• Animal cells and systems
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• 제7권4호
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• pp.309-315
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• 2003

Renal dipeptidase (RDPase, membrane dipeptidase, dehydropeptidase 1, EC 3.4.13.19) has been widely studied since it was first purified from porcine kidney brush border membrane. It was reported that RDPase activity in urine samples of acute and chronic renal failure patients decreases. Nitric oxide (NO) is a highly reactive free radical involved in a number of physiological and pathological processes. NO is able to act in a dual mode, leading either to induction of apoptosis or to blunted execution of programmed cell death. NO inhibited the RDPase release from porcine renal proximal tubules, which could be blocked by L-NAME. Chitosan, the linear polymer of D-glucosamine in $\beta$(1\longrightarrow4) linkage, not only reversed the decreased RDPase release by NO but also increased NO production in the proximal tubule cells. The stimulatory effect of NO on RDPase release from proximal tubules in the presence of chitosan must be different from the previously proposed mechanism of RDPase release via NO signaling pathway. Chitosan stimulated the RDPase release in the proximal tubules and increased RDPase activity to 220% and 250% at 0.1% and 1%, respectively. RDPase release was decreased to about 40% in the injured proximal tubules and was recovered in proportion to the increase of chitosan. Chitosan may be useful in recovery of renal function from $HgCl_2$injury.

• 동의생리병리학회지
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• 제22권4호
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• pp.810-814
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• 2008

Most inflammatory disorders are usually treated using anti-inflammatory drugs including non-steroidal anti-inflammatory drugs (NSAID) and steroidal anti-inflammatory drugs (SAID). Prolonged uses of NSAIDs and SAIDs may frequently cause adverse side-effects such as nausea, vomiting, diarrhea, constipation, decreased appetite, kidney and liver failure, ulcers, and prolonged bleeding after an injury or surgery. Thus, it is necessarily required to develop a new anti-inflammatory drug with little side-effects. Dandelion (Taraxacum officinale) possesses the therapeutic abilities to eliminate body heat and toxins and to remove swelling and inflammation. In order to verify the anti-inflammatory activity of dandelion, TPA(12-O-tetra decanoylphorbol-acetate)-induced or croton oil-induced acute edema was developed in the mouse ears, and dandelion extract dissolved in acetone was applied to both sides of inflamed ears. It was found that dandelion could significantly reduce the ear swelling, compared to that of non-treated control. In the case of $20{\mu}{\ell}$ application of $100mg/m{\ell}$ dandelion solution (DA-100), its anti-inflammatory effect was comparable to that of indomethacin, a non - steroidal anti-anflammatory drug. Taken together, it could be concluded that topically applied dandelion extract exhibited its potentials as a new drug candidate with an effective anti-inflammatory activity.

• Childhood Kidney Diseases
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• 제19권2호
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• pp.184-189
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• 2015

Poststreptococcal glomerulonephritis (PSGN) is one of the most well-known and important infectious renal diseases resulting from a prior infection with group A ${\beta}$-hemolytic streptococcus. The typical clinical characteristics of the disease reflect acute onset with gross hematuria, edema, hypertension and moderate proteinuria after the antecedent streptococcal infection. In children, usually PSGN is healed spontaneously but if it combines with fast progressing glomerulonephritis, it would be developed to chronic renal failure. Therefore, it is important to make a fast diagnosis and treatment by simple tools to predict the course and the prognosis of disease. Sonography is a simple tool for diagnosis but there is no typical renal sonographic finding in PSGN, so it is difficult to predict the course and the prognosis of disease by sonographic findings. In comparison between two cases of renal sonographic findings in PSGN, a patient who showed more increased echogenicity in more extended area of renal sonography had the severe results of renal pathology, prolonged treatment period and low serum C3 level. Here, we report the different findings of renal sonography and pathology depending on the degree of severity between two patients. Thus, it is necessary to gather more information from further studies to make a consensus about the relationship between the renal sonography and the prognosis of disease in PSGN.

