창상치유 실험 모델의 조직학적 연구

김상철,최서영,우인혜,김현혜,조애리 덕성여자대학교 약학연구소 2009 藥學論文誌 Vol.20 No.-

Full thickness surgical wound was created by 8mm biopsy punch to prepare a human resembled wound model. Wound progression was accessed by histology analysis. At 5 day post wounding, skin sections were harvested and stained with hematoxylin & eosin and Masson's trichrome: the histology was compared with those of normal skin. Presence of cartilage in rabbit ear prevents rapid wound contraction; repair was progressed mostly by re-epithelialization. The 5 day post wounding skin specimens showed initial inflammation and granulation with some edema. Regularity in weave-like collagen arrangements could be clearly accessed by Masson's trichrome staining.

식물조직배양에 의한 배초향유의 생산

신순희,김혜경,지형준 德成女子大學校 藥學硏究所 1992 藥學論文誌 Vol.3 No.1

Callus was derived from the seedlings of Agastache rugosa(Labiatae).The growth rate of callus and the production of essential oil were studied with the variationof culturing conditions. 2,4-D 2ppm in the medium was more effective for the production of essential oil than NAA 2ppm. The growth rate of callus and the production of essential oil were inhibited by the illumination of the light. The essential oils from Agastache rugosa and the callus cultivated on the medium containing 2,4-D 2ppm and kinetin 0.2ppm were analysed by TLC, gas chromatography and mass spectrometry. These two oils showed different compositions. The main component of the plant oil, methyl chavicol was not contained in the callus oil.

Synthesis and Analgesic and Anti-inflammatory Activities of 1,2-Benzothiazine Derivatives

Lee, Eun Bang,Kwon, Soon Kyoung,Kim, Sang Geon 德成女子大學校 藥學硏究所 1999 藥學論文誌 Vol.10 No.1

Three 1,2-benzothiazine derivatives were synthesized, and their analgesic/ anti-inflammatory efficacy and their effects on gastric irritation were evaluated. Among the three compounds, 39 exhibited the most potent analgesic action, but the effect was weaker than that of piroxicam. Nonetheless, the compound showed 4 times more potent analgesic action with less gastric damage than did ibuprofen. These compounds did not show anti-inflammatory effect at an oral dose of 5 ㎎/㎏.

Silver Oxide를 이용한 1,2-벤조티아진 유도체의 비대칭 중합체 합성 및 결정 구조

朴明淑 德成女子大學校 藥學硏究所 1999 藥學論文誌 Vol.10 No.1

새로운 비대칭 중합체인 7,7'-substituted(or H)-4-oxo-2,2'-dialkyl-1,1',2,2'-dibenzothiazine-3,3'-dicarboxylic acid methyl ester-1,1,1',1'-tetraoxide 3,4'-yl ethers 2a-d를 silver oxide(Ag_2O)를 이용한 산화적인 중합반응에 의해 7-substituted (or H)-4-hydroxy-2-alkyl-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxide 1a-d로 부터 합성하였다. 4-Oxo-2,2'-dialkyl-1,1'2,2'-dibenzothiazine-3,3'-dicarboxylic acid methyl ester-1,1,1',1'-tetraoxide 3,4'-yl ether 2c의 구조를 X-ray결정 구조 분석에 의해 확인하였다. New asymmetric dimer, 7,7'-substituted (or H)-4-oxo-2,2'- dialkyl-1,1',2,2'-dibenzothiazine-3,3'-dicarboxylic acid methyl ester-1,1,1',1'-tetraoxide 3,4'-yl ethers 2a-d were synthesized through the oxidative dimerization of 7-substituted (or H)-4-hydroxy-2-alkyl-1,2-benzothiazine-3-carboxylic acid methyl ester 1,1-dioxides 1a-d using silver oxide(Ag_2O). 4-Oxo-2,2'-dialkyl-1.1'2,2'-dibenzothiazine-3,3'-dicarboxylic acid methyl ester-1,1,1',1'-tetraoxide 3,4'-yl ether 2c was identified by X-ray crystal structure determination.

Correlation of Increased Mortality with the Suppression of Radiation-inducible Microsomal Epoxide Hyderolase and Glutathione S-Transferase Gene Expression by Dexamethasone : Effects on Vitalmin C and E-Induced Radioprotection

