한국의 유기농 목장에서 분만 후 대사성 질병의 예측을 위한 ROC 분석

학위논문(석사) -- 서울대학교대학원 : 수의과대학 수의학과, 2023. 2. 김단일.Postpartum diseases should be predicted to prevent productivity loss before calving especially in organic dairy farms. This study was aimed to investigate the incidence of postpartum metabolic diseases in an organic dairy farm in Korea, to confirm the association between diseases and prepartum blood biochemical parameters, and to evaluate the accuracy of these parameters with a receiver operating characteristic (ROC) analysis for identifying vulnerable cows. Data were collected from 58 Holstein cows (16 primiparous and 42 multiparous) out of 94 Holstein parturient cows (25 primiparous and 69 multiparous) having calved for 2 years on an organic farm. During a transition period from 4 weeks prepartum to 4 weeks postpartum, blood biochemistry was performed through blood collection every 2 weeks with a physical examination. Fourty-six cows among the 94 cows (48.9%) were diagnosed with at least one postpartum disease. Each incidence was 23.4% for subclinical ketosis, 19.1% for subclinical hypocalcemia, 13.8% for retained placenta, 10.6% for displaced abomasum and 6.4% for clinical ketosis. Data from 58 Holstein parturient cows (16 primiparous and 42 multiparous) were divided into two groups: 31 cows with at least one disease and 27 cows without disease. Between at least one disease and no disease, there were significant differences in the prepartum levels of parameters like body condition score (BCS), non-esterified fatty acid (NEFA), total bilirubin (T-bil), direct bilirubin (D-bil) and NEFA to total cholesterol (T-chol) ratio (p < 0.05). The ROC analysis of each of these prepartum parameters had the area under the curve (AUC) < 0.7. However, the ROC analysis with logistic regression including all these parameters revealed a higher AUC (0.769), sensitivity (71.0%), and specificity (77.8%). In summary, the ROC analysis with logistic regression including the prepartum BCS, NEFA, T-bil, D-bil, and NEFA to T-chol ratio can be used to identify cows that are vulnerable to postpartum diseases with a moderate accuracy.유기농 목장에서 분만 전 생산성 손실을 예방하려면 분만 후 질병을 예측해야 한다. 본 연구의 목적은 국내 유기농 목장에서 분만 후 대사성 질병의 발병률을 조사하고, 질병과 분만 전 혈액 생화학적 매개변수와의 연관성을 확인하고, 이들 매개변수의 정확도를 ROC(Receiver Operating Characteristic) 분석으로 질병에 취약한 소를 예측하는 것이다. 데이터는 유기농 목장에서 2년 동안 분만한 94마리의 홀스타인 젖소 (25마리의 초산 및 69마리의 다산) 중 58마리의 홀스타인 젖소 (16마리의 초산 및 42마리의 다산)에서 수집되었다. 분만 전 4주에서 분만 후 4주까지의 전이기 동안에 신체검사와 함께 2주마다 채혈을 통해 혈액 생화학을 시행하였다. 94마리의 분만한 젖소 중 46마리(48.9%)의 젖소가 적어도 하나의 분만 후 질병으로 진단되었다. 각 발생률은 준임상형 케톤증이 23.4%, 준임상형 저칼슘혈증이 19.1%, 태반정체가 13.8%, 4위 전위가 10.6%, 임상형 케톤증이 6.4%였다. 분만한 58마리의 홀스타인 젖소의 데이터를 하나이상의 질병이 있는 젖소 31마리와 질병이 없는 젖소 27마리, 두 그룹으로 나누었다. 적어도 하나의 질병이 있는 경우와 질병이 없는 경우 사이에 신체 상태 점수 (BCS), 비에스테르화 지방산 (NEFA), 총 빌리루빈 (T-bil), 직접 빌리루빈 (D-bil) 및 NEFA 대 총 콜레스테롤(T-chol) 비율에서 분만 전 수준에서 유의한 차이가 있었다 (p < 0.05). 이러한 분만 전 매개변수 각각에 대한 ROC 분석은 곡선 아래 면적 (AUC) < 0.7을 나타냈다. 그러나 이러한 모든 매개변수를 포함하는 로지스틱 회귀 분석을 사용한 ROC 분석에서는 민감도 (71.0%), 및 특이도 (77.8%), AUC(0.769)를 나타냈다. 결론적으로, 분만 전 BCS, T-bil, D-bil 및 NEFA 대 T-chol 비율을 포함한 로지스틱 회귀 분석을 사용한 ROC 분석을 사용하여 중증도의 정확도로 분만 후 질병에 취약한 젖소를 예측할 수 있다.Literature review 1 Introduction 6 Materials and Methods 9 1. Ethics 9 2. Experimental animal 9 3. Blood sampling 12 4. Case definition 12 5. Grouping 13 6. Statistical analysis 14 Results 17 1. Incidence of postpartum diseases 17 2. Statistical analysis 19 2-1. Significant difference in blood biochemistry parameters between diseased and non-diseased cows 19 2-2. ROC analysis 35 2-3. Predictive models using logistic regression 37 3. Further statistical analysis 40 Discussion 42 Conclusion 48 Conflict of Interests 49 References 50 Abstract in Korean 56석

