Cyclosporine-A에 의한 신독성 유발 쥐에서 cGMP phosphodiesterase 억제제가 eNOS와 VEGF의 발현에 미치는 영향

의학과/박사[한글] [영문]Background: Cyclosporine-A (CsA) inhibits the differentiation of T cells by suppressing calcineurin and thus blocks the activation of the IL-2 promotor gene which blocks the rejection of kidney transplants and is an essential immune suppressor used after kidney transplantation. However, when CsA is used long term, nephrotoxicity develops. Hence, long term CsA use must be limited. The mechanism of CsA induced nephrotoxicity have been suggested vasoconstriction due to the reduction of nitric oxide (NO), and tissue fibrosis caused by the elevation of transforming growth factor (TGF)-beta, vascular endothelial growth factor (VEGF). The cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) inhibitor (Udenafil, Zydena®), active in the NO/cGMP pathway, with its physiological function induced by cGMP, has been reported to ameliorate renal injury by the increase of cGMP through the suppression of cGMP-specific PDE-5. In this study, in a rat model of CsA-induced nephrotoxicity, the administration of the PDE-5 inhibitor udenafil was studied to determine whether it ameliorated kidney dysfunction and altered the expression of eNOS and VEGF.Methods: A right nephrectomy was performed in Sprague-Dawley rats (N=30, 200-250g, male). The Ischemia group (N=6), had ligation of the left renal artery for 45 minutes (IR) and was maintained for 28 days. The Udenafil group (N=6), after ischemia, was treated with 10 mg/kg udenafil orally for 28 days. The CsA group (N=6), after IR and then 15 mg/kg cyclosporine-A was injected subcutaneously for 28 days. The CsA with udenafil group (N=6), after IR received 15 mg/kg cyclosporine-A injected subcutaneously together with the oral administration of 10 mg/kg udenafil for 28 days. A low salt diet was provided to all groups. After the collection of blood on day 28, the remaining kidney was resected surgically and the injury was assessed by hematoxylin-eosin (H&E) staining, immunohistochemical staining, western blot, real time-PCR analysis was used to assess degree of renal injury and the expression of eNOS and VEGF.Results: The comparison with the Ischemia group and the CsA group, after the administration of udenafil, showed that the creatinine was significantly decreased (p=0.002, p=0.002, respectively). The H&E staining, comparing the Ischemia group and the CsA group, showed that the level of loss of the nuclei in the proximal tubules was significantly decreased after the administration of udenafil (p=0.004, p=0.002, respectively). The immunohistochemical staining showed that eNOS stained strongly in the Udenafil group and the CsA with udenafil group compared to the other groups. The results of the eNOS western blot showed that it was not changed in the Ischemia group; however, the expression of the protein was decreased in the CsA group, and increased in the Udenafil group. For the VEGF western blot, the expression of the protein was reduced only in the CsA with udenafil group. The eNOS mRNA assessed by real time-PCR was decreased in the CsA group compared to the other groups (p=0.000). VEGF mRNA was decreased in the CsA group, and after the administration of udenafil, it showed a tendency to decrease more (p=0.003, p=0.005, respectively).Conclusion: cGMP phosphodiesterase inhibitor ameliorated kidney injury in a rat model of CsA-induced nephrotoxicity. The mechanism appears to be associated with an increase of eNOS and reduction of VEGF.ope

Clinical significance of B-type natriuretic peptide levels and impedance cardiography in maintenance hemodialysis patie

