• Title/Summary/Keyword: Mechanism of action

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Influence of Hypoxia on Catecholamine Secretion Evoked by DMPP, McN-A-343, Excess $K^+$ and ACh from The Perfused Rat Adrenal Gland (저산소증이 흰쥐 관류부신에서 DMPP, McN-A-343, Excess $K^+$ 및 Ach의 카테콜아민 분비작용에 미치는 영향)

  • Lim Dong-Yoon;Heo Jae-Bong;Park Yoo Han
    • The Korean Journal of Pharmacology
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    • v.31 no.1 s.57
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    • pp.63-74
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    • 1995
  • It has been known that, during hypoxia, the adrenal medulla is activated to release catecholamines (CA) while hypoxia also inhibits high $K^+$ -induced CA secretion in the cultured bovine adrenal chromaffin cells. The present study was attempted to examine the effect of hypoxia on CA secretion evoked by chlinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal glands and also to clarify its mechanism of action. For this purpose, using the isolated rat adrenal glands, the effects of hypoxia on CA release evoked by nicotinic ($N_1$) and muscarinic ($M_1$) receptor agonists, membrane-depolarizing agent, $Ca^{++}$-channel activator, intracellular $Ca^{++}$-releaser and ACh were determined. Experiments were carried out, perfusing Krebs solution pre-equilibrated with a gas mixture of 95% N_2$ and 5% $CO_2$. Hypoxia was maintained for $3{\sim}4$ hours through the experiments. Hypoxia gradually caused a time-dependent seduction in CA secretion evoked by DMPP ($100{\mu}M$), McN-A-343 ($100{\mu}M$), ACh (5.32 mM), Bay-K-8644 ($10{\mu}M$) and high $K^+$ (56 mM) respectively. How-ever, it did not affect CA secretion evoked by cyclopiazonic acid ($10{\mu}M$). Hypoxia itself also did fail to produce any influence on spontaneous secretory response of CA. These experimental results suggest that hypoxia depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla, and that this inhibitory activity may be due to the result of the direct inhibition of $Ca^{++}$ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store.

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Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells (산화적 스트레스에 대한 여주 (Momordica charantia) 추출물의 항산화 효과 및 세포사멸 억제 기전을 통한 신경세포보호효과)

  • Kim, Kkot Byeol;Lee, Seonah;Heo, Jae Hyeok;Kim, Jung hee
    • Journal of Nutrition and Health
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    • v.50 no.5
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    • pp.415-425
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    • 2017
  • Purpose: Many studies have suggested that neuronal cells protect against oxidative stress-induced apoptotic cell death by polyphenolic compounds. We investigated the neuroprotective effects and the mechanism of action of Momordica charantia ethanol extract (MCE) against $H_2O_2-induced$ cell death of human neuroblastoma SK-N-MC cells. Methods: The antioxidant activity of MCE was measured by the quantity of total phenolic acid compounds (TPC), quantity of total flavonoid compounds (TFC), and 2,2-Diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging activity. Cytotoxicity and cell viability were determined by CCK-8 assay. The formation of reactive oxygen species (ROS) was measured using 2,7-dichlorofluorescein diacetate (DCF-DA) assay. Antioxidant enzyme (SOD-1,2 and GPx-1) expression was determined by real-time PCR. Mitogen-activated protein kinases (MAPK) pathway and apoptosis signal expression was measured by Western blotting. Results: The TPC and TFC quantities of MCE were 28.51 mg gallic acid equivalents/extract g and 3.95 mg catechin equivalents/extract g, respectively. The $IC_{50}$ value for DPPH radical scavenging activity was $506.95{\mu}g/ml$ for MCE. Pre-treatment with MCE showed protective effects against $H_2O_2-induced$ cell death and inhibited ROS generation by oxidative stress. SOD-1,2 and GPx-1 mRNA expression was recovered by pre-treatment with MCE compared with the presence of $H_2O_2$. Pre-treatment with MCE inhibited phosphorylation of p38 and the JNK pathway and down-regulated cleaved caspase-3 and cleaved PARP by $H_2O_2$. Conclusion: The neuroprotective effects of MCE in terms of recovery of antioxidant enzyme gene expression, down-regulation of MAPK pathways, and inhibition apoptosis is associated with reduced oxidative stress in SK-N-MC cells.

