• Title/Summary/Keyword: 약제 상호작용

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Application and Prospects of Molecular Imaging (분자영상의 적용분야 및 전망)

  • Choi, Guyrack;Lee, Sangbock
    • Journal of the Korean Society of Radiology
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    • v.8 no.3
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    • pp.123-136
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    • 2014
  • In this paper, we study to classify molecular imaging and applications to predict future. Molecular imaging in vivo at the cellular level and the molecular level changes taking place to be imaged, that is molecular cell biology and imaging technology combined with the development of the new field. Molecular imaging is used fluorescence, bioluminescence, SPECT, PET, MRI, Ultrasound and other imaging technologies. That is applied to monitoring of gene therapy, cell tracking and monitoring of cell therapy, antibody imaging, drug development, molecular interaction picture, the near-infrared fluorescence imaging of cancer using fluorescence, bacteria using tumor-targeting imaging, therapeutic early assessment, prediction and therapy. The future of molecular imaging would be developed through fused interdisciplinary research and mutual cooperation, which molecular cell biology, genetics, chemistry, physics, computer science, biomedical engineering, nuclear medicine, radiology, clinical medicine, etc. The advent of molecular imaging will be possible to early diagnosis and personalized treatment of disease in the future.

Lethal Effects of Radiation and Platinum Analogues on Multicellular Spheroids of HeLa Cells (HeLa 세포의 Spheroid에 대한 방사선과 Platinum 유사체의 치사 효과)

  • Hong, Seong-Eon
    • Radiation Oncology Journal
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    • v.7 no.2
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    • pp.149-156
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    • 1989
  • Multicellular tumor spheroids of HeLa cells have been grown in a static culture system. Samples of spheroids were exposed for 2 h to graded concentration of cis-platinum and its analogue, carboplatin, and then response assayed by survival of clonogenic cells. The purpose of present experiment is to clarify the effectiveness of these platinum compounds and to evaluate intrinsic radiosensitivity of cells using spheroids of HeLa cells as an experimental in vitro model. Variations of the drug sensitivity of monolayers as well as spheroids were also evaluated in cell-survival curves. In cis-platinum concentration-survival curve, there was a large shoulder extending as far as $Cq=3.4{\mu}M$, after which there was exponential decrease in survival curve having a Co Value of $1.2{\mu}M$ in spheroids. While the Co for the spheroids was essentially no significant change, but Cq value was larger than that of monolayers. This suggest that the effect of cis-platinum is greater En the monolayer with actively proliferaing cells than hypoxic one. In the carboplatin concentration-survival curves, the Co value of spheroids was $15.0{\mu}M$ and the ratio with the Co from monolayer cell $(32.5{\mu}M)$ was 0.40, thus indicating that the spheroids had a greater sensitivity to carboplatin than monolayers. Therefore, the effect of carboplatin is mainly on the deeper layers of spheroids acting as hypoxic cell sensitizer. The enhanced effect was obtained for monolayer cells using combined X-ray and carboplatin treatment 2 hours before irradiation. The result shown in isobologram analysis for the level of surviving fraction at 0.01 indicated that the effect of two agents was trusty supra-additive. From this experimental data, carboplatin has excited much recent interest as one of the most promising, since it is almost without nephrotoxicity and causes less gastrointestinal toxicity than cis-platinum. Interaction between carboplatin and radiation might play an important role for more effective local tumor control.

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Drug Interaction between Ketoconazole and Paclitaxel in Rats (케토코나졸과 파크리탁셀과의 약물상호작용)

  • Choi, Jun-Shik;Park, Bok-Soon
    • Journal of Pharmaceutical Investigation
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    • v.33 no.3
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    • pp.223-227
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    • 2003
  • The purpose of this study was to investigate the effect of ketoconazole (20 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (40 mg/kg) orally coadministered in rats. The plasma concentration of paclitaxel in combination with ketoconazole was significantly (p<0.05) increased from 8 hr to 24 hr compared to that of control. Area under the plasma concentration-time curve (AUC) of paclitaxel with ketoconazole was significantly (coadministration p<0.05, pretreatment p<0.0l) higher than that of control. Peak concentration $(C_{max})$ of paclitaxel pretreated with ketoconazole were significantly (p<0.05) increased compared to that of control. Time to peak concentation $(T_{max})$ of paclitaxel pretreated with ketoconazole were significantly (p<0.05) shorter than that of control. Half-life at elimination phase $(t_{1/2{\beta}})$ of paclitaxel pretreated with ketoconazole was significantly (p<0.05) prolonged compared to that of control. Based on these results, it might be due to both inhibition of the enzyme cytochrome P450 and p-glycoprotein, which engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.

