쥐의 선조체에 있어서 Physostigmine의 아급성 투여가 Dopamine 대사에 미치는 영향

임동구(Dong Koo Lim),최수형(Soo Hyung Choi) 대한약리학회 1992 대한약리학잡지 Vol.28 No.1

Physostigmine을 급성(0.75 mg/kg), 7일간 매일 1회(0.75 mg/kg) 그리고 7일간 연속(0.15 mg/kg/h) 투여한 쥐의 선조체에 있어서 dopamine(DA) 및 대사체와 tyrosine hydroxylase(TH)활성도의 변화를 검색하였다. 급성 투여 1시간 후 선조체의 DA 농도는 변화가 없었으나 dihydroxy-phenylacetic acid(DOPAC)과 homovanillic acid(HVA)농도는 증가하였다. 또한 DA의 turnover의 증가를 제시하는 DOPAC/DA와 HVA/DA의 비율도 증가하였다. 그러나 TH활성도는 24시간 후 감소를 나타내었다. Physostigmine을 매일 및 연속 투여군에서는 DA과 대사체의 농도에는 변화가 없었으나, DA의 turnover의 감소를 제시하는 DA과 대사체의 비율은 감소하였다. 그러나 TH활성도는 매일 투여군에서만 감소를 나타내었다. 이러한 결과는 physostigmine을 급성 및 아급성으로 투여시 dopamine대사의 변화가 있음을 제시한다. 또한 콜린 신경계의 아급성 자극은 dopamine 대사 및 활성도를 감소 시킬 가능성을 시사해 주었다. Rats were treated with physostigmine, using 0.75 mg/kg acutely, with 0.75 mg/kg daily for 7 dats, or with 0.15 mg/kg/h continuously for 7 days. Striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and tyrosine hydroxylase (TH) activities were studied. After acute treatment striatal DOPAC and HVA concentrations were significantly increased without changes in DA level 1 h, but not 24 h. And also the ratios of DOPAC/DA and HVA/DA were increased, suggesting an increased turnover of DA. however TH activities were decreased 24h, but not 1h after acute administration. After both daily and continuous treatment with physostigmine for 7 days, neither DA nor its metabolites were changed. However their ratios were decreased, suggesting a decreased turnover of DA. The TH activities were only decreased in the daily treated group, but not in the continously treated one. These results indicate that dopamine metabolisms are changed after acute and subacute administration with physostigmine. Further it suggest that the subacute stimulation of cholinergic activity may induce the dopamine metablism and activity to be decreased.

서울시(市) 대기중(大氣中) 유해(有害) 부유분진(浮遊粉塵) 성분(成分)에 관(關)한 조사연구(調査硏究) -부유분진중(浮遊粉塵中)의 Benzo(a)pyrene에 관(關)하여-

권숙표,정용,임동구,Kwon, Sook-Pyo,Chung, Yong,Lim, Dong-Koo 대한예방의학회 1978 Journal of Preventive Medicine and Public Health Vol.11 No.1

This study was carried out to investigate air pollution by total suspended particulate(T.S.P.), benzene soluble matter and benzo(a) pyrene in Seoul city. The sampling areas were divided into commercial(Kwang Hwa Moon), indus-trial(Ku Ro Dong) and residensial area(Shin Chon). Sampling was undertaken by High Voulme Air Sampler for four seasons from January 1917 to November 1977. The T.S.P. was extracted with Soxhlet apparatus by benzene and benzo(a) pyrene was separated by column chromatography and thin layer chromatography. The concentrations of benzo(a) pyrene were measured by means of fluorophotometer, and following results were obtained. 1. Arithmetic average concentration for 1-day averaging time of total suspended particulate were $275.6ug/m^3$ in Kwang Hwa Moon, $325.9ug/m^3$ in Ku Ro Dong and $193.0ug/m^3$ in Shin Chon. 2. The seasonal variance of total suspended parti-culate at Ku Ro Dong and Shin Chon were $102.7ug/m^3\;99.6ug/m^3$ respectively and at Kwang Hwa Moon $39.9ug/m^3$. And the concentration of autumn is higher than of that spring at Ku Ro Dong and at Shin Chon, but at Kwang Hwa Moon, the seasonal variance is very little. 3. The concentrations of 50% frequency from geometric mean for 1-day averaging time were $264ug/m^3,\;300ug/m^3\;and\;178ug/m^3$ at Kwang Hwa Moon, Ku Ro Dong and Shin Chon. And geometric standard deviation were 1.27, 1.38 and 1.41 respectively. 4. The concentrations of benzene soluble mater were $26.9ug/m^3$ at Kwang Hwa Moon, $22.7ug/m^3$ at Ku Ro Dong and $15.5ug/m^3$ at Shin Chon, and the ratios to the T.S.P. were 9.8%(range 5.6-14.8%), 7.0%(range 2.4-14.4%) and 8.0%(range 5.5-22.1%) respectively. 5. The concentrations of benzo(a) pyrene were $8.5ug/m^3$ (range $0.8-29.9ug/m^3$) at Kwang Hwa Moon $10.9ug/m^3$(range $1.1-52.0ug/m^3$) at Ku Ro Dong and $5.8ug/m^3$(range $1.5-11.4ug/m^3$) at Shin Chon. 6. The results of this investigation were relatively high in compared with the recommended standards of suspended particulate in air of U.S. Environmental Protection Agency and observed levels of benzo(a)-pyrene in U.S. city.