• Toxicological Research
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• 제24권4호
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• pp.281-287
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• 2008

Impairment of hepatic metabolism of sulfur-containing amino acids has been known to be linked with induction of liver injury. We determined the early changes in the transsulfuration reactions in liver of rats challenged with a toxic dose of $CCl_4$ (2 mmol/kg, ip). Both hepatic methionine concentration and methionine adenosyltransferase activity were increased, but S-adenosylmethionine level did not change. Hepatic cysteine was increased significantly from 4 h after $CCl_4$ treatment. Glutathione (GSH) concentration in liver was elevated in $4{\sim}8$ h and then returned to normal in accordance with the changes in glutamate cysteine ligase activity. Cysteine dioxygenase activity and hypotaurine concentration were also elevated from 4 h after the treatment. However, plasma GSH concentration was increased progressively, reaching a level at least several fold greater than normal in 24 h. ${\gamma}$-Glutamyltransferase activity in kidney or liver was not altered by $CCl_4$, suggesting that the increase in plasma GSH could not be attributed to a failure of GSH cycling. The results indicate that acute liver injury induced by $CCl_4$ is accompanied with extensive alterations in the metabolomics of sulfurcontaining amino acids and related substances. The major metabolites and products of the transsulfuration pathway, including methionine, cysteine, hypotaurine, and GSH, are all increased in liver and plasma. The physiological significance of the change in the metabolomics of sulfur-containing substances and its role in the induction of liver injury need to be explored in future studies.

• 대한한의학회지
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• 제22권3호
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• pp.21-30
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• 2001

목적 : 이전 연구에서 단삼 추출액이 강력한 항산화 작용이 있음을 확인한 바 있어 단삼 추출액이 신장세뇨관 세포에서 oxidant에 의한 세포사망 및 DNA 손상을 방지하는 지를 조사하고 이러한 효과가 지질의 과산화를 억제하는 효과에 기인하는 지를 시험하였다. 방법 : 신장 근위세뇨관 세포 유래 세포주인 opossum kidney (OK)세포를 이용하여 세포 사망은 frypan blue exclusion방법을 이용하여 평가하였고, DNA손상 정도는 double stranded DNA의 파괴를 측정하여 평가하였다. Oxidant 약물 모델로는 $H_2O_2$를 사용하였다. 결과 : $H_2O_2$는 적용시 간과 농도에 비례하여 세포 사망을 유도하였다. 단삼 추출액은 0.05% 농도에서 $H_2O_2$에 의한 세포사망 및 DNA 손상을 방지하였다. 이러한 방지효과는 $H_2O_2$ 제거 효소인 catalase와 철 착염제인 deferoxamine에 의해서도 나타났다. 그러나 강력한 항산화제인 DPPD는 $H_2O_2$에 의한 세포 사망이나 DNA손상을 방지하지 못하였다. $H_2O_2$는 세포내 ATP 농도를 감소시켰으며. 이러한 감소는 poly (ADP-ribose) polymerase억제제인 3-aminobenzamide에 의해 방지되었으나 단삼 추출액에 의해서는 영향을 받지 않았다. 3-aminobenzamide는 $H_2O_2$에 의한 세포 사망을 방지하였다. $H_2O_2$는 지질의 과산화를 증가시켰으며, 이러한 변화는 단삼 추출액과 DPPD에 의해 방지되었다 결론 : OK 세포에서 $H_2O_2$에 의한 세포사망과 DNA 손상에는 지질의 과산화가 중요한 역할을 하지 않으며, 단삼 추출액의 $H_2O_2$에 의한 세포 사망과 DNA 손상 방지 효과는 항산화 작용이 아닌 다른 기전에 기인하는 것으로 사료된다.

• Molecular & Cellular Toxicology
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• 제2권3호
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• pp.193-201
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• 2006

Cephalexin, one of most widely prescribed cephalosporin, has been reported to cause acute renal failure as a side effect in human and experimental animals. Although numerous animal studies have been reported for the cephalosporin nephrotoxicity, the molecular and cellular nephrotoxic mechanisms of cephalexin are still unknown. This investigation evaluated the time-dependent gene expression profile of kidney in mouse during cephalexin induced nephrotoxicity. C57BL/6 female mice were administered either saline or 1,000 mg/kg cephalexin intraperitoneally. Mice were sacrificed at 3, 6, and 24 hr after administration. Blood biochemical and histopathological results indicated cephalexin induced nephrotoxicity. Microarray experiment carried out using Affymetrix $GeneChip^{(R)}$. There were 198 informative genes that were significantly expressed >5-fold versus control at 3, 6, and 24 hr (p<0.01), of which 156 and 42 were up-and down-regulated, respectively. Major classes of up-regulated genes at 3, 6 hr included those involved in MAPK/Jak-STAT signaling pathway and immune response such as cytokine-cytokine receptor interaction and complement and coagulation cascades. At 24 hr, up-regulated genes were mainly involved in regeneration/repair and immune response; down-regulated genes were generally associated with transporters and intermediary metabolism. Among the up-regulated genes at 24 hr, several potential biomarkers on nephrotoxicity such as Kim-1, Fga, Timp1, and Slc34a2 were clustered in a same category. In addition, Tnfrsf12a and Lcn2 which were consistently up-regulated (>5 fold) were also included as potential biomarkers. These results may provide clues for elucidating the mechanism of cephalexin induced nephrotoxicity and evaluating potential biomarkers to assess nephrotoxicity.

