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Combination Treatment with Arsenic Trioxide and Sulindac Induces Apoptosis of NCI-H157 Human Lung Carcinoma Cells via ROS Generation with Mitochondrial Dysfunction (NCI-H157 폐암 세포주에서 활성산소종의 생성과 미토콘드리아 기능변화를 한 Arsenic Trioxide와 Sulindac 병합요법의 세포고사효과)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.1
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    • pp.30-38
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    • 2005
  • Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

Effects of Phloroglucinol Isolated from Ecklonia stolonifera on the Acetaminophen-Metabolizing Enzyme System in Rat (해조류 곰피로부터 분리한 Phloroglucinol이 흰쥐의 아세트아미노펜 대사효소활성에 미치는 영향)

  • 박종철;허종문;박주권;김현주;전순실;최재수;최종원
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.3
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    • pp.448-452
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    • 2000
  • 실험동물에서 곰피로부터 분리한 phlorglucinol은 acetaminophen의 투여로 현저히 증가된 간조직에 있어서 지질과선화의 함량을 억제하였다. Acetaminophen 투여에 따른 간 cytochrome P-450, aminopyrine N-deme-thylase 및 aniline hydroxylase 활성변동은 관찰할 수 없었다. 곰피 성분 투여군은 glutathione S-transferase의 활성에서는 대조군의 수준에는 미치지 않으나 효소의 활성이 acetaminophen 단독 투여군보다 현저히 증가되었다. 그리고 간조직중 glutathione의 함량은 phlorglucionl을 전처리군에서 acetaminophen 단독 투여군보다 증가되었다. Glutathione reductase 활성에서는 acetaminophen 투여군은 대조군보다 활성이 감소되었으며, 성분으로 전처리한 군은 acetaminophen 단독 투여군보다 증가 되었다. 따라서 곰피에서 분리한 페놀성화합물인 phloroglucinol은 acetaminophen 투여로 증가되던 지질과 산화함량을 감소시키며, acetaminophen 대사효소활성에서는 glutathione S-transferase의 활성이 증가되어 acetaminophen 의 대사를 촉진시키는 것으로 추정된다.

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Generation Method of Bezier Curves and Surfaces on Lie Groups (Lie-군상에서의 Bezier 곡선과 Bezier곡면의 생성방법)

  • Im, Jang-Hwan;Kim, Tae-Eun
    • The KIPS Transactions:PartA
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    • v.9A no.1
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    • pp.99-104
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    • 2002
  • The goal of this paper is to generalize the concept of Bezier curves and surfaces defined on the vector space $R_n$ to Lie groups, which is a new generation method of curves (called Bezier curves) on Lie groups. The defined Bezier curves and surfaces are alsways smooth because of the properties of Lie groups. We apply this method to smooth motion interpolation or smooth trajectory generation for moving rigid body in space.

The Increase of Apoptotic Neutrophils and Phagocytic Macrophage by Germanium in Acute Lung Injury Induced by Lipopolysaccharide (LPS에 의한 급성 폐손상에서 게르마늄에 의한 호중구 세포사와 큰포식세포의 포식능 증가)