Pyriproxyfen Inhibits Hemocytic Phagocytosis of the Beet Armyworm, Spodoptera exigua (파밤나방(Spodoptera exigua)의 혈구세포 식균반응에 대한 피리프록시펜의 억제효과 Nalini Madanagopal)

  • Madanagopal, Nalini;Lee, Yong-Joon;Kim, Yong-Gyun
    • The Korean Journal of Pesticide Science
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    • v.11 no.3
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    • pp.164-170
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    • 2007
  • The concept of innate immunity in insects which refers to the first line of host defense constitutes the humoral and cellular components which are involved in recognition and actively participate in the elimination of the intruding foreign micro- or macro-organisms. Several recent studies suggest that juvenile hormone (JH) modulates the cellular immune reactions in response to pathogen. In this study, pyriproxyfen (a JH agonist as an insect growth regulator) was tested in its any inhibitory effect on the immune reactions of the beet armyworm, Spodoptera exigua. To this end, five different hemocyte morphotypes of final instar S. exigua were identified by phase contrast microscopy. Plasmatocytes and granular cells, which constitute about 90% of the total hemocyte count, were prominently distinguished based on their basophilic/acidophilic nature using Giemsa stain. The role of pyriproxyfen on the functional ability of hemocytes was analyzed using FITC-labeled Providencia vermicola for the phagocytic potential of the hemocytes. Both granular cells and plasmatocytes exhibited phagocytosis behavior. Pyriproxyfen significantly inhibited the phagocytosis of both cell types, proposing its novel action as an immunosuppressant.

Pharmacokinetic Interaction between Diltiazem and Paclitaxel in Rats (딜티아젬과 파크리탁셀의 약물동태학적 상호작용)

  • Choi, Jun-Shik;Kim, Hyung-Joong
    • Journal of Pharmaceutical Investigation
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    • v.33 no.4
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    • pp.299-304
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    • 2003
  • The purpose of this study was to investigate the effect of coadministration (2.5, 10, 20 mg/kg) and 3 or 7 days-pretreatment (10 mg/kg) of diltiazem on the pharmacokinetic parameters of paclitaxel (50 mg/kg) given orally in rats. The plasma concentrations of paclitaxel coadministered or pretreated with diltiazem were significantly (p<0.05 at 20 mg/kg coadmin., p<0.05 at pretreat.) increased compared to that of control, from 0.5 hr to 24 hr. Area under the plasma concentration-time curve (AUC) of paclitaxel coadministered or pretreated with diltiazem was significantly (p<0.05 at 20 mg/kg coadmin., p<0.01 at pretreat.) higher than that of control. Peak concentrations $(C_{max})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg coadmn. and pretreat.) increased compared to that of control. Elimination rate constants $(K_{el})$ of paclitaxel with diltiazem were significantly (p<0.05 at 20 mg/kg and 7 days-pretreat.) reduced compared to those of control. Half-life $(t_{1/2})$ and mean residence time (MRT) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg ad 7 days-pretreat.) prolonged compared to those of control. Absolute bioavailability (AB%) of paclitaxel with diltiazem was significantly (p<0.05 at 20 mg/kg and 3 days-pretreat, p<0.01 at 7 days -pretreat.) increased compared to that of control. Based on these results, it might be considered that diltiazem may inhibit cytochrome $P_{450}$ and P-glycoprotein, which are respectively engaged in paclitaxel absorption and metabolism in liver and gastrointestinal mucosa.

