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The journal of applied pharmacology : the official... 15건

  1. [국내논문]   Protective Effect of Brazilin on Cisplatin Nephrotoxicity  

    Kong, Jae-Myeong ; Seo, Kyung-Won ; Choung, Se-Young
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 103 - 107 , 1994 , 1225-6110 ,

    초록

    Cisplatin is one of the most effective antitumor agents currently available for cancer therapy. However, its clinical use has been limited by its severe side effects, especially nephrotoxicity. Therefore, brazilin, which has a radical scavenging effect, was given intraperitoneally to evaluate the effect on cisplatin nephrotoxicity in rats. Remarkable protective effects against nephrotoxicity of cisplatin were observed when brazilin was administered to rats simultaneously with cisplatin. Hepatotoxicity induced by combination treatment of cisplatin and brazilin was evaluated by measuring serum glutamic pyruvate transaminase and serum glutamic oxalate transaminase. Combination treatment did not affect the levels of sGPT and SGOT, and any combination treatment did not induce metallothionein in kidney. Brazilin which has radical scavenging effect directly reduced nephrotoxicity of wisplatin in vivo. Thus, it seems that nephrotoxicity of cisplatin was caused by free radicals. The present results Indicate that brazilin, when it is given with cisplatin, may provide protection against cisplatin nephrotoxicity in rats.

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  2. [국내논문]   Studies on Hypersensitivity of Recombinant Hepatitis B Vaccine (LBD-008) in Mice and Guinea pigs  

    Park, Jong-Il ; Ha, Chang-Su ; Han, Sang-Seop
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 108 - 113 , 1994 , 1225-6110 ,

    초록

    Toxicity study of recombinant hepatitis B vaccine (LBD-008), a newly developed drug for acute and chronic hepatitis, was investigated in mice and guinea pigs. 1. Mice showed no production of antibodies against LBD-008 inoculated with aluminum hydroxide gel (Alum) as an adjuvant, judged by the heterologous anaphylaxis (PCA) test using rats. On the other hand, antibodies against ovalbumin (OVA) inoculated with alum were definitely detected. 2. In the studies with guinea pigs, both the inoculation of LBD-008 only and of LBD-008 with complete Freund's adjuvant (CFA) as an adjuvant did not produce positive reactions in any of homologous active systemic anaphylaxis (ASA). On the other hand, the inoculation of ovalbumin with complete Freund's adjuvant (CFA) produced positive reaction in both of PCA and ASA. 3. These findings suggested that LBD-008 has no antigenic potential in mice or guinea pigs.

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  3. [국내논문]   쥐 심실에서 Digitalis Receptor Desensitization에 관한 연구  

    이신웅 (영남대학교 약학대학 ) , 이정수 (영남대학교 약학대학 ) , 장태수 (영남대학교 약학대학)
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 114 - 119 , 1994 , 1225-6110 ,

    초록

    [ $^3$ H]Ouabain binding parameters ( $K_{D}$ and $B_{max}$ ) to control rat ventricular strips and Langendorff preparations which were not previously exposed to ouabain were compared with those to both preparations that had been first exposed to a complete ouabain dose range of dose-response curve (10 $^{-8}$ to 10 $^{4}$ M). In rat ventricular strips and Langendorff perfused heart preparations, cumulative dose-response curves of ouabain revealed biphasic positive inotropic effects, a "low-dose" effect and a "high-dose" effect with E $d_{50}$ values of 0.5 $\mu$ M and 35 $\mu$ M ouabain, respectively. The "low-dose" effect in ventricular strip disappeared or was diminished significantly when the ouabain dose-response curve was repeated after the washout of the effects of the first dose-response curve, whereas there were no significant differences in the maximal "high-dose"effect in both exposures to oubain. However, both of the control and ouabain-preexposed Langendorff perfused hearts revealed the same low-dose effects. The $K_{D}$ value for [ $^3$ H] ouabain binding and the ouabain binding site concentration ( $B_{max}$ ) estimated by [ $^3$ H]ouabain displacement assay in control preparations were 230 nM and 2 pmol/mg protein, respectively. [ $^3$ H]Ouabain binding parameters were not changed by repeated exposure to high concentrations of ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site ( $\alpha$ $_2$ isoform).).).).).