의학과/석사[한글] 정기적 혈액투석 치료 중인 환자에서 유병률과 사망률의 가장 많은 부분을 차지하는 심혈관계 질환에 대해 평가할 수 있는 비침습적인 방법 중의 한가지로 알려진 B-type natriuretic peptide (BNP)의 측정은 혈액투석을 받고 있는 환자들의 심장기능 평가에 제한적인 요소들이 많은 것이 사실이다. 이에 저자들은 비침습적인 방법으로 신체의 impedance를 이용하여 cardiac index (CI)와 같은 심장기능을 평가하고 BNP와 impedance cardiography (ICG)와의 연관성 및 임상적 유용성에 대해 평가하였다.정기적으로 혈액투석 치료를 받고 있는 환자 40명 (남자 18명, 여자 22명)과 10명의 정상 대조군을 대상으로 하였으며 환자군은 모두 투석 전후에 BNP와 ICG를 측정하여 비교하였다.1. BNP뿐만 아니라 ICG의 여러 요소들이 정상 대조군에 비해 환자군에서 의미있게 높았다 (p<0.05).2. BNP, stroke index (SI), stroke volume (SV) 및 thoracic fluid content (TFC)는 투석 후에 의미있는 변화를 보였다(p<0.05).3. 당뇨군은 투석전 BNP, 투석후 BNP, SI, SV 및 velocity index (VI) 등이 비당뇨군과 유의한 차이를 보였다(p<0.05).4. 투석전 BNP 측정치는 투석후 BNP, 수축기 혈압, 확장기 혈압, cardiac output (CO), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI) 및 TFC 등과 의미있는 상관관계를 보였다(p<0.05).이상의 결과로 BNP와 ICG의 측정은 비침습적인 방법으로 서로 상호보완 기능을 가지고 혈액투석을 받고 있는 환자의 심장변화를 평가할 수 있는 유용한 진단도구로써 생각되며 더 많은 환자를 대상으로 한 연구·검토가 필요할 것으로 생각된다. [영문]The risk for cardiovascular morbidity and mortality is higher in hemodialysis (HD) patients than in general population. Early diagnosis, treatment and prevention of cardiovascular disease (CVD) are the best way to reduce the most important cause of death. However, cardiac geometric and/or functional alterations including left ventricular hypertrophy, atherosclerosis and/or systolic and diastolic dysfunction are not easily known to nephrologist in that diagnostic procedure is limited because cardiac angiography and echocardiography are frequently needed.To evaluate the cardiac alteration by non-invasive tools, we measured pre- and post-HD B-type natriuretic peptide levels and performed impedance cardiography (ICG) in 40 HD patients and 10 healthy adults as control.Pre- and post-HD BNP level, cardiac index (CI), cardiac output (CO), stroke volume (SV), systemic vascular resistance index (SVRI), systemic vascular resistance (SVR), acceleration index (ACI), velocity index (VI) and thoracic fluid content (TFC) in patients were significantly higher than those in normal control group (p<0.05). Pre-HD BNP level, stroke index (SI), SV and TFC were significantly different after HD (p<0.05). There were significant differences in pre-HD BNP level, SI, SV and VI between diabetes and non-diabetes groups (p<0.05). Pre-HD BNP level correlated significantly with post-HD BNP level, systolic blood pressure, diastolic blood pressure, CO, SVRI, SVR and TFC (P<0.05). In multiple linear regression analysis, SVR and TFC were positively associated with pre-HD BNP level (R2 = 0.289). The area under the ROC curve for cardiac alterations was 0.749 for pre-HD BNP level. A cutoff-point of 560 pg/mL for pre-HD BNP level was 80% sensitive and 72% specific in determining cardiac alterations.Even though cardiac alterations of patients were heterogeneous in our study, serum BNP level and some parameters (SVR, TFC) of ICG seem to be available to nephrologist for detecting and monitoring cardiac conditions in HD patients.ope

