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Tramadol as a Voltage-Gated Sodium Channel Blocker of Peripheral Sodium Channels Nav1.7 and Nav1.5

  • Chan-Su, Bok;Ryeong-Eun, Kim;Yong-Yeon, Cho;Jin-Sung, Choi
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.168-175
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    • 2023
  • Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Nav1.7 or the cardiac sodium channel Nav1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Nav1.7 and 0.43 mM for Nav1.5 at a holding potential of -100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Nav1.7 and Nav1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Nav1.7 and Nav1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Nav1.7 or show cardiotoxicity by blocking Nav1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

A Study on the Settling of Suspended Material in 4 weirs of the Nakdong River (낙동강 본류 4개보에서 부유물질 침강에 관한 연구)

  • Lee, Jaesoon;Han, Gyusung;Kwon, Bomin;Choi, Kwangsoon
    • Proceedings of the Korea Water Resources Association Conference
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    • 2018.05a
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    • pp.488-488
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    • 2018
  • 본 연구는 보 구간에서 조류와 조류 발생원인 물질의 거동해석 및 조류예측모델의 입력 자료로 활용하기 위하여 부유물질의 침강량과 침강속도를 조사하였다. 낙동강 수계 4개보(달성보, 강정고령보, 합천창녕보, 창녕함안보)를 대상으로 2017년 6월, 7월, 11월, 12월에 조사하였으며, Sediment trap을 이용하여 포집한 침강물질에 대해 seston, POC, PON, POP, Chl-a, Pheo-a의 침강량, 침강속도 및 물질의 함량비를 분석하였다. 조사기간 동안 낙동강수계 4개보 지점에서 seston, POC, PON, POP, Chl-a, Pheo-a 의 침강량은 각각 $322.7{\sim}58,011.5mg/m^2/day$, $33.8{\sim}1,127.2mg/m^2/day$, $4.2{\sim}150.6mg/m^2/day$, $0.667{\sim}10.634mg/m^2/day$, $0.3{\sim}18.7mg/m^2/day$, $0.3{\sim}14.7mg/m^2/day$의 범위로 나타났으며, seston, POC, PN, PP, Chl-a의 침강속도는 각각 0.02~1.46m/day, 0.02~1.36m/day, 0.03~3.18m/day, 0.01~1.18m/day, 0.02~0.60 m/day의 범위로 나타났다. 조사기간 동안 4개보 지점의 평균 침강속도는 seston 0.94m/day, POC 0.44m/day, PON 0.52m/day, POP 0.21m/day, Chl-a 0.22m/day로 보 건설 전인 2004년도 낙동강 본류 지점에서의 침강속도(seston 14.54 m/day, POC 18.32m/day, PON 1.64m/day, POP 5.96m/day, Chl-a 0.29m/day)에 비해 적은 것으로 나타났다. 한편 활성을 잃은 식물플랑크톤을 나타내는 Pheo-a의 농도와 살아있는 식물플랑크톤의 현존량의 지표 Chl-a의 농도 비교결과 죽거나 활성을 잃은 식물플랑크톤의 양이 평균 1.5배 많은 것으로 나타났다. 조사기간 동안 4개 보 지점의 Sediment trap 포집된 침강물 내 C:N비는 2.0~7.4 범위로, N;P비는 14.2~52.5 범위로, C/Chl-a비는 14.4~253.3의 범위로 나타났다. 일반적으로 조류의 C/Chl-a 비가 40으로 볼 때 본 연구에서 조사된 보 지점에서의 침강물은 외부로부터 유입된 유기물이 많은 것으로 판단된다. 본 연구에서는 조류의 침강속도는 조류의 종을 구분하지 않은 총 조류에 대한 것으로, 향후 보 구간에서 종 조성을 고려한 조류예측 모델을 향상시키기 위해서는 조류 종별에 대한 침강속도에 대한 연구할 필요가 있다.

