• Title/Summary/Keyword: $S_N1$ mechanism

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저용량의 내독소가 쥐에서 고농도의 산소에 의한 급성폐손상을 경감시키는 기전 (Mechanism of Decrease in Lung Injury by Low Dose of Endotoxin During Hyperoxia in the Rats)

  • 송정섭;윤형규;김영균;김관형;문화식;박성학
    • Tuberculosis and Respiratory Diseases
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    • 제53권2호
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    • pp.148-160
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    • 2002
  • 배 경 : 쥐를 고농도의 산소에 60시간 이상 노출시켰을 때 급성 폐손상이 유발되지만 내독소를 저용량으로 투여시에는 이러한 폐손상이 경감된다고 알려져 있으나 그 기전에 대하여는 확실히 밝혀지지 않고 있다. 산화질소(nitric oxide, NO)는 내독소나 염증성 사이토카인(cytokine) 등의 자극에 의해서 폐내 여러 염증세포에서 만들어지며 이 산화질소는 경우에 따라 우리 몸에 이롭거나 해로운 양면성을 지니고 있다. 저자들은 쥐에서 고농도의 산소에 의한 폐손상이 저농도의 내독소 투여로 경감되는 기전에, 산화질소가 중요한 역할을 하는지 또는 황산화효소나 다른 항염증성 사이토카인이 중요한 역할을 하는지를 규명하고자 하였다. 방 법 : 총 120마리의 쥐 (Sprague-Dawley rat)를 24마리씩 5군으로 나누어 대조군은 실내 공기를, 고농도 산소군은 100%의 산소를 100%의 산소를 60시간 투여하였고 내독소군은 100% 산소 투여시 2일간 저용량의 내독소를 투여하였다. 다른 두 군은 산화질소 합성 억제물인 aminoguanidine(AG)과 N-nitro-L-arginine methyl ester (L-NAME)를 각각 2일간 고농도 산소와 내독소에 더하여 투여하였다. 각각의 군에서 폐손상의 정도와 사망률을 관찰하고 superoxide dismutase(SOD), catalase, nitric oxide, IL-6, IL-11을 기관지폐포세척액에서 측정하고, 고농도산소 투여군의 폐조직에서 iNOS synthase rnRNA의 발현을 비교하였다. 결 과: 1. 100%의 산소에 60시간 노출시켰을 때 쥐의 사망률은 8.3% 이었고 내독소 투여군은 4.2%, NAME 투여군이 37.5%, AG 투여군이 25%로 산화질소 합성 억제제에 의하여 사망률의 증가가 관찰되었다. 2. 폐의 손상 정도를 나타내는 폐의 wet/dry 중량비와 늑막액도 100%의 산소에 노출된 군에서 증가되었고 내독소 투여에 의하여 감소되었으며 NAME나 AG 투여군에서는 오히려 증가되었다. 3. 이러한 내독소에 의한 폐손상 억제효과가 항산화효소인 SOD나 catalase, 또는 protective cytokine인 IL-6나 IL-11등의 증가와 관련이 있는지를 관찰하였으나 이들 모두에서 유의한 변화를 관찰하지 못하였다. 4. 산화질소는 100% 산소에 노출시킨 군에서도 증가하였으나 내독소 투여군에서 유의하게 더욱 증가하였고 이는 L-NAME 나 aminoguanidine의 투여시 감소하였다. 5. iNOS mRNA의 발현도 내독소 투여군에서 유의하게 증가하였다. 결 론 : 쥐의 고농소 산소 투여에 의한 폐손상은 저용량의 내독소 투여로 경감되며, 이는 주로 내독소 투여에 의한 iNOS mRNA의 발현을 유도하여 생성된 산화질소의 증가에 기인하는 것으로 생각된다.