Une étude acoustique sur les voyelles nasales du français prononcées par les apprenants coréens

학위논문(석사) -- 서울대학교대학원 : 사범대학 외국어교육과(불어전공), 2021.8. 김선희.Une des grandes caractéristiques représentatives du français est la présence de voyelles nasales. Une voyelle nasale est un phonème qui n'existe pas dans le système phonologique coréen. Ce son résulte d’un abaissement du voile du palais et de l’envoi d’un flux d'air à la fois dans la bouche et la cavité nasale, et il se distingue ainsi des caractéristiques relatifs aux voyelles orales et aux consonnes nasales. Dans le français moderne d’aujourd’hui, il existe trois voyelles nasales /ɛ̃, ɑ̃, ɔ̃/, et quatre voyelles orales correspondant à chaque voyelle nasale /ɛ, ɑ, o, ɔ/. De nombreuses études comparatives et analytiques ont confirmé les diverses caractéristiques acoustiques de la voyelle nasale française et également démontré certaines différences acoustiques bien distinctes non seulement dans la descente du voile du palais, mais aussi dans la spécificité de l’articulation telle que la hauteur de la langue, sa position et l’arrondissement. Dans les recherches précédentes, divers linguistiques se sont forcés de comparer les caractéristiques phonétiques des voyelles nasales et celles des voyelles orales correspondantes. La plupart des recherches sur la phonétique acoustique se sont portées sur l’analyse des formants des voyelles à l'aide d'un spectre, d'un spectrogramme et d’une analyse cepstrale qui visualisaient les signaux sonores. Cependant, la majorité des études précédentes utilisaient seulement le premier formant (F1) et le deuxième formant (F2), qui reflètent la hauteur de la langue et la position de la langue. En ce qui concerne le troisième formant (F3), bien que celui-ci joue un rôle important dans la caractérisation des voyelles françaises, il était rarement utilisé. De plus, les données expérimentales ne sont pas constituées d’éléments sur la prononciation française standard et un seul phonème des aux voyelles orales /o/ et /ɔ/ correspondant à la voyelle nasale /ɔ̃/ a été utilisé, de sorte que la différence entre les deux voyelles n'a pas pu être comparée. Jusqu’à présent, il n’existe pas encore d’étude identifiant les caractéristiques des voyelles nasales chez les apprenants coréens. Cette présente recherche a pour objectif d’examiner les caractéristiques acoustiques des voyelles nasales en français à travers divers énoncés d’apprenants coréens et de locuteurs français natifs en utilisant les méthodes de recherche phonétique acoustique. Pour notre expérience, 8 apprenantes coréennes ainsi que 4 natives et utilisant un français standard, y ont participé et par la suite, nous avons analysé le F1, F2, F3 