Pharmacokinetic Interaction between Nifedipine and Quercetin in Rabbits (니페디핀과 켈세틴의 토끼에서의 약물동태학적 상호작용)

  • Han, Hyo-Kyung;Lee, Il-Kwun;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.34 no.4
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    • pp.283-288
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    • 2004
  • The pharmacokinetics of nifedipine was studied after oral coadministration of nifedipine (5 mg/kg) with quercetin (1.5, 7.5, 15 and 30 mg/kg, respectively) and 0.5 h or 3days pretreatment with quercetin (1.5 and 7.5mg/kg) in rabbits. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the plasma concentration of nifedipine, but not significant in coadministraiton. The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of nifedipine pretreated with quercetin were increased significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) compared to the control. By coadministration of quercetin, only 7.5 mg/kg of quercetin increased plasma AUC and $C_{max}$ of nifedipine significantly (p<0.05) compared to the control. Plasma AUC of intravenous nifedipine (1 mg/kg) is $4235\;{\pm}\;1192\;ng/ml{\cdot}hr$. Pretreatment of quercetin significantly (p<0.05, at 0.5 h; p<0.01, at 3 days) increased the absolute bioavailability (AB%) of nifedipine to 23.9-29.2% compared to the control (17.8%). Coadministration of quercetin showed no significant effect on the AB% of nifedipine except for 7.5 mg/kg. It is suggested that quercetin alters disposition of nifedipine by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of nifedipine should be adjusted when it is administered chronically with quercetin in a clinical situation.

Drug-Biomacromolecule Interaction (XIII)-Effect of ionic Strength, pH and Temperature on Binding of Cephalothin to Bovine Serum Albumin- (약물과 생체고분자 간의 상호작용(제 13보)-세파로친과 소혈청알부민의 결합에 미치는 이온강도, pH 및 온도의 영향)

  • Kim, Chong-Kook;Lim, Yun-Su;Yang, Ji-Sun;Jeong, Eun-Ju
    • Journal of Pharmaceutical Investigation
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    • v.19 no.3
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    • pp.163-171
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    • 1989
  • To investigate the protein binding characteristics of cephalothin, the effects of ionic strength, pH and temperature on the binding of cephalothin to bovine serum albumin (BSA) were studied by UV difference spectrophotometric method. With increasing ionic strength at constant PH and temperature, association constant decreased, but the number of binding sites sites was about 2 constantly. It may be deduced that the binding process is not only due to electrostatic forces. And the increased association constant at high ionic strength is explained by conformational changes of BSA from complex to subunits. The pH effect on the affinity of interaction indicated that the binding affinity of drug is higher in the neutral region than in the alkaline region. And, at high pH value, the number of binding sites decreased from 2 to 1 because of the conformational changes of BSA in alkaline region. The decrease in binding affinity of BSA to drug with increasing temperature was characteristic of an exothermic reaction. And the negative sign of ${\Delta}G^{\circ}$ meant that the binding process occurs spontaneously under the experimental conditions. In cephalothin-BSA complex formation, since the net enthalpy change value and entropy change value are positive, it is assumed that hydrophobic bindings are predominant in this binding process.

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Biorational Screening System Using Cyanobacteria(Anacystis nidulans $R_2$) for Searching the Photosynthetic Electron Transport Inhibitors (Cyanobacteria를 이용한 광합성 전자전달저해제의 생합리적 스크리닝)

  • Hwang, I.T.;Hong, K.S.;Cho, K.Y.;Yoshida, S.
    • Korean Journal of Weed Science
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    • v.13 no.2
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    • pp.81-88
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    • 1993
  • For searching the photosynthetic electron transport(PET) inhibitors, bio-rational screening system using thylakoid membranes extracted from wild and mutant cyanobacteria(Anacystis nidulans $R_2$) was developed. Generally, thylakoid membrane was more sensitive to the tested herbicides than the chloroplast from spinach in the Hill reaction. Higher resistant characteristics appeared in mutant D-5, Di-22 to diuron and mutant G-264 to atrazine as compared to wild type. To test the reaction of thylakoid membrane to herbicides, diuron and atrazine were applied simultaneously. Diuron and atrazine competed each other for binding with substituted amino acids, while diuron and dinoseb were non-competitive, and inhibiting activity was increased. Conclusively, bio-rational screening system using cyanobacteria was proved to be fast and efficient screening method for the development of PET inhibitors.