Effect of different levels of protein concentrates supplementation on the growth performance, plasma amino acids profile and mTOR cascade genes expression in early-weaned yak calves

  • Peng, Q.H.;Khan, N.A.;Xue, B.;Yan, T.H.;Wang, Z.S.
    • Asian-Australasian Journal of Animal Sciences
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    • 제31권2호
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    • pp.218-224
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    • 2018
  • Objective: This study evaluated the effects of different levels of protein concentrate supplementation on the growth performance of yak calves, and correlated the growth rate to changes occurring in the plasma- amino acids, -insulin profile, and signaling activity of mammalian target of rapamycin (mTOR) cascade to characterize the mechanism through which the protein synthesis can be improved in early weaned yaks. Methods: For this study, 48 early (3 months old) weaned yak calves were selected, and assigned into four dietary treatments according to randomized complete block design. The four blocks were balanced for body weight and sex. The yaks were either grazed on natural pasture (control diet) in a single herd or the grazing yaks was supplemented with one of the three protein rich supplements containing low (17%; LP), medium (19%; MP), or high (21%; HP) levels of crude proteins for a period of 30 days. Results: Results showed that the average daily gain of calves increased (0.14 vs 0.23-0.26 kg; p<0.05) with protein concentrates supplementation. The concentration of plasma methionine increased (p<0.05; 8.6 vs $10.1-12.4{\mu}mol/L$), while those of serine and tyrosine did not change (p>0.05) when the grazing calves were supplemented with protein concentrates. Compared to control diet, the insulin level of calves increased (p<0.05; 1.86 vs $2.16-2.54{\mu}IU/mL$) with supplementation of protein concentrates. Addition of protein concentrates up-regulated (p<0.05) expression of mTOR-raptor, mammalian vacuolar protein sorting 34 homolog, the translational regulators eukaryotic translation initiation factor 4E binding protein 1, and S6 kinase 1 genes in both Longissimus dorsi and semitendinosus. In contrast, the expression of sequestosome 1 was down-regulated in the concentrate supplemented calves. Conclusion: Our results show that protein supplementation improves the growth performance of early weaned yak calves, and that plasma methionine and insulin concentrations were the key mediator for gene expression and protein deposition in the muscles.

High $K^+$-Induced Relaxation by Nitric Oxide in Human Gastric Fundus

  • Kim, Dae-Hoon;Kim, Young-Chul;Choi, Woong;Yun, Hyo-Young;Sung, Ro-Hyun;Kim, Hun-Sik;Kim, Heon;Yoo, Ra-Young;Park, Seon-Mee;Yun, Sei-Jin;Song, Young-Jin;Xu, Wen-Xie;Lee, Sang-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • 제16권5호
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    • pp.297-303
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    • 2012
  • This study was designed to elucidate high $K^+$-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high $K^+$ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high $K^+$-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 ${\mu}M$) and KT 5720 (1 ${\mu}M$) which block protein kinases (PKG and PKA) had no effect on high $K^+$-induced relaxation. $K^+$ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent $K^+$ channel ($K_V$) blocker, did not affect high $K^+$ -induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High $K^+$-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high $K^+$-induced relaxation that was activated by the nitric oxide/sGC pathway through a $K_V$ channel-dependent mechanism.

ZrO2 첨가된 SnO2를 이용한 신경 및 수포작용제 검지에 대한 연구 (Sensing Properties of ZrO2-added SnO2 for Nerve and Blister Agent)

  • 윤기열;차건영;최낙진;이덕동;김재창;허증수
    • 센서학회지
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    • 제13권5호
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    • pp.323-328
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    • 2004
  • N-type semi-conducting oxides such as $SnO_{2}$, ZnO, and $ZrO_{2}$ have been known for the detecting materials of inflammable or toxic gases. Of those materials, $SnO_{2}$-based sensors are well known as high sensitive materials to detect toxic gases. And the sensitivity is improved if catalysts are added. Detecting toxic gases, especially DMMP (di-methyl-methyl-phosphonate) and DPGME (Dipropylene glycol methyl ether), was performed by a mixture of Tin oxide ($SnO_{2}$) and Zirconia ($ZrO_{2}$). The films consist of each three different mass% of Zr (from 1 mass% to 5 mass%), and they were tested by XRD, SEM, TEM, BET. Nano-structure, pore and particle size was controlled to verify the sensor's sensing mechanism. The sensors was evaluated at five different degrees (from $200^{\circ}C$ to $400^{\circ}C$) and three different concentrations (from 500 ppb to 1500 ppb). The sensors had good sensitivity of both simulants, and high selectivity of DMMP.

