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>

혈액암환자에서 조혈모세포 이식 후 따르는 헤르페스 바이러스 감영 양상

이호섭,탁희상,신성훈,김양수,남성진,김혜수,박진희,정수현,김성빈,김예나 고신대학교 의과대학 2010 고신대학교 의과대학 학술지 Vol.25 No.1

배경 : 헤르페스바이러스과에는 단순포진 바이러스(HERPES SIMPLEX VIRUS, HSV), 수두대상포진 바이러스 (VARICELLA-ZOSTER VIRUS, VZV), 엡스타인-바 바이러스 (EPSTEIN-BARR VIRUS, EBV), 그리고 거대세포 바이러스 (CYTOMEGALOVIRUS, CMV) 등이 있다. 헤르페스바이러스 감염은 혈액암환자에서 조혈모세포 이식 환자에서 전파 (dissemination), 이차감염, 세균 중복 감염의 심각한 합병증을 일으킬 수 있다. 하지만 항암약물치료를 받는 림파종 환자에서 항 바이러스 약제의 사용 용량과 기간에 대한 concensus는 없다. 헤르페스바이러스 감염에 대한 발생율과 위험인자를 후향성으로 분석하였다. 방법 : 고신대학교 복음 병원에서 1995년 6월부터 2009 년 2월 사이에 새롭게 진단되어 조혈모세포 이식을 받은 전체 58명의 환자들이 후향적으로 현 연구에 등록했다. 헤르페스 바이러스 감염은 임상적 진단, 혈청학적 검사 또는 병리학적 진단에 기초하여 확진한다. 환자들의 특성은 다음과 같다: 평균 연령은 44세 (범위 19-62세)였고 남녀비는 30:28이었다. 등록된 질환은 백혈병 (n=9, 15.5%), 림프종 (n=30, 51.7%), 다발성 골수종 (n=12, 20.7%), 재생불량성 빈혈 (n=6, 10.3%) 그리고 골수이형성증후군 (n=1, 1.7%)이 포함되었다. 결과는 chi-squre test나 independent samples T test를 사용하여 분석되었다. Multivariate analysises에 대해 logistic regression test를 사용하였다. 결과 : 15명의 환자들 (25.9%)에서 조혈모세포 이식후 헤르페스 바이러스 감염이 발생하였다. 조혈모세포 이식 5년간 누적 발생율은 53.9%였다. Univariate analyses에서 헤르페스 바이러스 감염에 대한 유의한 위험 인자는 없었다. 하지만 조혈모세포 이식후 생존 기간(40.18 ± 30.14 months vs 20.06 ± 26.67 months, p=0.018)은 헤르페스 바이러스 감염의 낮은 발병율과 유의한 관련성이 있었다. 이식 편대 숙주질환 (GVHD)의 존재 (37.5% in developed GVHD vs 0% in no GVHD, p=0.200), 동종조혈 모세포 이식에서 면역억제요법의 기간 (15.98 ± 14.02 months vs 6.78 ± 3.67 months, p = 0.374)은 헤르페스 바이러스 감염에 대한 위험인자가 아니었다. 결론 : 조혈모세포 이식 후 생존 기간은 어사이클로비어 예방을 받은 혈액암 환자에서 헤르페스 바이러스 감염의 낮은 발병율과 연관성이 있는 것으로 보인다. 저용량의 어사이클로비어 예방은 헤르페스 바이러스 감염의 고위험군인 조혈모세포 이식을 받은 혈액암 환자에 필요하리라 생각된다. Background : Herpesviridae family includes herpes simplex virus, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus, etc. Herpesviridae viral infection (HVI) can lead to serious complications including dissemination, secondary infection, bacterial superinfection in patients with hematologic malignancy following hematopoietic stem cell transplantation (HSCT). But there was no consensus on the dose and duration of antiviral agents prophylaxis in patients undergoing chemotherapy. We retrospectively analyzed the incidence and the risk factors for HVI. Method : A total of 58 patients who newly diagnosed and received HSCT with prophylaxis of acyclovir at the Kosin University Gospel Hospital, Busan, Korea between June 1995 and February 2009 were enrolled retrospectively in the current study. HVI was confirmed based on clinical diagnosis, serologic test or pathologic diagnosis. The characteristics of the patients were as follows: the median age was 44 years (range 19-62 years) with a female-to-male ratio of 30:28. The enrolled diseases included leukemia (n=9, 15.5%), lymphoma (n=30, 51.7%), multiple myeloma (n=12, 20.7%), aplastic anemia (n=6, 10.3%) and myelodysplastic syndrome (n=1, 1.7%). The results were analyzed using a chi-square test and independent samples T test. For the multivariate analysis, we used logistic regression test. Results : Fifteen patients (25.9%) developed HVI after HSCT. The cumulative incidence of HVI was 53.8% at 5 years after HSCT. In univariate analysis, there was no significant risk factor for HVI. The presence of graft-versus-host disease (GVHD) (37.5% in developed GVHD vs. 0% in no GVHD, p=0.200), duration of immunosuppressive therapy (IST) in allo-SCT (15.98 ± 14.02 months vs. 6.78 ± 3.67 months, p = 0.374) were not risk factors for HVI. Conclusion : The incidence of HVI was similar to that in historical other studies. There was no risk factor associated with development of HVI. Most of the HVI occurred within the first 24 months after transplantation. So long term use of antiviral prophylaxis may be needed to prevention of HVI after HSCT.

