• Title/Summary/Keyword: p-gp

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Expression of Human Thrombopoietin in Insect Cells by Polyhedrin-gp64 Dual Promoter-Based Baculovirus Vector System

  • Koh, Yeo-Wook;Park, Sang-Kyu;Kim, Kun-Soo;Kim, Seong-Ryong;Lee, Jeong-Kug;Yang, Jai-Myung
    • Journal of Microbiology and Biotechnology
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    • v.9 no.3
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    • pp.318-322
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    • 1999
  • A new baculovirus transfer vector (pPGP404) was constructed to increase the expression level of human thrombopoietin (hTPO) in insect cells. In pPGP404, hTPO was cloned next to the AcNPV polyhedrin-gp64 dual promoter and the leader sequence of hTPO was substituted with that of gp64. A recombinant baculovirus, AcPGP404, was constructed by using pPGP404 as a transfer vector. hTPO was expressed in AcPGP404-infected TN5 cells and it was observed that the expression levels of hTPO in TN5 cells increased three-fold ($6.0 {\mu}g/ml^{-1}$) compared to the level expressed under the control of the polyhedrin single promoter. These results indicate that the polyhedrin-gp64 dual promoter system would be useful for expression in large quantities of recombinant proteins in insect cells.

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Effects of Adamantyl Derivatives on Pharmacokinetic Behavior of Paclitaxel in Rats

  • Kim, Kyung Mi;Lee, Kyeong;Jang, Kyusic;Moon, Yae Seul;Lee, Hwa Jeong;Rhie, Sandy Jeong
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.553-558
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    • 2017
  • Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

Effects of Kaempferol, an Antioxidant, on the Bioavailability and Pharmacokinetics of Nimodipine in Rats

  • Park, Ji-Won;Choi, Jin-Seok;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.41 no.5
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    • pp.301-307
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    • 2011
  • The aim of this study was to investigate the effects of kaempferol on the pharmacokinetics of nimodipine in rats. Nimodipine and kaempferol interact with cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp), and the increase in the use of health supplements may result in kaempferol being taken concomitantly with nimodipine as a combination therapy to treat orprevent cardiovascular disease. The effect of kaempferol on P-gp and CYP3A4 activity was evaluated and Pharmacokinetic parameters of nimodipine were determined in rats after an oral (12 mg/kg) and intravenous (3 mg/kg) administration of nimodipine to rats in the presence and absence of kaempferol (0.5, 2.5, and 10 mg/kg). Kaempferol inhibited CYP3A4 enzyme activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of $17.1{\mu}M$. In addition, kaempferol significantly enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp. Compared to the oral control group, the area under the plasma concentration-time curve ($AUC_{0-\infty}$) and the peak plasma concentration ($C_{max}$) of nimodipine significantly increased, respectively. Consequently, the absolute bioavailability of nimodipine in the presence of kaempferol (2.5 and 10 mg/kg) was 29.1-33.3%, which was significantly enhanced compared to the oral control group (22.3%). Moreover, the relative bioavailability of nimodipine was 1.30- to 1.49-fold greater than that of the control group. The pharmacokinetics of intravenous nimodipine was not affected by kaempferol in contrast to those of oral nimodipine. Kaempferol significantly enhanced the oral bioavailability of nimodipine, which might be mainly due to inhibition of the CYP3A4-mediated metabolism of nimodipine in the small intestine and /or in the liver and to inhibition of the P-gp efflux transporter in the small intestine by kaempferol. The increase in oral bioavailability of nimodipine in the presence of kaempferol should be taken into consideration of potential drug interactions between nimodipine and kaempferol.

Studies on the cloning gp50 and gp63 genes of Pseudorabies virus(Shope strain) (Pseudorabies virus의 gp50과 gp63 유전자 클로닝에 관한 연구)

  • Kweon, Chang-hee;Song, Jae-young;Kim, Byoung-han;Lee, Jung-bok;Lee, jae-chin;An, Soo-hwan;Lee, Yong-soon;Susumu, Maeda
    • Korean Journal of Veterinary Research
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    • v.31 no.3
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    • pp.311-318
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    • 1991
  • The DNA fragment representing for Pseudorabies gp50 and gp60(Shope) was cloned by recombinant techniques. The viral DNA was extracted from the infected cells and digested with Bam HI. The 6.8 Kb of Bam HI fragment was isolated from agarose gel and further digested with Nde I followed by Klenow treatment. The blunt ended 4.9Kb fragment was cloned into pTZ18R plasmid vector. The upstream region of gp50 was further manipulated to remove its 5' promoter region and create EcoRl site for possible eukaryotic expression system. The result of partial sequencing of cloned DNA indicated that Shope strain showed 95% homology with gp50 of Rice strain.