Effects of vitamin C as antioxidant on recovery of left ventricular function after ischemia and reperfusion in isolated rat heart (항산화제로서 비타민 C가 적출된 쥐심장에서 허혈 및 재관류후 좌심실 기능회복에 미치는 영향)

  • 류한영;이철주
    • Journal of Chest Surgery
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    • v.29 no.6
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    • pp.593-598
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    • 1996
  • The large number of past investigation on extended myocardial protection clearly indicates that cold potassium cardioplegia and topical cooling have limited capabilities. Accordingly, more recent experimen- tal approaches have focused on the modalities of reperfusion and their implication on postischemic myo- cardial recovery. Oxygen may play a crucial role in the development of ischemic and reperfusion injury. Reactive oxygen radicals may be produced during ischemia or reperfusion after incomplete reduction of molecular oxygen or from other pathway and then induce fatal injury of the heart. The important obser- vation of oxygen-induced myocardial damage during reperfusion has led to the concept of applying oxy- gen free radical scavengers. So, this study is on dietary vitamin C supplementation as antioxidant in rats to determine whether or not they have a higher tolerance against cardiac ischemia-reperf'usion injury under Langendorff system. Male or female Sprague-Dawley rats (190-33Og) were randomly separated into two groups. Group A was not treated(n=10). Group B received vitamin C supplement (n=10). Experiment was performed 24 hours after vitamin C 200mg fed orally as injectable ascorbic acid. There were significant differences in contractile parameters between control and vitamin C-treated group. The RLVP (r te of post/preischemic left ventricular pressure) and Rdp/dt (rate of post/preischemic dp/dt) were significant statistically between two groups (p<0.05). But, RHR (rate of post/preischemic heart rate), time to first beat and sta'utilization were not significant. In conclusion, pretreatment with the antioxidant, ascorbic acid, was found to preserve left ventricular contractile function. But the precise mechanism of action of ascorbic acid has not as yet been determined, so further study will be required.

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Improvement in Antagonistic Ablility of Antagonistic Bacterium Bacillus sp. SH14 by Transfer of the Urease Gene. (Urease gene의 전이에 의한 길항세균 Bacillus sp. SH14의 길항능력 증가)

  • 최종규;김상달
    • Microbiology and Biotechnology Letters
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    • v.26 no.2
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    • pp.122-129
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    • 1998
  • It were reported that antifungal mechanism of Enterobacter cloacae is a volatile ammonia that produced by the strain in soil, and the production of ammonia is related to the bacterial urease activity. A powerful bacterium SH14 against soil-borne pathogen Fusarium solani, which cause root rot of many important crops, was selected from a ginseng pathogen suppressive soil. The strain SH14 was identified as Bacillus subtilis by cultural, biochemical, morphological method, and $API^{circledR}$ test. From several in vitro tests, the antifungal substance that is produced from B. subtilis SH14 was revealed as heat-stable and low-molecular weight antibiotic substance. In order to construct the multifunctional biocontrol agent, the urease gene of Bacillus pasteurii which can produce pathogenes-suppressive ammonia transferred into antifungal bacterium. First, a partial BamH I digestion fragment of plasmid pBU11 containing the alkalophilic B. pasteurii l1859 urease gene was inserted into the BamH I site of pEB203 and expressed in Escherichia coli JM109. The recombinant plasmid was designated as pGU366. The plasmid pGU366 containing urease gene was introduced into the B. subtilis SH14 with PEG-induced protoplast transformation (PIP) method. The urease gene was very stably expressed in the transformant of B. subtilis SH14. Also, the optimal conditions for transformation were established and the highest transformation frequency was obtained by treatment of lysozyme for 90 min, and then addition of 1.5 ${mu}g$/ml DNA and 40% PEG4000. From the in vitro antifungal test against F. solani, antifungal activity of B. subtilis SH14(pGu366) containing urease gene was much higher than that of the host strain. Genetical development of B. subtilis SH14 by transfer of urease gene can be responsible for enhanced biocontrol efficacy with its antibiotic action.

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Prevention of Discoloration and Storage Stability in Canned Ark Shell (새고막 통조림 변색방지 및 저장중 품질변화)