외상 후 근관내로의 치조골 함입

임예진,김영진,김현정,남순현 大韓小兒齒科學會 2011 大韓小兒齒科學會誌 Vol.38 No.4

영구치의 외상성 손상은 전체 외상 환자 중 높은 빈도로 발생하며 사고의 대부분은 치근이 미완성되어 있는 시기에 발생하 여 치수, 치주인대, 치조골, Hertwig 상피 근초(HERS)에 다양한 영향을 주게 된다. 손상 정도에 따라 치수의 완전한 재혈관 화, 근관 석회화, 근관내 치조골 함입 등의 다양한 치유 양상을 나타내며, 치근단의 성장 정지 및 치수 괴사로 인한 염증성 치 근 흡수 등의 합병증을 나타낼 수 있다. 본 증례에서는 미성숙 영구치 치근단을 가진 세 환아에서 외상에 의한 Hertwig 상피 근초의 손상으로 발치와 기저부에 존 재하는 치근막 세포와 골세포의 치수강내로의 증식으로 인해 치근 발육 정지 및 근관내로의 치조골 함입을 나타내어 보고하 고자 한다. 외상 후 Hertwig 상피 근초의 손상에 의한 근관내로의 치조골 함입 치유 양상은 치수는 정상적인 기능을 하는 것으로 생각 되며, 유착 등의 합병증이 동반되지 않는 경우 특별한 치료를 필요로 하지 않으므로 감별 진단이 요구되며, 외상 받은 치아의 치료시 Hertwig 상피 근초에 대한 부가적인 외상을 가하지 않도록 주의해야 한다. Traumatic injury on tooth occurs frequently among trauma patients, and mainly occurs on tooth with premature roots which influences pulp tissue, periodontal ligament, alveolar bone, and Hertwig’s epithelial root sheath. According to the degree of trauma, a number of kinds of healing process can be observed, such as complete re-vascularization of pulp, root canal obliteration, growth suspension of root apex, and invasion of alveolar bone into root canal, and there can be some complications such as necrotic change of inflammatory root resorption and partial pulp necrosis due to pulp necrosis toward complete necrosis. In this clinical case, 3 patients who had traumatic injury showed root growth suspension and alveolar bone invasion into root canal due to proliferation of periodontal ligament cell and osteocyte at the base of extraction socket into pulp chamber because of the injury on Hertwig’s epithelial root sheath. If intrusion of alveolar bone into root canal due to injury on Hertwig’s epithelial root sheath after having traumatic injury doesn’t show any complication, the pulp may be considered to have normal vitality and doesn’t need any further treatment, therefore differential diagnosis is very necessary. However, it may be accompanied with suspension of root growth, therefore, additional trauma during the treatment of injured tooth should not be applied.

