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        Biphenyl Dimethyl Dicarboxylate가 간내 Cytochrome P450 1A1과 2B1 및 CCl4 유도 간독성에 미치는 영향

        김순선(Soon Sun Kim),오현영(Hyun Young Oh),김학림(Hak Rim Kim),양지선(Ji Sun Yang),김동섭(Dong Sup Kim),신윤용(Yhun Yhong Sheen),최기환(Ki Hwan Choi) 대한약학회 1999 약학회지 Vol.43 No.6

        In this study, we have investigated the effect of Biphenyl Dimethyl Dicarboxylate (DDB), a synthetic analogue of Schizandrin C isolated from Schizandrae Fructus on cytochrome P450 1A1 and 2B1, and the protective mechanism against CCl4-induced hepatotoxicity in rat liver. After DDB was administered into male rats for different periods of time (1-7 days) and with different doses (25, 50, 100 and 200mg/kg), mRNA levels of CYP1A1 and CYP2B1 were measured by polymerase chain reaction (PCR) and assayed the activities of CYP1A1 specific ethoxyresorufin-0-dealkylase (EROD) and CYP2B1 specific benzyloxyresorufin-0-dealkylase (BROD). DDB treatment resulted in increase in CYP2B1 mRNA level and BROD activity, whereas there was no change in CYP1A1 mRNA level and EROD activity. This effect of DDB was time- and dose-dependent and reached maximal level by 3 day and 200mg/kg treatment. In addition, rats were pretreated with DDB at doses of 25, 50 or 100mg/kg daily for 4 days, 3-hr after final treatment on the 4th day, CCl4 0.3ml/kg was intraperitonially injected into the rats to examine the effect of DDB on CCl4-induced hepatic injury. Serum levels of ALT and AST were determined and histopathological examination was done in rat liver. Furthermore, we have measured hepatic microsomal malondialdehyde (MDA) level, a parameter of lipid peroxidation. Based on serum ALT level and lipid peroxidation, pretreatment of DDB, 50mg/kg appeared the most protective effect against CCl4-induced hepatotoxity. These results indicate that DDB stimulates CYP2B1 mRNA level and BROD activity in time and dose dependent manner and suggest that protective effect of DDB on CCl4-induced hepatotoxicity may be mediated through free radical scavenging.

      • KCI등재

        선진 외국의 동물대체시험법 개발현황과 전망

        이진구 ( Jin-koo Lee ),이은호 ( Eun-ho Lee ),김명주 ( Myeung-ju Kim ),김주환 ( Ju-hwan Kim ),민영실 ( Young-sil Min ),김형건 ( Hyung-gun Kim ),김학림 ( Hak Rim Kim ) 한국동물실험대체법학회 2016 동물실험대체법학회지 Vol.10 No.1

        The recognition of welfare for experimental animal based on 3Rs principles has been spreading throughout the developed countries and therefore, on the demand of alternatives to animal experiments have been continually increased, especially in advanced countries. Recently, EU prohibited animal uses for developing cosmetic products at any level and some other countries applied already or are trying to setting the similar level of limitation of animal uses for cosmetic industries. According to the global trends, the marketing ban for animal used cosmetics will be applied soon in Korea. In this study, we summarize the polices, regulations, research developments, and validation processes of the animal alternatives methods of foreign countries and use those as a basal information for improving the alternatives regulation and developments. This research project was mainly focused to summarize and analyze related topics including, 1) Investigation of current policies of alternatives in EU, Japan, and USA etc. 2) Investigation of current regulatory trends of alternatives in foreign countries. 3) Investigation of current research trends of alternatives in foreign countries 4) Investigation of current validation processes of alternatives in foreign countries. Investigating the latest data on the status of animal alternatives methods and based on those, someone could use our study for setting the important research theme, roadmap for long-term development strategy of animal alternatives. However, due to the dynamic update trends in the alternative methods in many countries, the newly updated documents could be released at any time.

