• Title/Summary/Keyword: PDE4

검색결과 127건 처리시간 0.024초

포스포디에스테라제 III의 저해물인 KR-30075의 흰쥐에서의 약물속도론 (Pharmacokinetics of KR-30075, A Potent Phosphodiesterase III Inhibitor in Rats)

  • 이광표;김효진;권광일;조송자
    • 약학회지
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    • 제36권3호
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    • pp.259-268
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    • 1992
  • A procedure for the determination of KR-30075 and its metabolites in plasma and urine by high performance liquid chromatography is described. For the study of pharmacokinetic properties of KR-30075, a new PDE III inhibitor, the plasma concentration and urinary excretion after an oral administration of KR-30075 (4 mg/kg) in the male rat (Sprague Dawley) were determined by high performance liquid chromatography. The best extraction efficiency of KR-30075 and KR-30072 is obtained with ethyl ether adjusted to pH 4.0. Retention times of both KR-30072 and KR-30075 were within 5 min and resolution was complete at the flow rate of 1.0 ml/min. The sensitivity and specificity of this HPLC assay appears to be satisfactory for the pharmacokinetic study of KR-30075 and its metabolites. One-compartment open model with first-order absorption was applied to evaluate the pharmacokinetic parameters of KR-30075 according to Minimum AIC Estimation. $T_{max}$ was 1 hr, $C_{max}$ was $0.789{\pm}0.31\;{\mu}g/ml$ and elimination half $T_{1/2}$ was 6.31 min after oral administration of 4 mg/kg KR-30075 to male rats.

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Relaxant and anti-inflammatory effect of two thalidomide analogs as PDE-4 inhibitors in pregnant rat uterus

  • Munoz-Perez, Victor Manuel;Fernandez-Martinez, Eduardo;Ponce-Monter, Hector;Ortiz, Mario I.
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권4호
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    • pp.429-437
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    • 2017
  • The aim of this study was to evaluate the relaxant and anti-inflammatory effects of two thalidomide analogs as phosphodiesterase-4 (PDE-4) inhibitors in pregnant rat uterus. Uteri from Wistar female rats were isolated at 19 day of pregnancy. Uterine samples were used in functional studies to evaluate the inhibitory effects of the thalidomide analogs, methyl 3-(4-nitrophthalimido)-3-(3,4- dimethoxyphenyl)-propanoate (4NO2PDPMe) and methyl 3-(4-aminophthalimido)- 3-(3,4-dimethoxyphenyl)-propanoate (4APDPMe), on prostaglandin-$F2{\alpha}$ ($PGF2{\alpha}$)-induced phasic, $K^+$-induced tonic, and $Ca^{2+}$-induced contractions. Accumulation of cAMP was quantified in uterine homogenates by ELISA. Anti-inflammatory effect was assessed by using ELISA for determination of the pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and interleukin (IL)-$1{\beta}$, and anti-inflammatory IL-10, from uterine explants stimulated with lipopolysaccharide (LPS). Nifedipine, forskolin and rolipram were used as positive controls where required. Both thalidomide analogs induced a significant inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. Nifedipine and forskolin were more potent than the analogs to inhibit the uterine contractility, but these were more potent than rolipram, and 4APDPMe was equieffective to nifedipine. Thalidomide analogs increased uterine cAMP-levels in a concentration-dependent manner. The LPS-induced $TNF{\alpha}$ and $IL-1{\beta}$ uterine secretion was diminished in a concentration-dependent fashion by both analogs, whereas IL-10 secretion was increased significantly. The thalidomide analogs induced utero-relaxant and anti-inflammatory effects, which were associated with the increased cAMP levels as PDE-4 inhibitors in the pregnant rat uterus. Such properties place these thalidomide analogs as potentially safe and effective tocolytic agents in a field that urgently needs improved pharmacological treatments, as in cases of preterm labor.

가상 심장 시뮬레이션에서 CPU와 GPU 병렬처리의 계산 성능 비교 (Computing Performance Comparison of CPU and GPU Parallelization for Virtual Heart Simulation)

  • 김상희;정다운;;임기무
    • 대한의용생체공학회:의공학회지
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    • 제41권3호
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    • pp.128-137
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    • 2020
  • Cardiac electrophysiology studies often use simulation to predict how cardiac will behave under various conditions. To observe the cardiac tissue movement, it needs to use the high--resolution heart mesh with a sophisticated and large number of nodes. The higher resolution mesh is, the more computation time is needed. To improve computation speed and performance, parallel processing using multi-core processes and network computing resources is performed. In this study, we compared the computational speeds of CPU parallelization and GPU parallelization in virtual heart simulation for efficiently calculating a series of ordinary differential equations (ODE) and partial differential equations (PDE) and determined the optimal CPU and GPU parallelization architecture. We used 2D tissue model and 3D ventricular model to compared the computation performance. Then, we measured the time required to the calculation of ODEs and PDEs, respectively. In conclusion, for the most efficient computation, using GPU parallelization rather than CPU parallelization can improve performance by 4.3 times and 2.3 times in calculations of ODEs and PDE, respectively. In CPU parallelization, it is best to use the number of processors just before the communication cost between each processor is incurred.