만성 견비통에 대한 동씨침 치료의 무작위 대조군의 임상 연구

김찬영,권나현,신예지,남동우,김건형,김종인,최도영,이윤호,이재동 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2007 東西醫學硏究所 論文集 Vol.2007 No.-

Objectives : To observe the effect of acupuncture treatment in chronic shoulder pain patients. Methods : 36 voluntary patients were randomly assigned to an acupuncture treatment group(E GrouP, n=18) and a control group(C GrouP, n=18). The E Group patients received acupuncture treatment on LI_(15), TE_(14), GB_(21) and Master Dong's acupuncture points, Shin-gwan and Gyun-joong, twice a week for four weeks. The C Group patients received no treatment. All patients in both groups were instructed to practise self exercise in their daily lives. Evaluations were made at baseline and after four weeks of study. The Constant Shoulder Assessment(CSA), Shoulder Pain and Disability Index(SPADI) and the patient's subjective pain was measured by Visual Analogue Scale(VAS). The obtained data was analyzed. Results '. The E Group showed significant(p<0.05) improvement in CSA, SPADI and VAS after four weeks of treatment. The C Group showed significant(p<0.05) improvement in CSA, but the change of SPADI and VAS was insignificant(P>0.05). CSA and SPADI of E Group significantly(p<0.05) improved compared to the C GrouP, but the difference of VAS change in the two groups was insignificant(p>0.05). Conclusions : Four weeks of acupuncture treatment significantly improved CSA, SPADI and VAS. The improvement of CSA and SPADI was significant(p<0.05) compared to untreated patients.

충북지역 대학생들의 음주정도와 식생활지침 이행도와의 관계

김기남, 김지현, 정예지 충북대학교 생활과학연구소 2013 생활과학연구논총 Vol.17 No.2

The purpose of this study was to investigate the association of alcohol drinking and the practices of dietary guidelines among university students in Chungbuk. Questionnaires were distributed to 351 university students and 348 (203 males and 145 females) were collected from May 21 to June 28, 2012. "Soju" was the most frequently consumed alcohol by university students. As for drinking amount, 32.7% of the students drank "ten glasses of soju or more" at one time. The frequency and the amount of drinking were significantly greater in male students than female students. While many students practiced "handling food hygienically when cooking" and "choosing clean ones when purchasing food or dining out", less students practiced "controlling energy consumption according to the activity level" and "removing fat when consuming meat." Those who drank four times per week or more responded a lower rate of practice than those who drank less frequently. As for drinking motive, those who drank "habitually" also recorded a lower rate of practice than those who drank "to fit in the mood." In conclusion, alcohol drinking had negative influences on the dietary practice of university students. Campaigns or nutrition education should be designed to help to establish a healthy drinking culture in university

올레산의 비율에 따른 아데노신의 경피 투과의 영향

남현빈,정세진,구민석,오예진,김용민,이훈희,윤수정,임정균 순천향대학교 부설 산업기술연구소 2021 순천향 산업기술연구소논문집 Vol.27 No.2

In addition to the development of functional cosmetics, technology to increase percutaneous absorption rate when applied to the skin is an important task. In this experiment, oleic acid was used as a skin absorption promoter, and its effect on transdermal permeability of adenosine was studied and analyzed using a skin-like membrane. As a result of the experiment, it was investigated that the permeability coefficient and concentration of adenosine are proportional to the content of oleic acid. This indicates that a high proportion of oleic acid is effective as a skin absorption promoter.

