• Title/Summary/Keyword: Channel Blocking

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Effects of Cyclobuxine D on Drug-Induced Contractions of the Isolated Rat Uterine Muscle and Potassium-Activated Calcium Channels in an Intestinal Smooth Muscle (흰쥐 적출 자궁의 수축 작용과 흰쥐 장관에 있어 칼륨에 의해 활성화되는 칼슘 채널에 대한 Cyclobuxine D의 영향)

  • Kwon, Jun-Tack;Lee, Jong-Hwoa;Park, Young-Hyun;Cho, Byung-Heon;Choi, Kyu-Hong;Kim, Yu-Jae;Kim, Jong-Bae;Kim, Chung-Mok;Kim, Chun-Sook;Cha, Young-Deog;Kim, Young-Suk
    • The Korean Journal of Pharmacology
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    • v.24 no.1
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    • pp.103-109
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    • 1988
  • Cyclobuxine D, extracted from Buxus microphylla var. koreana Nakai, is a steroidal alkaloid. Many pharmacological effects of cyclobuxine D were examined in our Lab. Cyclobuxine D showed a significant bradycardic effect in the rat heart and an inhibitory action on acetylcholine and $Ba^{++}-induced$ contraction of the longitudinal muscle isolated from the rabbit jejunum. In this study, we investigated the effect of cyclobuxine D on the contractile response-elicited by acetylcholine, oxytocin and $Ba^{++}$ in rat uterine. In order to analyse the inhibitory action of cyclobuxine D on the smooth muscle, we examined the inhibitory action of cyclobuxine D against the contractile response of the high potassium-depolarized rat ileum to calcium. Concentration-dependent decrease in the peak tension and duration of the acetylcholine, oxytocin and $Ba^{++}-induced$ contraction in the isolated rat uterus was observed when cyclobuxine D was added to the organ bath. The isolated longitudinal muscle from the rat ileum was immersed calcium-depleted potassium-depolarizing solution. Ten minutes after, 1.8 mM $CaCl_2$ was added to muscle bath and elicited a biphasic increase in muscle tension. Cyclobuxine D $(6.2{\times}10^{-5}\;M)$ produced an appreciable inhibition of both components of the mechanical response. In addition, $3.1{\times}10^{-4}\;M$ cyclobuxine D, introduced at a point when the tonic response had reached its maximum level, caused the muscle to exhibit a rapid lose of tension. Based on these experimental results, we propose the possibility that the inhibitory action of cyclobuxine D on the acetylcholine, oxytocin and $Ba^{++}-induced$ contraction in the isolated rat uterus may be due to blocking potassium-activated calcium channels, voltage-sensitive calcium channels.

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Analysis Trap and Device Characteristic of Silicon-Al2O3-Nitride-Oxide-Silicon Memory Cell Transistors using Charge Pumping Method (Charge Pumping Method를 이용한 Silicon-Al2O3-Nitride-Oxide-Silicon Flash Memory Cell Transistor의 트랩과 소자)

  • Park, Sung-Soo;Choi, Won-Ho;Han, In-Shik;Na, Min-Gi;Lee, Ga-Won
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.45 no.7
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    • pp.37-43
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    • 2008
  • In this paper, the dependence of electrical characteristics of Silicon-$Al_2O_3$-Nitride-Oxide-Silicon (SANOS) memory cell transistors and program/erase (P/E) speed, reliability of memory device on interface trap between Si substrate and tunneling oxide and bulk trap in nitride layer were investigated using charge pumping method which has advantage of simple and versatile technique. We analyzed different SANOS memory devices that were fabricated by the identical processing in a single lot except the deposition method of the charge trapping layer, nitride. In the case of P/E speed, it was shown that P/E speed is slower in the SANOS cell transistors with larger capture cross section and interface trap density by charge blocking effect, which is confirmed by simulation results. However, the data retention characteristics show much less dependence on interface trap. The data retention was deteriorated as increasing P/E cycling number but not coincides with interface trap increasing tendency. This result once again confirmed that interface trap independence on data retention. And the result on different program method shows that HCI program method more degraded by locally trapping. So, we know as a result of experiment that analysis the SANOS Flash memory characteristic using charge pumping method reflect the device performance related to interface and bulk trap.