• Journal of health informatics and statistics
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• 제43권4호
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• pp.329-335
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• 2018

Objectives: In recent years, there has been an increased need for a way to extract desired information from multiple medical literatures at once. This study was conducted to confirm the usefulness of unstructured data analysis using previously published medical literatures to search for new indications. Methods: The new indications were searched through text mining, network analysis, and topic modeling analysis using 5,057 articles of atorvastatin, a treatment for hyperlipidemia, from 1990 to 2017. Results: The extracted keywords was 273. In the frequency of text mining and network analysis, the existing indications of atorvastatin were extracted in top level. The novel indications by Term Frequency-Inverse Document Frequency (TF-IDF) were atrial fibrillation, heart failure, breast cancer, rheumatoid arthritis, combined hyperlipidemia, arrhythmias, multiple sclerosis, non-alcoholic fatty liver disease, contrast-induced acute kidney injury and prostate cancer. Conclusions: Unstructured data analysis for discovering new indications from massive medical literature is expected to be used in drug repositioning industries.

• Childhood Kidney Diseases
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• 제5권2호
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• pp.78-86
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• 2001

목 적 : 급속 진행성 사구체신염(Rapidly Progressive Glomerulonephritis)은 초기에는 급성 사구체신염이나 신증의 소견을 나타내다가 수주 내지 수개월 내에 급성 신부전에 빠지게 되는 임상 양상을 보이며, 조직학적으로 반월상, 즉 모세혈관외 증식과 분절성 사구체 괴사가 특징적이어서 반월상 사구체신염으로 불리기도 한다. 이 질환의 병인이나 임상양상, 치료 및 예후에 대한 보고는 아직 많지 않은 상태이며, 특히 소아와 관련된 국내 연구는 미미한 상태이다. 이에 저자들은 급속 진행성 사구체신염으로 진단받은 환아들을 대상으로 원인질환과 임상양상의 특징을 분석하였다. 대상 및 방법 : 1990년 5월부터 2000년 5월까지 소아과에 내원하여 임상 양상과 신생검 소견을 종합하여 급속 진행성 사구체신염으로 진단받고 계속적인 추적 관찰이 가능하였던 10명을 대상으로 치료반응 및 임상경과에 대하여 후향적으로 조사하였다. 급속 진행성 사구체신염의 진단 기준으로는 임상적으로 신기능의 급속한 감소(3개월 이내에 사구체 여과율이 $50\%$이상 감소) 소견이 있으면서, 신조직검사상 $50\%$ 이상의 사구체가 반월상을 형성하고 있는 경우로 정의하였다. 결 과 : 발병당시의 평균 연령은 $10.9{\pm}3.8세$였고, 7세 이상의 학동기 환아가 9명으로 대부분이었고 남녀비는 1.5:1이었다. 신조직검사상 원인질환으로는 Henoch-$Sch{\ddot{o}}nlein$ 자반증이 3례($30\%$), 특발성 급속 진행성 사구체신염과 루푸스 신염이 각각 2례 ($20\%$)씩 있었으며, 용혈성 요독 증후군, 막성 사구체신염, 현미경적 다발성 동맥염이 각각 1례($10\%$)씩 있었다. 내원 당시의 주증상으로는 핍뇨와 육안적 혈뇨가 가장 많았고, 발병당시의 임상양상으로는 핍뇨, 현미경적 혈뇨, 육안적 혈뇨, 단백뇨, 부종, 고혈압, 오심, 구토, 관절의 통증 등이 있었다. 혈중 요소 질소치는 평균 $74.2{\pm}39.1\;mg/dL$, 크레아티닌은 평균 $3.2{\pm}1.8\;mg/dL$, 크레아티닌 제거율은 평균 $26.5{\pm}13.2\;mL/min/1.73m^2$로 신기능이 많이 감소되어 있었다. 항호중구 세포질 항체(antineutrophil cytoplasmic antibody)가 양성으로 나온 경우는 현미경적 다발성 동맥염 1례($10\%$)이었고, 항핵 항체 및 항DNA 항체는 루푸스 신염 환아 2례($20\%$)에서 양성 소견을 보였고, 혈중 보체가는 4례($40\%$)에서 감소 소견을 보였다. 용혈성 요독 증후군을 제외한 모든 환아에서 스테로이드 충걱요법 및 면역억제제 병합요법을 시행하였으며, 응급 복막투석은 3례($30\%$), 혈장교환술은 2례($20\%$)에서 시행하였다. 이후 정상적인 신기능으로 회복된 경우는 6례($60\%$) 있었고. 만성 신부전으로 진행된 경우가 4례($40\%$) 있었는데, 2례($20\%$)에서 지속적인 복막투석을 시행하였으며, 이중 1례는 심부전으로 사망하였다. 결 론 : 아직까지 국내에서의 급속 진행형 사구체신염에 대한 연구보고는 미미한 상태로 질환의 정확한 이해를 통한 조기진단이 필요하며, 적극적인 치료와 더불어 장기예후에 대한 지속적인 조사와 연구가 필요할 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.8009-8013
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• 2015