DESIGN OF A SINGLE MODE VARIABLE BRIDGE TYPE SPLIT-POWERED CVT WITH AN INNER-SPHERICAL CONTINUOUSLY VARIABLE UNIT

  • Seong, S.H.;Lee, H.W.;Choi, J.H.;Park, N.G.
    • International Journal of Automotive Technology
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    • 제8권6호
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    • pp.799-806
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    • 2007
  • One method for improving the torque capacity of the CVT is to use a split-powered CVT(SPCVT) to reduce the power transmitted into a continuously variable unit(CVU). A variable bridge SPCVT with two planetary gear units(PGUs), which are composed of a sun gear, a ring gear, and carrier and planetary gears, can minimize the power to the CVU. However, a SPCVT with a conventional CVT should possess a dual mode, which would allow the conventional CVT to be used at high speeds and an additional gear train to be used at low speeds. The inner-spherical CVU(ISCVU) with an inner and outer spherical contact mechanism developed in this study can cover the range from low to high speeds. The rated power and the overall speed ratios were 100 kW and $0.09{\sim}0.36$, respectively. Power efficiency was numerically calculated to be over 90% over the speed ratio range of $0.1{\sim}0.29$. The maximum shear stress at the two contact areas of the rotor pairs, the minimum life and the overall size were estimated to be 700 MPa, 276 kh and $350{\times}350{\times}400mm^3$, respectively. This study shows that an ISCVU and a variable bridge type PGU can realize the SPCVT with a single mode for a vehicle.

Nitric Oxide Prevents the Bovine Cerebral Endothelial Cell Death Induced by Serum-Deprivation

  • Kim, Chul-Hoon;Ahn, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권5호
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    • pp.515-521
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    • 1997
  • Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

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K+ Ion Catalysis in Nucleophilic Displacement Reaction of Y-Substituted-Phenyl Picolinates with Potassium Ethoxide: Effect of Substituent Y on Reactivity and Transition State Structure

  • Im, Hyun-Ju;Lee, Jieun;Kim, Mi-Yeon;Um, Ik-Hwan
    • Bulletin of the Korean Chemical Society
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    • 제35권6호
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    • pp.1749-1753
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    • 2014
  • Pseudo-first-order rate constants ($k_{obsd}$) have been measured spectrophotometrically for the nucleophilic substitution reaction of Y-substituted-phenyl picolinates (7a-f) with potassium ethoxide (EtOK) in anhydrous ethanol at $25.0{\pm}0.1^{\circ}C$. The plot of $k_{obsd}$ vs. [EtOK] curves upward while the plot of $k_{obsd}/[EtO^-]_{eq}$ vs. $[EtO^-]_{eq}$ is linear with a positive intercept in all cases. Dissection of $k_{obsd}$ into $k_{EtO^-}$ and $k_{EtOK}$ (i.e., the second-order rate constants for the reactions with the dissociated $EtO^-$ ion and ion-paired EtOK, respectively) has revealed that the ion-paired EtOK is more reactive than the dissociated $EtO^-$. The ${\sigma}^{\circ}$ constants result in a much better Hammett correlation than ${\sigma}^-$ constants, indicating that the reaction proceeds through a stepwise mechanism in which departure of the leaving group occurs after the rate-determining step (RDS). $K^+$ ion catalyzes the reaction by increasing the electrophilicity of the reaction center through formation of a cyclic transition state (TS). The catalytic effect decreases as the substituent Y becomes a stronger electron-withdrawing group (EWG). Development of a positive charge on the N atom of the picolinyl moiety through resonance interactions is responsible for the decreasing $K^+$ ion catalysis.

DW2282의 용매의존성 항암효과 및 약동력학 (In Vivo Antitumor Activities and Pharmacokinetics of DW2282 Depending on Vehicles)

  • 문은이;최청하;성승규;이진;유제만;이문선;정상현;정용호;이덕근;윤성준
    • Biomolecules & Therapeutics
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    • 제6권4호
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    • pp.395-399
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    • 1998
  • DW2282, (S)- (+)-4-phenyl -1-[N-(4-am mob enzoyl) -indolin-5- sulfonyl]-4,5- dihydro-2-imidazolone hydrochloride, is a novel anticancer agent thought to have an unique mechanism of action on the inhibition of tumor growth. In this study, we estimated in vivo antitumor activities and pharmacokinetics of Dw2282 depending on various vehicles. The inhibition rate of tumor growth was increased by 50, 100 and 200 mg/kg of Dw2282 in a dose-dependent manner. When Dw2282 dissolved in 4 sorts of vehicles was orally single dosed to rats at 50 mg/kg, Cmax of Dw2282 in 0.5% CMC.Na was a half as high as those in PG, PG+CP and PG+CP+DW. When Dw2282 was orally administered to mice for 5 days, antitumor activity of 130 mg/kg suspended in 0.5% CMC.Na was as effective as that of 65 mg/kg dissolved in the rest of vehicles. Taken together, it is thought that antitumor activities of Dw2282 are resulted from the absorption extent of it and related to the vehicle used.