Effects of Subacute Administration of Physostigmine on Dopamine Metabolism in Rat Striatum

임동구,최수형,Lim, Dong-Koo,Choi, Soo-Hyung The Korean Society of Pharmacology 1992 대한약리학잡지 Vol.28 No.1

Physostigmine을 급성(0.75 mg/kg), 7일간 매일 1회(0.75 mg/kg) 그리고 7일간 연속(0.15 mg/kg/h) 투여한 쥐의 선조체에 있어서 dopamine(DA) 및 대사체와 tyrosine hydroxylase(TH)활성도의 변화를 검색하였다. 급성 투여 1시간 후 선조체의 DA 농도는 변화가 없었으나 dihydroxy-phenylacetic acid(DOPAC)과 homovanillic acid(HVA)농도는 증가하였다. 또한 DA의 turnover의 증가를 제시하는 DOPAC/DA와 HVA/DA의 비율도 증가하였다. 그러나 TH활성도는 24시간 후 감소를 나타내었다. Physostigmine을 매일 및 연속 투여군에서는 DA과 대사체의 농도에는 변화가 없었으나, DA의 turnover의 감소를 제시하는 DA과 대사체의 비율은 감소하였다. 그러나 TH활성도는 매일 투여군에서만 감소를 나타내었다. 이러한 결과는 physostigmine을 급성 및 아급성으로 투여시 dopamine대사의 변화가 있음을 제시한다. 또한 콜린 신경계의 아급성 자극은 dopamine 대사 및 활성도를 감소 시킬 가능성을 시사해 주었다. Rats were treated with physostigmine, using 0.75 mg/kg acutely, with 0.75 mg/kg daily for 7 dats, or with 0.15 mg/kg/h continuously for 7 days. Striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and tyrosine hydroxylase (TH) activities were studied. After acute treatment striatal DOPAC and HVA concentrations were significantly increased without changes in DA level 1 h, but not 24 h. And also the ratios of DOPAC/DA and HVA/DA were increased, suggesting an increased turnover of DA. however TH activities were decreased 24h, but not 1h after acute administration. After both daily and continuous treatment with physostigmine for 7 days, neither DA nor its metabolites were changed. However their ratios were decreased, suggesting a decreased turnover of DA. The TH activities were only decreased in the daily treated group, but not in the continously treated one. These results indicate that dopamine metabolisms are changed after acute and subacute administration with physostigmine. Further it suggest that the subacute stimulation of cholinergic activity may induce the dopamine metablism and activity to be decreased.

녹용의 약효 성분에 관한 연구 ( Ⅴ ) 녹용 및 판토크린의 당지질과 인지질의 조성에 관하여

김영은,임동구,신승언 ( Young Eun Kim,Dong Koo Lim,Seung Uon Shin ) 생화학분자생물학회 1977 BMB Reports Vol.10 No.3

The lipid soluble fraction of Antler velvet layer (cervus nippon taiouanous) was extracted and compared to that of pantocrin (ethanol preparation of Antler, commercially available). Lipid soluble components (801㎎/24.5g from Antler velvet ayer and 979.1㎎/143㎖ from pantocrin) were fractionated by gel filteration using a sephadex CT-25 into neutral lipids, sulfatides, cerebrosides, phospholipids and non-lipid components (lipoprotein and peptide). A silicic acid and a DEAE-sephadex A-25 column chromatography were followed from refractionation and purification. Each fraction was identified by thin layer chromatography using standard materials. Typical lipid soluble fraction of Antler contained 65.3% neutral lipid, 5.2% glycolipid, 12.9% phospholipid, 6.1% ganglioside and 2.9% non-lipid components. The glycolipid was composed of 63.5% cerebroside and 36.5% sulfatide. The cerebroside fraction of the Antler velvet layer showed four spots while pantocrin gave only one spot on a thin layer chromatogram. Among the four spots of Antler cerebroside two had almost same migration with standard but two had quite different mobility compared to the standard. The latter fractions were hydrolyzed by 0.025M methanolic HCl in order to desulfate. The two unknown materials were identified as sulfatides by the method of IR spectroscopy and thin layer chromatography. By two dimensional thin layer chroma tography, it was found that phospholipid of thr. Antler velvet layer were composed of phosphatidylethanolamine, sphingomyelin, phosphatidylcholine, lysophospahtidylethanolamine, and lysophosphatidylcholine and phosphatidic acid. On the other hand pantocrin contained phosphatidylcholine and sphingomyelin as phospholipids.

