• Title/Summary/Keyword: 약물의 기전과 효과

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Effect of endothelin receptor blockade on monocrotaline-induced pulmonary hypertension in rats (Monocrotaline으로 유발한 백서 폐동맥 고혈압에서 Endothelin 수용체 차단제 투여의 효과)

  • Lim, Kyoung Ah;Shim, Jung Yun;Cho, Sang Ho;Kim, Kwan Chang;Han, Jae Jin;Hong, Young Mi
    • Clinical and Experimental Pediatrics
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    • v.52 no.6
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    • pp.689-695
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    • 2009
  • Purpose : To examine the effect of bosentan, a dual endothelin receptor (ER) antagonist, on the development of monocrotaline (MCT)-induced pulmonary hypertension in rats by especially focusing on the pulmonary vascular morphology changes. Methods : Sprague-Dawley rats were treated as follows: controls received a subcutaneous saline injection, MCT-treated rats received a subcutaneous MCT injection, and bosentan-treated rats received a MCT injection followed by treatment with bosentan (20 mg/kg/day). To assess the effects of ER blockade on the time course, the animals were exsanguinated, and their hearts and lungs were dissected after 7, 14, or 28 days. Results : The mean body weights of the MCT- and bosentan-treated rats were significantly lower than that of the control rats on days 7, 14, and 28. Bosentan administration significantly inhibited the progression of right ventricular hypertrophy on day 28 (right ventricle/[left ventricle+septum]: $0.71{\pm}0.10$ in MCT-treated rats vs. $0.49{\pm}0.09$ in bosentan-treated rats; P<0.05). Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan-treated rats on day 28 ($49.96{\pm}10.06%$ in MCT-treated rats vs. $47.09{\pm}10.48%$ in bosentan-treated rats; P<0.05). In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on days 14 and 28. Conclusion : Bosentan administration in intermediate doses exerts inhibitory effects on lung vascular hypertrophy and right ventricular hypertrophy during the development of MCT-induced pulmonary hypertension in rats.

Interaction of Forskolin with the Effect of $N^6-Cyclopentyladenosine$ on $[^3H]-Acetylcholine$ Release in Rat Hippocampus (흰쥐 해마에서 Acetylcholine 유리에 미치는 $N^6-Cyclopentyladenosine$ 및 Forskolin의 영향)

  • Choi, Bong-Kyu;Park, Hie-Man;Kang, Yeon-Wook;Kook, Young-Johng
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.129-136
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    • 1992
  • As it has been reported that the depolarization-induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus and various lines of evidence indicate the involvement of adenylate cyclase system in $A_1-adenosine$ post-receptor mechanism in hippocampus, it was attempted to delineate the role of adenylate cyclase system in the $A_1-receptor-mediated$ control of ACh release in this study. Slices from rat hippocampus were incubated with $[^3H]-choline$ and the release of the labelled products was evoked by electrical stimulation $(3\;Hz,\;5\;Vcm^{-1},\;2\;ms,\;rectangular\;pulses)$, and the influence of various agents on the evoked tritium-outflow was investigated. $N^6-cyclopentyladenosine$ (CPA), a specific $A_1-adenosine$ receptor agonist, in concentrations ranging from 0.1 to $10\;{\mu}M$, decreased the $[^3H]-ACh$ release in a dose-dependent manner without the changes of basal rate of release. 8-cyclopentyl-1,3-dipropylxanthine $(DPCPX,\;1{\sim}10\;{\mu}M)$, a selective $A_1-receptor$ antagonist, increased the $[^3H]-ACh$ release in a dose-related fashion with slight increase of basal tritium-release. And the CPA effects were significantly inhibited by DPCPX $(2\;{\mu}M)$ pretreatment and the dose-response curve produced by CPA was shifted to the right. The responses to N-ethylmaleimide $(NEM,\;10\;&\;30\;{\mu}M)$, a SH-alkylating agent of G-protein, were characterized by increments of the evoked ACh-release and the basal release, and the CPA effect were completely abolished by NEM pretreatment. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from 0.3 to $10\;{\mu}M$, increased the evoked ACh-release in a dose-dependent manner and the CPA effects were inhibited by forskolin. These results indicate that the $A_1-adenosine$ heteroreceptor plays an important role in ACh-release via nucleotide-binding protein Gi in the rat hippocampus and that the adenylate cyclase system might be participated in this process.