à la fois des voyelles nasales /ɛ̃, ɑ̃, ɔ̃/ et des voyelles orales /ɛ, ɑ, o, ɔ/. En comparant le F1, F2 et F3 des voyelles nasales et des voyelles orales, nous avons constaté qu’il existait une différence significative en F1, F2, F3 entre tous les apprenantes coréennes et les natives. En outre, dans le cas des locutrices natives, la différence de F2 n’était pas significative dans la voyelle postérieure-arrondie /ɔ-ɔ̃/. L’analyse des sujets coréens a mis en lumière une différence de F3 n’était pas significative dans les voyelles antérieures non arrondies /ɛ-ɛ̃/. En d'autres termes, il n'y avait pratiquement aucun changement dans la position de la langue de /ɔ/ et /ɔ̃/ pour les locutrices natives, et l’arrondissement de /ɛ/ et /ɛ̃/ était également réalisée pour les apprenantes coréennes. D’après les résultats de l’expérience sur la comparaison de F1, F2 et F3 entre les deux groupes pour chaque voyelle nasale et voyelle orale, nous avons pu percevoir deux faits principaux : les deux groupes montraient une différence significative en F1 dans le cas des voyelles orales, et il existait une divergence significative de F1, F2 et F3 spécialement pour la voyelle postérieure-arrondie /ɔ/. Dans le cas des voyelles nasales, nous avons pu vérifier qu’il y avait de manière générale une différence de F2 entre les deux groupes. Ces résultats peuvent être interprétés comme suit : il s’agirait à la fois d’une erreur de la part des apprenantes coréennes concernant le degré d’ouverture en F1 lors de la prononciation des voyelles orales et d’une mauvaise position de la langue en F2 dans le cas de la prononciation de voyelles nasales. À la lumière des divers résultats de notre recherche, nous proposons, dans une dernière partie, une méthode d’enseignement relative aux voyelles nasales. Dans un premier temps, les enseignants sont amenés à comparer les voyelles orales et les voyelles nasales, puis à expliquer en utilisant des images et des vidéos montrant non seulement les différentes méthodes de prononciation, mais aussi les caractéristiques articulatoires entre les voyelles orales et nasales. Dans une second étape, les enseignants proposent des exercices de pratique concernant les prononciations /ɛ̃/ et /ɑ̃/, deux sons facilement à confondre, avec la paire minimale, et étendent progressivement les exercices de prononciation du mot vers la phrase. En effet, nous avons pu constater grâce à cette étude que les apprenantes coréennes ont bien réalisé la prononciation /ɔ̃/, qui a la position la plus postérieure dans la langue et la plus arrondie parmi toutes les voyelles nasales. Au sein d’une troisième étape, les enseignants demandent à leurs apprenants d’analyser eux-mêmes leur