• Title/Summary/Keyword: Leak effect

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In vitro Study of the Antagonistic Effect of Low-dose Liquiritigenin on Gemcitabine-induced Capillary Leak Syndrome in Pancreatic Adenocarcinoma via Inhibiting ROS-Mediated Signalling Pathways

  • Wu, Wei;Xia, Qing;Luo, Rui-Jie;Lin, Zi-Qi;Xue, Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4369-4376
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    • 2015
  • Background: To investigate in-vitro antagonistic effect of low-dose liquiritigenin on gemcitabine-induced capillary leak syndrome (CLS) in pancreatic adenocarcinoma via inhibiting reactive oxygen species (ROS)-mediated signalling pathways. Materials and Methods: Human pancreatic adenocarcinoma Panc-1 cells and human umbilical vein endothelial cells (HUVECs) were pre-treated using low-dose liquiritigenin for 24 h, then added into gemcitabine and incubated for 48 h. Cell viability, apoptosis rate and ROS levels of Panc-1 cells and HUVECs were respectively detected through methylthiazolyldiphenyl-tetrazoliumbromide (MTT) and flow cytometry. For HUVECs, transendothelial electrical resistance (TEER) and transcellular and paracellular leak were measured using transwell assays, then poly (ADP-ribose) polymerase 1 (PARP-1) and metal matrix proteinase-9 (MMP9) activity were assayed via kits, mRNA expressions of p53 and Rac-1 were determined through quantitative polymerase chain reaction (qPCR); The expressions of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and PARP-1 were measured via western blotting. Results: Low-dose liquiritigenin exerted no effect on gemcitabine-induced changes of cell viability, apoptosis rate and ROS levels in Panc-1 cells, but for HUVECs, liquiritigenin ($3{\mu}M$) could remarkably elevate gemcitabine-induced decrease of cell viability, transepithelial electrical resistance (TEER), pro-MMP9 level and expression of ICAM-1 and VCAM-1 (p<0.01). Meanwhile, it could also significantly decrease gemcitabine-induced increase of transcellular and paracellular leak, ROS level, PARP-1 activity, Act-MMP9 level, mRNA expressions of p53 and Rac-1, expression of PARP-1 and apoptosis rate (p<0.01). Conclusions: Low-dose liquiritigenin exerts an antagonistic effect on gemcitabine-induced leak across HUVECs via inhibiting ROS-mediated signalling pathways, but without affecting gemcitabine-induced Panc-1 cell apoptosis. Therefore, low-dose liquiritigenin might be beneficial to prevent the occurrence of gemcitabine-induced CLS in pancreatic adenocarcinoma.

Free Radical Scavenging of Flavonoids and Their Effects on Erythrocyte Na Leak, Platelet Aggregation and TBARS Production

  • Lee, Ji-Hyun;Kang, Young-Hee;Kang, Jung-Sook
    • Nutritional Sciences
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    • v.5 no.4
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    • pp.197-202
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    • 2002
  • We compared the radical scavenging activity of flavonoids and their antioxidant effects on erythrocyte Na leak, platelet aggregation and TBARS (thiobarbituric acid reactive substance) production, using Sprague Dawley rats. The concentrations of flavonoids needed for scavenging radicals by 50% ($SC_{50}$) in 0.1mM DPPH (2,2 Diphenyl 1-picryl hydrazyl) were: Quercetin, 7.4/$\mu$M; Catechin, 10.6$\mu$M; Morin, 22$\mu$M; Hesperidin, 400uM; and Naringin, 3.95mM. Morin completed its antioxidant activity in 2 minutes, while catechin, hesperidin and naringin had slow but long lasting antioxidant activity. Whole blood platelet aggregation, when incubated with quercetin or catechin, was significantly decreased (P<0.05) compared with the control. Sodium leak in intact erythrocytes was significantly lower when incubated with quercetin, compared with other flavonoids (P<0.05). Morin, hesperidin and naringin somewhat increased Na leak in intact erythrocytes. Sodium leak in erythrocytes treated with phenazine methosulfate (PMS) was increased overall, but was not affected by flavonoids. Intracelluar Na and K were not affected by treatment with PMS. TBARS production in platelet rich plasma (PRP) was significantly lower (P<0.05) than the control when incubated with quercetin or hesperidin. PMS treatment caused an increase in TBARS production regardless of flavonoids. In the present study antioxidant effects of flavonoids were not well correlated with their radical scavenging activities, although quercetin, which showed the strongest radical scavenging activity, had the greatest antioxidant effect.