  • 배태진;김귀식
    • The Korean Journal of Food And Nutrition
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    • v.11 no.2
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    • pp.243-248
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    • 1998
  • Ark shell was known as shellfish that had hemoglobin as blood pigment and the action of mecidine, was consumed the great part of it as raw material, though it was produced about 13,000 M/T per year. Ark shell was processed the infinitesimal quantity as conned product, bout canned ark shell had problem that occurrenced discoloration after heat treatment during processing and storage. This discoloration mechanism during processing and storage was not cleared. This study was carried out to understand characteristics of the hemoglobin as blood pigment and carotenoid as meat pigment in ark shell and management of proper processing conditions for prevention of oxidation and discoloration by thermal treatment. When treated by digestion of 0.1% BHA, 0.1% Tenox-II, 0.5% Na2EDTA, 0.05% NDGA and 3% salt soln., 0.1% BHA solution was most suitable for stability of carotenoid that the retention ratio of carotenoids were 63.1% after heating to 116$^{\circ}C$ for 120 minutes. In preparation of canned ark shell and storage at 37$\pm$1$^{\circ}C$ for 60 days, the chemical composition, pH and salinity ere stable. And contents of total carotenoid were decreased slightly from 0.83mg% to 0.727mg%. The viable cell count were 6.92$\times$103 cfu/ml at raw ark shell, after processed and storage were not detected. The predominant amino acids in the raw ark shell were glutamic acid(19.7%), arginine(16.0%), glycine(12.6%), alanine(12.2%) and aspartic acid(7.6%). When 60 days stored, the contents of amino acid were stable. And the predominant nuclotide and their related compounds in the raw ark shell were hypoxanthine(2.14$\mu$mol/g), IMP(1.94$\mu$mol/g) and ATP(0.87$\mu$mol/g), and storage at 37$\pm$1$^{\circ}C$ for 60 days, the quantity order were same as raw material.

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Analysis on Practicality of Seed Treatments for Medicinal Plants Published in Korean Scientific Journals (국내 학술지에 발표된 약용작물 종자처리의 실용성 분석)

  • Kang, Jin-Ho;Yoon, Soo-Young;Jeon, Seung-Ho
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.4
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    • pp.328-341
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    • 2004
  • Presowing seed treatments used to enhance the rates of germination and afterward seedling emergence have not occasionally shown the same rate in indoor and field. The treatments considering germination mechanism and factors affecting germination must be totally included in indoor experiments so that the results drawn can be reproduced in the field. Seed germination is controlled by Phytochrome-mediated action changed with composition rates of red and far-red lights. Sunlight can penetrate soil into $6{\sim}9\;mm$ depth, which in turn means that seeds having $2{\sim}3\;mm$ in their width may receive the light if soil was covered 3 times over them. The penetrating light, moreover, turns to more far-red light than red light reverse to the sunlight. For germination tests after the artificial presowing seed treatments, therefore, seeds of smaller than 2 mm (< 2 mm), $2{\sim}3\;mm$, and larger than 3 mm (> 3 mm) must be done with incandescent lamp (IL) having more far-red light, with IL or in darkness, and in darkness, respectively. The 96 papers published in 13 Korean scientific journals up to the end of 2003 were analysed on the basis of the above explanation. 91 species were used 147 times as experimental materials; 101 times for < 2 mm seeds, 24 times for $2{\sim}3\;mm$ seeds and 22 times for > 3 mm seeds. If they were analysed as the light sources used for germination tests, correct applications reached more and less than 60% in both $2{\sim}3\;mm$ and > 3 mm seeds but 23% in < 2 mm seeds, conclusionally meaning that when the experimental results in the scientific papers were applied into farming practices, care was taken of their application because most of medicinal plant seeds were very small.

Expression of Serotonin(5-HT) Receptor Isotypes in Reproductive Organs of Male Rat (수컷 흰쥐 생식기관에서의 세로토닌 수용체 아형 유전자 발현)

  • 이성호
    • Development and Reproduction
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    • v.6 no.2
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    • pp.111-115
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    • 2002
  • 5-Hydroxytryptamine(5-HT; serotonin) system has been implicated in the modulation of male sexual behaviors and the secretion of reproductive hormones. In human males, selective serotonin re-uptake inhibitors(SSRIs) are known to improve the major male sexual dysfunction, premature ejaculation, through the central nervous system-mediated pathways. As numerous hormone and local factors, 5-HT may have peripheral role in the regulation of male sexual function. The expression of 5-HT receptor subtypes in the target tissue, however, has not been explored yet. The present study was undertaken to test whether the 5-HT receptor subtypes are expressed in the reproductive tissues of male rat, especially in ejaculatory machinery such as seminal vesicle and vas deferens. To do this, reverse transcription-polymerase chain reaction(RT-PCR) and Southern blot analysis were employed. The transcripts for the 1A, 1B and 2C subtypes of 5-HT receptor were amplified in all the tested tissues. The present study demonstrated the expression of 5-HT receptor in the rat ejaculatory machinery, suggesting that 5-HT may play a pivotal role in the male sexual function via not only central pathway but also peripheral route. Further study on the receptor subtype-specific effect and their harmonized mode of action will be needed to establish the understanding of ejaculation mechanism and drug design.

