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      • 접착제(본드)흡입이 간장의 기능 및 조직변화에 미치는 영향

        김인수,손동렬,신인철 漢陽大學校 環境科學硏究所 1984 環境科學論文集 Vol.5 No.-

        접착제의 흡입으로 일어날 수 있는 유해작용에 대하여는 이미 많은 연구가 이루어져 왔으나 그 유해작용은 접착제 제조에 사용된 유기용매의 종류와 순수성에 따라 좌우되므로 만성독성으로 인한 신경장애에 대한 작용이외에 많은 연구들이 일치된 견해가 없고 각 나라마다 자국산의 접착제에 대하여 철저한 연구가 이루어져 왔으나 우리나라에선 거의 연구되어 있지 않는 실정이다. 따라서, 우리나라에서 생산되는 접착제의 흡입으로 일어날 수 있는 만성독성에 대한 연구가 필요하여 백서에 장기간 접착제를 흡입시켰을 때 특히 간 기능과 조직변화에 미치는 영향을 연구하였다. 접착제는 사용된 유기용매의 종류에 따라 toluene과 acetone이 주 용매인 Gt와 hexane과 acetone이 주 용매인 Gh 2 종류로 구분하였으며 실험동물은 체중 180g 내외의 웅성 백서를 대조군, Gt 흡입군과 Gh 흡입군 3군으로 나누었다. 1) 접착제를 10분간 흡입시키는 동안에는 약간의 흥분작용 이외에 별다른 증상을 볼 수 없었으나 40일간의 흡입에서 부터 흥분작용이 증가되어 공격적이며 적의심을 나타냈다. 이러한 중추신경에 대한 영향은 Gt 흡입군에서 더욱 심화하였고 흡입이 중단된지 60일이 경과되어도 정상으로 회복되지 않았다. 2) 혈청 GOT와 GPT는 10일에서 부터 증가되어 30∼40일에 최고의 증가치를 나타냈으나 흡입이 계속되고 있음에도 감소되였다. 혈청 alkaline phosphatase 수준은 20일에서부터 증가하여 50 일까지 지속되었으나(59.2%∼73.1%) 60일에서는 감소되었다. 총 bilirubin은 전 실험기간에서 별 변동이 없었으며 혈청효소의 변동은 흡입이 중단된 후 20일에서는 거의 정상수준으로 회복되었고 Gt와 Gh 흡입군에서 유의한 차이가 없었다. 3) 간의 무게를 체중비로 나타낸 결과 20일에서 부터 25% 증가되었고 60일에서는 50%의 증가를 나타냈으나, 흡입이 중단된 후 50일이 경과되어서는 정상으로 회복되는듯 하였다.(Gt 12.2%, Gh 16.3%) 4) 간의 병리 조직학적 소견으로는 20일에서 문맥주변부의 염증 세포 침윤, 충혈 및 간세포 종창이 관찰되었으나, 흡입이 계속되고 있음에도 더 이상 약화되지 않고 60일간 같은 변화를 보였다. 흡입이 중단된 후 40 일에서는 정상 조직상태를 나타냈으며 이러한 조직변화는 Gt와 Gh 흡입군에서 별 차이가 없었다. 이상의 결과로 보아 우리나라에서 생산되는 접착제의 만성흡입은 내성의 출현으로 인하여 특정적인 심한 간 손상을 유발하지 않는 것으로 판단되며 간 기능 손상은 조직변화에 선행되어 나타나고 간 기능 및 조직손상은 회복성이 있는 것으로 사료된다. 우리나라에서 생산되는 접착제는 비교적 장기간 백서에 흡입하여 다음과 같은 결론을 얻었다. 접착제의 만성흡입은 특징적인 심한 간 손상을 유발하지 않았으며 이는 내성의 출현으로 인한 것으로 판단되고 간 기능 손상은 조직 변화에 선행되어 나타나고 간 기능 및 조직 손상은 회복성이 있는 것으로 사료된다. There have been a number of studies on the acute and chronic toxicities induced by continuing, heavy exposure to glue or its solvents. However the reports besides on the neuronal damage are still controversial, for the toxic actions probably depend on the kind and purity of the solvents used in glue. The aim of the present study was to evaluate the effect of chronic exposure to the inhalation of glue on the functional and histological liver damages. 210 healthy Sprague-Dawely male rats weighing about 180g. were divided into 3 groups: 1)control group exposed to the inhalation of fresh air, 2) Gt group exposed to the inhalation of glue whose main solvents were toluene and acetone, 3) Gh group exposed to the inhalation of glue whose main solvents were hexane and acetone. The results obtained were as follows: 1) During 10 minutes exposure to the inhalation of glue, slight excitement was observed in all rats and in 40 days exposure, excitement was more profound and aggressiveness and hostility were found in Gt group rather than Gh group. The excitement was not subsided even 60 days after stopping inhalation. 2) Serum GOT and GPT levels were elevated in 10 days exposure and reached to the highest level in 30∼40 days exposure followed by decrease to normal ranges. Serum alkaline phosphatase level remained raised from 20 days to 50 days exposure (59.2%∼73.1%) and returned to almost normal level in 60 days exposure. Total bilirubin level were within normal limits in all experimental period. The serum enzyme levels were recovered to normal ranges 20 days after being exposed to the final inhalation and have no significant difference between Gt and group. 3) The relative liver weights were increased by 25% in 20 days exposure, and by 50% in 60 days exposure but it seemed to be returned to normal weight 50 days after stopping inhalation (Gt 12.2%, Gh 16.3%). 4) The histopathological changes induced by 20 days exposure to the inhalation of glues Gt and Gh were mononuclear cell infiltration in periportal zone, congestion and cellular swelling on the liver and were not enhanced even by increase in exposure time. These findings were completely subsided 40 days after receiving the final exposure. From these results, it may be concluded that the chronic inhalation of glues available in Korea fails to cause severe or characteristic liver disease, the functional damage is followed by the histological changes in liver and the functional and histological damages are reversible.