Toward a Social Sciences Methodology for Electronic Survey Research on the Internet or Personal Computer check (사회과학 연구에 있어 인터넷 및 상업용 통신망을 이용한 전자설문 조사방법의 활용)

  • Hong Yong-Gee;Lee Hong-Gee;Chae Su-Kyung
    • Management & Information Systems Review
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    • v.3
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    • pp.287-316
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    • 1999
  • Cyberspace permits us to more beyond traditional face-to-face, mail and telephone surveys, yet still to examine basic issues regarding the quality of data collection: sampling, questionnaire design, survey distribution, means of response, and database creation. This article address each of these issues by contrasting and comparing traditional survey methods(Paper-and-Pencil) with Internet or Personal Computer networks-mediated (Screen-and-Keyboard) survey methods also introduces researchers to this revolutionary and innovative tool and outlines a variety of practical methods for using the Internet or Personal Computer Networks. The revolution in telecommunications technology has fostered the rapid growth of the Internet all over the world. The Internet is a massive global network and comprising many national and international networks of interconnected computers. The Internet or Personal Computer Networks could be the comprehensive interactive tool that will facilitate the development of the skills. The Internet or Personal Computer Networks provides a virtual frontier to expand our access to information and to increase our knowledge and understanding of public opinion, political behavior, social trends and lifestyles through survey research. Comparable to other technological advancements, the Internet or Personal Computer Networks presents opportunities that will impact significantly on the process and quality of survey research now and in the twenty-first century. There are trade-offs between traditional and the Internet or Personal Computer Networks survey. The Internet or Personal Computer Networks is an important channel for obtaining information for target participants. The cost savings in time, efforts, and material were substantial. The use of the Internet or Personal Computer Networks survey tool will increase the quality of research environment. There are several limitations to the Internet or Personal Computer Network survey approach. It requires the researcher to be familiar with Internet navigation and E-mail, it is essential for this process. The use of Listserv and Newsgroup result in a biased sample of the population of corporate trainers. However, it is this group that participates in technology and is in the fore front of shaping the new organizations of interest, and therefore it consists of appropriate participants. If this survey method becomes popular and is too frequently used, potential respondents may become as annoyed with E-mail as the sometimes are with mail survey and junk mail. Being a member of the Listserv of Newsgroup may moderate that reaction. There is a need to determine efficient, effective ways for the researcher to strip identifiers from E-mail, so that respondents remain anonymous, while simultaneously blocking a respondent from responding to a particular survey instrument more than once. The optimum process would be on that is initiated by the researcher : simple, fast and inexpensive to administer and has credibility with respondents. This would protect the legitimacy of the sample and anonymity. Creating attractive Internet or Personal Computer Networks survey formats that build on the strengths of standardized structures but also capitalize on the dynamic and interactive capability of the medium. Without such innovations in survey design, it is difficult to imagine why potential survey respondents would use their time to answer questions. More must be done to create diverse and exciting ways of building an credibility between respondents and researchers on the Internet or Personal Computer Networks. We believe that the future of much exciting research is based in the Electronic survey research. The ability to communicate across distance, time, and national boundaries offers great possibilities for studying the ways in which technology and technological discourse are shaped. used, and disseminated ; the many recent doctoral dissertations that treat some aspect of electronic survey research testify to the increase focus on the Internet or Personal Computer Networks. Thus, scholars should begin a serious conversation about the methodological issues of conducting research In cyberspace. Of all the disciplines, Internet or Personal Computer Networks, emphasis on the relationship between technology and human communication, should take the lead in considering research in the cyberspace.