  • Lee, Yoon-Jeong;Cho, Hyun-Gug;Jeune, Kyung-Hee
    • Applied Microscopy
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    • v.38 no.4
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    • pp.293-306
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    • 2008
  • The essential factor of acute respiratory distress syndrome (ARDS), an acute lung injury accompanied commonly by sepsis syndrome is accumulation of neutrophils in lung tissue. The study attempted to confirm whether a lung injury would be decreased with the anti-inflammatory effect of germanium by the treated germanium prior to the development of ARDS and whether nitric oxide influence in suppressing a lung injury. Test groups were divided in the following structure for experiment; CON that has been administered with sodium chloride to airway, LPS administered with endotoxin for 5 hours in the same amount and 5 hours of endotoxin administered Ge+LPS following 1 hours of pre-treated germanium. The result of a test using experimental animals, infilteration of neutrophils (p<0.001) in bronchoalveolar lavage fluid (BALF) was significantly decreased, the structure of lung tissue was preserved relatively well, and much neutrophils with distinct positive were observed on tunel staining which showed increase of apoptotic neutrophils in the pre-treated germanium group compare to the endotoxin administrated group. In observation of ultrastructural changes of cell in BALF, phagocytic alveolar macrophage was increased in alveolar space, the nucleus of most engulfed neutrophils were condensed, and some apoptosis neutrophils appears to be DNA fragmentation and effacement of cellular organelles were found in intercellular matrix in the pre-treated germanium group. However, the nitric oxide showed increase in all the groups excluding CON, and the nitric oxide effect such as degranulation diminishing of mast cells and apoptosis increase of neutrophils in the pre-treated group only. The situation appears that there was change in internal environment of the experimental animal by the pre-treated germanium before the nitric oxide is produced and the anti-inflammatory effect activated the pre-processed germanium by nitric oxide which activated following the change. Therefore, the nitric oxide created from macrophage in accordance with the pre-treated germanium appears to influence in alleviating a lung injury. Accordingly, acute lung injury is alleviated by the anti-inflammatory effect of germanium such as inhibition of neutrophils migration, induction of neutrophil apoptosis and increase of phagocytic function of phagocyte, and the nitric oxide produced from activated macrophage by germanium would influence in suppressing a lung injury.

Effect of Types of Egg Shell Calcium Salts and Egg Shell Membrane on Calcium Metabolism in Rats (난각 칼슘염의 종류와 난막의 존재유무가 흰쥐의 칼슘대사에 미치는 영향)

  • Noh, Kyung-Hee;Lee, Sang-Hyun;Ma, Jie;Zhou, Yusi;Kim, Jae-Cherl;Kim, Myo-Jeong;Song, Young-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.7
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    • pp.853-859
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    • 2006
  • This study was carried out to investigate the effect of egg shell calcium salt types and egg shell membrane on calcium metabolism in rats. Sprague-Dawley male rats, 4 weeks of age, were fed on free-calcium diets for 2 weeks after adjustment period. Rats weighing approximately $247{\pm}2.3g$ were divided into 6 groups and were fed on the experimental diets containing 0.2% calcium for 4 weeks. Experimental groups were as follows; {ES(M+)} (egg shell powder diet with egg shell membrane), {ES(M-)} (egg shell powder diet without egg shell membrane), {AC(M+)} (egg shell calcium acetate diet with egg shell membrance), {AC(M-)} (egg shell calcium acetate diet without eg shell membrane), {GC(M+)} (egg shell calcium glucuronate diet with egg shell membrane) and {GC(M-)} (egg shell calcium glucuronate diet without egg shell membrane). Bone length of femur was significantly different by the types (p<0.05) of egg shell calcium salts. Bone mineral density of femur showed the highest level in AC(M-) group. Calcium content of femur and calcium absorption rate were higher in egg shell calcium salt groups than in eg shell powder groups. Calcium absorption rate and retention were significantly different (p<0.05) among the types of eg shell calcium salts and were higher in the AC(M-) group than in the other groups. Alkaline phosphatase activity, parathyroid hormone and osteocalcin levels of serum showed no significant difference among the experimental groups. From the above results, it is concluded that bioavailability of calcium is higher in groups of egg shell calcium salts compared to those in egg shell powder, even though egg shell membrane has no effect on calcium metabolism. Thus, these findings suggest the possibility of using egg shell calcium salts as a functional food material related to calcium metabolism.