      • KCI등재
      • 한국인에서의 CYP2E1 유전자형

        권준택,김형기,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

        Cytochrome P4502E1 (CYP2E1) is inducible by ethyl alcohol and activates procarcinogenic N-nitrosodimethylamine (NDMA), benzene, urethane and other lower molecular weight compound. CYP2E1 is also involved in metabolism of certain drugs, for example, alcohol, acetaminophen, tamoxifen, theophylline, fluorinated anesthetics, and chlorozoxazone. CYP2E1 activity was shown to be polymorphically distributed in humans and has been suggested to play a role in hepatocellular carcinoma and alcoholic related disorders. Although genetic predisposition to alcoholism and alcoholic liver disease has been reported, genetic susceptibility to alcoholic pancreatitis is still a matter of debate. The aims of this study were to investigate the allelic frequency of CYP2E1 Rsa I polymorphism in Koreans. We investigated the frequency distribution of CYP2E1 Rsa I polymorphism in 212 unrelated healthy Koreans and 42 hepatocellular carcinoma patients. Detection of the CYP2E1 alleles was performed by polymerase chain reaction and restriction fragment length analysis. The genomic DNA was isolated from peripheral blood with conventional phenol: chloroform extraction method. The allelic frequencies of c1 and c2 in healthy volunteers were 0.85 and 0.15, respectively. The rare type (c2/c2) of CYP2E1 Rsa I polymorphism was 0.005 in healthy volunteers.