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Fatty acid analysis and regulatory effects of citron (Citrus junos Sieb. ex TANAKA) seed oil on nitric oxide production, lipid accumulation, and leptin secretion (유자씨유의 지방산분석 및 Nitric Oxide 생성, 지방축적능, 렙틴분비 조절효과)

  • Kim, Tae Woo;Kim, Kyoung Kon;Kang, Yun Hwan;Kim, Dae Jung;Choe, Myeon
    • Journal of Nutrition and Health
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    • v.47 no.4
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    • pp.221-228
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    • 2014
  • Purpose: Citron seed oil (CSO) has been reported to have high antioxidant activity. However, the composition and other biologically activities of CSO have not been reported. In this study, we confirmed the fatty acid composition of CSO, which may be beneficial to vascular disease and obesity. Methods: We investigated the oil composition of CSO using gas chromatography coupled with mass spectrometry (GC-MS) analysis, and cytotoxicity was confirmed by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was measured using Griess reagent, and lipid accumulation and leptin secretion in 3T3-L1 cells were measured by Oil-Red O staining and commercial ELISA kit, respectively. Results: GC-MS analysis indicated that CSO contains several components, including linoleic acid, oleic acid, palmitic acid, stearic acid, linolenic acid, palmitoleic acid, and arachidic acid. In physiological activity analysis, CSO did not induce cytotoxic effects in HUVECs and 3T3-L1 cells. Further, CSO significantly induced nitric oxide and leptin secretion as well as inhibited lipid accumulation. Conclusion: CSO increased NO release, inhibited lipid accumulation, and induced leptin secretion, suggesting it may be useful for the management of vessels and weight gain. Although further studies are required to investigate the safety and mechanism of action of CSO, our results show that the composition and physiological activity of CSO are sufficient for its use as functional edible oil.

A Study on Legal and Institutional Improvement Measures for the Effective Implementation of SMS -Focusing on Aircraft Accident Investigation-

  • Yoo, Kyung-In
    • The Korean Journal of Air & Space Law and Policy
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    • v.32 no.2
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    • pp.101-127
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    • 2017
  • Even with the most advanced aviation technology benefits, aircraft accidents are constantly occurring while air passenger transportation volume is expected to double in the next 15 years. Since it is not possible to secure aviation safety only by the post aircraft accident safety action of accident investigations, it has been recognized and consensus has been formed that proactive and predictive prevention measures are necessary. In this sense, the aviation safety management system (SMS) was introduced in 2008 and has been carried out in earnest since 2011. SMS is a proactive and predictive aircraft accident preventive measure, which is a mechanism to eliminate the fundamental risk factors by approaching organizational factors beyond technological factors and human factors related to aviation safety. The methodology is to collect hazards in all the sites required for aircraft operations, to build a database, to analyze the risks, and through managing risks, to keep the risks acceptable or below. Therefore, the improper implementation of SMS indicates that the aircraft accident prevention is insufficient and it is to be directly connected with the aircraft accident. Reports of duty performance related hazards including their own errors are essential and most important in SMS. Under the policy of just culture for voluntary reporting, the guarantee of information providers' anonymity, non-punishment and non-blame should be basically secured, but to this end, under-reporting is stagnant due to lack of trust in their own organizations. It is necessary for the accountable executive(CEO) and senior management to take a leading role to foster the safety culture initiating from just culture with the safety consciousness, balancing between safety and profit for the organization. Though a Ministry of Land, Infrastructure and Transport's order, "Guidance on SMS Implementation" states the training required for the accountable executive(CEO) and senior management, it is not legally binding. Thus it is suggested that the SMS training completion certificates of accountable executive(CEO) and senior management be included in SMS approval application form that is legally required by "Korea Aviation Safety Program" in addition to other required documents such as a copy of SMS manual. Also, SMS related items are missing in the aircraft accident investigation, so that organizational factors in association with safety culture and risk management are not being investigated. This hinders from preventing future accidents, as the root cause cannot be identified. The Aircraft Accident Investigation Manuals issued by ICAO contain the SMS investigation wheres it is not included in the final report form of Annex 13 to the Convention on International Civil Aviation. In addition, the US National Transportation Safety Board(NTSB) that has been a substantial example of the aircraft accident investigation for the other accident investigation agencies worldwide does not appear to expand the scope of investigation activities further to SMS. For these reasons, it is believed that investigation agencies conducting their investigations under Annex 13 do not include SMS in the investigation items, and the aircraft accident investigators are hardly exposed to SMS investigation methods or techniques. In this respect, it is necessary to include the SMS investigation in the organization and management information of the final report format of Annex 13. In Korea as well, in the same manner, SMS item should be added to the final report format of the Operating Regulation of the Aircraft and Railway Accident Investigation Board. If such legal and institutional improvement methods are complemented, SMS will serve the purpose of aircraft accident prevention effectively and contribute to the improvement of aviation safety in the future.

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