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Association of Low Serum Ionized Magnesium Level with Fever-Triggered Seizures in Epileptic Children (소아 뇌전증 환자에서 발열이 동반된 경련을 하는 것과 저 이온화 마그네슘 혈증과의 관련성)

  • Suh, Sunny;Kim, Kyungju;Byeon, Jung Hye;Eun, So-Hee;Eun, Baik-Lin;Kim, Gun-Ha
    • Journal of the Korean Child Neurology Society
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    • v.26 no.4
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    • pp.205-209
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    • 2018
  • Purpose: Several studies have shown that magnesium plays an important role in modulating N-methyl-D-aspartate (NMDA)-related seizures by blocking NMDA ion channel receptors. Clinicians usually measure total serum magnesium levels instead of biologically active ionized magnesium levels. We compared the serum ionized magnesium ($iMg^{2+}$) level between epileptic children with and without a history of fever-triggered seizure (FTS). Methods: All epileptic children who visited the outpatient clinic or pediatric emergency department at Korea University Guro Hospital between January 2015 and July 2017 were included. Only epileptic children aged 1-8 years who were newly diagnosed within 2 years were included. Results: There were 12 children with FTS and 16 without FTS. Median serum $iMg^{2+}$ level was 0.93 (0.85-1.14, quartile) mEq/L. Serum $iMg^{2+}$ level was significantly lower in epileptic children with FTS (0.86 mEq/L) compared to those without FTS (1.10 mEq/L) (P=0.005). No difference was noted in clinical variables between the two groups. Lower serum $iMg^{2+}$ level significantly increased the risk of having FTS in epileptic children based on multivariable logistic regression analysis (odds ratio [OR]=0.028). Conclusion: Serum $iMg^{2+}$ level was significantly lower in epileptic children with FTS than in those without FTS. Measurement of biologically active serum $iMg^{2+}$ level could be considered in epileptic children with recurrent FTS. A large-scale prospective study is warranted.