한국 일반 성인 인구에서의 인슐린 저항성과 골밀도, 골강도와의 관련성

보건학과배경 및 목적 인슐린 저항성은 골밀도, 그리고 골강도와 연관성이 있는 것으로 보고되어 왔다. 그러나 대부분의 연구들이 골밀도를 뼈의 구획 별로 나누지 않고, 전체 골밀도만을 평가했으며, 이를 골강도와 함께 조사한 연구도 부족하다. 인슐린 저항성이 뼈 건강에 미치는 전반적인 영향을 평가하기 위해서는 골밀도와 골강도를 함께 조사할 필요가 있다. 본 연구의 목적은 한국의 지역사회 거주 일반 성인 인구를 대상으로 인슐린 저항성과 골밀도, 골강도와의 독립적인 관련성을 평가하는 것이다. 연구 방법 본 연구는 지역사회기반 코호트인 Cardiovascular and Metabolic Disease Etiology Research Center (CMERC) 에 연구참여 동의 및 기반조사를 마친 2,533명의 성인 (856명의 남자와 1,497명의 여자) 을 대상으로 진행하였다 (평균나이 49.3세). 인슐린 저항성은 HOMA-IR 지표를 이용하여 측정하였다. 골밀도는 Quantitative computed tomography (QCT)로 측정하였고, 골강도는 Compression strength index (CSI), Bending strength index (BSI), Impact strength index (ISI) 의 세 가지 평가방법을 이용하여 측정하였다. 혼란변수로는 연령, 체중, 흡연상태, 음주상태, 신체활동, 혈중 비타민 D 등을 보정하였다. 연구 결과 모든 혼란변수를 보정하였을 때, 남자에서는 인슐린 저항성이 total BMD (β=-0.029, p=0.001), trabecular BMD (β=-0.015, p=0.000), CSI (β=-0.286, p<0.001), ISI (β=-0.018, p=0.004) 와 통계적으로 유의한 음의 관련성을 보였지만, cortical BMD (β=-0.015, p=0.095), BSI (β=-0.058, p=0.946) 와는 통계적으로 유의한 관련성을 보이지 않았다. 여자에서는 모든 혼란변수를 보정하였을 때, 인슐린 저항성과 total BMD (β=-0.017, p=0.015), CSI (β=-0.182, p<0.001), ISI (β=-0.017, p<0.001) 와 독립적인 관련성이 있었으나, cortical BMD (β=-0.012, p=0.082), trabecular BMD (β=-0.04, p=0.174), 그리고 BSI (β=-0.074, p=0.879) 와는 연관성을 보이지 않았다. 연구 결론 본 연구에서, 한국 지역사회 일반 성인 인구에서는 높은 인슐린 저항성을 가진 사람들이 그렇지 않은 사람에 비해 더 낮은 골밀도와 골강도를 보이는 것이 관찰되었다. Introduction Insulin resistance has been reported to be associated with bone mineral density (BMD) and bone strength of femoral neck. Low BMD and bone strength are risk factors for falls or fracture and may even lead to cardiovascular disease (CVD). However, it has not been fully investigated whether compartment-specific BMD and bone strength of femur neck are associated with insulin resistance. The aim of this study was to investigate the association between insulin resistance and compartment-specific BMD and bone strength of femur neck. Methods This cross-sectional study used baseline data from the Cardiovascular and Metabolic Disease Etiology Research Center (CMERC) cohort study. A total of 2,533 study participants completed both questionnaire survey and health examinations between 2013 and 2015. After excluding participants who were taking drugs for diabetes (n=122) and osteoporosis (n=53) and who had missing data on key variables (n=5), 856 men and 1,497 women aged 30-64 years were included in this study. Cortical and trabecular BMD of femur neck were measured with quantitative computed tomography. Fasting insulin level was assayed using a RIA procedure on an immunoradiometric assay. Fasting glucose was determined by the colorimetry method. The association between insulin resistance and BMD (total bone compartment, cortical bone compartment and trabecular bone compartment) femur neck and bone strength index (compressive strength index, CSI; bending strength index, BSI; impact strength index, ISI;) was investigated by multiple linear regression model. Age, body mass index (BMI), smoking, alcohol intake, physical activity and 25-hydroxy vitamin D were considered as a covariates. Results In men, there was inversely associated with total BMD (ß=-0.029, p=0.001), trabecular BMD (ß=-0.015, p=0.000), CSI (ß=-0.286, p<0.001) and ISI (ß=-0.018, p=0.004) when adjusted for all covariates. However, the association with cortical BMD (ß=-0.015, p=0.095) and BSI was not significant (ß=0.058, p=0.946). In women, there was a negative association between HOMA-IR and total BMD (ß=-0.017, p=0.015), CSI (ß=-0.182, p<0.001) and ISI (ß=-0.017, p<0.001), not significant with compartment-specific BMD (Cortical: ß=-0.012, p=0.082, Trabecular: ß=-0.004, p=0.174) and BSI (ß=0.074, p=0.879). Conclusions High insulin resistance was negatively associated with total and trabecular BMD, CSI and ISI in men, however, there was significant association with CSI and ISI only in women.open석

충청남도 날씨경영 인증등록 추진

추진경과 보고서1. 서론 2. 날씨경영인증 현황 및 우수사례 3. 인증 절차 및 양식 4. 추진경과 및 추진계

First-principles calculation of electronic structure of YSZ

Maste

충청남도 날씨경영 인증등록 추진

추진경과 보고서1. 서론 2. 날씨경영인증 현황 및 우수사례 3. 인증 절차 및 양식 4. 추진경과 및 추진계

Stable Doping of Graphene by Intercalated Organic Solvent at Graphene/Substrate Interface

2

충남기후정보브리핑 15호-충청남도 2016년 8월 더위, 현황과 전망

◊ 올여름, 특히 8월은 극심한 무더위로 온열질환자 급증, 양식장 피해 증가등 사회 적반적으로 폭염에 의한 피해가 발생함 ◊ 이러한 폭염 피해 발생이 기후변화로 인해 지속될 것으로 전망됨에 따라올해 8월 폭염현황과 미래 전망을 통해 폭염대비 필요성 제고가 필요함 ※ 본 브리핑은 CNI 인포그래픽 22호(2016.9.28.) 원시자료를 활용하여 작성됨1. 충청남도 8월 폭염현황 2. 2016년 서해안 해수온도 3. 온열질환자 발생현황 4. 온도상승으로 인한 질병 환자 수 추이 5. 미래 8월 더위 전망-기후변화 시나리오(RCP8.5) 분석 6. 정책제

내포시 친환경 클러스터 체험교육 시범사업 지원

강의 발표자료N/

충남기후정보브리핑 11호-충청남도 기후변화 관련 정책통합 비전제안

◊ 제21차 유엔기후변화협약 당사국총회에서 파리협정이 채택되어 국가와 지자체의 대응전략 수립 필요성이 제기됨에 따라, ◊ 道 기후변화 관련 산업, 에너지, 녹색성장을 포함하는 정책통합 비전(네이밍)을 제안하여, 충청남도 기후변화 대응역량 강화를 위한 정책기반 조성에 기여하고자 함.1. 기후변화협상 동향 2. 비전(네이밍) 제안 절차 3. 기후변화 정책통합 비전개발을 위한 10대 현안도출 4. 기후변화 정책 통합 비전(안) 제안 5. 전문가 및 도민 설문을 통한 선호도 조사 6. 비전실현을 위한 로드맵 수립