Nam, Seon Young,Cho, Chul Koo,Kim, Sang Geon 德成女子大學校 藥學硏究所 1998 藥學論文誌 Vol.9 No.1

Previous studies in this laboratory have shown that γ-ray ionizing radiation in combination with oltipraz, a radioprotective agent, enhances hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) expression. The present study was designed to investigate the effects of dexamethasone on the radiation inducible expression of mEH and rGST genes and on the vitamin C and E-induced radioprotective effects in association with the expression of the genes. Treatment of rats with a single dose of dexamethasone(0.01-1 ㎎/㎏, p.o.) caused a dose dependent decrease in the constitutive mEH gene expression at 24 hr. The radiation-inducible mEH mRNA level (threefold increase after 3 Gy γ irradiation) was decreased by 21% and 88% by dexamethasone at the doses of 0.1 and 1 ㎎/㎏, respectively. Although dexamethasone alone caused 2 to 5 fold increases in the hepatic rGSTA2 mRNA level, rats treated with dexamethasone prior to 3 Gy irradiation exhibited 80%-93% suppression in the radiation inducible increases in the rGSTA2 mRNA level. The inducible rGSTA3 and rGSTA5 mRNA levels were also significantly decreased by dexamethasone, whereas the rGSTM1 mRNA level was reduced to a lesser extent. Vitamin C and/or E, however, failed to enhance the radiation-inducible increases in hepatic mEH and rGST mRNA levels. Whereas rats exposed to 3 Gy irradiation with or without vitamin C treatment (30 or 200 ㎎/㎏/day, p.o., 2 days) exhibited∼threefold increases in the mEH and rGSTA2/3/5 mRNA levels relative to untreated animals, dexamethasone treatment (1 ㎎/㎏, p.o.) resulted in 64%-96% decreases in the mRNA levels at 24 hr. The inducible rGSTM1/2 mRNA levels in the vitamin C/E treated rats were ∼50% suppressed by dexamethasone. Although vitamin C and/or E treatment (200 ㎎/㎏/day, p.o., 2 days) improved the 30-day survival rates of the 8Gy γ-irradiated mice from 39% up to 74%, the improved survival rate of γ-irradiated animals was reduced to 30% by dexamethasone pretreatment (1 ㎎/㎏/day, 2 days). The mean survival time of dexamethasone-treated animals was reduced to ∼2days from 14days in the animals with total body irradiation alone. No significant hematologic changes were observed in mice at 10 days after dexamethasone plus γ-irradiation, as compared with irradiation alone. These results demonstrate that: dexamethasone substantially suppresses radiation-inducible mEH, rGSTA and rGSTM expression in the liver, vitamins C/E exhibit radioprotective effects without enhancing radiation-inducible mEH and GST gene expression; and inhibition of radiation inducible mEH and rGST gene expression in the vitamin C and E treated animals by dexamethasone was highly correlated with reduction in the survival rate and the mean survival time of γ-irradiated animals.

Human CYP1A2 Promoter Fused-Luciferase Gene Constructs Hardly Respond to Polycyclic Hydrocarbons in Transient Transfection Study in HepG2 Cells

Chung, Injae 德成女子大學校 藥學硏究所 2000 藥學論文誌 Vol.11 No.1

In previous study. both constitutive expression and 3-methylcholanthrene (3MC)-mediated elevation of CYP1A2 mRNA were demonstrated in human hepatoma HepG2 cells by reverse transcription-polymerase chain reaction (RT-PCR), suggesting that HepG2 cells would be appropriate for the study of human CYP1A2 regulation(Chung and Bresnick. 1994). Further studies were conducted to detemine the basis of this induction phenomenon that is observed in HepG2 cells. Since CYP1A1 gene. another polycyclic hydrocarbon(PH)-inducible gene. is regulated by PHs through their interactions via receptors with cis-elements, the 5-flanking region of human CYP1A2 gene was analyzed to search such responsive elements. The promoter activity of various lengths of CYP1A2 gene sequence (-3203/+58 bp) was measured in transiently-transfected HepG2 cells by fusion constructs containing the CAT,hGH or luciferase genes as a reporter. This region of the CYP1A2 gene,although containing a XRE, was only weakly responsive (less than 2 fold induction) to 10 nM of TCDD or 1 uM 3 MC treatment. This small enhancement of promoter activity is inconsistent with the previous observation, i.e.. 12 to 14 fold-enhanced CYP1A2 mRNA from 1 uM 3 MC treated HepG2 cells, suggesting that additional mechanisms would exist for PH-mediated induction of CYP1A2 in these cells.

Pharmacokinetics of methotrexate after intravenous infision of methotrexate-rabbir serum in conjugate to rabbits

Yoon, Eun J,Chang, Hong W,Lee, Myung G,Lee, Hee joo,Park, Man K,Kim, Chong K 德成女子大學校 藥學硏究所 1992 藥學論文誌 Vol.3 No.1