Evaluation of Piping Failure Probability of Reactor Coolant System in Kori Unit 1 Considering Stress Corrosion Cracking (응력부식균열을 고려한 고리 1호기 원자로냉각재계통의 배관 파손확률 평가)

  • Park, Jeong Soon;Choi, Young Hwan;Park, Jae Hak
    • Transactions of the Korean Society of Pressure Vessels and Piping
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    • v.6 no.1
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    • pp.43-49
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    • 2010
  • The piping failure probability of the reactor coolant system in Kori unit 1 was evaluated considering stress corrosion cracking. The P-PIE program (Probabilistic Piping Integrity Evaluation Program) developed in this study was used in the analysis. The effect of some variables such as oxygen concentration during start up and steady state operation, and operating temperature, which are related with stress corrosion cracking, on the piping failure probabilities was investigated. The effects of leak detection capability, the size of big leak, piping loops, and reactor types on the piping failure probability were also investigated. The results show that (1) LOCA (loss of coolant accident) probability of Kori unit 1 is extremely low, (2) leak probability is sensitive to oxygen concentration during steady state operation and operating temperature, while not sensitive to the oxygen concentration during start up, and (3) the piping thickness and operating temperature play important roles in the leak probabilities of the cold leg in 4 reactor types having same inner diameter.

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Effect of Nozzle on LBB Evaluation for Small Diameter Nuclear Piping (직경이 작은 원자력배관의 파단전누설 해석에 미치는 노즐의 영향)

  • Yu, Yeong-Jun;Kim, Yeong-Jin
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.20 no.6
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    • pp.1872-1881
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    • 1996
  • LBB(Leak-Before-Break) analysis is performed for the highest stress location of each different type of mateerials in the nuclear piping line. In most cases, the highest stress occurs in the pipe and nozzle interface location. i.e. terminal end. The current finite element analysis approach utilizes the symmetry condition both for locations near the nozzle and for locationa away from the nozzle to minimize the size of the finite element model and to make analysis simple when calculating the J-integral values at the crack tip. In other words, the nozzle is not included in the finite element model. However, in reality, the symmetric condition is not applicable for the pipe-nozzle interface location. Because the pipe-nozzle interface location is asymmetric due to different stiffenss of the pipe and nozzle(both material and dimensions). The simplified analysis approach for pipe-nozzle interface locaiton is too conservative for a smaller diameter piping. In tlhis paper, various analyses are performed for the range of materials and crack sizes to evaluate the nozzle effect for a LBB anlaysis. This paper presents methodology for developing the piping evaluaiton diagram at the pipe-nozzle interface location.

Effect of Coenzyme Q10 and green tea on plasma and liver lipids, platelet aggregation, TBARS production and erythrocyte Na leak in simvastatin treated hypercholesterolmic rats

  • Kim, Yang-Hee;Moon, Young-In;Kang, Young-Hee;Kang, Jung-Sook
    • Nutrition Research and Practice
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    • v.1 no.4
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    • pp.298-304
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    • 2007
  • This study was conducted to investigate the hypocholesterolemic effect of simvastatin (30 mg/kg BW) and antioxidant effect of coenzyme Q10 (CoQ10, 15 mg/kg BW) or green tea (5%) on erythrocyte Na leak, platelet aggregation and TBARS production in hypercholesterolemic rats treated with statin. Food efficiency ratio (FER, ADG/ADFI) was decreased in statin group and increased in green tea group, and the difference between these two groups was significant (p<0.05). Plasma total cholesterol was somewhat increased in all groups with statin compared with control. Plasma triglyceride was decreased in statin group and increased in groups of CoQ10 and green tea, and the difference between groups of statin and green tea was significant (p<0.05). Liver total cholesterol was not different between the control and statin group, but was significantly decreased in the group with green tea compared with other groups (p<0.05). Liver triglyceride was decreased in groups of statin and green tea compared with the control, and the difference between groups of the control and green tea was significant (p<0.05). Platelet aggregation of both the initial slope and the maximum was not significantly different, but the group with green tea tended to be higher in initial slope and lower in the maximum. Intracellular Na of group with green tea was significantly higher than the control or statin group (p<0.05). Na leak in intact cells was significantly decreased in the statin group compared with the control (p<0.05). Na leak in AAPH treated cells was also significantly reduced in the statin group compared with groups of the control and CoQ10 (p<0.05). TBARS production in platelet rich plasma was significantly decreased in the groups with CoQ10 and green tea compared with the control and statin groups (p<0.05). TBARS of liver was significantly decreased in the group with green tea compared with the statin group (p<0.05). In the present study, even a high dose of statin did not show a cholesterol lowering effect, therefore depletion of CoQ10 following statin treatment in rats is not clear. More clinical studies are needed for therapeutic use of CoQ10 as an antioxidant in prevention of degenerative diseases independent of statin therapy.