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다자간의 통신환경에서 다양한 수신품질을 고려한 One-Time 오버레이 멀티캐스트 기법에 관한 연구 (One-Time Overlay Multicast Techniques Considering Receipt Quality for m-to-n Comunication over Large Internet)

  • 윤미연;김기영;김대원;신용태
    • 한국통신학회논문지
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    • 제30권1B호
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    • pp.27-38
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    • 2005
  • 오버레이 멀티캐스트 기법은 기존의 IP 멀티캐스트에서의 하드웨어적 문제를 해결할 수 있는 기법으로 최근 들어 활발한 연구가 진행 중에 있다. 그러나 호스트간의 가상의 네트워크를 구성하여 그 위에서 전송 트리를 구성하기 때문에 멀티미디어 데이터의 실시간 전송의 경우 해당 멤버 중 가장 낮은 품질의 수신환경을 가진 호스트에게 동기화가 된다는 문제점을 가지고 있다. 따라서 본 논문에서는 다자간의 통신환경에서 다양한 수신 환경을 지원하는 One-Time 오버레이 멀티캐스트 트리 구성 기법에 대해 제안한다. 본 논문은 각 수신자가 자신의 만족할 만한 수신 품질로 데이터를 전송받음을 증명하고 트리는 구성을 위한 제어정보의 오버헤드가 적고 구성 시간 복잡도가 짧음을 보임으로써 다자간의 환경에서 동적으로 트리가 생성 소멸 가능함을 보였다 마지막으로 대규모의 인터넷상에서 운영 가능하므로 보이기 위해 본 트리 구성 기법의 확장성이 우수함을 보였다.

하수오(何首烏)가 고혈압과 수축혈관에 미치는 영향 (Effect of Aqueous Extract of Polygoni Multiflori Radix on Hypertension and Arterial Contraction in Animal Models)

  • 서용원;김호현;고흥
    • 동의생리병리학회지
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    • 제22권3호
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    • pp.593-599
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    • 2008
  • This research was aimed to examine the effect of Polygoni Multiflori Radix extract on the blood pressure in spontaneous hypertensive rat (SHR) and norepinephrine - induced arterial contraction in rabbit. In order to investigate the effect of Polygoni Multiflori Radix on rabbit's contracted vascular ring detached from common carotid artery, vascular ring with intact or damaged endothelium was used for the experiment using organ bath. To analyze the mechanism of Polygoni Multiflori Radix-induced relaxation, Polygoni Multiflori Radix extract was infused into contracted vascular ring which had been pretreated by $N{\omega}$-nitro-L-arginine(L-NNA), Methylene blue(MB), and $Ca^{2+}$ was infused into contracted vascular ring induced by NE after treatment of Polygoni Multiflori Radix extract in $Ca^{2+}$-free solution. The results were as follows: Systolic blood pressure was significantly attenuated by administration of Polygoni Multiflori Radix. Blood flow and aldosterone were significantly decreased, but velocity and renin were not affected by Polygoni Multiflori Radix. Polygoni Multiflori Radix had an effective relaxation to the contracted vascular ring by NE in 0.03 mg/ml, 0.1 mg/ml and 0.3 mg/ml level. Polygoni Multiflori Radix had an effective relaxation to the intact endothelium vascular ring, but when endothelium was removed, vascular ring did not relax. Polygoni Multiflori Radix-induced relaxation was inhibited by the pretreatment of L-NNA and MB. Pretreatment of Polygoni Multiflori Radix extract inhibit the contraction by influx of extra-$Ca^{2+}$ in contracted vascular ring induced by NE in $Ca^{2+}$-free solution. As mentioned above, we suggest that Polygoni Multiflori Radix relaxes vascular ring through suppress influx of extra-cellular $Ca^{2+}$ by the action of nitric oxide from endothelium.