• Biomolecules & Therapeutics
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• 제18권3호
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• pp.343-349
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• 2010

This study was designed to investigate the effects of ticlopidine on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Carvedilol was administered orally (3 mg/kg) or intravenously (1 mg/kg) without or with oral administration of ticlopidine (4, 12 mg/kg) to rats. The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 2C9 activity were also evaluated. Ticlopidine inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of $25.2\;{\mu}M$. In addition, ticlopidine could not significantly enhance the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. Compared with the control group (given carvedilol alone), the area under the plasma concentration-time curve (AUC) was significantly (12 mg/kg, p<0.05) increased by 14-41%, and the peak concentration ($C_{max}$) was significantly (12 mg/kg, p<0.05) increased by 10.7-73.3% in the presence of ticlopidine after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.14- to 1.41-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of ticlopidine was increased by 36.2-38.5%. Compared to the i.v. control, ticlopidine could not significantly change the pharmacokinetic parameters of i.v. administered carvedilol. The enhanced oral bioavailability of carvedilol may result from inhibition of CYP2C9-mediated metabolism rather than P-gpmediated efflux of carvedilol in the intestinal and/or in liver and renal eliminatin of carvedilol by ticlopidine.

• 한국해양학회지:바다
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• 제12권3호
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• pp.125-132
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• 2007

조식동물-해조류 상호작용의 크기 분포를 추정하기 위하여 12종의 조식동물에 대하여 개체 당 일평균 섭식률 (PCGR, per capita grazing rate, g seaweeds/individual/day)을 구하고, 다른 종들의 섭식률을 추정할 수 있는 회귀모형을 만들었다. 조식동물의 생체량과 사제곱근 변환 PCGR은 power curve($y=0.2310x^{0.3290}$)에 적합되었고 모형의 r값은 0.8864였다. 이로부터 조식동물의 PCGR 변동은 생체량과 관계가 있으며, 섭식 효율성은 관찰된 생체량 범위내에서 균일하지 않다는 것이 파악되었다. 따라서 각 종별 생체량 효과가 보정된 PCGR을 추정하였고, 작은 몸체를 갖는 종일수록 보다 효율적인 섭식자인 것으로 밝혀졌다. 서식밀도를 감안한 개체군 별 상호작용(grazing impact, $mg/m^2$)을 계산한 결과, 해조장에 가장 큰 영향을 갖는 개체군은 군소(Aplysia kurodai, 약 $2,513mg/m^2$)인 것으로 나타났고, 다음은 둥근성게(Strongylocentrotus nudus, 약 1,500 mg/)와 새치성게(S. intermedius, $733mg/m^2$) 등인 것으로 나타났다. 단각류 가운데 단위 면적당 밀도가 4,000 개체 이상인 멜리타옆새우류, Elasmopus sp.와 2,000 개체 이상인 가시꼬리육질꼬리옆새우붙이, Jassa falcata의 섭식량은 각각 3.435와 $1.697mg/m^2/day$인 것으로 나타났다. 본 연구에서 추정한 조식동물 군집의 종 조성과 서식 밀도가 동일할 때 상호작용의 총합은 $5,045mg/m^2/day$인 것으로 나타났다. 실험과 모형 연구로부터 성게류와 군소 외에도 적잖은 상호작용이 높은 밀도를 갖는 많은 수의 종들로부터 해조류에 가해지고 있음을 추정할 수 있었다. 성게류의 경우 3 개체/$m^2$의 평균 서식밀도에서 발생하는 섭식량은 국내 천해 양식업의 평균 해조류 생산량(약 5 ton/ha)을 초과하는 것으로 예측되었다. 미소 갑각류 역시 낮은 포식압 조건에서 서식밀도가 증가하면 적잖은 충격(해조류 생산량의 약 16%)을 가할 것으로 예측되었다. 해조장에 서식하는 조식동물의 밀도가 어류에 의해 강도 높게 조절되고 있음을 감안하면, 어류와 조식동물 간 상호작용에 대한 인간의 간섭(어류의 남획 등)은 해조장에 커다란 변화를 유발할 수 있는 잠재력을 가질 것으로 예상된다.