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  4. [국내논문]   Sandwich ELISA 방법을 이용한 생물공학의약품에 잔류하는 숙주유래단백질의 검출법개발  

    성혜윤 (국립보건원 ) , 최규실 (국립보건원 ) , 김창민 (국립보건원 ) , 민홍기 (국립보건원 ) , 용군호 (국립보건안전연구원)
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 120 - 125 , 1994 , 1225-6110 ,

    초록

    We obtained the total protein antibodies of Saccharomyces cerevisiae KCTC 1720 and Escherichia coli K-12 from the rabbit and the guinea pig to determine the host-derived proteins which may be remained in biotechnological products. The protein concentration of rabbit antibodies was 4.05 mg/mι in the case of yeast, 7.14 mg/mι in the case of E. coli and that of guinea pig antibodies was 1.90 mg/mι in the case of yeast, 7.17 mg/mι in the case of E. coli, respectively. To determine remained host-derived proteins in biotechnological products which produced by the hosts, S. cerevisiae or E. coli, we used a sandwich enzyme linked immunosorbent assay method in 96 well microplate. When the method applied to determine the remained host-derived proteins in commercial biotechnological products, it detected less than 3.5 ng/vial in human growth hormone, less than 1 ng/vial in hepatitis B vaccine and interferon- ${\gamma}$ and 2~23 ng/vial in interferon- $\alpha$ . The method can be used to determine the remained host-derived protein in biotechnological products.

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  5. [국내논문]   Immunopotentiating and Antitumor Activities of Purified pectins and Polysaccharides from Trichosnnthes Rhizoma and Taraxii Herba   피인용횟수: 1

    Park, Soo-Wan ; Chung, Yeoun-Bong ; Kim, Hye-Kyung ; Lee, Chung-Kyu
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 126 - 130 , 1994 , 1225-6110 ,

    초록

    Water-soluble pectins isolated from Trichosanthes Rhizoma and Taraxii Herba and their deproteinized polysaccharides were purified through DEAE cellulose column and were applied to immunopotentiating and antitumor studies to clarify the nature of their activities of our previous reports. As the results of works, the lectins and deproteinized polysaccharides increased the number of circulating leukocytes and total peritoneal cells. And they markedly elevated the lowered production of antibody and reactivity of T Iymphocyte in tumor-bearing mice, which were rapidly recovered by discontinuance of sample treatments. They also decreased the growth of Sarcoma 180 solid tumor in mice.

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  6. [국내논문]   Effect of Ginsenoside on Basal and Nitro-L-Arginine Suppressed Nitric Oxide Production in Rat Kidney  

    Kim, Hye-Young ; Han, Sang-Won
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 131 - 135 , 1994 , 1225-6110 ,

    초록

    The effect of ginsenoside (GS) from Panax ginseng on basal and nitro-L-arginine suppressed nitric oxide (NO) production was studied in rat kidney. NO production was determined by conversion to [ $^{14C}$ ]=L-citrulline from [ $^{14C}$ ]-L-arginine both in whole kidney and three renal segments; glomerulus, cortex excluding glomerulus (cortex-) and medulla. Nitro-L-arginine (total dose of 30 mg/kg/3 days, i.p.) significantly reduced NO production in whole kidney, which was prevented by GS pretreatment (30 mg/kg/3 days, i.p.). Relative high dose of GS (120 mg/kg/4 days, i.p..) selectively increased NO production in glomerulus and cortex-. Protein content, on wet weight basis, in cortex- and glomerular DNA content were significantly reduced by GS. Our results confirm the existence of constitutive nitric oxide synthase in kidney and it seems that target nephron segment for volume expansion due to GS'NO-mediated vasodilation and for NO production stimulated by GS is cortex including glomerulus.lus.

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  7. [국내논문]   Another Evidence for Nitric Oxide as Mediator of Relaxation of Isolated Rabbit and Human Corpus Cavernosum  

    Chang, Ki-Churl
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 136 - 140 , 1994 , 1225-6110 ,

    초록

    To prove the hypothesis that NO- and N $O_2$ -carrying molecules potentiate photorelaxation by generating NO, investigation was carried out using isolated rabbit and human corpus cavernosum. Corporal smooth muscle, in the presence or absence of endothelium, relaxed only slightly upon ultraviolet light (366 nm) irradiation. But, NO-and/or N $O_2$ -containing compounds such as streptozotocin and $N^{G}$ -nitro-L-arginine methyl ester significantly (p $N^{G}$ -nitro-D-arginine methyl ester, known to lack inhibitory action on NO synthase, showed concentration-dependent potentiation of the photorelaxation. Oxygen radical generating system via copper+ascorbic acid and guanylate cyclase inhibitor, methylene blue, significantly (p $N^{G}$ -nitro-L-arginine methyl ester and $N^{G}$ -nitro-D-arginine methyl ester, in a concentration and exposure time dependent manner. These observations indicate that NO is a potent relaxant of rabbit and human corpus cavernosum and further support the hypothesis that NO is released by photolysis from NO- and N $O_2$ -carrying molecules.lecules.

