• 생명과학회지
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• 제17권3호통권83호
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• pp.334-339
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• 2007

본 연구는 우황청심원을 비롯한 상용되는 20종의 한약제제를 대상으로 9종의 시토크롬 동종효소에 대한 대사능의 저해정도를 고속 스크리닝 기법을 이용하여 탐색함으로써, 한약제제와 약물의 병용으로 인한 약물 상호작용 가능성을 평가하고자 하였다. 인체 간 마이크로좀 시료에 9종의 주요 시토크롬 약물대사효소의 지표약물과NADPH-generating system및 한약제제(500 ${\mu}g/ml$)를 첨가한 후 $37^{\circ}C$에서 15분간 반응시켜 생성된 각각의 대사물을 LC/MS/MS를 이용하여 정량하여 시토크롬 동종효소 활성의 변화를 평가하였다. 그 결과 우황청심원 현탁액 및 황련해독탕 물 추출물이 각각 CYP2B6 및 CYP2D6 효소 활성을 선택적으로 강력하게 저해하였다. 이러한 결과는 약국에서 쉽게 구입할 수 있는 한약제제들 중 일부는 인체 간 시토크롬 활성 저해능을 가지고 있고, 이들 효소에 의해 대사되는 약물과의 병용 복용시 약물상호작용 발생 가능성이 있음을 의미한다. 향후 한약제제에서 저해능을 나타내는 주된 성분을 규명하여 이 성분의 저해능과 저해 기전을 살피는 노력이 필요할 것이다.

• 공업화학
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• 제21권4호
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• pp.405-410
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• 2010

P25와 Dyesol $TiO_2$ (Titanium dioxide)를 사용하여 두께와 소성 온도가 다른 전극을 제조하여 염료감응형 태양전지(Dye Sensitized Solar Cell, DSSC)를 제조한 후 광 변환 효율을 측정하였다. 소성 전 후의 $TiO_2$ 작업 전극의 두께 변화는 FE-SEM을 사용하여 시편의 cross section을 확인하여 비교하였다. 또한 상대전극인 Pt의 소성 온도에 따른 DSSC의 효율 변화도 측정하였다. P25를 활용한 DSSC는 doctor blade로 1층으로 도포 후, $500^{\circ}C$에서 30 min 동안 소성한 작업 전극(${\sim}20.4{\mu}m$)과 $350^{\circ}C$에서 30 min 동안 소성한 Pt 상대 전극으로 제조한 셀이 3.8%의 광효율을 나타내었다. Dyesol $TiO_2$를 활용하여 1층으로 도포 후, $500^{\circ}C$에서 30 min 동안 소성한 작업전극(${\sim}9.1\;{\mu}m$)과 $450^{\circ}C$에서 30 min 동안 소성한 Pt 상대 전극으로 제조한 셀이 5.8%의 광 효율을 나타냄을 알았다.

• 약학회지
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• 제55권3호
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• pp.240-246
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• 2011

The present study was to investigate the effect of glipizide on the pharmacokinetics of losartan in rats. Losartan was administered intravenously (3 mg/kg) and orally (9 mg/kg) in the presence and absence of glipizide (0.3 and 1 mg/kg) to rats. The pharmacokinetic parameters of losartan were significantly altered by the presence of glipizide compared with the control group (given losartan alone). Presence of glipizide significantly (p<0.05, 0.3 mg/kg) increased the area under the plasma concentration-time curve (AUC) of losartan by 48.2% and peak plasma concentration ($C_{max}$) of losartan by 47.4%. Consequently, the absolute bioavailability (AB%) of losartan in the presence of glipizide was 38%, which was enhanced significantly (p<0.05) compared to that in the oral control group (25%). The relative bioavailability (RB%) of losartan increased by 1.18- to 1.48-fold in the presence of glipizide. However, there was no significant change in the peak plasma concentration ($T_{max}$) and terminal half-life ($T_{1/2}$) of losartan in the presence of glipizide. In contrast, glipizide did not affect the pharmacokinetics of intravenous losartan. In conclusion, the presence of glipizide significantly enhanced the oral bioavailability of losartan, implying that glipizide might be mainly to inhibit the cytochrome P450 (CYP) 2C9-mediated metabolism, resulting in reducing gastrointestinal and/or hepatic first-pass metabilism of losartan rather than in reducing P-glycoprotein-mediated efflux and renal elimination of losartan. Concurrent use of glipizide with losartan should require close monitoring for potential drug interactions.

