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Archives of pharmacal research : a publication of ... 24건

  1. [국내논문]   Determination of Microviscosity and Location of 1,3-Di(1-pyrenyl) propane in Brain Membranes  

    Kang, Jung-Sook (Departments of Oral Biochemisrty and Molecular, College of Dentisty and Research Institute for Oral Biotechnology ) , Kang, In-Goo (Departments of Dental Pharmacology and Biophysics, College of Dentistry and Research Institute for Oral Biotechnology, Pusan University ) , Yun, Il (Departments of Dental Pharmacology and Biophysics, College of Dentistry and Research Institute for Oral Biotechnology, Pusan University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 1 - 6 , 1997 , 0253-6269 ,

    초록

    We determined the microviscosity of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex and liposomes of total lipids (SPMTL) and phospholipids (SPMPL) extracted from SPMV. Changes in the microviscosity induced by the range and rate of lateral diffusion were measured by the intramolecular excimerization of 1, 3-di(1-pyrenyl)propane (Py-3-Py). The microviscosity values of the direct probe environment in SPMV, SPMTL and SPMPL were 38.17, 31.11 and 27.64 cP, respectively, at $37^{\circ}C$ and the activation energies $(E_a)$ of the excimer formation of Py-3-Py in SPMV, SPMTL and SPMPL were 8.236, 7.448 amd 7.025 kcal/mol, respectively. Probe location was measured by polarity and polarizability parameters of the probe Py-3-Py and probe analogues, pyrene, 1-pyrenenonanol and 1-pyrenemethyl-3 ${\beta}$ -hydroxy-22, 23-bisnor-5-cholenate (PMC), incorporated into membranes or solubilized in reference solvents. There existed a good linear relationship between the first absorption peak of the $^1_a$ band and the polarizability parameter $(n^{2}-1)/(2n^{2}+1)$ .The calculated refractive index values for SPMV, SPMTL and SPMPL were close to 1.50, which is higher than that of liquid paraffin (n=l.475). The probe location was also determined by using a polarity parameter $(f-1/2f^{I})$ . Here f= $({\varepsilon}-1)/(2{\varepsilon}+1)$ is the dielectric constant function and $f^I=(n^2-1)/(2n^2+1)$ is the refractive index function. A correlation existed between the monomer fluorescence intensity ratio and the solvent polarity parameter. The probes incorporated in SPMV, SPMTL, and SPMPL report a polarity value close to that of 1-hexanol $({\varepsilon}=13.29)$ . In conclusion, Py-3-Py is located completely inside the membrane, not in the very hydrophobic core, but displaced toward the polar head groups of phospholipid molecules, e.g., central methylene region of aliphatic chains of phospholipid molecules.

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  2. [국내논문]   Effects of L-trans-pyrrolidine-2,4-dicarboxylate, a glutamate uptake inhibitor, on NMDA receptor-mediated calcium influx and extracellular glutamate accumulation in cultured cerebellar granule neurons.  

    Oh, S , Shin, C S , McCaslin, P P , Seong, Y H , Kim, H S
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 7 - 12 , 1997 , 0253-6269 ,

    초록

    Glutamate uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxylate (PDC, 20 muM) elevated basal and N-methyl-D-aspartate (NMDA, 100 muM)-induced extracellular glutamate accumulation, while it did not augment kainate (100 muM)-induced glutamate accumulation in cultured cerebellar granule neurons. However, pretreatment with PDC for 1 h significantly reduced NMDA-induced glutamate accumulation, but did not affect kainate-induced response. Pretreatment with glutamate (5 muM) for 1 h also reduced NMDA-induced glutamate accumulation, but did not kainate-induced response. Upon a brief application (3-10 min), PDC did neither induce elevation of intracellular calcium concentration ([Ca(2+)](i)) nor modulate NMDA-induced [Ca(2+)](i) elevation. Pretreatment with PDC for 1 h reduced NMDA-induced [Ca(2+)](i) elevation, but it did not reduce kainate-induced [Ca(2+)](i) elevation. These results suggest that glutamate concentration in synaptic clefts of neuronal cells is increased by prolonged exposure (1 h) of the cells to PDC, and the accumulated glutamate subsequently induces selective desensitization of NMDA receptor.