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Investigation of DPPH Radical Scavenging and Pyolyl Endopeptidase Inhibitory Activities of Plant Extracts (천연 식물자원에서 DPPH 라디칼 제거능과 Prolyl Endopeptidase 활성 저해능 탐색)

  • Lee Young Min;Kim Dae Ik;Lee Sung Hyeon;Cho Soo Muk;Chun Hye Kyung;Park Hong Ju;Lee Yeon Sook
    • The Korean Journal of Community Living Science
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    • v.16 no.4
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    • pp.95-102
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    • 2005
  • The present study was performed to investigate the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging and Proly1 endopeptidase (PEP) inhibitory activities of plant extracts. The whole extract of Fragaria yezoensis inhibited the DPPH radical by $90.4\%$ and the stem of Gingko biloba, Gardenia jasminoides for. grandiflora and Rhododendron yedoensa var. poukhanene, the loaves of Rhododendron mucronulatum var. ciliatum, Gardenia jasminoides for. grandiflora and Corylus sieboldiana var. mandshurice, the fruit of Cornus officinalis, and the root of Gingko biloba showed high DPPH radical scavenging activities. In the case of PEP inhibitory activities, high inhibition was observed in the whole Plant of Fragaria ananassa, Fragaria yezoensis and Hypericum erectum, the stem of Actinidia arguta and Rhododendron yedoensa var. poukhanese, the leaves of Rhododendron yedoensa var. poukhanense and Rosa davurica, the fruit of Cornus officinalis. and the root of Acer okamotoanum. There was significant correlation (P=0.000) between DPPH radical scavenging and prolyl endopeptidase inhibitory activities, thus some of plant extracts such as whole Fragaria yezoensis, fruit of Cornus officinalis had high activities in both DPPH-scavenging and prolyl endopeptidase inhibition. Therefore, it is required to examine the mechanical interaction between DPPH-scavenging and prolyl endopeptidase inhibitory activities and further studying plant extracts with both these activities is desired to develop agents for preventing and treating of Alzheimer's disease.

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Effect of Proteinase Activity on the Cheddar Cheese Quality (단백분해 효소 활성(蛋白分解 酵素 活性)이 Cheddar Cheese의 품질(品質)에 미치는 영향(影響))

  • Kim, Min-Bae
    • Journal of Dairy Science and Biotechnology
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    • v.14 no.2
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    • pp.157-164
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    • 1996
  • This study aimed increase the quality during ripening of Cheddar cheese made with proteinase-negative mutant of Streptococcus lactis KCTC 1913 selected by curing. The degradation of protein during cheese ripening were investigated by electrophoresis and chromatography. The results were summarized as follow ; 1. The number of lactic acid bacteria decreased with the ripening stage, and that of the control cheese decreased faster than that of the cheese made with mutant. 2. Polyacrylamide gel electrophoretic analysis of cheese caseins revealed no difference between the cheese made with mutant and the control cheese, but differences along with the ripening stage were evident. 3. On Sephadex G-25 column chromatography, the extracts of bitter components from the green cheese and 3 month ripended cheese were fractionated into 3 fractions. With the progress of ripening, bitter peptides were degraded to rather small peptides or free amino acids. 4. Sensory evaluation of the 3 month ripended Cheddar cheese found no significant differences in color but the cheese made with mutant evidenced higher palatability in flavor and better texture than the control cheese. 5. The yields of the cheddar cheese made with mutant was 0.14% higher than that of the control cheese.

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Comparison of Paraquat Actions on Oxygen Radical Generation and Lipid Peroxidation between Submitochondrial Particle and Microsome of Mouse Liver (Paraquat에 의한 산소 Radical 생성 및 지질과산화 작용의 Mouse 간 Submitochondria Particle과 Microsome에서의 비교)