      • KCI등재

        광양만권 오존농도 특성 조사 (순천지역을 중심으로)

        박혜영 ( Hye-young Park ),박현수 ( Hyun-su Park ),김학림 ( Hak-rim Kim ),오길영 ( Gil-young Oh ),임항선 ( Hang-sun Lim ),이해훈 ( Hae-hun Lee ),박종수 ( Jong-su Park ) 한국환경기술학회 2020 한국환경기술학회지 Vol.21 No.4

        This study investigates distribution of highly concentrated ozone generation for the last 5 years(2015~2019). To analyze the air flow and weather relation when highly concentrated ozone generated, the air current pattern was analyzed by using HYSPLIT model of National Center for Atmospheric Research, US. After HYSPLIT analysis, the characteristics of Case 1 ~ 4 were analyzed according to the travel distance. Case 3, 4 showed the most influence on generating highly concentrated ozone; it showed short travel distance. Also for Suncheon in Gwangyang-Bay area, the cause of considerable frequency and lasting time of YH and SD monitoring sites was analyzed. The total accumulated time of high ozone concentration 242 hours at YH site and 179 hours at SD site. The characteristics of the monitoring sites were analyzed by analyzing the correlation among ozone concentration, meteorological data and air pollutants. YH monitoring site showed the lowest wind speed and high correlation of Insolation. SD monitoring site showed considerably strong correlation of fine dust and ultrafine dust. Also the locations of the two sites are in leeward of the industrial complex area, therefore ozone can easily be generated and the wind speed is low, which can cause atmospheric congestion and generate highly concentrated ozone for a long time.

      • Streptozotocin으로 유발된 당뇨병쥐의 신경전도속도에 대한 Evening primrose oil (EPO), Vit.C, Vit.E의 약물효과

        신창열,류정수,김학림,강봉수,손의동,허인회 중앙대학교 약학연구소 1997 약학 논총 Vol.11 No.-

        The effects of evening primrose oil (EPO). Vit.C and Vit.E on nerve conduction velocity (NCV) in streptozotocin -induced diabetic rats were investigated. 5 weeks- diabetes caused 27±0.5 % reduction in sciatic motor conduction velocity as compared with normal control. Dietary supplement of 5% EPO. 125mg/kg Vit.C. and lg/kg Vit.E prevented significantly the development of the motor nerve conduction velocity deficit about 21±0.5, 21±0.5, 26±0.5% respectively. The total serum cholesterol and triglyceride were decreased by administration 5% EPO. Vit.C, and Vit.E as compared with diabetic control. However, the serum glucose was not decreased by administration 5% EPO. 125mg/kg Vit.C but the serum glucose was decreased by administration lg/kg Vit.E as compared with diabetic control.

      • 천연물이 간대사에 미치는 영향에 관한 연구(Ⅲ)

        김순선,최기환,김학림,황인창,김동섭,신윤용,류항묵,장영섭 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-