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Ingestion size of food microalgae of the Pacific oyster Crassostrea gigas larvae (굴, Crassostrea gigas 유생의 먹이생물 섭취 크기)

  • Hur, Young-Baek;Jeon, Chang-Young;Cho, Kee-Chae;Hur, Sung-Bum
    • The Korean Journal of Malacology
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    • v.27 no.4
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    • pp.307-315
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    • 2011
  • Digestibility index of 12 phytoplankton species were invested during the larval development sizes. Ingestible size of phytoplankton varied depending on larval sizes: Isochrysis galbana, I. aff. galbana, Pavlova lutheri, Chlorella ellipsoidea, Nannochloris oculata was ingested 94.2-99.7% all larval sizes. Cheatoceros calcitrans, C. gracilis and C. simplex could ingest over 90.0% after umbo stage (mean shell length $189.3{\pm}13.8{\mu}m$). Phaeodactylum triconutum, Dunaliella tertiolecta and Tetraselmis tetrathele could not ingested D-shaped larvae (shell length $65.0-100.0{\mu}m$) but ingested 97.3-99.7%, 43.3-99.3%, 48.5-99.3% after then larval stages, respectively. But Thalassiosira weissflogii was ingested 1.0-1.7% only at full grown stage. Over 50.0% ingestion cell size was D-shape stage larvae with smaller than mean $102.3{\mu}m$ in shell length could ingest phytoplankton with $4.6{\mu}m$ in both major and minor axis and up to $9.3{\mu}m$ in minor axis basis for larger than mean $158.3{\mu}m$ in shell length, respectively. At all larval stages, phytoplankton with larger than $10.0{\mu}m$ in both major and minor axis could not be ingested.

A Study on a Calculation Method of Economical Intake Water Depth in the Design of Head Works (취입모의 경제적 계획취입수심 산정방법에 대한 연구)

  • 김철기
    • Magazine of the Korean Society of Agricultural Engineers
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    • v.20 no.1
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    • pp.4592-4598
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    • 1978
  • The purpose of this research is to find out mathemetically an economical intake water depth in the design of head works through the derivation of some formulas. For the performance of the purpose the following formulas were found out for the design intake water depth in each flow type of intake sluice, such as overflow type and orifice type. (1) The conditional equations of !he economical intake water depth in .case that weir body is placed on permeable soil layer ; (a) in the overflow type of intake sluice, {{{{ { zp}_{1 } { Lh}_{1 }+ { 1} over {2 } { Cp}_{3 }L(0.67 SQRT { q} -0.61) { ( { d}_{0 }+ { h}_{1 }+ { h}_{0 } )}^{- { 1} over {2 } }- { { { 3Q}_{1 } { p}_{5 } { h}_{1 } }^{- { 5} over {2 } } } over { { 2m}_{1 }(1-s) SQRT { 2gs} }+[ LEFT { b+ { 4C TIMES { 0.61}^{2 } } over {3(r-1) }+z( { d}_{0 }+ { h}_{0 } ) RIGHT } { p}_{1 }L+(1+ SQRT { 1+ { z}^{2 } } ) { p}_{2 }L+ { dcp}_{3 }L+ { nkp}_{5 }+( { 2z}_{0 }+m )(1-s) { L}_{d } { p}_{7 } ] =0}}}} (b) in the orifice type of intake sluice, {{{{ { zp}_{1 } { Lh}_{1 }+ { 1} over {2 } C { p}_{3 }L(0.67 SQRT { q} -0.61)}}}} {{{{ { ({d }_{0 }+ { h}_{1 }+ { h}_{0 } )}^{ - { 1} over {2 } }- { { 3Q}_{1 } { p}_{ 6} { { h}_{1 } }^{- { 5} over {2 } } } over { { 2m}_{ 2}m' SQRT { 2gs} }+[ LEFT { b+ { 4C TIMES { 0.61}^{2 } } over {3(r-1) }+z( { d}_{0 }+ { h}_{0 } ) RIGHT } { p}_{1 }L }}}} {{{{+(1+ SQRT { 1+ { z}^{2 } } ) { p}_{2 } L+dC { p}_{4 }L+(2 { z}_{0 }+m )(1-s) { L}_{d } { p}_{7 }]=0 }}}} where, z=outer slope of weir body (value of cotangent), h1=intake water depth (m), L=total length of weir (m), C=Bligh's creep ratio, q=flood discharge overflowing weir crest per unit length of weir (m3/sec/m), d0=average height to intake sill elevation in weir (m), h0=freeboard of weir (m), Q1=design irrigation requirements (m3/sec), m1=coefficient of head loss (0.9∼0.95) s=(h1-h2)/h1, h2=flow water depth outside intake sluice gate (m), b=width of weir crest (m), r=specific weight of weir materials, d=depth of cutting along seepage length under the weir (m), n=number of side contraction, k=coefficient of side contraction loss (0.02∼0.04), m2=coefficient of discharge (0.7∼0.9) m'=h0/h1, h0=open height of gate (m), p1 and p4=unit price of weir body and of excavation of weir site, respectively (won/㎥), p2 and p3=unit price of construction form and of revetment for protection of downstream riverbed, respectively (won/㎡), p5 and p6=average cost per unit width of intake sluice including cost of intake canal having the same one as width of the sluice in case of overflow type and orifice type respectively (won/m), zo : inner slope of section area in intake canal from its beginning point to its changing point to ordinary flow section, m: coefficient concerning the mean width of intak canal site,a : freeboard of intake canal. (2) The conditional equations of the economical intake water depth in case that weir body is built on the foundation of rock bed ; (a) in the overflow type of intake sluice, {{{{ { zp}_{1 } { Lh}_{1 }- { { { 3Q}_{1 } { p}_{5 } { h}_{1 } }^{- {5 } over {2 } } } over { { 2m}_{1 }(1-s) SQRT { 2gs} }+[ LEFT { b+z( { d}_{0 }+ { h}_{0 } )RIGHT } { p}_{1 }L+(1+ SQRT { 1+ { z}^{2 } } ) { p}_{2 }L+ { nkp}_{5 }}}}} {{{{+( { 2z}_{0 }+m )(1-s) { L}_{d } { p}_{7 } ]=0 }}}} (b) in the orifice type of intake sluice, {{{{ { zp}_{1 } { Lh}_{1 }- { { { 3Q}_{1 } { p}_{6 } { h}_{1 } }^{- {5 } over {2 } } } over { { 2m}_{2 }m' SQRT { 2gs} }+[ LEFT { b+z( { d}_{0 }+ { h}_{0 } )RIGHT } { p}_{1 }L+(1+ SQRT { 1+ { z}^{2 } } ) { p}_{2 }L}}}} {{{{+( { 2z}_{0 }+m )(1-s) { L}_{d } { p}_{7 } ]=0}}}} The construction cost of weir cut-off and revetment on outside slope of leeve, and the damages suffered from inundation in upstream area were not included in the process of deriving the above conditional equations, but it is true that magnitude of intake water depth influences somewhat on the cost and damages. Therefore, in applying the above equations the fact that should not be over looked is that the design value of intake water depth to be adopted should not be more largely determined than the value of h1 satisfying the above formulas.