• 대한의생명과학회지
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• 제18권1호
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• pp.1-9
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• 2012

Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

• Preventive Nutrition and Food Science
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• 제9권1호
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• pp.53-57
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• 2004

The purpose of this study was to investigate the effects of green tea catechin on mixed function oxidase system (MFO), lipofuscin contents, carbonyl value, oxidative damage and the antioxidative defense system in lung of microwave exposed rats. Experimental groups were divided to normal group and microwave exposed group. The microwave exposed groups were subdivided into three groups: catechin free diet (MW-0C) group, 0.25% catechin (MW-0.25C) group and 0.5 ％ catechin (MW-0.5C) group according to the levels of dietary catechin supplementation. The rats were irradiated with microwave at frequency of 2.45 GHz for 15 min. Experimental animals were sacrificed at 6th day after microwave irradiation. The contents of cytochrome P$_{450}$ contents in MW-0C group was increased to 95% , compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 16% and 31%, respectively, compared with MW-0C group. The activity of NADPH-cytochrome P$_{450}$ reductase in MW-0C group was increased to 44%, compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 12% and 17％, respectively, compared with MW-0C group. The activity of superoxide dismutase (SOD) in MW-0C group was decreased to 21 ％, compared with normal group. MW-0.25C and MW-0.5C group were significantly (p < 0.05) increased, compared with MW-0C group. The activity of glutathione peroxidase (GSHpx) in MW-0C group was significantly decreased, compared with normal group. MW-0.25C and MW-0.5C groups were recovered to the level of normal group. The thiobarbituric acid reactive substances (TBARS) content in MW-0C group was increased to 34 ％, compared with normal group. Catechin supplementation groups were maintained the level of normal group. The levels of caybonyl value in MW-0C group was increased to 21 ％, compared with normal group. MW-0.25C and MW-0.5C groups were reduced to 14% and 12%, respectively, compared with MW-0C group. The lipofuscin contents in MW-0C group were increased to 23.4 ％, compared with normal group. That of MW-0.5C group was significantly reduced, compared with MW-0C group. In conclusion, MFO system was activated and the formation of oxidized protein, lipofuscin was increased and antioxidative defense system was weakened of lung tissue in microwave exposed rats, thus oxidative damage was increased. But it was rapidly recovered to normal level by green tea catechin supplementation.n.

• 전자공학회논문지A
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• 제29A권3호
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• pp.87-95
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• 1992

The electrical characteristics of Al/TaS12TOS15T/SiOS12T/Si metal insulator-semiconductor (MIS) capacitors were studied. Tantalum pentoxide thin films on SiOS12T/p-Si substrate have been prepared by thermal oxidation at 450-$600^{\circ}C$ of sputter deposited tantalum films. Composition and structures of the tantalum oxide films were examined by AES and XRD. From the C-V analysis, dielectric constant of TaS12TOS15T which were oxidized at 55$0^{\circ}C$ for 1h in OS12T were 18-23, the value depending on the oxidation and annealing temperature. The leakage current density was found to be about 10S0-10T-10S0-9T A/cmS02T at an applied electric field of 1 MV/cm. The dielectric breakdown strength of the tantalum oxide films annealed at 100$0^{\circ}C$ were in the range from 2.5MV/cm to 2.8 MV/cm.

• Journal of Pharmaceutical Investigation
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• 제37권2호
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• pp.107-111
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• 2007

Epigallocatechin gallate (EGCC), a flavonoid, is the main component of green tea extracts. EGCG has been reported to be an inhibitor of P-glycoprotein (P-gp) and cytochrom P450 3A(CYP3A4). This study investigated the effect of long-term administration of EGCG on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats pretreated with EGCG (7.5 mg/hg) for 3 and 9 days. Compared to oral control group, the presence of EGCG significantly (p<0.01) increased the area under the plasma concentration-time curve (AUC) of verapamil by 102% (coad), 83.2% (3 days) and 52.3% (9 days), and the peak concentration $(C_{max})$ by 134% (coad), 120% (3 days) and 66.1% (9 days). The absolute bioavailability (A.B.%) of verapamil was significantly (p<0.01) higher by 8.4% (coad), 7.7% (3 days), 6.4% (9 days) compared to control (4.2%), and presence of EGCG was no significant change in the terminal half-life $(t_{1/2})$ and the time to reach the peak concentration $(T_{max})$ of verapamil. Our results indicate that EGCG significantly enhanced oral bioavailability of verapamil in rats, implying that presence of EGCG could be effective to inhibit the CYP3A4-mediated metabolism and P-gp efflux of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with EGCG or EGCG-containing dietary.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.255-260
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• 2011