  • Choi, Jung-Hwan;Kim, Yong-Sik;Park, Jong-Hwan;Chung, Myung-Hee;Yunn, Chong-Ku
    • The Korean Journal of Pharmacology
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    • v.27 no.2
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    • pp.155-166
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    • 1991
  • In order to evaluate a potential role of mitochondria in the mediation of toxicity of paraquat (PQ), submitochondrial particle and microsome of mouse liver were compared by oxygen radical generation and lipid peroxidation. With NADH in submitochondrial particle and NADPH in microsome as electron donors, PQ stimulated production of superoxide anion and $H_2O_2$ in both fractions. Under the same conditions, PQ enhanced the generation of ethylene from methional suggestiong stimulation of OH production by PQ. But these effects by PQ were somewhat lower in submitochondrial particle than in microsome. In addition, lipid peroxidation(measured as MDA production) was stimulated by PQ in both fractions. The stimulation of lipid peroxidation in both fractions seemed to occur by the same mechanism probably through perferryl ion. This was supported by the following findings: i) The lipid peroxidation in both fractions was partially inhibited by SOD and completely inhibited by DETAPAC(an iron chelator) but not by catalase or OH scavenger. ii) Addition of $ADP-Fe^{3+}$ further increased PQ-induced lipid peroxidation but decreased ethylene production from methional suggesting no correlation between OH production and lipid peroxidation. The redox-cycling of PQ in mitochondria appeared to be linked to NADH dehydrogenase, not to CoQ since all of the observed stimulations by PQ in submitochondrial particle were inhibited by p-hydroxymercuribenzoate(a NADH dehydrogenase inhibitor) but not affected by other respiratory chain blockers. The above results demonstrate that redox-cycling properties of PQ leading to oxygen radical generation and lipid peroxidation can also occur in mitochondria in the same manner as in microsome. Therefore, the observed actions of PQ in mitochondria suggest that mitochondria may also contribute to toxicity of this drug in vivo.

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An Appreciation of Functional Role of Macrophage in the Acute Lung Injury in the Neutropenic Rat. (호중구 감소증을 보이는 백서의 급성폐손상에서 대식세포의 기능적 역할)

  • Kim, Yong-Hoon;Ki, Sin-Young;Im, Keon-Il;Moon, Seung-Hyug;Cheong, Seung-Whan;Kim, Hyeon-Tae;Uh, Soo-Taek;Park, Choon-Sik;Jin, Byung-Won
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.379-390
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    • 1997
  • Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

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Effect of Microwave Hyperthermia on Radiotherapy of Human Malignant Tumors -An Analysis of Clinical Response of 42 Patients- (극초단파를 이용한 국소온열 치료 효과 -표재성 종양 42예의 분석-)

  • Yoon Sei Chul;Oho Yoon Kyung;Gil Hak Jun;Chung Su Mi;Shinn Kyung Sub;Bahk Yong Whee
    • Radiation Oncology Journal
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    • v.5 no.1
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    • pp.31-36
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    • 1987
  • Radiobiological and clinical evidences indicate that hyperthermia combined with ionizing radiation produces a significant improvement in therapeutic effect of cancer. In general, malignant cells are more sensitive to heat than normal cells in the heat range of $41\~45^{\circ}C$. We report the experiences obtained from 42 patients with advanced malignant neoplasms managed with 2,450MHz microwave-induced local hyperthermia and ionizing radiation at the Department of Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. A clinical analysis of 42 thermoirradiated patients showed result of 11(26\%),\;15(36\%),\;11(26\%)\;and\;5(12\%)$ patients with complete response (CR), partial response (PR), minor response (MR) and no response (NR), respectively. Histologically there were $17(40.2\%)$ squamous cell carcinomas, $12(28.6\%)$ adenocarcinomas and $6(14.3\%)$ miscellaneous cancers. Eleven patients with CR consisted of five squamous cell carcinomas, five adenocarcinomas, and one chloroma. Among 15 patients with PR were five squamous cell carcinomas, five adenocarcinomas, three unknown primary tumors, and one poorly differentiated, and miscellaneous tumor each.

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Anti-Inflammatory Effects of Extracts from Ligustrum ovalifolium H. Leaves on RAW264.7 Macrophages (RAW264.7 대식세포에서 왕쥐똥나무잎 추출물의 항염증 효과)

