南大醫大 2001 전남의대학술지 Vol.37 No.2

독성물질의 세포사 기전 및 세포사 유발물질의 검색법 개발에 관한 연구(Ⅰ) : 독성물질로 인한 파킨슨병 모델에서의 세포사 기전 연구 Study on the cell-death mechanisms of toxin-induced parkinsonism

강태석,김종민,서경원,김영옥,김준규,오재호,이윤동,김규봉,오정자,송연정,임종준,전범석,문전옥,최광식 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

MPTP 독성물질이 도파민성 신경세포에 선택적으로 작용하여 산화성 손상에 의한 신경세포사를 일으키는 것을 이용하여 파킨슨병의 동물모델을 만들고, 이를 통해서 아폼토시스를 비롯한 포사의 기전에 대한 연구 및 너코틴의 신경세포 보호효과 여부를 판정하는 실험을 병행하고자 하였다. 파킨슨꾐의 동물모델을 MPTf 독성 물질을 이용하여 확립하였으며, MPTP(30mgag, i.p.)를 투여한 후 1, 2,3, 4, 5일째 흑질 조직을 채춰하여 tarm로 박걸하여 tyrosine hydroxylase 면역조직화학염색을 수행하여 cell countif우한 결과, control은 57.635ce11s, 1일째 친.OfDells,2일째 57.9±6cells,3일릴 없.3±죠ells, 4일째 49.0츠3cells, 5일째 39.4±Scells료 4, 3일째 뚜렷한 신경세포 수의 감소를 보였다. 신경세포사 기전 규명을 위한 아폼토시스 분걱에서는 벼PTP 투여 후 1, 2, 3, 4, 5일째 조직을 채취하여 Hoechst staining, TUNEL staining을 수곡하였는데 양성 반응을 보인 신경세포는 관찰되지 않아. 아폼토시스로 인한 세포사가 관찰되지 않았다. bIPTP 파킨슨병 동물모델에서 nicotine 보호효과 탐색에 관한 실험은 nicat푸e 0.2mgAg을 5일 퐁안 투여 후 리『fP(30mgag)를 CS7Bt/6 마은스에 복강 내주사로 nicotine과 병용 투여한 후 1, 2, 3, 4, 5일째 뇌를 적출하땄다. 신경세포사가 뚜렷이 관찰되기 시작하는 4, 5일째의 신경세포 수의 감소 정도를 20. 30% 정도 약화시키는 경향을 보였으나, nicotine 보호효과에 대한 추가 실헝이 현재 수행 중에 있다. The cause of Parkinson's disease (PD) is largely unknown. However, free radical toxicit? may plaf a role ip. the degeneration of substantia nigra, which is the Hajorfocus of pathological damages in PD. Recently, a neuroprotective effect of nicotine in PD has been suggested. Therefore, the mechanism of neurodegenerafion and protective potential o( nicotine in PD were investigated in the experimental modeB of Pll using a neurotoxin, C57BL/6mice were administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg,j.p.). The degree of neurodegenerafion was determined by immunohistochemical stainiHB oftyrosine hydroxylase (TH). TH-positive cells on nigral sections were found 56.0 ±4, 57.9 ±6,52.315ce11s, 49.0±3cells, and 39,4±Scells at days 1, 2, 3, 4, 5, respectively (controls : 57.6±Scells). Hoechst and TUNEL staining showed no evidence of apoptosis. The exandnation on themice co-adrunistered with nicotine(0.2mgAg) and MPTP(30mgag) revealed a tendency ofnicotine protective effects. At days 4 and 5, the degree of TH-positive cells was decreased by20-30%, In corclusiffn, the role of apoptosis was not evidenced in this MPTP modeB of PB.The possible proteccon by nicotine should be elucidated with further studies.