• Title/Summary/Keyword: blocking effects

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Effects of MK-801, CNQX, Cycloheximide and BAPTA-AM on Anoxic Injury of Hippocampal Organotypic Slice Culture (해마 조직 절편 배양을 이용한 무산소 손상에 대한 MK-801, CNQX, Cycloheximide 및 BAPTA-AM의 효과)

  • Moon, Soo-Hyeon;Kwon, Taek-Hyon;Park, Youn-Kwan;Chung, Heung-Seob;Suh, Jung Keun
    • Journal of Korean Neurosurgical Society
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    • v.29 no.8
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    • pp.1008-1018
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    • 2000
  • Objective : Glutamate induced excitotoxicity is one of the leading causes of cell death under pathologic condition. However, there is controversy whether excitotoxicity may also participate in the neuronal death under low intensity insult such as simple hypoxia or hypoglycemia. To investigate the role of NMDA receptor in low intensity insult, we chose anoxia as the method of injury and used organotypically cultured hippocampal slice as the material of experiment. Materials & Methods : The hippocampal slices cultured for 2-3 weeks were exposed to 60 minutes of complete oxygen deprivation(anoxia). Neuronal death was assessed with Sytox stain. Corrected optical density of fluorescence in gray scale, used as cellular death indicator, was obtained from pictures taken at 24 and 48 hours following the insult. The well-known in vivo phenomenon of regional difference in susceptibility of hippocampal sub-fields to ischemic insult was reproduced in HOSC(hippocampal organotypic slice culture) by complete oxygen deprivation injury. Results : $CA_1$ was the most vulnerable to complete oxygen deprivation in hippocampus while $CA_3$ was resistant. Oxygen deprivation for 10 and 20 minutes with glucose(6.5g/l) present was insufficient to induce neuronal death in the cultured hippocampal slice. However, after 30 minutes exposure under anoxic condition, neuronal death was able to be detected in the center of $CA_1$ area. The intensity and area of fluorescence indicating cell death correlated with the duration of oxygen deprivation. NMDA receptor and non-NMDA receptor blocking with MK-801(30 & $60{\mu}M$) and CNQX($100{\mu}M$) did not provide cellular protection to HOSC against damage induced by oxygen deprivation, but increased intracellular calcium buffering capacity with BAPTA-AM($10{\mu}M$) was effective in preventing neuronal death (p=0.01, Student's t-test). Cycloheximide($1{\mu}g/ml$, $10{\mu}g/ml$) provided no protection to HOSC against insult of complete oxygen deprivation for 60 minutes and combined therapy of MK-801(30 & $60{\mu}M$) and cycloheximide(1 & $10{\mu}g/ml$) was also ineffective in preventing neuronal death. Conclusion : The results of this study show that the another mechanism not associated with glutamate receptor(NMDA & non NMDA) may play major role in cell death mechanisms induced by complete oxygen deprivation and increased intracellular calcium during anoxia may participate in the neuronal death mechanism of oxygen deprivation. Further investigation of the calcium entry channel activated during oxygen deprivation is necessary to understand the neuronal death of anoxia.

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Suppression of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice by transduced Tat-Annexin protein

  • Lee, Sun-Hwa;Kim, Dae-Won;Eom, Seon-Ae;Jun, Se-Young;Park, Mee-Young;Kim, Duk-Soo;Kwon, Hyung-Joo;Kwon, Hyeok-Yil;Han, Kyu-Hyung;Park, Jin-Seu;Hwang, Hyun-Sook;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.45 no.6
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    • pp.354-359
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    • 2012
  • We examined that the protective effects of ANX1 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in animal models using a Tat-ANX1 protein. Topical application of the Tat-ANX1 protein markedly inhibited TPA-induced ear edema and expression levels of cyclooxygenase-2 (COX-2) as well as pro-inflammatory cytokines such as interleukin-1 beta (IL-$1{\beta}$), IL-6, and tumor necrosis factor-alpha (TNF-${\alpha}$). Also, application of Tat-ANX1 protein significantly inhibited nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) and phosphorylation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) in TPA-treated mice ears. The results indicate that Tat-ANX1 protein inhibits the inflammatory response by blocking NF-${\kappa}B$ and MAPK activation in TPA-induced mice ears. Therefore, the Tat-ANX1 protein may be useful as a therapeutic agent against inflammatory skin diseases.