Background: Orthotopic organ transplantation, a treatment option for irreversible organ dysfunction according to organ failure, severe damaged organ or malignancy in situ, was usually accompanied with massive blood loss thus transfusion was required. We aimed to evaluate the adverse impact of blood transfusion on solid organ transplantation. Materials and Methods: From January, 2009 to December, 2014, patients who received orthotopic organ transplantation at Far Eastern Memorial Hospital medical center were enrolled. Clinical data regarding anemia status and red blood cell (RBC) transfusion before, during and after operation, as well as patient outcomes were collected for further univariate analysis. Results: A total of 105 patients who underwent orthotopic transplantation, including liver, kidney and small intestine were registered. The mean hemoglobin (Hb) level upon admission and before operation were $11.6{\pm}1.8g/dL$ and $11.7{\pm}1.7g/dL$, respectively; and the nadir Hb level post operation and the final Hb level before discharge were $8.3{\pm}1.6g/dL$ and $10.2{\pm}1.6g/dL$, respectively. The median units (interquartile range) of RBC transfusion in pre-operative, peri-operative and post-operative periods were 0 (0-0), 2 (0-12), and 2 (0-6) units, respectively. Furthermore, the median (interquartile range) length of hospital stay (LHS) from admission to discharge and from operation to discharge were 28 (17-44) and 24 (16-37) days, respectively. Both peri-operative and post-operative RBC transfusion were associated with longer LHS from admission to discharge and from operation to discharge. Furthermore, it increased the risk of post-operative septicemia. While peri-operative RBC transfusion elevated the risk of acute graft rejection in patients who received orthotopic transplantation. Conclusions: Worse outcome could be anticipated in those who had received massive RBC transfusion in transplantation operation. Hence, peri-operative RBC transfusion should be avoided as much as possible.

• 대한핵의학회지
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• 제25권2호
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• pp.227-236
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• 1991

Background: The evaluation of individual renal function is important to diagnosis and follow-up of various diseases. Ureteral catheterization of each kidney has been widely used for this purpose, but this method had some technical difficulty, frequent complications and much restriction in reapplication. Therefore we tried to applicate radiopharmaceuticals for the evaluation of individual renal function. Methods: We measured 2 hour, 4 hour and 24 hour relative renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate of $^{99m}Tc-DTPA$ with 59 patients with various renal diseases to determine their usefulness for assessment of individual renal function and to compare correlations between every renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate. Results: The correlations between 2 hour-, 4 hour- and 24 hour- relative renal uptake of $^{99m}Tc-DMSA$ and relative glomerular filteration rate of $^{99m}Tc-DTPA$ were R=0.9190 (p < 0.001), R: 0.9229 (p<0.001) and R=0.9917 (p<0.001). In acute obstructive uropathy, the correlations at 2 hour and 4 houre were poor as R=0.1812 (p<0.05) and R=0.4923 (p < 0.05), but the correlation at 24 hour was good as R=0.9942 (p<0.001). Conclusions: We concluded that relative renal uptake at 2 hour and 4 hour had good correlation with relative DTPA uptake ratio in the cases without chronic renal failure and obstructive uropathy. Delayed image with 24 hour relative renal uptake $^{99m}Tc-DTPA$ had the best correlation with relative glomerular filteration rate of $^{99m}Tc-DTPA$ and that might be useful in evaluation of chronic renal disease in which showed increased beckground activity or acute obstructive uropathy.