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Characteristics and Purification of Bacteriocin Produced by Lactobacillus acidophilus GP4A (Lactobacillus acidophilus GP4A가 생산하는 박테리오신의 특성 및 정제)

  • Han, Gyeong-Sik;Joo, Gwan-Seok;Kim, Se-Heon
    • Journal of Dairy Science and Biotechnology
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    • v.17 no.1
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    • pp.1-10
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    • 1999
  • A bacteriocin produced by Lab. acidophilus GP4A isolated from fecal contents of pig was characterized. Lab. acidophilus GP4A produced a heat-stable and pH-resistant bacteriocin, which was hydrolyzed by trypsin and pepsin and active against various microorganisms. Lab. acidophilus GP4A produced bacteriocin at maximum rate when grown in MRS broth(pH 6.5${\sim}$7.5) at$37^{\cric}C$ or $40^{\cric}C$. The bacteriocin produced by Lab. acidophilus GP4A inhibited the growth of Lactobacillus delbrueckii subsp. lactis 4794 in early logarithmic phase. The bacteriocin was purified by ammonium sulfate precipitation and Octyl sepharose CL-4B column chromatography. The purification resulted in a final yield of 21.7% and a 13.6-fold increase in the specific activity.

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Replacing groundnut cake with gluten meals of rice and maize in diets for growing Sahiwal cattle

  • Malik, Tariq A.;Thakur, S.S.;Mahesh, M.S.;Yogi, R.K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.10
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    • pp.1410-1415
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    • 2017
  • Objective: This experiment investigated the effect of isonitrogenous replacement of groundnut cake (GNC) by rice gluten meal (RGM) and maize gluten meal (MGM) at 75% level on nutrient intake, apparent digestibility, growth performance and related blood constituents in growing Sahiwal cattle. Methods: Eighteen Sahiwal calves were divided into three groups, based on average body weight (87.24 kg) and age (6 to 12 mo), and treatments were assigned to the different groups randomly. The first group (GP-I) was kept as control and received GNC-based concentrate mixture. In second (GP-II) and third (GP-III) groups, 750 g/kg nitrogen (N) of GNC was substituted by RGM and MGM respectively, with similar forage:concentrate ratio (56:44). Results: The 90 days of experimental feeding revealed that intake of dry matter, crude protein and digestibility coefficients for all nutrients did not differ among groups. Furthermore, although N balance was greater ($p{\leq}0.05$) for GP-III than GP-I and GP-II, average daily gain was similar between GP-I and GP-II but greater ($p{\leq}0.05$) for GP-III. In addition, feed efficiency and related haematological variables did not differ due to treatments. Conclusion: Nutritional worth of GNC and RGM was highly comparable in terms of intake, digestibility and growth in growing calves. However, MGM was found to be more efficacious in improving growth rate than RGM at 75% replacement level of GNC protein.

Effect of Natural Compounds on P-glycoprotein Activity in Human Uterine Sarcoma Cells (인체 자궁암 세포에서 천연 성분이 P-당단백질의 활성에 미치는 영향)

  • Chung, Soo-Yeon;Go, Eun-Jung;Kim, Na-Hyung;Sung, Min-Kyung;Jang, Jung-Ok;Lee, Hwa-Jeong
    • Journal of Pharmaceutical Investigation
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    • v.35 no.4
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    • pp.249-254
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    • 2005
  • Multidrug resistance (MDR) of cancer cells is, at least in part, associated with the overexpression of P-glycoprotein (P-gp). Many studies have demonstrated that natural compounds obtained from fruits, vegetables, teas and medicinal plants may modulate P-gp activity. The objective of the present investigation was to examine the effect of seven natural compounds on the P-gp activity in human uterine sarcoma cell line, MES-SA/DX5. Daunomycin uptake was significantly increased by biochanin A and silymarin (p<0.0001) whereas it was reduced by morin (p<0.01). The efflux of daunomycin from the cells was significantly inhibited by biochanin A, morin, cephalotaxine, berberine (p<0.05) and silymarin (p<0.0001). Biochanin A, berberine and silymarin significantly decreased $IC_{50}$ value of daunomycin (p<0.05) while morin increased it (p<0.05). These results suggest that some natural compounds such as biochanin A and silymarin may inhibit P-gp function and can be developed as MDR reversing agents to improve the efficacy of chemotherapeutic drugs when administered concomitantly.