Influence of Intracerebroventricular Isoproterenol on the Renal Function of the Rabbit (가토신장기능에 미치는 측뇌실내 Isoproterenol의 영향)

  • Kim, Haeng-Bae;Choi, Bong-Kyu;Kook, Young-Johng
    • The Korean Journal of Pharmacology
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    • v.18 no.1
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    • pp.1-10
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    • 1982
  • In an attempt to delineate the role of beta-adrenoceptors found to be existing in the brain tissue in the central regulation of renal function, isoproterenol, a ${\beta}-adrenergic$ agonist, was administered directly into a lateral ventricle of the rabbit brain and the changes of renal function were observed. Also, the effects of propranolol, a specific ${\beta}-adrenergic$ blocking agent, and its influence upon the isoproterenol action were studied. Isoproterenol, in doses ranging from 5 to $50\;{\mu}g/kg\;i.c.v.$, elicited antidiuresis which seemed to be related to the decreased renal hemodynamics brought about by the systemic hypotension. With moderate doaes of $15\;{\mu}g/kg$ the antidiuresis was less prominent and there was a tendency toward natriuresis, but with higher doses the natriuretic effect became less evident, overrun by the systemic hypotension. Propranolol, $500\;{\mu}g/kg\;i.c.v.$, produced little effect on the renal function, but it eliminated the antidiuretic action of $50\;{\mu}g/kg$ isoproterenol i.c.v. and reversed it to a diuretic and natriuretic one, along with increases in renal plasma flow and glomerular filtration rate. The systemic hypotension also was markedly attenuated by propranolol pretreatment. Thus, it was evident that the renal action of i.c.v. isoproterenol was not blocked by propranolol and became explicit only when the hypotensive action of isoproterenol which seems to he propranolol-sensitive is removed. Various possibilities to account for this disparity in sensitivity were discussed. It is suggested from these observations that the central ${\beta}-adrenoceptors$ might also be involved in the regulation of renal function along with ${\alpha}-adrenoceptors$, though less significant than the latter.

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Effects of Sterilization Temperatures and Internal Air Volumes of a Pouch on the Quality of Retort Rice (살균온도 및 포장재내 공기량이 레토르트 쌀밥의 품질에 미치는 영향)

  • Koh, Ha-Young;Park, Moo-Hyun
    • Korean Journal of Food Science and Technology
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    • v.22 no.2
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    • pp.150-154
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    • 1990
  • Various sterilization temperatures $(110^{\circ}C,\;120^{\circ}C,\;130^{\circ}C)$ and air volumes (air, 31ml, half-vacuum; 13ml, vacuum; -0.7ml) within the retort pouch were tested for the development of the simple retort rice processing techniques in which the pouch were filled with rice and water, and then sterilized. Water content of retort rice was found to be 59.0-63.3% resulting from mixing the rice and water in the ratio of 1:1.1. The most uniform water content was obtained from retort rice sterilized at $130^{\circ}C$ and packaged under vacuum. The larger water content differences were observed with the increase in internal air volumes within the retort pouch. Spreading degree of retort rice was geater than that of general cooked rice, was lower in upper layer than in low layer, and became lower with the larger air volume and higher sterilization temperature. a degree of rice became higher with the Increase of sterilization temperature but that was not affected by the internal air volume of the pouch. The higher sterilization temperature and the lower the air volume, the higher the whiteness was. The highest whiteness was obtained by packaging under vacuum and sterilizing at $130^{\circ}C$. Intact degree was much higer in packaging under air than vacuum. In sensory evaluation the retort rice of vacuum pack was good in color and spreading degree but not in appearance because of blocking and deforming, but that of air pack was good in texture on the contrary. The best quality was obtained by packaging under half-vacuum and sterilizing at $130^{\circ}C$.

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Effects of Healing Beats program on patients' anxiety, stress, systolic blood pressure, heart rate and Bis Index after epidural blocking : A randomized controlled trial (Healing Beats 프로그램이 경막외강차단 시술 후 환자의 불안, 스트레스, 수축기 혈압, 심박동수 및 Bis Index에 미치는 효과 : 무작위대조군)

  • Bae, Ik Lyul;Song, Ji Ah
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.7
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    • pp.54-65
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    • 2020
  • This randomized pre-post-controlled experimental study determined the effect on patients' anxiety, stress, systolic blood pressure, heart rate and Bis index when the Healing Beats program is applied after epidural blockage. The subjects were selected from the patients who visited the Department of Anesthesiology and Pain for the treatment of epidural blockage and volunteered through the recruitment announcement. A total of 74 sets of data were collected and analyzed with 25 subjects in the experimental group, 24 in the placebo group, and 25 in the control group. The data was analyzed using descriptive statistics, x2-tests, F-tests and repeated measures of ANOVA. As a result of the study, the general characteristics and variables of the experimental group, placebo group, and control group were all the same, and anxiety was measured twice before and after the study. There were significant differences between groups (F=27.175, p<.001), and stress (F=4.78, p<.001), heart rate (F=4.22, p<.001) and the Bis index (F=7.96, p<.001) were analyzed by variance according to population and time. There was a significant difference. However, there was no significant difference in systolic blood pressure (F=1.23, p=.298). In conclusion, the Healing Beats program can be used as an effective and effective intervention for sedation in clinical situations or stressful situations.