Effect of Ulmus Davidiana Planch Herbal Acupuncture Solution on Inhibition of Experimental Bone Resorption in Mouse Calvarial Bone Cells (유근피 약침액이 생쥐의 두개골 파골세포에서 골재흡수의 저해에 미치는 영향)

  • Kang, Mi-Suk;Back, Song-Ook;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.25 no.2
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    • pp.119-127
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    • 2008
  • 목적 : 골관절염치료에 빈용되는 유근피 약침액의 처치가 생쥐의 파골세포에 있어서 골재흡수의 저해에 미치는 영향을 알아보고자 하였다 방법 : 생쥐에게 유근피 약침액을 두개골 세포에 전, 후 처치하여 골재흡수에 대한 유근피 약침액의 억제 활성능을 검토하였다. 결론 : 염증성 cytokine 중 $IL-1{\beta}$ 유도인자인 PGE와 LPS처리로 $IL-1{\beta}$생성이 증가되었으나, 유근피 약침액 처치군은 이를 억제하였다. 유근피 약침액 전처리군에서도 $IL-1{\beta}$ 생성이 억제되었다. 유근피 약침액 처치군은 PGE2유발 $IL-1{\beta}$ 전사를 억제하였으며, PGE2 유발 $IL-1{\beta}$ 유도는 cAMP antagonist인 Rp-cAMP와 protein kinase A(PKA)저해제에 의해서도 억제되어 $IL-1{\beta}$ 발현에 cAMP, PKA 신호전달경로가 관여함을 시사하였다. 본 연구에서 유근피 약침액은 강한 항 관절염효과와 골재흡수 저해 활성이 있으며, 관절염 치료, 예방에 유의함을 밝힌 것으로 사료된다.

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벼 물바구미의 방제를 위한 곤충 병원성 선충 및 공생박테리아의 야외포장시험

  • Park, Seon-Ho;Park, Jae-Seong;Jo, Han-Gyu;Nam, Min-Hui;Park, No-Bong;Im, Sang-Jong
    • 한국생물공학회:학술대회논문집
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    • 2001.11a
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    • pp.914-917
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    • 2001
  • The rice water weevil, Lissorhoptrus oryzophillus are major pests of aquatic rice plant throughout the country. In field, we examined efficacy of Steinernema carpocapsae and Xenorhabdus nematophilus against rice water weevil, Lissorhoptrus oryzophilus. Steinernema carpocapsae showed 71-74.2% mortality after 15days in the field. Also symbiotic bacteria Xenorhabdus nematophilus isolated from Steinernema carpocapsae showed 33.3-58.3% mortality after 15days at vat against rice water weevil, Lissorhoptrus oryzophilus.

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신물질의 간독성 평가방법 개발 및 기작에 관한 연구

  • 차영남
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.97-97
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    • 1993
  • 본 연구과제에서는 적출판류간실험법 (isolated perfused liver technique)을 약물의 간독성 유발 및 보간작용에 관한 실험법으로 개발하고자 butylated hydroxyanisole (BHA) 을 이용하여 보간실험을 하였다. BHA를 식이투여한 흰쥐로부터 적출한 간에 간독성 모델물질로 2,6-dichlorophenolindophenol (DCPIP) 을 관류시켜 관류액내의 DCPIP의 유리형, 환원형, glucuronide, sulfate 포합체의 대사체를 측정하여 DCPIP 외 대사양상을 관찰하였으며, 동시에 간세포 손상으로 관류액내로 유출된 lactate dehydrogenase (LDH)의 활성도를 측정하여 DCPIP예 의할 간세포독성 유발정도를 간접적으로 측정하여 대조군과 비교하였다. 그리고 BHA에 의한 보간작용이 약물대사효소의 변와에 기인한 것인가를 관찰하기 위하여 모델약물로 7-ethoxycoumarin (EC) 이나 EC의 phase I 대사산물인 7-hydroxycoumarin (HC) 을 관류시켜 관류액내의 HC의 유리체, glucuronide 포합체, sulfate 포합체로의 대사량을 측정하여 약물대사시 약물의 활성화에 관계하는 phase I mixed function oxidase (MFO) 효소와 약물의 해독화에 관계하는 phase II 포합효소 (UDP-glucuronyltranesferase(UDPGT)와 sulfotransferase (ST))의 활성도 변화를 측정하여 대조군과 비교하였다. 간독성 모델물질인 DCPIP를 적출한 흰쥐의 간에 관규시켰을때 BHA 전처리군이 LDH가 유출되기 시작하는 시간이 대조군에 비하여 유의적으로 늦었으며, LCH가 유출량도 유의적으로 감소되어 DCPIP에 의한 간독성 유발능력이 BHA에 의하여 감소됨을 관찰하였다. 아울러 DCPIP의 대사체중 환원체와 glucuronide 포합체의 생성량이 증가되어 BHA에 의하여 quinone reductase와 UDPGT 활성도가 증가되었음을 알 수 있었다. 그리고 BHA 전처리에 의하여 MFO효소계와 ST의 활성도에는 변화가 없었으나 UDOGT 의 활성도는 약 2.2배 증가되었다. 이상의 결과로 BHA에 의한 보간작용은 간독성 물질을 활성화시키는 phase I MFO 효소의 활성도에는 변화없이 해독작용에 관여하는 phase II효소들의 활성도 증가에 기인된 것을 알 수 있었다. 그리고 이러한 결과는 적출한 관류간실험법은 여러 약물의 보간효과를 관찰하는 실험법으로 적합할 것으로 사료되었다.