• Journal of Pharmaceutical Investigation
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• 제41권5호
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• pp.273-278
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• 2011

The aim of this study was to investigate the effect of efonidipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of efonidipine (1 or 3 mg/kg) in rats. The effect of efonidipine on the cytochrome P450 (CYP) 3A4 activity was also evaluated. Efonidipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $0.08{\mu}M$. Compared to those in the oral control group (warfarin without efonidipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (1 mg/kg, P<0.05; 3 mg/kg, P<0.01) by 25.9-59.0%, and the peak plasma concentration ($C_{max}$) was significantly higher (3 mg/kg, P<0.05) by 26.2% after oral administration of warfarin with efonidipine, respectively. The total body clearance of warfarin was significantly (3 mg/kg, P<0.05) decreased by efonidifine. Consequently, the relative bioavailability of warfarin was increased by 1.26- to 1.59-fold and the absolute bioavailability of warfarin with efonidipine was significantly greater by 59.7-75.4 % compared to that in the control group (47.4%). In contrast, efonidipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver and to reduction of total body celarance rather than renal elimination, resulting in reducing first-pass metabolism by efonidipine.

• 한국임상약학회지
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• 제20권1호
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• pp.25-29
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• 2010

The purpose of this study was to investigate the effect of atorvastatin on the pharmacokinetics of nifedipine (6 mg/kg) after oral administration of nifedipine with or without atorvastatin (0.5 and 2.0 mg/kg) in rats, and also was to evaluate to the effect of atorvastatin on the CYP3A4 activity. The 50% inhibiting concentration ($IC_{50}$) values of atorvastatin on CYP3A4 activity is 46.1 ${\mu}M$. Atorvastatin inhibited CYP3A4 enzyme activity in a concentration-dependent manner. Coadministration of atorvastatin increased significantly (p<0.05, 2.0 mg/kg) the plasma concentration-time curve (AUC) and the peak concentration ($C_{max}$) of nifedipine compared to the control group. The relative bioavailability (RB%) of nifedipine was increased from 1.15- to 1.37-fold. Coadministration of atorvastatin did not significantly change the terminal half-life ($T_{1/2}$) and the time to reach the peak concentration ($T_{max}$) of nifedipine. Based on these results, we can make a conclusion that the significant changes of these pharmacokinetic parameters might be due to atorvastatin, which possesses the potency to inhibit the metabolizing enzyme (CYP3A4) in the liver and intestinal mucosa, and also inhibit the P-glycoprotein (P-gp) efflux pump in the intestinal mucosa. It might be suggested that atorvastatin altered disposition of nifedipine by inhibition of both the first-pass metabolism and P-glycoprotein efflux pump in the small intestine of rats. In conclusion, the presence of atorvastatin significantly enhanced the oral bioavailability of nifedipine, suggesting that concurrent use of atorvastatin with nifedipine should require close monitoring for potential drug interation.

• Bulletin of the Korean Chemical Society
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• 제23권2호
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• pp.330-336
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• 2002

A quantum-chemical investigation on the conformations and electronic properties of bis[2-{2-methoxy-4,6-di(t-butyl)phenyl}ethenyl]benzenes (MBPBs) as building block for ${\pi}$-conjugate polymer are performed in order to display the effects of t-butyl and methoxy group substitution and of kink(ortho and meta) linkage. The conjugation length of the polymers can be controlled by substituents and kink linkages of backbone. Structures for the molecules, o-, m-, and p-MBPBs as well as unsubstituted o-, m-, and p-DSBs were fully optimized by using semiempirical AM1, PM3 methods, and ab initio HF method with 3-21G(d) basis set. The potential energy curves with respect to the change of single torsion angle are obtained by using semiempirical methods and ab initio HF/3-21G(d) basis set. The curves are similar shape in the molecules with respect to the position of vinylene groups. It is shown that the conformations of the molecules are compromised between the steric repulsion interaction and the degree of the conjugation. Electronic properties of the molecules were obtained by applying the optimized structures and geometries to the ZINDO/S method. ZINDO/S analysis performed on the geometries obtained by AM1 method and HF/3-21G(d) level is reported. The absorption wavelength on the geometries obtained by AM1 method is much longer than that by HF/3-21G(d) level. The absorption wavelength of MBPBs are red shifted with comparison to that of corresponding DSBs in the same torsion angle because of electron donating substituents. The absorption wavelength of isomers with kink(orth and meta) linkage is shorter than that of para linkage.