propre prononciation via un outil d’analyse vocale, appelé « praat », et font un retour critique individualisé sur les erreurs de prononciation en les comparant avec les données relatives aux locuteurs natifs. Dans une dernière partie, les enseignants proposent un pré-test au début du cours et un post-test à la fin du cours afin que les apprenants puissent vérifier leur progrès concernant la prononciation.프랑스어의 대표적인 특징 중 하나는 비강모음이 존재하는 것이다. 비강모음은 한국어 음운 체계에 존재하지 않는 음소로써 연구개를 낮추어 기류를 구강과 비강으로 동시에 내보내는 소리로 구강모음과 비강자음의 특징과 구별된다. 현대 프랑스어에서 비강모음은 /ɛ̃, ɑ̃, ɔ̃/의 3개가 존재하며, 각 비강모음에 대응하는 구강모음은 /ɛ, ɑ, o, ɔ/의 4개가 있다. 선행연구에 따르면 프랑스어 비강모음은 구강모음과 비교하여 연구개의 하강뿐만 아니라 혀의 높이, 혀의 위치, 원순성과 같은 조음 특징에 상응하는 음향적 차이를 보이는 것으로 보고되었다. 본 논문은 음향음성학적 연구 방법을 활용하여 한국인 학습자가 발화한 프랑스어 비강모음의 음향적 특징을 프랑스어 원어민의 발화와 비교하고, 이를 바탕으로 비강모음의 발음 교육 방법을 제안하는 것을 목적으로 한다. 실험에는 표준 프랑스어를 사용하는 원어민 여성 4명과 한국인 학습자 여성 8명이 참여하였다. 먼저, 프랑스어 원어민과 한국인 학습자가 발화한 구강모음 /ɛ, ɑ, o, ɔ/과 비강모음 /ɛ̃, ɑ̃, ɔ̃/의 F1, F2, F3를 각각 측정하여 구강모음과 비강모음의 차이를 분석하였다. 그런 다음, 원어민과 학습자의 구강모음과 비강모음을 각각 비교하여 그 차이를 분석하였다. 실험 결과, 원어민과 한국인 학습자는 구강모음과 비강모음의 F1, F2, F3의 차이가 대부분 유의한 것으로 나타났지만, 원어민은 후설 원순모음 /ɔ-ɔ̃/에서 F2의 차이가 무의미했고, 한국인 학습자는 전설 비원순모음 /ɛ-ɛ̃/에서 F3의 차이가 무의미했다. 즉, 원어민의 경우 /ɔ/와 /ɔ̃/의 조음할 때 거의 동일한 위치에서 발음하는 것을 알 수 있었고, 한국인 학습자의 경우는 /ɛ/와 /ɛ̃/를 조음할 때의 원순성이 비슷하게 실현되는 것을 알 수 있었다. 또한, 비강모음과 구강모음별로 원어민과 한국인 학습자의 F1, F2, F3 차이를 살펴보았다. 그 결과, 구강모음의 경우 두 그룹은 대체로 F1에서 그 차이가 유의미했고, 특히 후설 원순모음 /ɔ/에서는 F1, F2, F3의 차이가 모두 유의미했다. 비강모음의 경우 공통적으로 F2에서 유의미한 차이가 존재했다. 이러한 결과는 한국인 학습자가 원어민보다 구강모음 발화시 F1값에 상응하는 개구도에서 오류를 보이며, 비강모음 발화시에는 F2에 상응하는 혀의 위치에서 오류를 보이는 것으로 해석할 수 있다. 실험 결과를 토대로 한국인 학습자들을 대상으로 다음과 같은 비강모음 교육 방안을 제안한다. 첫째, 구강모음과 비강모음의 조음 방법과 조음적 특징의 차이를 보여주는 그림과 동영상을 활용하여 두 모음을 비교하여 설명한다. 둘째, 실험을 통해 한국인 학습자는 비강모음 중에서 후설성과 원순성이 가장 강한 /ɔ̃/의 경우는 발음을 잘 실현하고 있는 것으로 나타났다. 따라서, 혼동하기 쉬운 /ɛ̃/과 /ɑ̃/의 최소대립쌍을 활용하여 발음을 훈련하고 발음 연습은 단어에서 점차 문장으로 확대해 간다. 셋째, 음성분석 툴인 praat를 활용하여 학습자 스스로 본인의 발음을 분석하게 하고 교수자는 원어민의 데이터와 비교하여 발음 오류에 대한 피드백을 제공한다. 넷째, 수업 초반부에 pre-test와 후반부에 post-test를 진행하여 학습자의 발음이 얼마나 개선되었는지 확인한다.1. 서론 1 2. 프랑스어 비강모음의 음성학적 특징 및 교육방법론 6 2.1 프랑스어 원어민 발화 비강모음의 음성적 특징 6 2.2 프랑스어 학습자 발화 비강모음의 음성적 특징 12 2.3 프랑스어 발음 교육 17 3. 연구방법 21 3.1 실험 대상 21 3.2 실험 데이터 22 3.3 녹음 24 3.4 포먼트 추출 방법 24 3.5 통계 분석 방법 27 4. 실험결과 28 4.1 프랑스어 원어민 발화 비강모음의 음향적 특징 28 4.1.1 구강모음과 비강모음의 F1, F2, F3 비교 28 4.1.2 구강모음과 비강모음의 F1, F2, F3 차이에 대한 통계 분석 29 4.1.3 프랑스어 원어민의 개별 발화 양상 33 4.2 한국인 학습자 발화 비강모음의 음향적 특징 36 4.2.1 구강모음과 비강모음의 F1, F2, F3 비교 36 4.2.2 구강모음과 비강모음의 F1, F2, F3 차이에 대한 통계 분석 37 4.2.3 한국인 학습자의 개별 발화 양상 41 4.3 프랑스어 원어민과 한국인 학습자의 구강모음과 비강모음 발화 양상 비교 45 4.4 요약 51 4.5 논의 52 5. 프랑스어 비강모음 발음 교수법 제안 59 5.1 비강모음의 조음적 특징 설명 61 5.2 비강모음 발음 연습 62 5.3 비강모음 발음 피드백 65 5.4 비강모음 발음 평가 66 6. 결론 68 참고문헌 70 Rsum 76석