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pH-mediated Regulation of Pacemaker Activity in Cultured Interstitial Cells of Cajal

  • Kim, Byung-Joo;Lee, Jae-Hwa;So, In-Suk;Kim, Ki-Whan
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.1
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    • pp.7-11
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    • 2006
  • Interstitial cells of Cajal (ICCs) are pacemakers in gastrointestinal tracts, regulating rhythmicity by activating nonselective cation channels (NSCCs). In the present study, we investigated the general characteristics and pH-mediated regulation of pacemaker activity in cultured interstitial cells of Cajal. Under voltage clamp mode and at the holding potential of -60 mV, the I-V relationships and difference current showed that there was no reversal potential and voltage-independent inward current. Also, when the holding potentials were changed from +20 mV to -80 mV with intervals of 20 mV, there was little difference in inward current. In pacemaker activity, the resting membrane potential (RMP) was depolarized (In pH 5.5, $23{\pm}1.5$ mV depolarized) and the amplitude was decreased by a decrease of the extracellular pH. However, in case of increase of extracellular pH, the RMP was slightly hyperpolarized and the amplitude was decreased a little. The melastatin type transient receptor potential (TRPM) channel 7 has been suggested to be required for intestinal pacemaking activity. TRPM7 produced large outward currents and small inward currents by voltage ramps, ranging from +100 to -100 mV from a holding potential of -60 mV. The inward current of TRPM7 was dramatically increased by a decrease in the extracellular pH. At pH 4.0, the average inward current amplitude measured at -100 mV was increased by about 7 fold, compared with the current amplitude at pH 7.4. Changes in the outward current (measured at +100 mV) were much smaller than those of the inward current. These results indicate that the resting membrane potential of pacemaking activity might be depolarized by external acidic pH through TRPM7 that is required for intestinal pacemaking activity.

