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위암종과 Epstein-Barr 바이러스와의 연관성에 대한 연구
심광용,김호영,김효열,백순구,권상옥,조미연,이창훈,이종인 건국대학교 의과학연구소 2004 건국의과학학술지 Vol.14 No.-
Objectives: Epstein-Barr virus (EBV) has been known to be linked to a spectrum of neoplastic conditions, including nasopharyngeal carcinoma, Burkitt's lymphoma, peripheral T-cell lymphoma and Hodgkin's disease. This study aims to investigate the association of EBV with gastric carcinoma in Korea. Methods: Fifty-three cases of gastric adenocarcinoma were studied for evidence of EBV infection by EBV-encoded small RNA (EBER) in situ hybridization (ISH) on the paraffin sections and amplifying the EBV genome encoding envelop glycoprotein (gp220) with polymerase chain reaction (PCR) in fresh gastric cancer specimens. Results: EBER was detected in 7 (13.2%) of 53 gastric carcinomas and all cases were male. In 6 (85.7%) of 7 EBER-positive cases, the tumors were located in the upper and middle part of the stomach. EBER ISH study showed strong positivity in all the tumor cells, but negativity in surrouning lymphocytes, stromal cells and normal gastric mucosa. DNA PCR was positive in 23 (43.4%) of 53 gastric carcinomas, including all of 7 EBER-positive cases. Conclusion: We could observe some association of EBV with gastric carcinoma, and our findings about the charateristics of EBV-positive gastric cancers involving sex, site and histological type are similar to those in Japan. However, EBV-positive rate of gastric cancer is higher than in Japan and lower than in Western countries. Further studies to elucidate oncogenic mechanism of EBV in gastric cancer should be performed.
Sodium Azide와 2-AF에 대한 마(Dioscorea batatas Decene)의 항변이원성
이임선,정세영,심창섭,구성자 동아시아식생활학회 1996 동아시아식생활학회지 Vol.6 No.2
The objective of this study was to screen the antimutagenicity of yam enzymatic browning reaction product(YEBRP), mucopolysaccharide and dietary fiber from yam to the mutagen of sodium azide and 2-aminoflourene(2-AF). Antimutagenicity of YEBRP on the mutagenicity of sodium azide showed no difference compared to control without YEBRP but that of 2-AF was high in all substrate.(P<0.01) On the mutagenicity of sodium azide and 2-AF, antimutagenicity of mucopolysaccharide and dietary fiber were high (p<0.01) in α-cellulose and hemicellulose. Antimutagenicity of α-cellulose on the mutagenicity of 2-AF was high at 5 hours reaction time but that was decreased as the reaction time increased.
Lin, Hongxia,Lee, Chi-Ho,Shim, Chang-Koo,Chung, Suk-Jae,Kim, Dae-Duk 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.6
Fexofenadine·HC1 is non-sedating histamine HI receptor antagonist that can he used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of defonnable liposomes can enhance the transepithelial permeability of ferofenadine·HCl across the in vitro ALl human nasal monolay et model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of 28521482 ohm x cm: on 11 days of seeding and maintained high TEER value for 3 days. The defonnable liposome of fexofenadine.HC1 was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 mn and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and 100 μg/ml ferofenadine·HC1. The toxicity of the defonnable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However. defonnable liposome could not enhance the transepithelial permeability (Pap,) and cellular uptake of ferofenadine·HC1. In conclusion. the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.
고인습성 약물인 피리도스티그민의 마이크로캅셀화에 의한 분체 특성의 개선
김대석,김인화,정석재,심창구 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.1
The purpose of this study is to microencapsulate a highly hygroscopic drug, pyridostigmine bromide (PB), with a waterproof wall material, in order to increase the flowability of the drug particles. Polyvinylacetaldiethylaminoacetate (AEA), Eugragit E and Eugragit RS were examined as the wall materials. Microcapsules containing PB were prepared by the evaporation technique in an acetone/liquid paraffin system using aluminum tristearate as a core material, and evaluated for drug encapsulation efficiency, surface morphology, particle size and drug dissolution. The encapsulation of PB in the wall material was almost complete. Among the wall materials examined, AEA exhibited the most excellency in shape, surface texture, flowability, size distribution of microcapsules. Above results suggest that AEA would be a potential wall material for microcapsulation of highly hygroscopic drugs, such as PB. Through microencapsulation with AEA, inconvenience of handling of PB powders encountered in the process of weighing and packing the powders to tableting die or capsule body could be greatly improved.