Implications of differences in expression of sarcosine metabolism-related proteins according to the molecular subtype of breast cancer.

BACKGROUND: The goal of this study was to investigate the expression of sarcosine metabolism-related proteins, namely glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX), in the different breast cancer subtypes and to assess the implications of differences in expression pattern according to subtype. METHODS: We analyzed the expression of GNMT, SARDH, and PIPOX in a tissue microarray of 721 breast cancer cases using immunohistochemistry (IHC). We classified breast cancer cases into subtype luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) according to the status for the estrogen receptor (ER), progesterone receptor (PR), HER-2, and Ki-67. Sarcosine metabolism phenotype was stratified according to IHC results for GNMT, SARDH, and PIPOX: GNMT(+), SARDH and PIPOX(-) was classified as high sarcosine type; GNMT(-), SARDH or PIPOX(-) as low sarcosine type; GNMT(+), SARDH or PIPOX(+) as intermediate sarcosine type, and GNMT(-), SARDH and PIPOX(-) as null type. RESULTS: Expression of sarcosine metabolism-related proteins differed significantly according to breast cancer subtype (GNMT, p=0.005; SARDH, p=0.012; tumoral PIPOX, p=0.008; stromal PIPOX, p<0.001). These proteins were the most frequently expressed in HER-2 type tumors and the least in TNBC. Sarcosine metabolism phenotype also varied according to breast cancer subtype, with high sarcosine type the most common in HER-2, and null type the most common in TNBC (p=0.003). Univariate analysis revealed that GNMT expression (p=0.042), tumoral PIPOX negativity (p=0.039), and high sarcosine type (p=0.021) were associated with shorter disease-free survival (DFS). Multivariate analysis also revealed GNMT expression was an independent factor for shorter DFS (hazard ratio: 2.408, 95% CI: 1.154-5.024, p=0.019). CONCLUSION: Expressions of sarcosine metabolism-related proteins varied according to subtype of breast cancer, with HER-2 type tumors showing elevated expression of these proteins, and TNBC subtype showing decreased expression of these proteins. Expression of sarcosine metabolism-related proteins was also associated with breast cancer prognosis.ope

Expression of metabolism-related proteins in triple-negative breast cancer.

To investigate the dominant metabolic type of triple-negative breast cancer (TNBC) and evaluate its clinical implication through analysis of protein expression related to glycolysis, glutaminolysis, and mitochondrial oxidative phosphorylation. Tissue samples from 129 patients with TNBC who underwent mastectomy due to invasive breast cancer from 2000 to 2005 were prepared for tissue microarray. By immunohistochemical staining of the tissue microarrays, the markers of glycolysis-related proteins (Glut-1, CAIX, MCT4), glutaminolysis-related proteins (GLS1, GDH, ASCT2), and mitochondrial enzymes (ATP synthase, SDHA and SDHB) were analyzed. Based on the results, the metabolic phenotypes were defined based on positivity for more than two of three markers for each phenotype as follows: glycolysis type (Glut-1, CAIX and MCT4), glutaminolysis type (GLS1, GDH and ASCT2) and mitochondrial type (ATP synthase, SDHA and SDHB). The percentages of samples with metabolic phenotypes of tumor and stroma of TNBC were as follows: for tumor, mitochondrial type (85.3%) > glutaminolysis type (67.4%) > glycolysis type (63.0%); and for stroma, glutaminolysis type (37.2%) > glycolysis type (16.3%) > mitochondrial type (14.0%). The most common metabolic phenotype of TNBC was glycolysis type for basal-like type and non-glycolysis type for non-basal-like type (p=0.047). The correlation between glutaminolysis and mitochondrial type was statistically significant in both tumor and stroma (p<0.001). In conclusion, tumor cells of TNBC express glycolysis and mitochondrial metabolism-related proteins. Glycolysis type is the most common phenotype of basal-like type, and reversely, non-glycolysis type is the most common phenotype of non basal-like type.ope

Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer.