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after oral administration of diltiazem (15 $mg{\cdot}kg^{-1}$) with ticlopidine (3 or 9 $mg{\cdot}kg^{-1}$). The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activities were also evaluated. Ticlopidine inhibited CYP3A4 enzyme activity in a concentrationdependent manner with a 50% inhibition concentration ($IC_{50}$) of 35 ${\mu}M$. In addition, ticlopidine did not significantly enhance the cellular accumulation of rhodamine-123 in NCI/ADR-RES cells overexpressing P-gp. Compared with the control (given diltiazem alone), ticlopidine significantly altered the pharmacokinetic parameters of diltiazem. The peak concentration ($C_{max}$) and the area under the plasma concentration-time curve (AUC) of diltiazem were significantly (9 $mg{\cdot}kg^{-1}$, p<0.05) increased in the presence of ticlopidine. The AUC of diltiazem was increased by 1.44-fold in rats in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$). Consequently, the absolute bioavailability (A.B.) of diltiazem in the presence of ticlopidine (9.3-11.5%) was signifi cantly higher (9 $mg{\cdot}kg^{-1}$, p<0.05) than that in the control group (8.0%). Although ticlopidine significantly (p<0.05) increased the AUC of desacetyldiltiazem, the metabolite-parent AUC ratio (M.R.) in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$) was significantly decreased compared to that in the control group, implying that ticlopidine could effectively inhibit the metabolism of diltiazem. In conclusion, the concomitant use of ticlopidine significantly enhanced the oral bioavailability of diltiazem in rats by inhibiting CYP3A4-mediated metabolism in the intestine and/or liver rather than by inhibiting intestinal P-gp activity or renal elimination of diltiazem.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.194-199
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• 2002

Many oxidative metabolites of tetrahydrocannabinols (THCs), active components of marijuana, were pharmacologically active, and 11-hydroxy-THCs, 11-oxo-${\Delta}^8$-THC, 7-oxo-${\Delta}^8$-THC, 8$\beta$, 9$\beta$-epoxyhexahydrocannabinol (EHHC), 9$\alpha$, l0$\alpha$-EHHC and 3'-hydroxy-${\Delta}^9$-THC were more active than THC in pharmacological effects such as catalepsy, hypothermia and barbiturate synergism in mice. Cannabidiol (CBD), another major component, was biotransfomred to two novel metabolites, 6-hydroxymethyl-${\Delta}^9$-THC and 3-pentyl-6, 7, 7a, 8, 9, lla-hexahydro-I, 7-dihydroxy-7, 1O-dimethyldibenzo[b, d]oxepin (PHDO) through 8R, 9-epoxy-CBD and 85, 9-epoxy-CBD, respectively. Both metabolites exhibited some pharmacological effects comparable to d9 - THe. Cannabinol (CBN), the other major component, was mainly metabolized to ll-hydroxy-CBN by hepatic microsomes of animals including humans. The pharmacological effects of the metabolite were higher than those of CBN demonstrating that II-hydroxylation of CBN is metabolic activation pathway of the cannabinoid as is the case in THCs. Tolerance and reciprocal cross-tolerance developed to pharmacological effects d8 - THC and ll-hydroxy-d8-THC , and the magnitude of tolerance development produced by the metabolite was significantly higher than that by d8-THC. The results indicate that ll-hydroxy-d8-THC has an important role not only in the pharmacological effects but also its tolerance development of d8 - THe. THCs and their metabolites competed to the specific binding of CP-55, 940, an agonist of cannabinoid receptor, to synaptic membrane from bovine cerebral cortex. The Ki value of THCs and their metabolites were closely paralleled to their pharmacological effects in mice. A novel cytochrome P450 (cyp2c29) was purified and identified as a major enzyme responsible for the metabolic activation of d8-THC at the II-position in the mouse liver. cDNA of CYP2C29 was cloned from a mouse cDNA library and its sequence was determined. The oxidation mechanism of THC by cyp2c29 was proposed.

• Advances in Energy Research
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• 제8권4호
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• pp.223-231
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• 2022

An ex-situ gravitational fixed bed pyrolysis reactor was used over Al₂O₃ supported Ni₂P based catalyst with various Ni/P molar ratios (0.5-2.0) and constant nickel loading of 5.37 mmol/g Al₂O₃ to determine the hydrodeoxygenation of rubberwood sawdust (RWS) at atmospheric pressure. The 3D catalysts formed were characterized structurally as well as acidic properties were determined by hydrogen-temperature programmed reduction (TPR). The Ni₂P phase formed completely on Al₂O₃ for 1.5 Ni/P ratio, although lesser crystallite sizes of Ni₂P were seen at Ni/P ratios less than 1.5. Additionally, it was shown that when nickel loading level increased, acidity increased and specific surface area dropped, probably because nickel phosphate is not easily converted to Ni₂P. When Ni/P ratio was 1.5, Ni₂P phase fully formed on Al₂O₃. The catalytic activity was explained in terms of impacts of reaction temperature and Ni/P molar ratio. At relatively high temperature of 450℃, the high-value deoxygenated produce was predominantly composed of n-alkanes. Based on the findings, it was suggested that hydrogenolysis, hydrodeoxygenation, dehydration, decarbonylation, and hydrogenation are all part of mechanism underlying hydrotreatment of RWS. In conclusion, the synthesized Ni₂P/ Al₂O₃ catalyst was capable of deoxygenating RWS with ease at atmospheric pressure, primarily resulting in long chained (C₉-C₂₄) hydrocarbons and acetic acid.