Paraquat-Induced Apoptotic Cell Death in Lung Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. METHODS: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. RESULTS: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. CONCLUSION: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

Acute Renal Failure in Paroxysmal Nocturnal Hemoglobinuria / 대한신장학회잡지

It has been reported that paroxysmal nocturnal hemoglobinuria (PNH) kidneys are prone to urinary tract infection, variable functional or anatomical abnormalities, renal venous or intrarenal microvascular thromboembolic events, and variable courses of renal failure. Acute renal failure which is rarely developed in PNH patients is often associated with infection, hemolytic crisis or thrombotic complications. A 40-year-old man, who has been treated as iron deficiency anemia and duodenal ulcer for about 2 months, presented with urinary tract infection, intravascular hemolytic anemia, cholestasis, thrombocytopenia, and acute renal failure. Subsequently he showed progressively aggravating azotemia and refractory hypervolemia during evaluation, and then he eventually was diagnosed as PNH. So, we report a case of PNH which was diagnosed due to the advent of acute renal failure possibly due to hemolytic crisis precipitated by urinary tract infection and documented by flow cytometry, kidney magnetic resonance imaging, and renal biopsy.

Optimal Cut-off Value of PIVKA-II for Diagnosis of Hepatocellular Carcinoma: Using ROC Curve / 대한간학회지

BACKGROUND/AIMS: Protein induced by vitamin K absence or antagonist-II (PIVKA-II), also known as des-carboxyprothrombin (DCP), can be used as an alternative tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma (HCC). The aims of the present study were to compare PIVKA-II levels between the patients with HCC and patients with non-HCC chronic liver disease, to evaluate the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the receiver operating characteristic (ROC) curve. METHODS: A total of 227 consecutive patients with HCC (n=42) or chronic liver disease (n=185) were enrolled in this study. HCC was diagnosed histologically or by imaging such as computed tomography, magnetic resonance imaging or angiography. The serum PIVKA-II and AFP levels were measured by electrochemiluminoimmunoassay with using the Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. RESULTS: The PIVKA-II level in the HCC patients was significantly higher than the non-HCC chronic liver disease patients (903.0+/-1156.7 vs. 111.7+/-211.0 mAU/ mL, respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%. CONCLUSIONS: PIVKA-II was as useful surveillance tool for differentiating HCC from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a significant cut-off value for diagnosis of hepatocellular carcinoma.