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Anatomical Difference in Selectivity between Paddy Rice and Weed Species by Mixture Use of Oxyfluorfen and Bensulfuron (Oxyfluorfen 및 Bensulfuron 조합처리(組合處理)에 의한 벼 및 수종(數種) 잡초종간(雜草種間)의 선택반응상(選擇反應相)의 해부학적(解剖學的) 비교연구(比較硏究))

  • Guh, J.O.;Chon, S.U.;Han, S.U.;Kuk, Y.I.
    • Korean Journal of Weed Science
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    • v.12 no.2
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    • pp.132-143
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    • 1992
  • The study was conducted to find out synergistic effects by interaction on the basis on anatomical changes between paddy rice and weed species by mixture use of oxyfluorfen and bensulfuron at 0, $10^{-6}$ and $10^{-4}$M, respectively. Tissues were sampled at 72 hrs after soaking treatment and prepared for light microscopic examination and sectioned longitudinally and transversely stem into $8{\mu}m$ thick. As the results of microscopic examination, the major response of treated plant involved rupture and constrict in mesophyll cells and epidermal cells, and shrinks in bundle sheath cells by oxyfluorfen and disorganization and swelling in meristems by bensulfuron. Anatomical changes in rice was the least affected by even high concentration and two herbicide mixtures, whereas Echinochloa crus-galli was severely disorganized in meristem regions and ruptured in epidermal cells by mixture use. Monochoria vaginalis was completely ruptured by any treatment concentrations and mixtures. Scirpus juncoides was considerably tolerant to both herbicides and their mixture and was similar to those that occur in rice. Perennial weed, Sagittaria pigmaea was observed vacuolation, non-nucleation of cell, and irregular cell layering but in mixture injury was slight. Cyperus serotinus was severely shrunk and ruptured by mixture treatment. Eventually anatomical variations in all weed species was shown synergistic effect by use of herbicide mixtures.

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Butachlor and Silicate Fertilizer Interaction to Rice (Butachlor와 규산질비료(珪酸質肥料)의 수도(水稻)에 대(對)한 상호작용(相互作用))

  • Oh, B.Y.;Ryang, H.S.;Shin, Y.H.
    • Korean Journal of Weed Science
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    • v.4 no.1
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    • pp.52-61
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    • 1984
  • Pot and laboratory tests were undertaken to investigate the influence of silicate fertilization on butachlor phytotoxicity to rice. Growth of rice seedlings at 150 ppm of $SiO_2$ was stimulated, while adverse effect was observed over 300 ppm of $SiO_2$ and growth reduction was enhanced with combination of butachlor and $SiO_2$ Rice growth in pot trial at 150kg/10a of silicate fertilization was not influenced by recommended amounts of butachlor and nitrofen, however, the growth of Seokwang byeo at 300kg/10a of silicate was markedly retarded by butachlor in the initial stage of growth. Growth reduction of Seokwang byeo caused by combined application of silicate and butachlor was recovered 50 days after herbicide application. Growth reduction from butachlor was not influenced by pH level and also degradation behaviors of butachlor in submerged soil was not altered by silicate fertilization. Adsorbed amount of butachlor on rice root was increased with addition of $SiO_2$ and its amount in Seokwang byeo was higher than that of Jinju byeo. Butachlor absorption by Seokwang byeo was accelerated by 150 ppm of $SiO_2$ applied simultaneously, but those effect was not encountered in Jinju byeo. Butachlor absorption of rice seedlings was also increased by 150 ppm of $K_2O$, while CaO hindered the absorption and $Na_2O$ had no effect on the absorption. Residual level of butachlor in Seokwang byeo treated with combined solution of butachlor and $SiO_2$ was continued higher than that with butachlor alone during 10 days after transplantation to culture solution.

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