특정 인지질 결합 단백질의 과발현이 HEK293 세포모양에 미치는 영향 분석 (Analysis of the Effects of Overexpression of Specific Phospholipid Binding Proteins on Cellular Morphological Changes in HEK293T Cells)

  • 전용우;이진아;장덕진
    • 생명과학회지
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    • 제26권8호
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    • pp.875-880
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    • 2016
  • 진핵세포의 원형질막은 외부환경으로부터 세포를 격리하는 물리적인 장벽뿐만 아니라, 선택적 물질수송, 신호전달등 중요한 기능을 수행한다. 원형질막의 세포질쪽 지질층은 주로 Phosphatidylethanolamine (PE), Phosphatidylserine (PS), Phosphatidylinositides (PIs) 등의 인지질로 구성되어 있는데, 다양한 단백질들이 이들과 직접 결합하거나 이들의 성질을 이용해 원형질막으로 위치된다. 본 연구에서는 원형질막의 안쪽 지질층에 존재하는 특정 인지질과 결합하여, 원형질막에 위치되는 단백질을 과발현시켰을 때 나타나는 세포의 모양변화를 분석하였다. 이를 위해 PS와 PI등과의 선택적 결합으로 원형질막에 위치하는 단백질들과 소수성 또는 정전기적 상호작용으로 원형질막으로 위치되는 단백질들을 HEK293T세포에 과발현시켜 보았다. 그 결과, 대조군으로 사용한 EGFP 단백질과 PI4P에 선택적으로 결합하는 EGFP-P4M-SidM단백질의 발현은 세포의 모양변화를 유도하지 않았다. 반면, PI(4,5)P2에 결합하는 EGFP-PLCδ1(PH), PI(3,4,5)P3에 결합하는 EGFP-AKT1(PH), PI4P와 PI(4,5)P2에 결합하는 OSH2(PH)x2-EGFP의 발현은 세포의 크기가 줄어드는 수축현상이 일어나면서, Lamilapodia나 Filopodia가 형성되는 것을 확인할 수 있었다. 반면에, PS결합을 통해 원형질막에 위치되는 Lact-C2-EGFP과 소수성결합에 의해 원형질막에 위치되는 ApPDE4 long-form인 L(N20)-EGFP이나, 정전기적인 결합을 통해 원형질막으로 위치되는 ApPDE4 short-form인 S(N-UCR1-2)-EGFP단백질의 경우는 세포의 크기가 줄어드는 수축현상은 일어나지만 Lamilapodia나 Filopodia와 같은 모양변화는 나타나지 않는 것을 확인할 수 있었다. 본 연구를 통해, 특정 인지질에 결합하여 원형질막에 위치되는 단백질들이 각각의 인지질 결합 특성에 따라 분류 가능한 세포의 모양변화가 일어남을 확인할 수 있었다.

Improved measurement uncertainty of photon detection efficiency for single pixel Silicon photomultiplier

  • 양슬기;이혜영;전진아;김석환;이직;박일흥
    • 천문학회보
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    • 제37권2호
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    • pp.210.1-210.1
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    • 2012
  • We report technique used for improved measurement uncertainties for Photon detection efficiency(PDE) of $1mm^2$ single pixel SiPM. It consists of 470nm LED light source, two 2-inch integrating sphere and two NIST calibrated silicon photodiodes that have ${\pm}2.4%$ calibration error. With raytracing simulation of our experimental setup, we predict number of photon into SiPM and measurement uncertainty. For MPPC, Hamamatsu suggested PDE(1600 micro pixel) including crosstalk and afterpulse is 23.5% at 470 nm. By using new low calibration error photodiode and raytracing simulation, our simulation result has ${\pm}3%$ measurement uncertainty. The technical detail of measurement, simulation are presented with the results and implication.

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전영역 탐색 방식의 움직임 예측에서 매칭 스캔 방법을 이용한 불가능한 후보 벡터의 고속 제거 알고리즘 (A Past Elimination Algorithm of Impossible Candidate Vectors Using Matching Scan Method in Motion Estimation of Full Search)

  • 김종남
    • 한국멀티미디어학회논문지
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    • 제8권8호
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    • pp.1080-1087
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    • 2005
  • 움직임 예측의 전영역 탐색 (full search)에서 방대한 계산량은 실시간 비디오 압축에 큰 장애물이 되어왔으며, 이는 최근 MPEG-4 AVC (Advanced Video Coding) 표준이 기존의 MPEG-2 보다 움직임 예측에서 더 많은 계산량을 요구하고 있다. 전영역 움직임 예측의 계산량을 줄이기 위해, 본 논문에서는 기존의 전영역움직임 예측에 비하여 예측 화질의 저하가 없는 새로운 고속 매칭 알고리즘을 제안한다. 가능한 후보의 움직임 벡터를 빨리 제거함으로써 예측화질의 저하 없이 계산량만 줄일 수 있게 되는 것이다. 본 논문에서는 영상의 복잡한 영역의 효율적인 매칭 단위와 디더링 (dithering) 순서에 기초한 매칭 방식을 통하여 불가능한 후보 벡터를 더 빨리 제거한다. 제안된 알고리즘은 예측 화질의 저하 없이 기존의 PDE (partial distortion elimination) 알고리즘을 이용한 전영역 탐색 방법에 비해 $30\%$의 계산량을 줄였으며, MPEG-2 및 MPEG-4 AVC를 이용하는 비디오 부호화 응용분야에 유용하게 사용될 수 있을 것이다.