퇴행성 척추관 협착증의 치료 방법에 대한 비교

원예연,김남현 대한척추외과학회 1995 대한척추외과학회지 Vol.2 No.2

The authors reviewed 114 patients of degenerative lumbar spinal stenosis who were admitted to the Department of Orthopaedic Surgery, Severance Hospital from January 1986 to January 1991. The male to female ratio was 1:1.9 and the mean age of patient was 54 years(range 42-78). Follow-up ranged from 2 years to 5 years 4 months with a mean of 2 years 8 months. Patients could be divided into two groups. degenerative lumbar stenosis(50 patients, 44%) and with degenerative spondylolisthesis(64 patients, 56%) Of the 90 patients who had degenerative lumbar stenosis, twenty four patients(21%) was treated conservatively, fifteen patients(13%) underwent posterolateral fusion without instrumentation after posterior decompression and fifty one patients(45%) underwent posterolateral fusion with segmental spinal instrumentation using transpedicular screw after extensive posterior decompression. Among the cases applied transpedicular screw, 29 cases were Cotrel-Dubousset system, 19 cases were Steffe system and 3 cases were others. For the remaining 24 patients who had degenerative lumbar stenosis with degenerative spondylolisthesis underwent anterior interbody fusion after discectomy. According to Kim's criteria(1991), ten patients(42%) were classified as good in conservative treatment group but there was no excellent result, and seventy eight patients(87%) were classified as excellent or good in surgical treatment groups. In conclusion, for the treatment of degenerative lumbar spinal stenosis, anterior interbody fusion orposterolateral fusion after extensive decompression of stenosed neural elements are considered more reliable and satisfactory treatment than conservative treatment

미세알부민뇨를 동반한 인슐린 비의존성 당뇨병 환자에서 혈장 Endothelin의 변화

서예경,정상원,남직화,신병호,전종민,김정국,김동희,하승우,김보완 慶北大學校 醫科大學 1996 慶北醫大誌 Vol.37 No.3

목적 : 혈관내피세포에서 생성되는 endothelin(ET)는 강력한 혈관수축작용을 가진 펩타이드로 당뇨병 환자에서 혈관내피세포의 손상여부에 따라 혈중 농도가 증가할 수 있으며 혈관합병증과 관련이 있다는 보고가 있다. 그러나. 혈중 ET치의 상승과 당뇨병성 합병증의 상관성에 대해서는 논란이 많다. 이에 저자들은 인슐린 비의존성 당뇨병 환자에서 미세알부민뇨의 동반유무에 따른 혈중 ET치의 변화 및 혈장 ET치와 요중 알부민 배설률과의 상관성을 검토하였다. 대상 및 방법 : 인슐린 비의존성 당뇨병 환자중 미세알부민뇨를 보인 22명과 정상알부민뇨를 보인 43명을 대상으로 하였으며 혈장 ET를 측정하여 요중 알부민 배설률, 당뇨병성 망막증 및 당뇨병 관련인자들과의 관계를 비교하였다. 결과 : 당뇨병성 망막증이 합병된 군에서 망막증이 합병되지 않은 군에 비하여 혈장 ET치가 유의하게 높았던 반면 (각각 1.9±0.66, 1.5±0.76pg/㎖, p<0.05) 미세알부민뇨를 보인 군과 정상알부민뇨를 보인 군사이에 혈장 ET치는 통계학적으로 유의한 차이가 없었다(각각 1.9±1.14, 1.7±0.69pg/㎖). 또한 요중 알부민 배설률과 혈장 ET치 사이에 유의한 상관관계는 없었으며 미세알부민뇨를 동반한 인슐린 비의존성 당뇨병 환자군에서 혈장 ET치는 당뇨병의 관련인자들과도 유의한 상관관계가 없었다. 결론 : 인슐린 비의존 당뇨병 환자에서 혈장 ET치가 초기 당뇨병성 신증의 합병여부나 미세알부민뇨의 정도를 반영하기는 어려울 것임을 시사한다. Background : Endothelin(ET), a potent vasoconstritor peptide released from vascular endothelial cells, is known to be increased in diabetic patients with vascular damage and related with diabetic angiopathy. However, whether plasma ET levels may be related to diabetic complications is controversial. We studied the change of ET levels in non-insulin dependent diabetics with microalbuminuria and relation between ET and urinary albumin excretion rate. Methods : Plasma ET levels of 22 non-insulin dependent diabetics with microalbuminuria and 43 patients with normoalbuminuria were measured and relations of plasma ET to diabetic complications such as urinary albumin excretion rate, retinopathy and other associated factors were studied. Results : Plasma ET levels were significantly higher in patients with diabetic retinopathy than those without retinopathy(1.9 ± 0.66 vs 1.5 ± 0.76 pg/㎖. p<0.05). The difference, however, between diabetics with and without microalbuminuria was not significant(1.9 ± 1.14 vs 1.7 ± 0.69 pg/㎖). There were no correlations of plasma ET to urinary albumin excretion rate and to the other associated factors in non-insulin dependent diabetics. Conclusion : These results suggest that plasma ET levels may not seem to act as a predictor of diabetic nephropathy or microalbuminuria in non-insulin dependent diabetics.