Bacterial Community Analysis of Lake Soyang in Winter by Using 16S and 23S rRNA-targeted Probes (16S와 23S rRNA에 결합하는 probe를 이용한 겨울철 소양호 세균 군집 구조의 분석)

  • Hong, Sun-Hee;Byeon, Myeong-Seop;Ahn, Tae-Seok
    • Korean Journal of Microbiology
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    • v.33 no.4
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    • pp.257-261
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    • 1997
  • To scrutinize the bacterial community composition of Lake Soyang in winter, bacterial numbers belonging to Eubacteria, Proteobacteria and Cytophaga-Flavobacterium group were estimated by using 16S and 23S rRNA targeted oligonucleotide probes. Total bacterial numbers ranged from $0.7{\times}10^6$ to $1.1{\times}10^6cells{\cdot}ml^{-1}$, and vertical profile of total bacteria showed a peak at 5 m depth. The ratio of eubacteria to total bacteria were 34~90% and at 5 m and 10 m depths those were low exhibiting, 39 and 34%, respectively. The percentage of proteobacteria ${\alpha}$-group ranged 10.8~28.7%, ${\beta}$-group 4.5~53.5%, ${\gamma}$-group 4.9~35.5% and Cytophaga-Flavobacterium group 6.1~21.1%. The dominant groups were ${\beta}$-group at 0, 2 and 5 m, ${\gamma}$-group at 10 m, ${\alpha}$-group at 30 m and Cytophaga-Flavobacterium group at 50 m depth. In winter season, Lake Soyang can be divided into three layer, 0~2 m, 5~10 m and 30~50 m, by the bacteria community composition. By this method, new informations about aquatic ecosystem were developed.

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Distribution characteristics of dioxin concentration in pyrolysis-gasification-melting process facilities (생활폐기물 열분해-가스화-용융공정시설에서 다이옥신의 분포특성)

  • Son, Jihwan;Kim, Kiheon;Kang, Youngyeol;Park, Sunku
    • Analytical Science and Technology
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    • v.20 no.1
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    • pp.10-16
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    • 2007
  • This research was designed to investigate the formations of hazardous air pollutants in the MSWs pyrolysis-gasification-melting process. In this survey, PCDDs/PCDFs (polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofuran) were investigated in the two facilities (A and B facilities). In A facility, the PCDDs/DFs concentrations were 0.88, 2.29, 0.16 ng I-TEQ/$m^3$ respectively on the secondary incinerator, boiler and stack. In B facility, the PCDDs/PCDFs concentrations were 0.22, 0.05 ng I-TEQ/$m^3$ respectively on the pyrolysis-gasification-melting furnace and stack. The concentrations of PCDDs/PCDFs increased due to resynthesis during cooling process in the both facilities. High concentrations of PCDDs/PCDFs isomers were founded as 2, 3, 4, 7, 8-PeCDF, 2, 3, 4, 6, 7, 8-HxCDF and 1, 2, 3, 6, 7, 8-HxCDF orderly in A facility, and 2, 3, 4, 7, 8-PeCDF, 1, 2, 3, 7, 8-PeCDD and 2, 3, 4, 6, 7, 8-HxCDF orderly in B facility.

Anti-inflammatory Effect of Angelicae acutilobae Radix Water Extract on LPS-stimulated Mouse Macrophages (마우스 대식세포를 이용한 일당귀 물추출물의 항염효능 연구)

  • Han, Hyo-Sang
    • The Korea Journal of Herbology
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    • v.28 no.6
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    • pp.129-133
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    • 2013
  • Objectives : The purpose of this study was to investigate the effects of Angelicae acutilobae Radix Water Extract (AA) on the production of cytokines in RAW 264.7 cell stimulated with lipopolysaccharide (LPS). Method : RAW 264.7 cells were cotreated with AA (50 and $100{\mu}g/mL$) and lipopolysaccharide (LPS; $1{\mu}g/mL$) for 24 hours. After 24 hours treatment, using bead-based multiplex cytokine assay, concentrations of various cytokines such as interleukin(IL)-6, tumor necrosis factor-alpha(TNF-${\alpha}$) granulocyte colony-stimulating factor(G-CSF), granulocyte macrophage colony-stimulating factor(GM-CSF), and macrophage inflammatory protein(MIP)-$1{\alpha}$ were measured. Result : AA significantly inhibited LPS-induced production of IL-6 and MIP-$1{\alpha}$ from LPS-stimulated RAW 264.7 cells at the concentration of $50{\mu}g/mL$. AA significantly inhibited LPS-induced production of TNF-${\alpha}$ from LPS-stimulated RAW 264.7 cells at the concentration of $100{\mu}g/mL$. AA significantly inhibited LPS-induced production of G-CSF and GM-CSF in RAW 264.7 cells at the concentrations of 50 and $100{\mu}g/mL$. Conclusion : These results suggest that AA has anti-inflammatory effect related with its inhibition of proinflammatory cytokines such as IL-6, TNF-${\alpha}$, G-CSF, GM-CSF, and MIP-$1{\alpha}$ in LPS-induced macrophages.