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RECENT DEVELOPMENTS IN NONLINEAR HYPERBOLIC PDE

  • Christodoulou, Demetrios
    • 대한수학회지
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    • 제38권4호
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    • pp.843-852
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    • 2001
  • In this lecture I shall discuss some recent progress in the development of methods for attacking the central questions of the formation and structure of singularities and of global regularity for solutions of the Cauchy problem for nonlinear systems of partial differential equations of hyperbolic type. Applications to the Einstein equations of general relativity and to the equations of compressible fluid flow shall be particularly emphasized and detailed.

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Analysis of gene expression during mineralization of cultured human periodontal ligament cells

  • Choi, Hee-Dong;Noh, Woo-Chang;Park, Jin-Woo;Lee, Jae-Mok;Suh, Jo-Young
    • Journal of Periodontal and Implant Science
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    • 제41권1호
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    • pp.30-43
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    • 2011
  • Purpose: Under different culture conditions, periodontal ligament (PDL) stem cells are capable of differentiating into cementoblast-like cells, adipocytes, and collagen-forming cells. Several previous studies reported that because of the stem cells in the PDL, the PDL have a regenerative capacity which, when appropriately triggered, participates in restoring connective tissues and mineralized tissues. Therefore, this study analyzed the genes involved in mineralization during differentiation of human PDL (hPDL) cells, and searched for candidate genes possibly associated with the mineralization of hPDL cells. Methods: To analyze the gene expression pattern of hPDL cells during differentiation, the hPDL cells were cultured in two conditions, with or without osteogenic cocktails (${\beta}$-glycerophosphate, ascorbic acid and dexamethasone), and a DNA microarray analysis of the cells cultured on days 7 and 14 was performed. Reverse transcription-polymerase chain reaction was performed to validate the DNA microarray data. Results: The up-regulated genes on day 7 by hPDL cells cultured in osteogenic medium were thought to be associated with calcium/iron/metal ion binding or homeostasis (PDE1A, HFE and PCDH9) and cell viability (PCDH9), and the down-regulated genes were thought to be associated with proliferation (PHGDH and PSAT1). Also, the up-regulated genes on day 14 by hPDL cells cultured in osteogenic medium were thought to be associated with apoptosis, angiogenesis (ANGPTL4 and FOXO1A), and adipogenesis (ANGPTL4 and SEC14L2), and the down-regulated genes were thought to be associated with cell migration (SLC16A4). Conclusions: This study suggests that when appropriately triggered, the stem cells in the hPDL differentiate into osteoblasts/cementoblasts, and the genes related to calcium binding (PDE1A and PCDH9), which were strongly expressed at the stage of matrix maturation, may be associated with differentiation of the hPDL cells into osteoblasts/cementoblasts.

Changes in expression of insulin signaling pathway genes by dietary fat source in growing-finishing pigs

  • Kim, Seung-Chang;Jang, Hong-Chul;Lee, Sung-Dae;Jung, Hyun-Jung;Park, Jun-Cheol;Lee, Seung-Hwan;Kim, Tae-Hun;Choi, Bong-Hwan
    • Journal of Animal Science and Technology
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    • 제56권4호
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    • pp.12.1-12.7
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    • 2014
  • This study investigated changes in gene expression by dietary fat source, i.e., beef tallow, soybean oil, olive oil, and coconut oil (each 3% in feed), in both male and female growing-finishing pigs. Real-time PCR was conducted on seven genes (insulin receptor; INSR, insulin receptor substrate; IRS, phosphatidylinositol (3,4,5)-triphosphate; PIP3, 3-phosphoinositide-dependent protein kinase-1; PDK1, protein kinase B; Akt, forkhead box protein O1; FOXO1 and cGMP-inhibited 3', 5'-cyclic phosphodiesterase; PDE3) located upstream of the insulin signaling pathway in the longissimus dorsi muscle (LM) of pigs. The INSR, IRS, PIP3, and PDE3 genes showed significantly differential expression in barrow pigs. Expression of the PIP3 and FOXO1 genes was significantly different among the four dietary groups in gilt pigs. In particular, the PIP3 gene showed the opposite expression pattern between barrow and gilt pigs. These results show that dietary fat source affected patterns of gene expression according to animal gender. Further, the results indicate that the type of dietary fat affects insulin signaling-related gene expression in the LM of pigs. These results can be applied to livestock production by promoting the use of discriminatory feed supplies.