The pharmacokinetics of methotrexate(MTX) were compared after 30 min intravenous infusion of the same dose(10 ㎎/㎏ as MTX) of MTX(treatment Ⅰ)or MTX-rabbit serum albumin (RSA)conjugate(treatment Ⅱ) to rabbits. In treatment Ⅱ, the mean peak plasma level of MTX was significantly lower (48.1 vs 13.8㎍/ml), and plasma levels declined more slowly thereafter (mean apparent half-lives of 3.26 vs 4.96h) than those in treatment Ⅰ. In treatment Ⅱ, the values of AUC(2360 vs 1510㎍ min ml^-1)and CL_R(2.49 vs 0.452 ml min^-1㎏^-1)were significantly increased. The above data suggested that MTX resides longer in the rabbit, and that nonrenal metabolism of MTX increases in treatment Ⅱ. It could be explained by the fact that MTX is released slowly from MTX-RSA conjugate, and that the disposition of MTX is saturable. The amounts of MTX(㎍/g tissue)remaining in kidney, stomach, small intestine, and large intestine after 30 min infusion of MTX-RSA conjugate were 33, 6.1, 3.1, and 10 times lower,respectively, than those after 30 min infusion of free MTX. It might suggest that the administration of MTX-SA conjugate has less side effects of MTX in these organs of tissues than those of free MTX. The in vitro release of MTX from MTX-RSA conjugate in phosphate buffer of pH 7.4, the buffer with protease, rat liver himogenate, or human plasma was biphasic process. For example, and initial rapid release over approx. 6 h appears to be due to physically acsorbed MTX with the slower secondary release due to covalently bound drug. The release of MTX from the conjugate in vitro was accelerated in the presence of protease or liver homogenate.

Apicidin, an inhibitor of histone deacetylase, prevents H-ras-induced invasive phenotype

Kim, Mi-Sung,Son, Mi-Won,Kim, Won-Bae,Park, Young In,Moon, Aree 德成女子大學校 藥學硏究所 2000 藥學論文誌 Vol.11 No.1

Cancer metastasis represents the most important cause of cancer death and agents that may inhibit tumor cell invasion have been extensively pursued. In the present study, we have examined the anti-invasive effect of apicidin [cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)], a fungal metabolite that was identified as an antiprotozoal agent known to inhibit parasite histone deacetylase (HDAC). We show that apicidin significantly inhibits H-ras-induced invasive phenotype of MCF10A human breast epithelial cellsin paraliel with a specific downregulation of matrix metalloproteinase (MMP)-2, but not MMP-9. We also show that apicidin induces a morphological reversal and growth inhibition of H-ras MCF10A cells similar to that induced by other HDAC inhibitors. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our data showing the anti-invasive and detransforming activities of apicidin in H-ras-transformed MCF10A cells may suggest a potential use of HDAC inhibitors for treatment of cancer. ⓒ 2000 Elsevier Science Ireland Ltd. All rights reserved

누릅나무 수피추출물의 약리학적 연구

김양신,김재완 德成女子大學校 藥學硏究所 1991 藥學論文誌 Vol.2 No.1

The barks of Ulmus daviana var. japonica(Ulmaceae) has been described in Dongeueibogam written by Joon Huh to have diuretic and laxative actions, to amliorate edematous disease, and to be used in insomnia and gastrointestinal disorders. Thus this study was carried out to elucidate some of the pharmacological activities of the plant extracts. From the results obtained it was identified that is methanol extract elicited remarkable inhibition of HCI · ethanol induced gastric lesion, of gastric secretion and of gastric Shay ulceration. However, it showed neither sedative nor antiinflammatory actions. The acute toxicity of the extract was low, that is, the minimum lethal dose was more than 2000mg per kg by oral administration in mice. The systematic fractionation of the methanol extract by hexane, ether, ethylacetate and butanol resulted in potent prevention of gastric lesion and ulceration in butanol and water fractions.

두릅나무 根皮抽出物의 藥理學的 硏究

정춘식,김재완 德成女子大學校 藥學硏究所 1991 藥學論文誌 Vol.2 No.1

The plant of Aralia elata (Araliaceae) is described to be used for treatment of diabetes, gastritis, neuralgegia and rheumatoid arthritis in oriental medicinal books. This study is concerned with the effect on the gastritis and ulcer in rats and some general pharmacological action in rats. It was observed that the methanol extract of the rootbark of Aralia elata showed effectiveness in gastritis and pain in rats. From the result obtained that the methanol extract exhibited antigastritic activity. Thus, It was fractionated into hexane, chloroform, ethylacetate and butanol, and further bioassays for the fractions resulted in potent activity in the butanol fraction. The fraction elicited analgesic effect by inhibition of writhing syndrome induced by acetic acid and by increment of pain-threshold in inflamed tail of mice. The fraction showed inhibition of HCl · ethanol and absolute ethanol induced gastritis and inhibition of Shay ulcer in rats. It also exhibited inhibition of gastric secretion in rats. The fraction showed low acute toxicity, i.e., the minimum lethal dose was more than 5000 ㎎/㎏ in oral administration in rats and LD_50 was 740 ㎎/㎏ given subcutaneous by in rats.