The Actual Conditions of the Management of the Factory Ship GAECHEOG (공모선(工母船) 개척호(開拓號)의 운용(運用)에 관한 실태(實態) 분석(分析))

  • Jeong, Dong-Hee;Kim, Jin-Kun
    • Journal of Fisheries and Marine Sciences Education
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    • v.9 no.2
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    • pp.149-166
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    • 1997
  • This thesis is studied by means of operation diary of the factory ship GAECHEOG in the Sea of Okhotsk and the Sea of Bering from Jul. 1993 to Dec. 1996, We summarize these results as follows : 1. The factory ship GAECHEOG equipped trawl winch able to haul raw fish 700M/T per day and cargo winch able to unload manufactured goods 900M/T. The crews consist of 290~330 persons. 2. Factory machineries equipped surimi making plant able to process about 150M/T per day and fish meal plant able to manufacture about 70M/T per day. 3. The fishing ground from June to Nov. was the western Bering sea lying in the eastern Kamchaka peninsula and from Dec. to May, the fishing period to gather roe of a Pollack, was the Sea of Ohotsk lying in the western Kamchaka peninsula. 4. The buying catch of fish per each voyage from Dec. to May, the fishing period gathering Pollack-roe, was about 17,000~33,000M/T and from Jul. to Oct., the fishing period gathering non Pollack-roe, was about 10,000~21,000 M/T. 5. Raw fish was the most about 33,000M/T of the 2nd voyage in 1994 and was the least about 8,300M/T of the 1st voyage in 1993. Other voyages were about 13,000~18,000M/T. 6. The Pollack buying from Jul. to Nov. in the Bering sea was 5~7 fishes for one row in pan and body length about 40~50cm, and from Dec. to May in the Sea of Ohotsk was 6~8 fishes for one row in pan and body length about 37~45cm. 7. Surimi production in the 2nd voyage in 1994 was the most about 7,300 M/T, in the 1st voyage in 1993 was the least 1,900M/T and in other voyages was about 2,500~3,800M/T. The extraction rate of surimi goods for raw fish was about 17.4~26.5%. 8. Fish meal production in the 2nd voyage in 1994 was the most about 2,300 M/T, in the 1st voyage in 1993 was the least about 780M/T and in other voyages was about 1,100~1,700M/T. The extraction rate of fish meal goods for raw fish was about 7.3~10.7%. 9. Pollack-roe production was very much from Jan. to Apr. and was about 380~700M/T per each voyage. The extraction rate of Pollack-roe for raw fish was about 1.2~4.9%.

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Phonotaxis of the African Mole Cricket, Gryllotalpa africana Palisot de Beauvois (땅강아지의 주음성에 관한 연구)

  • 김기황
    • Korean journal of applied entomology
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    • v.32 no.1
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    • pp.76-82
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    • 1993
  • Phonotaxis of the African mole cricket, Gryllotalpa africana palisot de Beauvois, was investigated in 1990 and 1992 at the agronomy Experiment Station of Korea Ginseng & Tobacco Research Institute in Hwaseong-gun, Kyonggi-do, Male adults produced calling sounds (calling songs) through the openings of subsurface burrows. Intensities of the sound were 77-80 dB at 15 cm above the openings. When tape recordings of male calling songs were broadcasted outdoors at 105-110 dB by two horn speakers installed at the center of a 1.4 m diameter-funnel, flying adults were attracted for 1.5 hours from about 30 minutes after sunset. Among attracted adults, 14.3-16.9% landed in the funnel, and 65.7-74.7% landed on the ground within 2m form the sound source. Females were 66.7-74.3%, which seemed to be due to the sex ratio of the population in the field. Adults landing in the funnel and at the distance of within 2m from the center of the funnel were tend to be a little more than those attracted to a blacklight trap.

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