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  3. [국내논문]   Cytotoxicity and L-Amino Acid Oxidase Activity of Animal Venoms  

    Ahn, Mi-Young (Natural Products Research Institute, Seoul National University, Division of Toxicology, College of Pharmacy, Sungkyunkwan University ) , Lee, Byung-Mu (Division of Toxicology, College of Pharmacy, Sungkyunkwan University ) , Kim, Yeong-Shik (Natural Products Research Institute, Seoul National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 13 - 16 , 1997 , 0253-6269 ,

    초록

    The cytotoxicity of animal venoms (snakes, insects and marine animals) was measured against SNU-1 (stomach cancer cells) by dye uptake assay (MTT method). And also L-amino acid oxidase (AAO) activity of the venoms was compared. Among them, the venom from Ophiophagus hannah (king cobra) showed a strong AAO activity as well as a high potent cytotoxicity. Cytotoxic protein having a AAO was then partially purified by HPLC-GPC and two fractions (Fr. I and Fr. II) were collected. The $IC_{50}$ values of Fr. I and Fr. II were 0.19 ${\mu}g/ml$ and 1.36 ${\mu}g/ml$ , respectively. The results suggested that the cytotoxicity of king cobra venom may be due to its AAO activity.

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  4. [국내논문]   Evaluation of the in vivo Antithrombotic, Anticoagulant and Fibrinolytic Activities of Lumbricus rubellus Earthworm Powder  

    Hahn, Bum-Soo (Natural Products Research Institute,Seoul National University ) , Jo, You-Young (Natural Products Research Institute,Seoul National University ) , Yang, Kyung-Youl (Natural Products Research Institute,Seoul National University ) , Wu, Song-Ji (Natural Products Research Institute,Seoul National University ) , Pyo, Mi-Kyung (Natural Products Research Institute,Seoul National University ) , Yunchoi, Hye-Sook (Natural Products Research Institute,Seoul National University ) , Kim, Yeong-Shik (Natural Products Research Institute,Seoul National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 17 - 23 , 1997 , 0253-6269 ,

    초록

    A saline suspension of Lumbricus rubellus earthworm powder (EWP) was administered to rats (1 g/kg/day) orally for 15 days to evaluate an oral effectiveness for thrombotic disorders. Blood was drawn at 2-day interval after the administration. Several parameters for antithrombotic, anticoagulant and fibrinolytic activities were measured, including platelet aggregation, clotting time, plasmin activity and the levels of FDP (fibrin/fibrinogen degradation products), D-dimer, and t-PA antigen. It did not affect platelet aggregation induced by ADP and collagen but anticoagulant activity (aPTT and TT) was gradually increased to two-folds for the first 5 days of administration and back to normal. Fibrinolytic activity of euglobulin fraction was highest on the 11 th day after the administration. The level of FDP was elevated to be comparable to the positve control $ (5-10 {\mu}g/ml)$ after 9-day treatment. Oral administration of the EWP could also reduce the formation of venous thrombus induced with viper venom. Complete blood count (CBC) profiles were within normal ranges except for a slight increase in white blood cells after the oral administration for 15 days. These results suggested that the EWP may be valuable for the prevention and/or treatment of thrombotic diseases.

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  5. [국내논문]   Effects of diffusional barriers on the extent of presystemic and systemic intestinal elimination of drugs  

    Kwon, Young-Gil (Presystemic,Systemic,Intestine,Liver,Diffusional Diffusional barrier,Pharmacokinetics)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 24 - 28 , 1997 , 0253-6269 ,

    초록

    In the present study, a pharmacokinetic model to address the effects of the diffusional barrier between splanchnic bed and enterocytes on the extent of presystemic and systemic intestinal elimination of drugs was developed. The model is composed of five compartments, ie., gut lumen, enterocyte, splanchnic bed, liver and central compartments. The equations for various pharmacokinetic parameters important for estimating the quantitative differences between presystemic and systemic intestinal and hepatic elimination of drugs were derived. A simulation study demonstrated that the diffusions[ barrier present between splanchnic blood and enterocytes can have significant effects on oral bioavailability and systemic clearance of drugs. In conclusion, the model can be useful for a better understanding of the effects of diffusional barrier on the extent of administration-route dependent intestinal and hepatic elimination of drugs, especially those with high hydrophilicity and/or charge(s) under physiological conditions.