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  8. [국내논문]   간장내 허혈 및 재관류시 약물대사 효소계의 지질 과산화에 관한 연구  

    이선미 (성균관대학교 약학대학 ) , 박미정 (성균관대학교 약학대학 ) , 이상호 (성균관대학교 약학대학 ) , 박두순 (성균관대학교 약학대학 ) , 조태순 (성균관대학교 약학대학)
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 141 - 148 , 1994 , 1225-6110 ,

    초록

    This study was done to determine whether specific alterations exist in hepatic microsomal function after varying periods of ischemia (IS) and reperfusion (RP) during microsomal lipid peroxidation occurs. Rats were pretreated with $\alpha$ -tocopherol to inhibit lipid peroxidation or with vehicle (soybean oil). Control animals were time-matched sham-ischemic animals. Four groups of animals were studied: Group 1 (sham), group 2 (30 mins IS), group 3 (60 mins IS) and group 4 (90 mins IS). After 1, 5 or 24 hr of reperfusion, liver microsomes were isolated and cytochrome P-450s were studied. In all vehicle-treated ischemic rats, serum ALT levels peaked at 5 hr and were significantly reduced by $\alpha$ -tocopherol pretreatment. Similarly, microsomal lipid peroxidation was elevated in all vehicle-treated ischemic animal groups, but this elevation was prevented by $\alpha$ -tocopherol pretreatment. Cytochrome P-450 content was significantly decreased in both group 3 and group 4. In all vehicle-treated ischemic animal groups, aminopyrine N-demethylase activity was significantly decreased for the entire reperfusion period. $\alpha$ -Tocopherol inhibited reductions of cytochrome P-450 content and aminopyrine N-demethylase activity at both 1 hr and 5hr of reperfusion but did not affect the reduced levels of cytochrome P-450 content and aminopyrine N-demethylase activity at 24 hr of reperfusion. Aniline p-hydroxylase activity was significantly decreased in group 4, whereas it was increased in group 3. These decreases and increases were prevented by $\alpha$ -tocopherol pretreatment. Our finding suggests that abnormalities in microsomal drug metabolizing function occur during hepatic ischemia and reperfusion in vivo and this is attributed to microsomal lipid peroxidation.

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  9. [국내논문]   Anti-allergic and Anti-inflammatory Actions of Cimicifuga heracleifolia: Partial Purification of Active Components  

    Kim, Young-Ran ; Park, Soo-Hyung ; Kim, Kyeong-Man
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 149 - 154 , 1994 , 1225-6110 ,

    초록

    Anti-allergic and anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were evaluated in mice and rats. Several criteria were employed to assess the anti-allergic and anti-inflammatory actions of Cimicifuga heracleifolia, such as hyaluronidase activity, mediators-induced vascular permeability changes, 48 hour homologous passive cutaneous anaphylaxis (PCA) histamine release from mast cells, and the carrageenan-induced rat paw edema. To further characterize the active components, the water extract was either extracted with organic solvent or fractionated according to molecular weight, and each fraction was tested for some of anti-allergic parameters. Hyaluronidase activities, both in activating and in activated states, were significantly inhibited by the water extract of Cimicifuga heracleifolia and by some of its subfractions, molecular weight less than 1,000. The water extracts (50~400 mg/kg) significantly inhibited 48 hr homologous PCA and vascular permeability changes induced by chemical mediators (histamine, serotonin, and leukotriene $C_4$ ) in mice. In the case of histamine-induced vascular permeability changes, more extensive studies were conducted; water extract was either fractionated according to molecular weight or extracted with butanol. Anti-histamine actions were observed only from the water layer, and these active components were of the molecular weight less than 1,000. These anti-allergic actions were observed mainly from mice than from rats. On the other hand, anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were significant in rats.

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  10. [국내논문]   Inhibition of HIV-1 Pretense by Novel Dipeptide Isosteres Containing 2-Isoxazoline or $\alpha$-Hydroxy Ketomethylene  

    Kim, Do-Hyung ; Park, Kwan-Yong ; Chung, Yong-Jun ; Kim, Byeang-Hyean
    The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology v.2 no.2 ,pp. 155 - 160 , 1994 , 1225-6110 ,

    초록

    Human immunodeficiency virus type 1 (HIV-1) protease is essential for the replication of the virus and it is therefore an attractive target for antiviral drugs of HIV-1. Several dipeptide isosteres containing 2-isoxazoline or $\alpha$ -hydroxy ketomethylene have been synthesized and their inhibitory effects on the HIV-1 protease examined. The enzymatically active HIV-1 protease was purified to homogeniety from E. coli transformed with a recombinant plasmid (pMAL-pro) containing the entire gene encoding the protease. The purified protease had the substrate specificity with Km value of 9.8 $\mu$ M when an undecapeptide His-Lys-Ala-Arg-Val-Leu-(p-nitro)Phe-Glu-Ala-Nle-Ser-amide was used as a substrate, and the products from the substrate after specific cleavage by HIV-1 protease were analyzed by HPLC. The synthetic compounds containing dipeptide isosteres showed specific inhibitory effects while a dipeptide isostere containing an isoxazoline ring inhibited the HIV-1 protease competitively with Ki value of 500 $\mu$ M. Even if the inhibition effects of HIV-1 protease were not very high, these novel dipeptide isosteres can be used as key structural moieties for developing specific inhibitors of HIV-1 protease.

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