Sesquiterpenoids Bioconversion Analysis by Wood Rot Fungi

  • Lee, Su-Yeon;Ryu, Sun-Hwa;Choi, In-Gyu;Kim, Myungkil
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.19-20
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    • 2016
  • Sesquiterpenoids are defined as $C_{15}$ compounds derived from farnesyl pyrophosphate (FPP), and their complex structures are found in the tissue of many diverse plants (Degenhardt et al. 2009). FPP's long chain length and additional double bond enables its conversion to a huge range of mono-, di-, and tri-cyclic structures. A number of cyclic sesquiterpenes with alcohol, aldehyde, and ketone derivatives have key biological and medicinal properties (Fraga 1999). Fungi, such as the wood-rotting Polyporus brumalis, are excellent sources of pharmaceutically interesting natural products such as sesquiterpenoids. In this study, we investigated the biosynthesis of P. brumalis sesquiterpenoids on modified medium. Fungal suspensions of 11 white rot species were inoculated in modified medium containing $C_6H_{12}O_6$, $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ for 20 days. Cultivation was stopped by solvent extraction via separation of the mycelium. The metabolites were identified as follows: propionic acid (1), mevalonic acid lactone (2), ${\beta}$-eudesmane (3), and ${\beta}$-eudesmol (4), respectively (Figure 1). The main peaks of ${\beta}$-eudesmane and ${\beta}$-eudesmol, which were indicative of sesquiterpene structures, were consistently detected for 5, 7, 12, and 15 days These results demonstrated the existence of terpene metabolism in the mycelium of P. brumalis. Polyporus spp. are known to generate flavor components such as methyl 2,4-dihydroxy-3,6-dimethyl benzoate; 2-hydroxy-4-methoxy-6-methyl benzoic acid; 3-hydroxy-5-methyl phenol; and 3-methoxy-2,5-dimethyl phenol in submerged cultures (Hoffmann and Esser 1978). Drimanes of sesquiterpenes were reported as metabolites from P. arcularius and shown to exhibit antimicrobial activity against Gram-positive bacteria such as Staphylococcus aureus (Fleck et al. 1996). The main metabolites of P. brumalis, ${\beta}$-Eudesmol and ${\beta}$-eudesmane, were categorized as eudesmane-type sesquiterpene structures. The eudesmane skeleton could be biosynthesized from FPP-derived IPP, and approximately 1,000 structures have been identified in plants as essential oils. The biosynthesis of eudesmol from P. brumalis may thus be an important tool for the production of useful natural compounds as presumed from its identified potent bioactivity in plants. Essential oils comprising eudesmane-type sesquiterpenoids have been previously and extensively researched (Wu et al. 2006). ${\beta}$-Eudesmol is a well-known and important eudesmane alcohol with an anticholinergic effect in the vascular endothelium (Tsuneki et al. 2005). Additionally, recent studies demonstrated that ${\beta}$-eudesmol acts as a channel blocker for nicotinic acetylcholine receptors at the neuromuscular junction, and it can inhibit angiogenesis in vitro and in vivo by blocking the mitogen-activated protein kinase (MAPK) signaling pathway (Seo et al. 2011). Variation of nutrients was conducted to determine an optimum condition for the biosynthesis of sesquiterpenes by P. brumalis. Genes encoding terpene synthases, which are crucial to the terpene synthesis pathway, generally respond to environmental factors such as pH, temperature, and available nutrients (Hoffmeister and Keller 2007, Yu and Keller 2005). Calvo et al. described the effect of major nutrients, carbon and nitrogen, on the synthesis of secondary metabolites (Calvo et al. 2002). P. brumalis did not prefer to synthesize sesquiterpenes under all growth conditions. Results of differences in metabolites observed in P. brumalis grown in PDB and modified medium highlighted the potential effect inorganic sources such as $C_4H_{12}N_2O_6$, $KH_2PO_4$, $MgSO_4$, and $CaCl_2$ on sesquiterpene synthesis. ${\beta}$-eudesmol was apparent during cultivation except for when P. brumalis was grown on $MgSO_4$-free medium. These results demonstrated that $MgSO_4$ can specifically control the biosynthesis of ${\beta}$-eudesmol. Magnesium has been reported as a cofactor that binds to sesquiterpene synthase (Agger et al. 2008). Specifically, the $Mg^{2+}$ ions bind to two conserved metal-binding motifs. These metal ions complex to the substrate pyrophosphate, thereby promoting the ionization of the leaving groups of FPP and resulting in the generation of a highly reactive allylic cation. Effect of magnesium source on the sesquiterpene biosynthesis was also identified via analysis of the concentration of total carbohydrates. Our current study offered further insight that fungal sesquiterpene biosynthesis can be controlled by nutrients. To profile the metabolites of P. brumalis, the cultures were extracted based on the growth curve. Despite metabolites produced during mycelia growth, there was difficulty in detecting significant changes in metabolite production, especially those at low concentrations. These compounds may be of interest in understanding their synthetic mechanisms in P. brumalis. The synthesis of terpene compounds began during the growth phase at day 9. Sesquiterpene synthesis occurred after growth was complete. At day 9, drimenol, farnesol, and mevalonic lactone (or mevalonic acid lactone) were identified. Mevalonic acid lactone is the precursor of the mevalonic pathway, and particularly, it is a precursor for a number of biologically important lipids, including cholesterol hormones (Buckley et al. 2002). Farnesol is the precursor of sesquiterpenoids. Drimenol compounds, bi-cyclic-sesquiterpene alcohols, can be synthesized from trans-trans farnesol via cyclization and rearrangement (Polovinka et al. 1994). They have also been identified in the basidiomycota Lentinus lepideus as secondary metabolites. After 12 days in the growth phase, ${\beta}$-elemene caryophyllene, ${\delta}$-cadiene, and eudesmane were detected with ${\beta}$-eudesmol. The data showed the synthesis of sesquiterpene hydrocarbons with bi-cyclic structures. These compounds can be synthesized from FPP by cyclization. Cyclic terpenoids are synthesized through the formation of a carbon skeleton from linear precursors by terpene cyclase, which is followed by chemical modification by oxidation, reduction, methylation, etc. Sesquiterpene cyclase is a key branch-point enzyme that catalyzes the complex intermolecular cyclization of the linear prenyl diphosphate into cyclic hydrocarbons (Toyomasu et al. 2007). After 20 days in stationary phase, the oxygenated structures eudesmol, elemol, and caryophyllene oxide were detected. Thus, after growth, sesquiterpenes were identified. Per these results, we showed that terpene metabolism in wood-rotting fungi occurs in the stationary phase. We also showed that such metabolism can be controlled by magnesium supplementation in the growth medium. In conclusion, we identified P. brumalis as a wood-rotting fungus that can produce sesquiterpenes. To mechanistically understand eudesmane-type sesquiterpene biosynthesis in P. brumalis, further research into the genes regulating the dynamics of such biosynthesis is warranted.

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