We aimed to evaluate the expression of sarcosine metabolism-related proteins according to site of metastatic breast cancer, and the clinical implications. Immunohistochemical staining for glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX) was performed on tissue microarrays from 162 metastatic breast cancer (bone metastases = 47, brain metastases = 39, liver metastases = 24, and lung metastases = 52). Sarcosine metabolism-related proteins showed variable expression with regard to metastatic sites. GNMT was expressed in brain and lung metastases, but not in bone and liver metastases (P = 0.016). In view of the sarcosine metabolic phenotype, high sarcosine and intermediate type were only found in the brain and lung metastases, and low sarcosine type was observed more frequently in bone and lung metastases (P = 0.047). By univariate analysis, PIPOX positivity was correlated with shorter overall survival (OS) (P = 0.031). In lung metastases, PIPOX positivity (P = 0.019) and stromal PIPOX positivity (P = 0.001) were associated with shorter OS. In conclusion, in metastatic breast cancer, sarcosine metabolism-related proteins are differently expressed according to the metastatic site. Expression of GNMT and high sarcosine type are predominantly observed in brain and lung metastases.ope

Succinate dehydrogenase expression in breast cancer

The aim of this study was to investigate succinate dehydrogenase (SDH) expression in breast cancer according to breast cancer molecular subtype using immunohistochemistry and to assess the clinical implications of SDH expression. Immunohistochemical staining for ER, PR, HER-2, Ki-67, HIF-1α, SDHA, and SDHB was performed on tissue microarrays of 721 breast cancers. According to the immunohistochemistry results for ER, PR, HER-2, and Ki-67 and fluorescence in situ hybridization (FISH) results for HER-2, breast cancer molecular subtypes were classified into luminal A, luminal B, HER-2, and triple-negative breast cancer (TNBC). HER-2 subtype breast cancers most frequently showed high-level expression of SDHA in tumor cells, while the luminal A subtype most frequently showed low or negative expression of SDHA in tumor cells (P = 0.032). Stromal SDHB expression rate was highest in HER-2 subtype and lowest in TNBC (P  SDHA(-)/SDHB(-) > SDHA(-)/SDHB(+) > SDHA(+)/SDHB(-) in order of frequency. The stromal phenotypes were SDHA(-)/SDHB(-) > SDHA(+)/SDHB(+) > SDHA(-)/SDHB(+) > SDHA(+)/SDHB(-). In conclusion, loss of SDHA or SDHB expression was observed in about 3% of breast cancers in this study. Low SDH expression status in breast tumor cells was associated with younger age at diagnosis and low-grade histology.ope

Gamma linolenic acid exerts anti-inflammatory and anti-fibrotic effects in diabetic nephropathy

PURPOSE: This study was undertaken to investigate the effects of gamma linolenic acid (GLA) on inflammation and extracellular matrix (ECM) synthesis in mesangial and tubular epithelial cells under diabetic conditions. MATERIALS AND METHODS: Sprague-Dawley rats were intraperitoneally injected with either a diluent [n=16, control (C)] or streptozotocin [n=16, diabetes (DM)], and eight rats each from the control and diabetic groups were treated with evening primrose oil by gavage for three months. Rat mesangial cells and NRK-52E cells were exposed to medium containing 5.6 mM glucose and 30 mM glucose (HG), with or without GLA (10 or 100 μM). Intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin (FN) mRNA and protein expression levels were evaluated. RESULTS: Twenty-four-hour urinary albumin excretion was significantly increased in DM compared to C rats, and GLA treatment significantly reduced albuminuria in DM rats. ICAM-1, MCP-1, FN mRNA and protein expression levels were significantly higher in DM than in C kidneys, and these increases were significantly abrogated by GLA treatment. In vitro, GLA significantly inhibited increases in MCP-1 mRNA expression and protein levels under high glucose conditions in HG-stimulated mesangial and tubular epithelial cells (p<0.05, respectively). ICAM-1 and FN expression showed a similar pattern to the expression of MCP-1. CONCLUSION: GLA attenuates not only inflammation by inhibiting enhanced MCP-1 and ICAM-1 expression, but also ECM accumulation in diabetic nephropathy.ope

Effects of an oral adsorbent on oxidative stress and fibronectin expression in experimental diabetic nephropathy

BACKGROUND: Previous studies have demonstrated that AST-120 (Kremezin((R))), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function. METHODS: Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production. RESULTS: Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05). CONCLUSION: In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.ope