        본 연구에서는 만성간염둥 간낄환 01방 및 치료제로서 오래전부터 널러 사용죄고 있으나 그 작용기전이 화실히 밝궈져있지 않은오미자에서 추출한 을hisandrin C의 합성 동족체, biphenf·1 dimethrt carboxylate(ODB)의 간장 보호자용 기전 연구의 일환으로 DDB를 시간(I~T일) 및 용량(25, 50, 100, 200mg/kg)별로 랫드에 투여한 훌 간장내 약물대사효소, CYPtAl과 CYPEBI mRNA 합량을 PolyrEerasff chain reation(PCR)밟법으로 측정하고 CfPIAl에 특이한 ethoxyruesorfin-o-deethylase(EROD)와 CYPaBt에 특이한 benzyloxyresorufin-o- dealkrlase(BROD) 활성을 측정한 결꽈, DDB가 CYPIAI mRNA 힘·량 및 EROD활성에는 영향을 미치지 않았으나 CYPfBl 유전자 발현을 유도시키고 CYPEBI에 특이한 fiROD 될성을 증가시켰다. DD8의 이러한 CYPEBI 유전자 발현유도 효과는 투여시간, 용량에 비례하여 3일, 200rag/kg투여시에 극대치를 나타내었으며 BROD찰상 역시 투여시간, 용량에 비례하여 증가하였다. 또한 DDB의 간보호 효과를 평가하기 위해 DDB를 용량(25, 50, 100,200mgJkg)별로 4일간 연속 길구투여하고 DDB 최종투여 3시간후 CCI,(0.3mJ/kg, i.p)를 처치하여 간독성을 유발 시킨 후, CYPfBl mRNA 함량과 BROD 활성을 조사하고 간조직 검사를 실시하였으며 혈청내 aminotransferase 꽉성 및 간소포체내 lipid perflxidation을 측정하였다. DOB 전투여는 CCI, 처치에 의왜 감소된 CYPBBI mRNA 함량자 BHOD 활성을 용량의콘적으로 증가시켰으며 CCI, 처치에 의해 증가된 혈청내 ALT 활성과 간 소포체 막의 lipid peroxidation을 감소시켰다. 혈청내 ALT 활성같 간 소포체 막치 lipid peroxidation에 근거하면 DDB는 CCI, 처치로 유발된 간독성에 럴호효롸를 나타내며 그 효과는 50mg/kg;투여시에 최대인 것으로 보인다. 반면, CCI, 처치에 의해 유발된 간 표면의 섬유화, 간세포 괴사 및 공포화 변성은 DDB 투여에 의해 통계적으로 유의성있는 개선 효과를보이지 않았다. 이상의 결과는 DDB가 CYP2린1 유전자 발현 및 BROD 활성을 시간 및 용량의존적으로 증가시킴을 나타내며 DDB의 free radical scavenger가능성을 제시한다. 미와 더불어 전년도 시험물질, 대황 및 마황의 환셩성분인 rhein, eptledrine과 황금의 지표성분인 baicalin이 간 대사 및 독성에 미치는 영향을 비교평가 하기 위해 rhein 및 ephedrinr·을 각각 20, 10mg/kg 용량으로 랫드에 4일간 복강주사하고 baicalin은 4mg/kg 용량으로 7일간 경구투여한 후, 간장내 약물대사 효소 CYPIAI과 CYPaBl 유전자 발현정도를 조사하고 애들에 특이한 EROD 와 BROD활성, 혈청내 ALT, AST 활성 및 간소포체내 지질과 산화물(rnslondialdehyde) 함량을 측정한 결과, ephedrine은 만성간염지표인 ALT/AS? ratio을 증가시키고(p (0.03) rhein은 MDA함량을 증가시켰는데,(p(0.01) 이는 대황 투여에 의한 간 소포체 막의 lipid peroxidation증가는 rhein에,마황에 의한 혈청내 ALT/AST ratio증가는 ephedrine에 기인함을 시사해주는 결과이며 금의 지표성분인 baicalin투여에 의해서는 혈청중 ALT 및 AST 활성이 재조군에 비해 유의적으로 감소되어(p(0.05) baiealin의 간보호 가능성을 제시하였다. Biphenyl diinethyl dicarboxylate(DDB) is a synthetic analogue of SchiBandrin C isolated from SchiBandrae Fructus and has been widely used for its hepatic protective effect. This study has beenundertaken to examine the effect of DDB on rat liver drug metaboliEing enzymes and to understand theprotective mechanism of D:DB against carbon tetrachloride(CCl4) -induced hepatic toxicity in rat liver.After DDB was administered into male rats for different periods of time(1 ~7 days) ana with differentdoses(25, 50, 100 and 200mg/kg), mRNA levels of CYPIAI and CYPaHl were measured by polymerasechain reaction (PCR) and also assayed the activities of CYP IAI specific ethoxyresorufin-o-deethylase(EROD) and CYPfBl sf)ecific benzyloxyresorufin-o-dealkylase (BROD) . Furthermore, rats werepretreated with DDB 25, 5() and 100 mg/ltg daily for 4 days, 3-hours after final treatrneBt on the 4thday, CCI, 0.3mf/kg was intraperitonially injected into the rats. Activities of serum aminotransferaseswere assayed and determirled lipid peroxidation(production of ualondialdehyde) in hepatic microsomeand done histopathological examination. DDB treatment resulted in increase in CYPaBl mRMA leveland BROD activity whereas there was no change in CYPIAI niRNA level and EROD activity. This ef-fect of DDB was time and dose dependent reaching maximal level by 3 day and 200mg/kg treatment.Based oi?'studies of serum ALT level and lipid peroxidation, D:DB SOmg/kg pretreatinent appeared themost effective protection against CCI,-induce4 hepatotoxicity. :However, histopathological examinationdid not significantly show any improving effect on balloning degeneration and necrosis caused by CCI,treatment. These results in.dicate that DDB stimulates CYPEBI ruRNA level and BROD activity in timeand dose dependent manner and suggest protective effect of DDB against CCI,-induced hepatotoxicitymight be exerted through free radical scavenging. In addition, we have also investigated the effects ofrhein, ephedrine and baicaBin on hepatic toxicity and metabolism in rat liver in order to compare withtheir natural products f·hick are Rhei Rhizoma, Ephedrae Hel·ba and Scutellariae Radix, respectively.After rhein 20 and ephedrine 10mg/kg were intraperitonially injected into the rats daily for 4 daysrespectively compared as bacaBin was treated orally for 7 days, the expression of CYPIAI and CYPfBlwere examined and tlleir dependent EROD and BROD activities were assayed. The levels of serumaainotransferases and hepatic rnaiondialdehyde(MDA ) were Beasured as well. Ephedrine treatment in-creased in CYPIAI specific EROD activity and the ratio of serum ALT/AST ratio, a marker of chronichepatitis(p <0.01). MDA level was enhanced by rhein treatmentfp < 0.01), but baicalin reduced serumALT and AST levels compared to control group (p < 0.05) .