Effect of Feral Peach Sugar Extracts and Gomchwi Extracts on Physicochemical Properties and Shelf-Life of Woorimatdag Chicken Marinated with Red Pepper Sauce (개복숭아 당절임액 및 곰취 추출물이 우리맛닭 고추장 양념육의 이화학적 특성 및 저장성에 미치는 영향)

  • Yousung Jung;Dong-Jin Shin;Hye-Jin Kim;Hyo-Jin Jeong;Hee-Jeong Lee;Dongwook Kim;Aera Jang
    • Korean Journal of Poultry Science
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    • v.50 no.1
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    • pp.51-61
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    • 2023
  • This study was designed to evaluate the effects of feral peach (Prunus persica Batsch var. davidiana Max.) sugar extracts (peach extracts) and Gomchwi (Ligularia fischeri) extracts on physicochemical properties of Woorimatdag 1breast marinated with red pepper sauce during cold storage for 18 days. Experimental groups were divided into five groups; CON: marinated breast with basic red pepper sauce, GP15 and GP30: added with 15% and 30% of peach extracts into CON, respectively, GG5 and GG10: added with 5% and 10% of Gomchwi extracts into CON, respectively. Moisture and fat contents of GP30 were lower than those of CON, GG5, and GG10 (P<0.05). Cholesterol content of GP15 was similar to that of CON, while it was lower than the other treatments. GP15 and GP30 showed significantly lower pH than the others. Especially, GP30 showed significantly lower total aerobic bacteria count than other treatment on day 10. During storage, peach and Gomchwi extracts were not significantly effect on meat shear force. Overall acceptability of GP15 was higher than that of GG10 at day 10 and 15 (P<0.05). These results indicated that the treatment of peach extracts has a tendency to improve the storage stability maintaining the sensory preference of marinated Woorimatdag 1 breast compared to Gomchwi extracts. Further study would be needed to identify the specific flavor-enhancing factors of GP treatments.

Conformation of Group "a" Epitope in Hepatitis B Surface Antigen

  • Chun, Mun-Ho;Park, Won-Bong;Bok, Jin-Woo;Kim, Ha-Won;Choi, Eung-Chil;Kim, Byong-Kak
    • Archives of Pharmacal Research
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    • v.15 no.4
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    • pp.347-355
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    • 1992
  • To elucidate structure of group "a" epitope, mouse antibodies that express idiotype monoclonal antibody and anti-idiotype monoclonal antibody against the group specific "a" determinant were purified by hydroxyapatite column. To obtain hepatitis B surface antigens (HBsAg). HBsAg positive blood was sequencially purified by ammonium sulfate precipitation, hydroxyapatite, sepharose 4B column chromatography and ultracentrifugation. The major protein (p25) and glycoprotein (gp30) of HBsAg were isolated by concanavalin-A-sepharose 4B. The ability of p25-gp30 among the HBsAg to inhibit the idiotype-anti-idiotype reaction was dependent on conformation, since reduced and alkylated p25-gp30 virtualy lost their inhibitory capacity when compared to native HBsAg. The data suggest that hepatitis B antigen is a conformational antigen critically dependent upon the disulfide bonds of p25-gp30.

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Evaluation of Three Pork Quality Prediction Tools Across a 48 Hours Postmortem Period

  • Morel, P.C.H.;Camden, B.J.;Purchas, R.W.;Janz, J.A.M.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.2
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    • pp.266-272
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    • 2006
  • Numerous reports have evaluated the predictive ability of carcass probes for meat quality using measurements taken early postmortem or near 24 h. The intervening time period, however, has been largely ignored. In this study, the capacity of three probes [pH, electrical conductivity (EC), and grading probe light reflectance (GP)] to predict pork longissimus muscle quality (drip and cooking losses, Warner-Bratzler shear, $L^*$, n = 30) was evaluated at 45 min, 90 min, 3, 6, 12, 24, and 48 h postmortem. The strongest relationships were observed between cooking loss and 6 h EC and GP ($R^2$ = 0.66, 0.72), and $L^*$ and GP ($R^2$ = 0.57-0.66, 12-48 h). pH was most valuable early postmortem ($R^2$ = 0.63, 90 min with cooking loss). GP at 6 h most effectively ($R^2$ = 0.84) predicted a two factor (cooking loss+$L^*$) meat quality index. Results emphasize the predictive value of measures taken between 3 and 12 h postmortem.