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  6. [국내논문]   Induction of Apoptosis in HepG2 Human Hepatocellular Carcinoma Cells by a Novel Derivative of Ursodeoxycholic Acid (UDCA)  

    Park, Yoo-Hoi (Department of Molecular Biology, Pusan National University ) , Kim, Jung-Ae (Department of Molecular Biology, Pusan National University ) , Baek, Jin-Hyen (Department of Molecular Biology, Pusan National University ) , Jung, Eun-Jin (Department of Chemistry, Pusan National Unversity ) , Kim, Tae-Hyong (Department of Chemistry, Pusan National Unversity ) , Suh, Hongsuk (Department of Chemistry, Pusan National Unversity ) , Park, Myung-Hwan (ResearchandDeveolopment Center, Daewoong Pharmaceuical Co. ) , Kim, Kyu-Won (Department of Molecular Biology, Pusan National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 29 - 33 , 1997 , 0253-6269 ,

    초록

    The effects of ursodeoxycholic acid (UDCA) and its novel derivative, named as HS-1030, on the proliferation of HepG2, human hepatocellular carcinoma cells were investigated. Whereas UDCA had no significant effect in a concentration range we have tested, HS-1030 inhibited the proliferation of HepG2 cells in a concentration dependent manner. Surprisingly, HS-1030 had no effect on the proliferation of Human Chang liver cell which is a normal liver cell line. We also found that proliferation-inhibitory effect of HS-1030 was due to the induction of apoptosis of HepG2 cells, which was confirmed by observing the internucleosomal DNA fragmentation and morphological changes (ie., cell shrinkage, nuclear condensation and the formation of apoptotic bodies). These results suggest that HS-1030 may be a good candidate as a drug for the treatment of liver cancer.

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  7. [국내논문]   Effect of Protease Inhibitors on Degradation of Recombinant Human Epidermal Growth Factor in Skin Tissue  

    Ryou, Hae-Won (College of Pharmacy, Sung Kyun Kwan University ) , Lee, Jang-Won (College of Pharmacy, Sung Kyun Kwan University ) , Kyung, Kyung-Ae (College of Pharmacy, Sung Kyun Kwan University ) , Park, Eun-Seok (College of Pharmacy, Sung Kyun Kwan University ) , Chi, Sang-Cheol (College of Pharmacy, Sung Kyun Kwan University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 34 - 38 , 1997 , 0253-6269 ,

    초록

    Recombinant human epidermal growth factor (rhEGF), a polypeptide of 53 amino acid residues, is subject to degradation by numerous enzymes, especially proteases, when it is applied on the skin for the treatment of open wound. Amastatin, aprotinin, bestatin, EDTA, EGTA, gabexate, gentamicin, leupeptin, and TPCK were investigated for the possible protease inhibitors, which may use to protect rhEGF from degradation by the enzymes in the skin. Skin homogenates containing protease inhibitors and rhEGF were incubated at $37^{\circ}C$ for 30 minutes. After the reaction was stopped with trifluoroacetic acid, the amount of rhEGF remaining in the sample was determined with an HPLC method. The percentages of rhEGF degraded, at the skin/PBS ratio of 0.25, in the mouse, rat, and human skin homogenate were 85%, 70%, and 46%, respectively. The degree of degradation of rhEGF in the cytosolic fraction was higher than that in the membrane fraction and these enzyme reactions were completed in 30 minutes. Bestatin, EGTA, and TPCK showed significant inhibitory effects on the degradation of rhEGF in the two fractions (p

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  8. [국내논문]   Effects of I.C.V. administration of ethylcholine aziridinium (AF64A) on the central glutamatergic nervous systems in rats  

    Ma, Young , Lim, Dong Koo
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 39 - 45 , 1997 , 0253-6269 ,

    초록

    Recombinant human epidermal growth factor (rhEGF), a polypeptide of 53 amino acid residues, is subject to degradation by numerous enzymes, especially proteases, when it is applied on the skin for the treatment of open wound. Amastatin, aprotinin, bestatin, EDTA, EGTA, gabexate, gentamicin, leupeptin, and TPCK were investigated for the possible protease inhibitors, which may use to protect rhEGF from degradation by the enzymes in the skin. Skin homogenates containing protease inhibitors and rhEGF were incubated at $37^{\circ}C$ for 30 minutes. After the reaction was stopped with trifluoroacetic acid, the amount of rhEGF remaining in the sample was determined with an HPLC method. The percentages of rhEGF degraded, at the skin/PBS ratio of 0.25, in the mouse, rat, and human skin homogenate were 85%, 70%, and 46%, respectively. The degree of degradation of rhEGF in the cytosolic fraction was higher than that in the membrane fraction and these enzyme reactions were completed in 30 minutes. Bestatin, EGTA, and TPCK showed significant inhibitory effects on the degradation of rhEGF in the two fractions (p

