• 대한수의학회지
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• 제52권1호
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• pp.9-18
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• 2012

Rabies is a major zoonotic disease that causes approximately 55,000 human deaths worldwide on an annual basis. The nucleocapsid protein and glycoprotein genes of the Korean rabies virus (RABV) have been subjected to molecular and phylogenetic analyses. Although the phosphoprotein (P) has several important functions in viral infection and pathogenicity, the genetic characterizations of the P of Korean RABV isolates have not yet been established. In the present study, we conducted genetic analyses of P genes of 24 RABV isolates circulating in the Republic of Korea (hereafter, Korea) from 2008 to 2011. This study revealed that the P genes of Korean RABVs are genetically similar to those of RABV strains of lyssavirus genotype I including V739 (dogs, Korea), NNV-RAB-H (humans, India), NeiMeng925 (raccoon dogs, China), and RU9.RD (raccoon dogs, Russia). Among Korean isolates, the RABV P genes showed low variability in the variable domains among Korean isolates; they had specific consensus sequences and amino acid substitutions capable of identifying geographic characteristics and retained specific sequences thought to be important for viral function. These results provide important genetic characteristics and epidemiological information pertaining to the P gene of the Korean RABV.

• 약학회지
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• 제48권1호
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• pp.1-5
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• 2004

The purpose of this study was to investigate the effect of coadministration and 3 days-pretreatmemt of niledipine (2, 10 mg/kg) on the pharmacokinetic parameters and bioavailability of paclitaxel (50 mg/kg) after oral administration in rats. Coadministration of nifedipine with paclitaxel did alter the $C_{max}$ (115${\pm}$29 ng/ml without nifedipine; 135${\pm}$35 ng/ml with nifedipine (10 mg/kg): p<0.05) and AUC (188${\pm}$459 ng/mlㆍhr with-out nifedipine; 2546${\pm}$642 ng/mlㆍhr with nifedipine; p<0.05). Three days treatment of nifedipine on the prior to paclitaxel administration increased the $t_{1/2}$ 〔9.90${\pm}$2.47 hr without nifedipine; 12.37${\pm}$3.12 hr with nifedipine (2 mg/kg): 12.83${\pm}$3.32 hr with nifedipine (10 mg/ml); p<0.05] and AUC [1833${\pm}$459 ng/mlㆍhr without nifedipine; 2663${\pm}$648 ng/mlㆍhr with nifedipine (2 mg/kg): 3006${\pm}$734 ng/mlㆍhr with nifedipine (10 mg/ml): p <0.05]. Drug interaction between nifedipine and paclitaxel decreased the elimination rate constant and increased the oral bioavailability of paclitaxel. On the basis of the results of this study, it might be considered that nifedip ine may inhibit cytochrome P450, which are engaged in paclitaxel metabolism, result in increased $t_{1/2}$ and AUC of paclitaxel. However, further study should be conducted to clarify the roles of cytochrome P450 and P-glycoprotein on paclitaxel bio-availability wit/or without nifedipine.

• 한국임상약학회지
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• 제21권2호
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• pp.115-121
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• 2011

에토포시드와 아피제닌의 약동학적 상호작용 연구를 위하여 아피제닌 (0.4, 2.0 또는 8 mg/kg)과 에토포시드의 경구(6 mg/kg) 및 정맥 (2 mg/kg) 투여 하여 본 연구를 실시하였다. 아피제닌이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 아피제닌의 CYP3A4의 50% 효소활성억제는 $1.8{\mu}M$ 이었다. 아피제닌은 MCF-7/ADR 세포의 로다마인-123 세포 축적을 증가 시키므로 P-gp를 억제시켰다. 아피제닌은 에토포시드의 혈장곡선하면적과 최고혈장농도 (AUC and $C_{max}$)를 유의성 있게 증가시켰으나, 에토포시드의 최고혈장농도 도달시간 ($T_{max}$)과 생물학적 반감기 ($t_{1/2}$)에는 영향을 미치지 않았다. 따라서, 아피제닌 존재하에 에토포시드의 절대적생체이용률 (AB)은 대조군과 비교하여 유의성있게 증가되었다. 경구투여시와는 대조적으로, 아피제닌은 정맥 내로 투여된 에토포시드에서는 약동학적 파라미터에 어떤 영향도 미치지 않았다. 따라서 아피제닌이 에토포시드의 생체이용률을 증가시킨 것은 아피제닌이 소장과 간장에서 CYP3A4을 억제 및 소장에서 P-gp를 억제 시켰기 때문으로 사료된다.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.313-317
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• 2008

This study investigated the effect of naringin, a flavonoid, on the bioavailability of etoposide administered orally to rats. Etoposide (6 mg/kg) was administered orally to rats alone or with naringin (1, 4 or 12 mg/kg). Compared with the control group, the co-administration of etoposide with 4 and 12 mg/kg of naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak plasma concentration ($C_{max}$) of the oral etoposide. Consequently, the absolute bioavailability (AB) of etoposide in the presence (4 and 12 mg/kg) of naringin was significantly (p<0.05) increased by $9.4{\sim}10.6%$ compared with the control group (7.4%). The relative bioavailability (RB) of etoposide was increased 1.13- to 1.44-fold compared to the control group. Enhanced bioavailability of etoposide might be due to inhibition of both cytochrome P450 (CYP) 3A4 in the intestine or liver and P-glycoprotein (P-gp) transport efflux of etoposide in the intestinal membrane. This data indicate that careful consideration of the dosage for therapy with etoposide is required in a case of clinical application of the co-administration of etoposide and naringin.