Hermetic Characteristics of Negative PR (Negative PR의 기밀 특성)

  • Choi, Eui-Jung;Sun, Yong-Bin
    • Journal of the Semiconductor & Display Technology
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    • v.5 no.2 s.15
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    • pp.33-36
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    • 2006
  • Many issues arose to use the Pb-free solder as adhesive materials in MEMS ICs and packaging. Then this study for easy and simple sealing method using adhesive materials was carried out to maintain hermetic characteristic in MEMS Package. In this study, Hermetic characteristic using negative PR (XP SU-8 3050 NO-2) as adhesive at the interface of Si test coupon/glass substrate and Si test coupon/LTCC substrate was examined. For experiment, the dispenser pressure was 4 MPa and the $200\;{\mu}m{\Phi}$ syringe nozzle was used. 3.0 mm/sec as speed of dispensing and 0.13 mm as the gap between Si test coupon and nozzle was selected to machine condition. 1 min at $65^{\circ}C$ and 15 min at $95^{\circ}C$ as Soft bake, $200\;mj/cm^2$ expose in 365 nm wavelength as UV expose, 1 min at $65^{\circ}C$ and 6 min at $95^{\circ}C$ as Post expose bake, 60 min at $150^{\circ}C$ as hard bake were selected to activation condition of negative PR. Hermetic sealing was achieved at the Si test coupon/ glass substrate and Si test coupon/LTCC substrate. The leak rate of Si test coupon/glass substrate was $5.9{\times}10^{-8}mbar-l/sec$, and there was no effect by adhesive method. The leak rate of Si test coupon/LTCC substrate was $4.9{\times}10^{-8}mbar-l/sec$, and there was no effect by dispensing cycle. Better leak rate value could be achieved to use modified substrate which prevent PR flow, to increase UV expose energy and to use system that controls gap automatically with vision.

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Effect of the Inhibition of Platelet Activating Factor on Oxidative Lung Injury Induced by Interleukin-$1\;{\alpha}$

  • Lee, Young-Man;Park, Yoon-Yub
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.4
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    • pp.479-491
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    • 1998
  • In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$.

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Effect of the Inhibition of Phospholipase $A_2$ in Generation of Free Radicals in Intestinal Ischemia/Reperfusion Induced Acute Lung Injury

  • Lee, Young-Man;Park, Yoon-Yub;Kim, Teo-An;Cho, Hyun-G.;Lee, Yoon-Jeong;Repine, John E.
    • The Korean Journal of Physiology and Pharmacology
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    • v.3 no.3
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    • pp.263-273
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    • 1999
  • The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

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LEAK-BEFORE-BREAK ANALYSIS OF THERMALLY AGED NUCLEAR PIPE UNDER DIFFERENT BENDING MOMENTS

  • LV, XUMING;LI, SHILEI;ZHANG, HAILONG;WANG, YANLI;WANG, ZHAOXI;XUE, FEI;WANG, XITAO
    • Nuclear Engineering and Technology
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    • v.47 no.6
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    • pp.712-718
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    • 2015
  • Cast duplex stainless steels are susceptible to thermal aging during long-term service at temperatures ranging from $280^{\circ}C$ to $450^{\circ}C$. To analyze the effect of thermal aging on leak-before-break (LBB) behavior, three-dimensional finite element analysis models were built for circumferentially cracked pipes. Based on the elasticeplastic fracture mechanics theory, the detectable leakage crack length calculation and J-integral stability assessment diagram approach were carried out under different bending moments. The LBB curves and LBB assessment diagrams for unaged and thermally aged pipes were constructed. The results show that the detectable leakage crack length for thermally aged pipes increases with increasing bending moments, whereas the critical crack length decreases. The ligament instability line and critical crack length line for thermally aged pipes move downward and to the left, respectively, and unsafe LBB assessment results will be produced if thermal aging is not considered. If the applied bending moment is increased, the degree of safety decreases in the LBB assessment.

A Study on the Effect of Gear Teeth End-Gaps for Hydraulic Gear Pumps and Motors (기어펌프.모터 이끝 틈새의 영향에 관한 연구)

  • Jeong H.S.;Peng L.;Oh S.H.
    • Transactions of The Korea Fluid Power Systems Society
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    • v.2 no.4
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    • pp.23-29
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    • 2005
  • In order to improve the efficiency of hydraulic gear pumps or motors especially for high operating pressure, power losses due to viscous friction and leak flow through gear teeth end-gaps are considered in this paper. Optimal gaps minimizing the power loss for pumps and motors with uniform heights of gaps are analysed first. And the effect of the shapes of gaps with unequal heights on the power loss are studied and discussed by simulation. Considering that the outer shell lacing gear teeth may expand due to high internal pressure or thermal stress, the results drawn in this paper can be used for the design of high efficiency pumps and motors.

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