The Effects of Aging on Retrieval of Phonological Knowledge in Korean: The Tip-of-the-Tongue Phenomenon in Young and Older Adults (한국어 음운 정보 산출에서 노화의 영향: 청년과 노인의 설단현상)

  • Park, Jiyoon;Lee, Ko Eun;Lee, Hye-Won
    • Korean Journal of Cognitive Science
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    • v.24 no.2
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    • pp.111-132
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    • 2013
  • Previous research has shown that aging asymmetrically affects various functions in language. It is known that older adults show deficits in language production compared to young adults, while the performance in semantic processing is similar between older and young adults. The tip-of-the-tongue (TOT) phenomenon effectively reflects failure in retrieval of phonological knowledge. Older adults report TOTs more often than young adults and the cause of this phenomenon has been explained by two frameworks: the 'blocking hypothesis' and 'transmission deficit hypothesis'. This study examines the effect of aging on the retrival of phonological knowledge by inducing TOTs in the laboratory. Two variables were manipulated: age and word category. Participants were young and older adults, and stimuli was selected from 5 categories of words. After the participants read a definition about a target word, they reported three conditions: 'know', 'don't know', 'TOT'. The results were as follows: First, the older adults reported TOTs more often than the young adults. Second, TOTs occurred more in proper nouns such as names of persons and places. Third, in the category that TOTs occurred more often, there was a bigger age difference. Fourth, older adults reported fewer alternative words during TOT than young adults. Fifth, participants tended to report the partial information during TOT in characters. These results show the age-related difficulty in the retrieval of phonological knowledge in Korean. It is explained by the transmission deficit hypothesis and the characteristics of Korean orthography and phonology.

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The effect of flavonoids on the TREK-1 channel (TREK-1 채널에 대한 플라보노이드의 효과)

  • Kim, Yang-Mi;Kim, Kyung-Ah
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.6
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    • pp.2660-2667
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    • 2011
  • TREK-1 channel is a member of the two-pore domain potassium (K2P) channel family that is regulated by intracellular pH, membrane stretch, polyunsaturated fatty acids, temperature, and some neuroprotectant agents. TREK-1 channel can influence neuronal excitability by regulating leakage of potassium ions and resting membrane potential. TREK-1 channel has been shown to be overexpressed in prostate cancer cells. Although the importance of these properties, relatively little is known about flavonoid effects in the regulations of TREK-1 channel. The purpose of the study was to screening of flavonoids as the TREK-1 channel modulator using one of electrophysiological techniques such as excised inside-out patch configuration. We demonstrated blocking effect on TREK-1 channel by flavonoids such as epigallocatechin-3-gallate (EGCG), curcumin and quercetin in CHO cells transiently expressing TREK-1 channel. The inhibition of TREK-1 channel by quercetin and curcumin was reversible, whereas EGCG was little reversible. Quercetin, EGCG and curcumin decreased the relative channel activity to 73%, 91% and 94%, respectively. The half-inhibitory concentration (IC50) of curcumin, quercetin and EGCG was $1.04{\pm}0.19\;{\mu}M$, $1.13{\pm}0.26\;{\mu}M$ and $13.5{\pm}2.20\;{\mu}M$ in CHO cells expressing TREK-1 channel, respectively. These results indicate that flavonoids might regulate TREK-1 and this regulation might be one of the pharmacological actions of flavonoid in nervous systems and cancer cells.

Resveratrol Inhibits Nicotinic Stimulation-Evoked Catecholamine Release from the Adrenal Medulla