Caco-2 세포 단층막 투과 실험시 교반이 약물의 투과계수에 미치는 영향
홍순선,유호정,이홍,정석재,김대덕,심창구 한국약제학회 2005 Journal of Pharmaceutical Investigation Vol.35 No.2
The unstirred water layer (UWL), which has been known to exist in the boundary of the intestinal lumen and intestinal wall, often behaves as an absorption barrier especially for lipophilic drugs. The intestinal absorption of drugs is often characterized using Caco-2 cell monolayers grown on Transwell polycarbonate membranes. The permeability (Pare) of drugs across the cell monolayer might be influenced by the agitation of the donor compartment, since the width of UWL on the surface of the cell monolayer would be reduced by the agitation. In this study, the effect of agitation of the donor compartment with 60 rpm on the permeability was measured for 12 drugs with a wide range of lipophilicity and permeability. The of mannitol, tributylmethyl ammonium, cimetidine, ranitidine, hydrocortisone, benzylpenicillin and loxoprofen was not influenced by the agitation, while the P_(app) of theophylline, propranolol, YH439, phenylpropanolarnine and testosterone was increased by the agitation. There was a significant correlation between the increase of P_(app) by agitation and the lipophilicity for the compounds having P_(app) > 2 x 10^(-5) cm/sec. No correlation was observed for the difference in P_(app) by agitation and the molecular weight, or lipophilicity of the drugs. Therefore, the agitation rate of the donor compartment in the Caco-2 cell monolayer study should be carefully controlled in order to estimate Pap, reproducibly especially for iipophilic drugs.
Dae-Duk Kim,Hongxia Lin,Chi-Ho Lee,Chang-Koo Shim,Suk-Jae Chung 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.6
Fexofenadine • HCl is non-sedating histamine H1 receptor antagonist that can be used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of deformable liposomes can enhance the transepithelial permeability of fexofenadine • HCl across the in vitro ALI human nasal monolayer model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of 2852482 ohm´cm2 on 11 days of seeding and maintained high TEER value for 5 days. The deformable liposome of fexofenadine • HCl was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 nm and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and 100 mg/ml fexofenadine • HCl. The toxicity of the deformable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However, deformable liposome could not enhance the transepithelial permeability (Papp) and cellular uptake of fexofenadine • HCl. In conclusion, the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.
흰쥐 생체시료 중 5-플루오로우라실 및 테가푸르의 안정성
장지현,박종국,강진형,정석재,심창구,구효정 한국약제학회 2004 Journal of Pharmaceutical Investigation Vol.34 No.3
5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and 100 μg/ml over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and 100 μg/ml. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 ㎎/㎏ of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.
Effect of Probenecid on the Biliary Excretion of Belotecan
NamKoong, Eun-Mi,Kim, In-Wha,Kim, Dae-Duk,Chung, Suk-Jae,Shim, Chang-Koo 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11
The purpose of this study was to investigate the effect of probenecid, an inhibitor of the MRP2/ABCC transporter, on the pharmacokinetics and transport of belotecan (7-[2-(N-isopropy-lamino)ethyl]-(20S)-camptothecin). The effect of probenecid on the pharmacokinetics of belotecan was studied in rats. When belotecan was injected as a bolus dose of 5 mg/kg after probenecid was infused at a rate of 42.8 mg/2 mL/h/kg, the cumulative biliary excretion amounts and biliary clearance $(CL_b)$ of belotecan decreased ($28.29{\pm}2.83$ versus $19.96{\pm}1.45%$ of dose and $161.01{\pm}26.95$ versus $92.66{\pm}1.45$ mL/min/kg), whereas the systemic pharmacokinetics did not change. This indicates that the MRP2 transporter is involved in the biliary excretion of belotecan. The involvement of MRP2 in the secretory transport was further characterized using Caco-2 cell monolayers expressing MRP2. The apparent permeability across Caco-2 cell monolayers from basolateral to apical was 2.3 times greater than that from the apical to the basolateral side at the $50{\mu}M$ belotecan. In addition, probenecid significantly decreased the basolateral-to-apical transport of belotecan (52.9%). These results indicate that MRP2 is involved in the secretory transport of belotecan in biliary excretion.
김호정,윤미옥,이수정,최현철,김지영,김인화,심창구,강신정 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2
A method that describes the determination of the in vitro release of ketoprofen from gels was suggested. The experimental system of the method consists of a Franz diffusion cell, which contains a pH 7.4 phosphate buffer as a receptor medium, and a 70 μm mesh woven nylon membrane as a diffusion barrier. Under the given condition of the system, the diffusion of ketoprofen across the membrane was rapid enough that the apparent release profile of ketoprofen obtained from the present method could represent the release of the drug from gel preparations. The release of ketoprofen in the present method was reproducible, and the rate increased in proportion to the concentration of ketoprofen in the gel. These suggest that the present method is applicable to the quality evaluation of gel preparations containing ketoprofen.