• Computers and Concrete
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• 제10권4호
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• pp.331-347
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• 2012

This paper describes the varying material model, the analysis method and the software development for reinforced concrete circular columns confined by spiral or hoop transverse steel reinforcement and subjected to eccentric loading. The widely used Mander model of concentric loading is adapted here to eccentric loading by developing an auto-adjustable stress-strain curve based on the eccentricity of the axial load or the size of the compression zone to generate more accurate interaction diagrams. The prediction of the ultimate unconfined capacity is straight forward. On the other hand, the prediction of the actual ultimate capacity of confined concrete columns requires specialized nonlinear analysis. This nonlinear procedure is programmed using C-Sharp to build efficient software that can be used for design, analysis, extreme event evaluation and forensic engineering. The software is equipped with an elegant graphics interface that assimilates input data, detail drawings, capacity diagrams and demand point mapping in a single sheet. Options for preliminary design, section and reinforcement selection are seamlessly integrated as well. Improvements to KDOT Bridge Design Manual using this software with reference to AASHTO LRFD are made.

• 국제초고층학회논문집
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• 제13권1호
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• pp.85-95
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• 2024

A composite member made of concrete-filled steel tubes (CFT columns) has been recognized for its fire resistance due to the thermal mass effect of concrete inside the steel tube, as shown in various studies. In this study, the fire resistance performance of reinforced CFT columns under constant axial load was evaluated using finite element analysis with ABAQUS. For this purpose, the variables including cross-section size, steel tube thickness, and concrete cover thickness were set, and the temperature distribution in the column cross-section exposed to a standard fire was investigated using heat transfer analysis. Ultimately, a P-M interaction curve was obtained by evaluating the overall residual strength of columns, and the fire resistance time was determined by evaluating axial displacement-time responses due to the reduction in load capacity during fire through stress analysis.

• 한국가축번식학회지
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• 제17권1호
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• pp.49-56
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• 1993

Mouse mammary epithelial cells(NMuMG) were plated onto 24 well phates(100,000 cells/well), in DMEM supplemented with 10% fetal calf serum. After serum starvation for 24 hours, EGF)0~100ng/ml) was added simultaneously with IGF-I(10ng/ml), 1$\mu$M photoreactive cAMP(4,5-dimethoxy-2-nitrobenzyl adenosine-3',5' cyclic monophosphate, DMNB) or IGF-I plus DMNB. After 2 hours, the cells were expposed to UV light(300nm, 3 second pulse0 in order to activate DMNB which induces a rapid transient increase in intracellular cAMP upon UV irradiation. DNA synthesis was estimated as incorporation of 3H-thymidine into DNA(1 hour pulse with 1$\mu$Ci/ml, 18~19 hours after UV exposure). Without IGF-I or DMNB, EGF(10 or 100ng/ml) increased DNA synthesis from 8,362 dpm/well in control to 16,345 or 18,684 dpm/well with EGF(pooled SE=1,239 dpm/well, P<0.05). IGF-I or IGF-I plus DMNB alone increased DNA synthesis from 8,362 dpm/well in control to 17,307 or 20,427 dpm/well, respectively(P<0.05). Addition of IGF-I, DMNB or IGF-I plus DMNB into 0~100ng/ml EGF did not significantly change the shape of dose response curve of EGF alone. In other experiment, EGF or IGF-I plus DMNB into 10ng/ml EGF group exhibited interaction effect in DNAsynthesis [EGF(10ng/ml)=18,497; IGF-I＋EGF=22,837; DMNB＋EGF=20,658 ; IGF-I＋DMNB＋EGF=29,658, pooled SE=1,055, P<0.05]. These results indicate that simultaneous activation of EGF, IGF-I and intracellular cAMP interact in DNA synthesis of mouse mammary epithelial cells.