척추마취 후 통증 자가조절법 시행이 척추강 내 몰핀의 용량에 미치는 영향

이예철,우남식,김윤수 건국대학교 의과학연구소 1998 건국의과학학술지 Vol.8 No.-

Intrathecal administration of morphine is a highly efficacious modality for the treatment of postoperative pain. However, side effects are often present and rarely life-threatening. Routine management of postoperative pain have been changed as a result of technological advances in drug delivery systems(patient controlled analgesia: Ⅳ-PCA). The purpose of this study was to observe the effect of Ⅳ-PCA on variable dosage of intrathecal morphine, and to evaluate the minimal dosage of intrathecal morphine for pain relief. Eighty patients requiring spinal anesthesia for operation were randomly assigned to receive intrathecal morphine 0.01mg(Group Ⅰ: n=20), 0.02mg(Group Ⅱ: n=20), 0.04mg(Group Ⅲ: n=20), and 0.1mg(Group Ⅳ: n=20). All patients were operated under spinal anesthesia with 0.5% bupivacaine 10-15mg, and taken Ⅳ-PCA. PCA unit was filled with 60ml: mixed with fentanyl 50㎍, ketorolac 18mg, and normal saline. It had a flow rate of 0.5ml/hr and lockout interval was 15minutes. The degree of analgesia was subjectively evaluated by visual analogue scale(VAS). Patients were evaluated 3, 6, 12, 24, and 48 hours after operation for pain relief, nausea, vomiting, pruritus, and respiratory depression. VAS pain score were significantly lower in group Ⅱ,Ⅲ, and Ⅳ than group Ⅰ at postoperative 6, 12, 24hours(p<0.05), but were no significant difference at 3 and 48hours. There were no apparent cases of respiratory depression. Nausea or vomiting occurred in 10-25% of all patients. Pruritus occurred in 5-10% ofⅠ,Ⅱ,Ⅲ group, and occurred in 40% of group Ⅳ. Urinary retention occurred in 5% ofⅠ and Ⅱ group, and in 35-40% of group Ⅲ and Ⅳ. We conclude that the Ⅳ-PCA with 0.02mg of morphine is an effective and safe method for pain control after spinal anesthesia.

다시마 푸코이단추출물과 지질대사의 연관성

강금석,남천석,김인덕,권륜희,이동찬,허예영,하배진 신라대학교 자연과학연구소 2007 自然科學論文集 Vol.16 No.-

The effects of Laminaria japonica fucoidan extract (LJFE) on the biochemical parameters of lipid-related function were investigated in liver and serum of CCl_(4)-treated rats. LJFE of 100 mg/kg concentration was intraperitoneally administered into rats at dose of 1.5 ml/kg for 14 days. On the day 15, 3.3 ml/kg of CCl_(4) dissolved in olive oil (1:1) was injected 12 hours before anesthetization. We examined the lipid-related functions and enzyme activitys by measuring the levels of total cholesterol (TC), triglyceride (TG), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in serum. The results showed that CCl_(4) treatment increased the high values of TG, LDH and ALP decreased the low values of TC but LJFE pretreatment decreased the high values of TG, LDH and ALP to the low values, increased the TC. It was suggested that LJFE can be used as the potential candidate for the lipid-metabolism natural supplement.