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  9. [국내논문]   Effects of I.C.V Administration of Ethylcholine Aziridinuim(AF64A) on the Central Glutamatergic Nervous Systems in Rats  

    Ma, Young (College of Pharmacy, Chonnam National University ) , Lim, Dong-Koo (College of Pharmacy, Chonnam National University)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 39 - 45 , 1997 , 0253-6269 ,

    초록

    Changes in glutamatergic nervous activities following intracerebroventricular (icv) administration of ethylcholine aziridinium (AF64A) were studied in rats. The levels of total glutamate, those of glutamate in cerebrospinal fluid (CSF) and in extracellular fluid (ECF) of striatum, the activities of glutamine synthetase (GS), glutaminase and glutamate dehydrogenase (GDH) and the specific binding sites of $[^3H]$ MK801 in striatum, hippocampus and frontal cortex were assessed a week after the infusion of AF64A (3 nmol) into lateral ventricle. The levels of total glutamate were significantly decreased in striatum, hippocampus and frontal cortex after AF64A treatment. Although the levels of glutamate in CSF weren't changed after AF64A treatment, the levels of glutamate in ECF of striatum were significantly decreased (62.6%). GS activities in striatum were significantly decreased. But, glutaminase activities in striatum were significantly increased. However, the activities of GS and glutaminase in frontal cortex and hippocampus weren't changed. Although GDH activities in frontal cortex were significantly decreased, those in striatum and hippocampus weren't altered. The striatal densities of $[^3H]$ MK 801 binding sites were increased without changes in its affinity. Also, the specific binding sites of $[^3H]$ MK801 were increased in frontal cortex but not in hippocampus. These results indicate that the glutamatergic nervous activities were altered with the infusion of AF64A into lateral ventricle. Furthermore, it suggest that the decreased levels of glutamate after AF64A treatment may affect the change in the other parameters of glutamatergic neuronal activities.

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  10. [국내논문]   The optimization of ELISA for methamphetamine determination : the effect of immunogen, tracer and antibody purification method on the sensitivity  

    Choi, Jeongeun (Doping Control Center, Korea Institute of Science and Technology ) , Choi, Myung-Ja (Doping Control Center, Korea Institute of Science and Technology ) , Kim, Choonmi (College of Pharmacy, Ewha Womans University ) , Cho, Young-Shik (Department of Diagnostic Products, Korea Green Cross Corporation ) , Chin, Jaeho (Doping Control Center, Korea Institute of Science and Technology ) , Jo, Young-Ah (Doping Control Center, Korea Institute of Science and Technology)
    Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea v.20 no.1 ,pp. 46 - 52 , 1997 , 0253-6269 ,

    초록

    To obtain more sensitive immunoassay for methamphetamine (MA) determination, the optimum condition of enzyme-linked immunosorbent assay (ELISA) was investigated in regard to immunogens, antibody purification methods and coating tracers. Activated MA, N-(4-aminobutyl)methamphetamine (4-ABMA), was conjugated with bovine serum albumin (BSA) or keyhole limpet hemocyanin (KLH) and used as immunogen. The antibodies were purified by protein G chromatography or various immunoaffinity chromatography-linked MA-protein ligands, such as MA-BSA, MA-KLH or MA-ovalbumin (OVA). Each purified antibody was characterized by means of sensitivity and cross-reactivity using the three MA-protein coating tracers, MA-BSA, MA-KLH and MA-OVA. The best sensitivity of each antibody was acquired with the MA-OVA tracer although the tracer concentration and the antibody titer level at optimum condition were varied. The antibody with high titer level did not always yield good sensitivity. At optimum condition, immunoaffinity chromatography-purified antibodies were better for sensitivity and for specificity than protein G-purified antibodies. The cross-reactivity of the purified antibodies seemed to be affected by immunogen structure and showed somewhat different patterns according to the immunoaffinity ligand utilized. These data show that the antibody purification method as well as choice of coating tracer and immunogen is essential for the sensitivity and specificity of EIA; the optimum condition for assay should be discovered using various methods and combinations.

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    Fig. 1 이미지

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