• Asian-Australasian Journal of Animal Sciences
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• 제32권1호
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• pp.14-22
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• 2019

Objective: The aim of the study was to find a possible association between the ${\beta}-$ and ${\kappa}-casein$ and ${\beta}-lactoglobulin$ genotypes and important milk physiochemical and technological characteristics such as acidity, alcohol stability, the contents of some minerals and the parameters of acid fermentation ability (FEA) in Czech Fleckvieh Cattle. Methods: Milk and blood samples were collected from 338 primiparous Czech Fleckvieh cows at the same stage of lactation. The genotypes of individual cows for ${\kappa}-casein$ (alleles A, B, and E) and ${\beta}-lactoglobulin$ (alleles A and B) were ascertained by polymerase chain reaction-restriction fragment length polymorphism, while their ${\beta}-casein$ (alleles $A^1$, $A^2$, $A^3$, and B) genotype was determined using melting curve genotyping analysis. The data collected were i) milk traits including active acidity (pH), titratable acidity (TA), alcohol stability (AS); calcium (Ca), phosphorus (P), sodium (Na), magnesium (Mg), and potassium (K) contents; and ii) yoghurt traits including active acidity (Y-pH), titratable acidity (Y-TA), and the counts of both Lactobacilli and Streptococci in 1 mL of yoghurt. A linear model was assumed with fixed effects of herd, year, and season of calving, an effect of the age of the cow at first calving and effects of the casein and lactoglobulin genotypes of ${\beta}-CN$ (${\beta}-casein$, CSN2), ${\kappa}-CN$ (${\kappa}-casein$, CSN3), and ${\beta}-LG$ (${\beta}-lactoglobulin$, LGB), or the three-way interaction between those genes. Results: The genetic polymorphisms were related to the milk TA, AS, content of P and Ca, Y-pH and Lactobacilli number in the fresh yoghurt. The CSN3 genotype was significantly associated with milk AS (p<0.05). The effect of the composite CSN2-CSN3-LGB genotype on the investigated traits mostly reflected the effects of the individual genes. It significantly influenced TA (p<0.01), Y-pH (p<0.05) and the log of the Lactobacilli count (p<0.05). Conclusion: Our findings indicate that the yoghurt fermentation test together with milk proteins genotyping could contribute to milk quality control and highlight new perspectives in dairy cattle selection.

• The Korean Journal of Physiology and Pharmacology
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• 제4권3호
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• pp.243-251
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• 2000

In order to provide a basis for studying the molecular mechanism of pharmacological action of local anesthetics and to develop a fluorescence spectroscopic method which can detect the microviscosity of native and model membranes using intramolecular excimerization of 1,3-di(l-pyrenyl)propane (Py-3-Py), we examined the effect of lidocaine HCl on the microviscosity of model membranes of phosphatidylcholine fraction extracted from synaptosomal plasma membrane vesicles (SPMVPC). The excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in liquid paraffin was a simple linear function of $T/{\eta}.$ Based on this calibration curve, the microviscosity values of the direct probe environment in SPMVPC model membranes ranged from $234.97{\pm}48.85$ cP at $4^{\circ}C$ to %19.21{\pm}1.11$ cP at $45^{\circ}C.$ At $37^{\circ}C,$ a value of $27.25{\pm}0.44$ cP was obtained. The lidocaine HCl decreased the microviscosity of SPMVPC model membranes in a concentration-dependent manner, with a significant decrease in microviscosity value by injecting the local anesthetic even at the concentration of 0.5 mM. These results indicate that the direct environment of Py-3-Py in the SPMVPC model membranes is significantly fluidized by the lidocaine HCl. Also, the present study explicitly shows that an interaction between local anesthetics and membrane lipids is of importance in the molecular mechanism of pharmacological action of lidocaine HCl.