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Improvement of SLAM Using Invariant EKF for Autonomous Vehicles (Invariant EKF를 사용한 자율 이동체의 SLAM 개선)

  • Jeong, Da-Bin;Ko, Nak-Yong;Chung, Jun-Hyuk;Pyun, Jae-Young;Hwang, Suk-Seung;Kim, Tae-Woon
    • The Journal of the Korea institute of electronic communication sciences
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    • v.15 no.2
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    • pp.237-244
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    • 2020
  • This paper describes an implement of Simultaneous Localization and Mapping(SLAM) in two dimensional space. The method uses Invariant Extended Kalman Filter(IEKF), which transforms the state variables and measurement variables so that the transformed variables constitute a linear space when variables called the invariant quantities are kept constant. Therefore, the IEKF guarantees convergence provided in the invariant quantities are kept constant. The proposed IEKF approach uses Lie group matrix for the transformation. The method is tested through simulation, and the results show that the Kalman gain is constant as it is the case for the linear Kalman filter. The coherence between the estimated locations of the vehicle and the detected objects verifies the estimation performance of the method.

The Radioprotective Effects of Grifola umbellata Hot Water Extract on Mice (저령(Grifola umbellata)의 열수 추출물이 생쥐에 미치는 방사선 방호 효과)

  • Park, Jun-Chul
    • Journal of radiological science and technology
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    • v.28 no.4
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    • pp.333-340
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    • 2005
  • In this study, the radioprotective effects of Grifola umbellata hot water extracts (Gu-extract) on mice were investigated. Single pre-administration of Gu-extract increased the 40-day survival ratio of irradiated mice from 65.5% to 78.6%. The growth of 3 week old male mice in the irradiated group was slightly retarded as compared to those of the control and Gu-extract treated mice. The average spleen and thymus weights of the irradiated mice were lower than those of the control and Gu-extract treated mice. The weight reduction of testis in the irradiated mice was significant. While it was relatively slight in the Gu-extract treated mice as compared to that of control mice. No significant difference in the weight was observed in heart, kidney or liver among three groups. The leukocytes of the Gu-extract treated mice did not decrease dramatically as in the irradiated group, but recovery patterns were similar in both groups. Reduction of erythrocytes were similar in both groups but its recovery occurred more rapidly in the extract treated group. The glucose level of the Gu-extract treated group did not change during the period examined, while it was still higher in the irradiated group than the level in the control group in two weeks. The cholesterol levels in the irradiated and the Gu-extract treated groups were higher than that of control group on day 7, but decreased to the level of the control group on day 14. No difference was observed in total protein amount of the serum among the three groups. SDS-polyacrylamide gel electrophoresis of the soluble proteins extracted from various organs did not reveal differences to any extent in all groups except in the livers of the irradiated and extract treated groups, in which some proteins were missing or less present.

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