      • PBPK(생리학적약동력) 방법을 이용한 화학물질의 체내동태에 관한 연구

        김동섭,나한광,박인숙,서수경,최기환,김학림,황인영 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-

        PBPK model은 물질을 투여한 후 시간에 따른 각 조직내의 농도를 예측하는데 생리학적 인자(체중,조직의 체적,켤류량, 심박동수, 체포순환 둥f, 물질의 분배계수 및 생화학적 상수(분포.율. 대사율, 단백질결합상수 둥)를 사용하는 것으로 이 방법은 고롱도에서 저농도로의 변화에 따른 조직의 농도추정, 투여경로에 따른 농도의 변화 그리고 실험동울을 통하여 얻어진 실험값의 잃체로의 적용에 매우 유용한 방법이다. 또한 여러물질의 약동력 기전에 대한 정보를 규명하기에 용이한 장점이 있어 국태에서도 PBPK model의 확립이 필요하다. 이에 사용빈도it 높은 진통소염제인 케토로락의 모델을 확립 후, 그 if!확성을 밉증하고 향후 이 약물들과 병통하는 타 약물과의 상호작용 예측에 필요한 기초를 화립하고자 하였다. A physiologically-based pharrnacokinetic (PBPK) model for a target chemical baa the tissue dosirRetry and PBPK approach (or the tissue dosimetry has several advantages against data-based mathem,ttical pharmacokinetics. Main issue to build and use a PBPK model is to carry out route-to-route aBd high-to-low dose extrapolations as welt as species extrapolation. Kineticfelg HLtn;naf frnw, #vnDr;mpnlt wrrp f;flpf wifh n nrim iliup PTPf mnApl nnd in vivo kinetic COnEtantsconstants and biochemical parameters calculated from experimental results for estiraating distributionrnt n rhpm irnl iT farrpl liTTllrl Kefnrotnr has been shown to be effective for moderate to severe Pain 『☞lief such as postpartum and postoperative pain. We investigated PBPK modet of ketorolac and thenup PBPK modeling/ACSL si3uulation.

      • Omeprazole-cholestyramine resine 복합체의 안정성

        이영욱,우종수,정지훈,김진학,송현주,김학림,손의동,허인회 중앙대학교 약학연구소 2000 약학 논총 Vol.14 No.-

        We have performed stability studies of omeprazole-cholestyramine resinate, which has been developed to increase the stability of omeprazole, the well-known proton pump inhibitor, in an acidic condition. We compared omeprazole-cholestyramine resinate with omeprazole in terms of quantitative assay, dissolution and acid-resistance at 40 ℃ × 75 % relative humidity (RH) in order to confirm the advanced stability of omeprazole-cholestyramine resinate. The check points were at baseline, 3 and 6 month after accelerated condition. In every tests, quantiative assay, dissolution and acid-resistant test, omeprazole-cholestyramine resinate have showed more stable ingredient reduction compared to omeprazole. At 6 month, the remaining ingredients of omeprazole-cholestyramine resinate were 86.3±1.4, 84.2±3.1 and 84.8±1.1 whereas that of omeprazole 62.7±2.0, 27.9±1.2 and 40.6±10.7 in assay, dissolution and acid resistance, respectively. These data suggest that omeprazole-cholestyramine resinate is more stable than omeprazole in not only accelerated but also acidic condition. [

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