  • Woo, Seong-Chang;Na, Gwang-Moon;Lim, Dong-Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.4
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    • pp.155-164
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    • 2008
  • Resveratrol has been known to possess various potent cardiovascular effects in animal, but there is little information on its functional effect on the secretion of catecholamines (CA) from the perfused model of the adrenal medulla. Therefore, the aim of the present study was to determine the effect of resveratrol on the CA secretion from the isolated perfused model of the normotensive rat adrenal gland, and to elucidate its mechanism of action. Resveratrol (10${\sim}100{\mu}$M) during perfusion into an adrenal vein for 90 min inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_n$ receptor agonist, 100${\mu}$M) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100${\mu}$M) in both a time- and dose- dependent fashion. Also, in the presence of resveratrol (30${\mu}$M), the secretory responses of CA evoked by veratridine 8644 (an activator of voltage-dependent$Na^+$ channels, 100${\mu}$M), Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, 10${\mu}$M), and cyc1opiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10${\mu}$M) were significantly reduced. In the simultaneous presence of resveratrol (30${\mu}$M) and L-NAME (an inhibitor of NO synthase, 30${\mu}$M), the CA secretory evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyc1opiazonic acid were recovered to a considerable extent of the corresponding control secretion compared with the inhibitory effect of resveratrol alone. Interestingly, the amount of nitric oxide (NO) released from the adrenal medulla was greatly increased in comparison to its basal release. Taken together, these experimental results demonstrate that resveratrol can inhibit the CA secretory responses evoked by stimulation of cholinergic nicotinic receptors, as well as by direct membrane-depolarization in the isolated perfused model of the rat adrenal gland. It seems that this inhibitory effect of resveratrol is exerted by inhibiting an influx of both ions through $Na^+$ and $Ca^{2+}$ channels into the adrenomedullary cells as well as by blocking the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are mediated at least partly by the increased NO production due to the activation of NO synthase.

Factors Impacting Public Technology Transfer and Commercialization and Its Strategy for R&D Management (공공기술이전·사업화 영향요인 및 연구개발 관리전략)

  • Sung, Oong-Hyun;Moon, Hye-Jung;Kang, Hun
    • Journal of Korea Technology Innovation Society
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    • v.18 no.3
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    • pp.468-491
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    • 2015
  • The major objective of this research is to suggest the proactive strategy and management of public R&D for the active transfer of technology based on the influential factor analysis of technology transfer. This study identified influential factors which make the greatest impact on the success of public technology transfer and commercialization through three points of view-technology supplier's view, technology adopter's view and view of commercialization-which contribute to successful technology transfer and commercialization. The core influential variables for blocking technology transfer are identified such as additional technological development, search for technology adopter followed by mass production technology and testing of confidence. Technology adopter is to create new markets or expand existing markets through the superiority (innovation) of licensing technology, increasing the internal innovation capabilities and maximizing the impacts of technology. This research suggests two effective strategies for improving technology transfer such as technology planning and marketing in the view of technology license. The strategy of technology planning should be established and executed to meet both technology trends and adopter's needs. And strong patents should be secured in terms of licensing of technology. Also the technological performance should be evaluated at mid-term appraisal, confirming the needs of adopter and competitive advantage of technology and patent. In addition to this, the customized technology marketing strategy for different fields of applications is also required in order to improve the likelihood of technology transfer. If the performance of R&D organization could be evaluated by global technological competitiveness and spillover effects of commercialization rather than quantitative output, the flow of technology transfer and commercialization would be accelerated.

Multiple Residues in the P-Region and M2 of Murine Kir 2.1 Regulate Blockage by External $Ba^{2+}$

  • Lee, Young-Mee;Thompson, Gareth A.;Ashmole, Ian;Leyland, Mark;So, In-Suk;Stanfield, Peter R.
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.1
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    • pp.61-70
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    • 2009
  • We have examined the effects of certain mutations of the selectivity filter and of the membrane helix M2 on $Ba^{2+}$ blockage of the inward rectifier potassium channel, Kir 2.1. We expressed mutant and wild type murine Kir 2.1 in Chinese hamster ovary(CHO) cells and used the whole cell patch-clamp technique to record $K^+$ currents in the absence and presence of externally applied $Ba^{2+}$. Wild type Kir2.1 was blocked by externally applied $Ba^{2+}$ in a voltage and concentration dependent manner. Mutants of Y145 in the selectivity filter showed little change in the kinetics of $Ba^{2+}$ blockage. The estimated $K_d(0)$ was 108 ${\mu}M$ for Kir2.1 wild type, 124 ${\mu}M$ for a concatameric WT-Y145V dimer, 109 ${\mu}M$ for a WT-Y145L dimer, and 267 ${\mu}M$ for Y145F. Mutant channels T141A and S165L exhibit a reduced affinity together with a large reduction in the rate of blockage. In S165L, blockage proceeds with a double exponential time course, suggestive of more than one blocking site. The double mutation T141A/S165L dramatically reduced affinity for $Ba^{2+}$, also showing two components with very different time courses. Mutants D172K and D172R(lining the central, aqueous cavity of the channel) showed both a decreased affinity to $Ba^{2+}$ and a decrease in the on transition rate constant(${\kappa}_{on}$). These results imply that residues stabilising the cytoplasmic end of the selectivity filter(T141, S165) and in the central cavity(D172) are major determinants of high affinity $Ba^{2+}$ blockage in Kir 2.1.