• 약학회지
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• 제55권4호
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• pp.332-337
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• 2011

The purpose of this study was to investigate the effect of epigallocatechin gallate (EGCG) on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral and iv administration of nimodipine with or without EGCG and also the effect of EGCG on the cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp) activity were evaluated. EGCG inhibited CYP3A4 and P-gp activity. EGCG significantly increased the area under the plasma concentration-time curve (AUC) and peak plasma concentration ($C_{max}$) of nimodipine. The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by EGCG were increased by 16% and by 48%, respectively, compared to the control. In contrast, EGCG did not affect the intravenous pharmacokinetics of nimodipine. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of CYP3A4 in the small intestine and/or in the liver and inhibition of P-gp in the small intestine by EGCG.

• Archives of Pharmacal Research
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• 제17권1호
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• pp.21-25
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• 1994

Physico-chemical characterization of human renal dipeptidase was carried out. It was a glycoprotein with a subunit MW of approximately 47,700 dalton. The pH optimum was at 8 and its stable conformation was retained between pH 5 and 12. The kinetic parameters determined with imipenem, a noval ${\beta}-lactam$ antibiotic, were Vmax, $5.21\;\mu{mol/min/mg}$; km, 4.35 mM ; and Ki with cilastatin, $0.25\;\mu{M}$ Cilastatin demonstrated reversible competitive inhibition.

• BMB Reports
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• 제31권6호
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• pp.548-553
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• 1998

A minor anionic isoperoxidase named $A_{3n}$, was isolated from Korean radish (Raphanus sativus L.) root. Purification of the enzyme was accomplished by CMcellulose chromatography, DEAE-Sephacel chromatography, and Sephadex G-75 gel filtration. The enzyme was a glycoprotein with molecular weight of approximately 31,000 as determined by SDS-PAGE and 33,000 by Sepadex G-150 gel filtration, which is by far the smallest among the reported isoperoxidases. The pI value was 3.5. The optimum pH of the enzyme was 6.5 for guaiacol and $H_2O_2$, and the $K_m$ values for guaiacol and $H_2O_2$ were 13.3 mM and 1.5 mM, respectively. Kinetic studies with various substrates revealed that only A3n, unlike other isoperoxidases from radish, did not use scopoletin as a substrate and had very low $K_m$ value of 0.25 mM for ferolic acid among naturally occurring phenolic substrates.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.863-867
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• 2004

$\alpha$-Galactosidase from A. oryzae DR-5 was induced in the presence of melibiose, raffinose, galactose, and locust bean galactomannan. The enzyme was purified to homogeneity by precipitation with acetone followed by ion-exchange chromatography using DEAE-Sephacel. The purified enzyme showed a single band in both nondenaturing-PAGE and SDS-PAGE. The enzyme was a glycoprotein in nature by activity staining. The molecular weight of the purified enzyme was 93-95 kDa by SDS-PAGE. The enzyme exhibited the optimum pH and temperature at 4.7 and $60^\circ{C}$, respectively. $\alpha$-Galactosidase activity was strongly inhibited by $Ag^{2+}, Hg^{2+}, Cu^{2+}$, and galactose. EDTA, 1,10-phenanthraline, and PMSF did not inhibit the enzyme activity, whereas N-bromosuccinimide completely inhibited enzyme activity. Investigation by TLC showed complete hydrolysis of stachyose and raffinose in soymilk in 3 h at pH 5.0 and $50^\circ{C}$.

• Preventive Nutrition and Food Science
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• 제3권2호
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• pp.152-156
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• 1998

A Fructan-degrading enzyme was partially purified from onion (Allium cepa)bulbs by a combination of ammonium sufate precipitation, concanavalin-A-Affinity chromatography, and ion-exchange and gel-filtration chromatography. The enzyme hydrolyzed sucrose more effectively than inulin and was identified as a $\beta$- fructofuranosidase (invertase). The optimum pH and temperature were pH 5.5 and 35$^{\circ}C$, respectively. The enzymehydrolyzed sucrose with a Km of 1.2mM . The soluble $\beta$-fructofuranosidase is likely glycoprotein based on its ability to bind the lectin concanavalin-A. The enzyme was heatlabie, with mose activity being lost at 5$0^{\circ}C$ in 1 hr of incubation. The onion $\beta$-fructofuranosidase was partially inhibited by ZnCl2 HgCl2 and CuSo4.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.166.1-166.1
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• 2003

Autotaxin (ATX) is a 125-kDa glycoprotein and a strong motogen that can increase invasiveness and angiogenesis, originally isolated from the conditioned medium of human melanoma A2058 cells. And it is a strong. Recently, we suggested that ATX promotes motility via G protein-coupled PI3K$\gamma$, and Cdc42/Racl are essential for ATX-induced tumor cell motility in A2058 melanoma cells. In the present study, we found that activation of p21-activated kinase1 (PAK1) was required for ATX-induced cell motility. (omitted)