      • Cefixime 경구제제의 생물학적 동등성 연구

        김형기,권준택,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

        The bioequivalence of generic cefixime(Pofixim^(®), Kwangmyung Pharmaceutical Co.) capsule to the cefixime capsule(Suprax^(®), Dong-A Pharmaceutical Co.) as a reference drug. Single dose of 100 mg cefixime was administered to 20 healthy male volunteers in a balanced, randomized crossover design with a washout between the two study periods. Blood samples were collected up to 14 hours and plasma concentration of cefixime was measured by well validated reverse phase high-performance liquid chromatography. Pharmacokinetic parameters were analyzed by non-compartmental analysis and ANOVA test was used for the statistical analysis of parameters. No statistically significant formulation, period, or sequence effect was encountered. Ninety percent confidence intervals of log transformed C_(max) and AUC_(t) were comprised in the stipulated 0.80-1.25 range. These results suggest that test formulation of cefixime can be declared bioequivalent with the reference, both formulations in 100 mg capsule.

      • 한국인에서의 CYP2C19 유전자형의 다형성

        권준택,김형기,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

        The S-mephenytoin 4'-hydroxylase (CYP2C19) metabolizes a number of clinically used drugs and shows a marked interethnic difference in the incidence of the poor metabolizer (PM). In the present study, we genotyped 215 healthy unrelated Koreans (64 females, aged 20-41 yr, residing in Chungcheong province) for functionally defective alleles, CYP2C19_(m1) and CYP2C19_(m2). Detection of the normal (CYP2C19_(wt)) and defective alleles was performed by polymerase chain reaction/restriction enzyme analysis. The genomic DNA was isolated from peripheral blood. The allelic frequencies of the wild-type (CYP2C19_(wt)) and CYP2C19_(m1) were 72.6% and 27.4%, and the wild-type (CYP2C19_(wt)) and CYP2C19_(m2) were 85.1% and 14.9%, respectively. For each CYP2C19_(m1) and CYP2C19_(m2), the observed numbers of three genotypes were similar to those calculated in accordance with the Hardy-Weinberg equation. The frequencies of homozygotes for CYP2C19_(m1), CYP2C19_(m2) and compound heterozygotes were 9.7%, 2.8% and 4.2%, respectively. The mutants of CYP2C19 were identified in 36 subjects (16.7%). These results suggest that frequency of mutants of CYP2C19 in Koreans resembled the Orientals rather than Caucasians.

      • Aceclofenac 경구제제의 생물학적 동등성 연구

        권준택,김형기,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

        The bioequivalence of generic aceclofenac(Anacle^(®), Korea Pharma Co.) tablet to the aceclofenac tablet(Arital^(®), DaeWoong Pharmaceutical Co.) as a reference drug. Single dose of 100 mg aceclofenac was administered to 20 healthy male volunteers in a balanced, randomized crossover design with a washout between the two study periods. Blood samples were collected up to 12 hours and plasma concentration of aceclofenac was measured by well validated reverse phase high-performance liquid chromatography. Pharmacokinetic parameters were analyzed by non-compartmental analysis and ANOVA test was used for the statistical analysis of parameters. No statistically significant formulation, period, or sequence effect was encountered. Ninety percent confidence intervals of log transformed C_(max) and AUC_(t) were comprised in the stipulated 0.80-1.25 range. These results suggest that test formulation of aceclofenac is bioequivalent with the reference, both formulations in 100 mg tablet.

      • Simvastatin 정제의 생물학적 동등성 연구

        김형기,권준택,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

        The bioequivalence of generic simvastatin tablet(Dongsung Pharmaceutical Co.) to the simvastatin tablet(Zocor^(®), MSD Korea Co.) as a reference drug. Single dose of 20 mg simvastatin was administered to 20 healthy male volunteers in a balanced, randomized crossover design with a washout between the two study periods. Blood samples were collected up to 12 hours and plasma concentration of simvastatin was measured by well validated LC-MS/MS. Pharmacokinetic parameters were analyzed by non-compartmental analysis and ANOVA test was used for the statistical analysis of parameters. No statistically significant formulation, period, or sequence effect was encountered. Ninety percent confidence intervals of log transformed C_(max) and AUC_(t) were comprised in the stipulated 0.80-1.25 range. These results suggest that test formulation of simvastatin is bioequivalent with the reference, both formulations in 20 mg tablet.

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