녹용의 약효 성분에 관한 연구(V) 녹용 및 판토크린의 당지질과 인지질의 조성에 관하여

김영은,임동구,신승언,Kim, Young-Eun,Lim, Dong-Koo,Shin, Seung-Uon 생화학분자생물학회 1977 한국생화학회지 Vol.10 No.3

녹용의 지용성 성분에 관한 생화학적 연구의 일환으로 대만산 꽃사슴(Cervus nippon taiouans)의 녹용을 직접 절단하여 동결시킨 후, 벨?殼?(velvet layer)과 해면상 골조직층(spongybone layer)을 분리하였다. 조직을 Virtis homogenizer로 분쇄한 후 $CHCl_3$ : $CH_3OH$ (1 : 2) 및 (2 : 1) 비율의 혼합 용매로 지용성 성분을 추출하고, Rouser 법에 따라서 Sephadex G-25 column chromatography를 행하여 총지질로부터 ganglioside 및 nonlipid를 분리하고 이어서 Rouser의 방법에 준하여 silicic acid column chromatography를 행하여 총지질을 중성지질, 당지질, 인지질로 분리하였다. 대조시험으로, 녹용의 수성에탄올 제제인 Pantocrin을 질소 기류하에서 감압 건조한후, 상기와 동일한 방법으로 지질 성분을 분획하였다. 지용성 성분의 건조 중량에 대한 각 분획의 백분율은 녹용의 경우 neutrallipid 65.30%, glycolipid 5.22%, phospholipid 12.86%, ganglioside 6.12%, nonlipid(proteolipid & peptide) 10.51%의 비율로 합류되어 있었으며, Pantocrin은 neutral lipid 41.7%, glycolipid 0.62%, phospholipid 5.39%, ganglioside 49.32%, nonlipid(proteolipid & peptide) 2.93%의 함량이었다. 녹용의 glycolipid는 DEAE Sephadex A-25 column chromatography를 행하여 glycolipid의 전체양에 대하여 cerebroside 63.5%, sulfatide 36.5%를 얻었으며 각각을 표준품과 비교하여 T.L.C.를 행하여 7종의 spots를 얻었으며 그중 2종은 cerebroside로 3종은 sulfatide로 확인되었으나 2종은 미지물질로 확인되지 않았다. Pantocrin에서는 1종의 cerebroside를 확인하였다. 녹용과 Pantocrin에 존재하는 ganglioside는 Sephadex G-25 column chromatography법보다는 용매 분획법에 의해 얻은 시료에서 T.L.C.법으로 확인하였다, 또 녹용에서 얻은 phospholipid로는 phosphatidyl ethanolamine, phosphatidyl choline, sphingomyelin, phosphatidic acid, lysophosphatidyl ethanolamine 및 lysophosphatidyl choline등으로 동정되었으며, Pantocrin에서는 phosphatidyl choline, sphingomyelin을 검출하였다. The lipid soluble fraction of Antler velvet layer (cervus nippon taiouanous) was extracted and compared to that of pantocrin (ethanol preparation of Antler, commercially available). Lipid soluble components (801mg/24.5g from Antler velvet ayer and 979.1mg/143ml from pantocrin) were fractionated by gel filteration using a sephadex CT-25 into neutral lipids, sulfatides, cerebrosides, phospholipids and non-lipid components (lipoprotein and peptide). A silicic acid and a DEAE-sephadex A-25 column chromatography were followed from refractionation and purification. Each fraction was identified by thin layer chromatography using standard materials. Typical lipid soluble fraction of Antler contained 65.3% neutral lipid, 5.2% glycolipid, 12.9% phospholipid, 6.1% ganglioside and 2.9% non-lipid components. The glycolipid was composed of 63.5% cerebroside and 36.5% sulfatide. The cerebroside fraction of the Antler velvet layer showed four spots while pantocrin gave only one spot on a thin layer chromatogram. Among the four spots of Antler cerebroside two had almost same migration with standard but two had quite different mobility compared to the standard. The latter fractions were hydrolyzed by 0.025M methanolic HCl in order to desulfate. The two unknown materials were identified as sulfatides by the method of IR spectroscopy and thin layer chromatography. By two dimensional thin layer chroma tography, it was found that phospholipid of the Antler velvet layer were composed of phosphatidylethanolamine, sphingomyelin, phosphatidylcholine, lysophospahtidylethanolamine, and lysophosphatidylcholine and phosphatidic acid. On the other hand pantocrin Ccontained phosphatidylcholine and sphingomyelin as phospholipids.