  • Kim, Yon-Suk;Lee, Seung-Jae;Hwang, Jin-Woo;Kim, Ee-Hwa;Park, Pyo-Jam;Jeong, Jae-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.9
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    • pp.1205-1210
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    • 2012
  • This study investigated the anti-inflammatory effects of Ligustrum ovalifolium H. (LOH) leaf extracts on RAW264.7 macrophages. Cell toxicity was determined by MTT assay. We evaluated the anti-inflammatory effects of LOH extracts by measuring nitric oxide (NO), reactive oxygen species (ROS), inducible NOS (iNOS) production, and cyclooxygenase-2 (COX-2) expression by Western blotting. LOH ethanolic extracts (0.05, 0.1, and 0.2 mg/mL) significantly suppressed LPS-stimulated production of NO. The intracellular ROS level also significantly decreased. LOH ethanolic extracts reduced the expression of iNOS and COX-2 proteins. The present results show that LOH ethanol extract has potent anti-inflammatory effects on RAW264.7 macrophages. These results also suggest that the anti-inflammatory effects of LOH extracts may be related to the inhibition of LPS-stimulated ROS and NO production. Therefore, ethanolic extracts of LOH leaves may be utilized as a good source of functional foods for protection against inflammatory diseases.

INHIBITORY EFFECT OF Er:YAG LASER ON THE GROWTH OF STREPTOCOCCUS MUTANS (Er:YAG 레이저 조사가 Streptococcus mutans의 증식억제에 미치는 효과)

  • Song, Gwang-Chul;Lee, Chang-Seop;Lee, Sang-Ho;Lee, Nan-Young
    • Journal of the korean academy of Pediatric Dentistry
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    • v.30 no.1
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    • pp.15-24
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    • 2003
  • The purpose of this study is to investigate the sterilization effect of Er:YAG laser against the intraoral acid producing bacterium, S. mutans, by irradiating the culture solution containing S. mutans KCTC 3065 with Er:YAG laser having a $650{\mu}m$ diameter beam through the non-contact method. We obtained the following results after examining the temperature changes of the culture solution, numbers of bacterial colonies, and acid-producing ability and attaching ability on teeth by measuring the amount of extracellular polysaccharide produced by S. mutans. The number of bacterial colony was decreased in $10{\mu}l$ culture solution irradiated with laser in overall compared to the control solution. The number decreased as the irradiation intensity and pulse repetition rate were larger and as the exposure time was increased. However, it did not change significantly in $100{\mu}l$ culture solution compared to the control solution. Although the acid-producing ability of S. mutans was inhibited for a certain duration after laser irradiation in 10r1 bacterial culture solution, it did not change in $100{\mu}m$ solution compared with the control solution. The amount of extracellular polysaccharide synthesized by S. mutans was partially decreased through laser irradiation in $10{\mu}m$ culture solution but did not change in $100{\mu}m$ culture solution. Based on these findings, we concluded that Er:YAG laser has an sterilization effect on S. mutans in which we presume that the mechanism is through the heat effect rather than the mechanical effect from development of ultrasound.

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Protective effects of quality certified traditional Doenjang in Korea on TNF-α-induced vascular inflammation in human umbilical vein endothelial cells (혈관내피세포에서 TNF-α 자극에 의해 유도되는 혈관염증에 대한 전통식품 품질인증 된장의 효능 평가)

  • Kim, Eun-Ju;Jang, Yeon-Jeong;Kim, So-Young;Choi, Hye-Sun;Park, Shin-Young
    • Food Science and Preservation
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    • v.23 no.3
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    • pp.378-386
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    • 2016
  • Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved in the suppression of oxidative stress, cell adhesion molecules, and pro-inflammatory factors. This study investigated the vascular inflammation inhibitory activity of traditional Doenjang plays a key role in the pathogenesis and progression of atherosclerosis. The protective effects of Korean Deonjang was investigated on the expression of cell adhesion molecules (CAMs) in tumor necrosis factor (TNF)-${\alpha}$-induced human umbilical vascular endothelial cells (HUVECs). Deonjang extracts (20, 50, $100{\mu}g/mL$) decreased the expression of 20 ng/mL TNF-${\alpha}$-induced vascular cell adhesion molecule (VCAM)-1 intracellular adhesion molecule (ICAM)-1 proteins, and their corresponding mRNA levels. Nitric oxides (NO) produced by endothlial nitric oxides synthase (eNOS) dilated blood vessels, which had protective effects against platelet and leukocyte adhesion. While TNF-${\alpha}$-induced suppressed the production of nitric oxide in HUVECs, Doenjang restored NO production in HUVECs. In addition, Deonjang reduced the TNF-${\alpha}$-induced expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 mRNA levels. These results suggested that Doenjang can inhibited the production of cell adhesion molecules and inflammatory mediators, which could be a potential candidate for preventing atherosclerosis.