서울시(市) 대기중(大氣中) 유해(有害) 부유분진(浮遊粉塵)의 성분(成分) -부유분진(浮遊粉塵)의 중금속(重金屬)에 관하여-

권숙표,정용,임동구,Kwon, Sook-Pyo,Chung, Yong,Lim, Dong-Koo 대한예방의학회 1979 Journal of Preventive Medicine and Public Health Vol.12 No.1

In order to investigate air pollution by heavy metals in Seoul city, the suspended particulates in the atmosphere were sampled with high volume air sampler in industrial area(Ku Ro Dong), commerical(Kwang Hwa Moon) and residential(Shin Chon Dong) from January to November, 1977. The sampled suspended particulates were digested and extracted from suspended particulates with the acidic solution by reflux-extraction technique, and were measured by atomic absorption spectrophotometry. And mercury was measured by mercury analyzer applying the reducing sublimation technique. Among heavy metals analyzed, the iron was identified at the highest level in the suspended particulates and the chromium was the least. Through the surveyed area, the concentration of heavy metals of the industrial area was comparatively high among others and the commercial was the second. It was detected that lead was the most concentrated in the suspended particulate of the commercial area, that might be caused of the traffic emissions. The seasonal variations were analyzed and the correlations among heavy metals and total suspended particulate were also calculated. Especially, the iron was highly correlated with total suspended particulate in all the surveyed areas.

프레탈 정 ( 시로스타졸 50mg ) 에 대한 로사졸 정의 생물학적 동등성

김수진(Soo Jin Kim),임동구(Dong Koo Lim),오인준(In Joon Oh),조행남(Haeng Nam Cho),서순팔(Soon Pal Suh),이용복(Yong Bok Lee) 한국약제학회 1998 Journal of Pharmaceutical Investigation Vol.28 No.3

Bioequivalence of two cilostazol tablets, the Pletaal^(TM) (Korea Otsuka Pharmaceutical Co., Ltd.) and the Losazol^(TM) (Kyoung Dong Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Fourteen normal male volunteers (age 20∼28 years old) were divided into two groups and a randomized 2×2 cross-over study was employed. After two tablets containing 50 ㎎ of cilostazol were orally administered, blood was taken at predetermined time intervals and the concentration of cilostazol in plasma was determined with an HPLC method using UV detector. The pharmacokinetic parameters (C_(max), T_(max) and AUC_t) were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in C_(max), T_(max) and AUC_t between two tablets were 3.14%, 10.0% and 7.35%, respectively. The powers (1-β) for C_(max), T_(max) and AUC_t were 89.67%, 80.97% and 83.87%, respectively. Detectable differences (Δ) and confidence intervals were all less than 20% except T_(max), but confidence interval of T_(max), was also less than 20% at the significance level(α) of 0.1, All of these parameters met the criteria of KFDA for bioequivalence, indicating that Losazol^(TM) tablet is bioequivalent to Pletaal^(TM) tablet.

장기간 납의 투여에 따른 뇌 glutamate 신경계 변화에 대한 연구

박선희(Sun Hee Park),임동구(Dong Koo Lim) 한국독성학회 1999 Toxicological Research Vol.15 No.2

To determine changes in the central glutamatergic nervous activities following chronic lead-exposure rats were continuously treated from mating to 4 week-old of the second generation with 0.25% lead acetate in their drinking water. As the pups became 4-week old, the levels of glutamate and glutamine, the activities of various glutamate metabolizing enzymes and the specific binding of [³H]MK-801 to NMDA receptors were determined in striatum, hippocampus and frontal cortex. The total levels of glutamate were not changed in all examined regions after lead-exposure. However, the concentration of glutamine was only decreased in hippocampus. The activities of glutamate dehydrogenase and glutaminase were decreased and increased, respectively. But the activities of glutamine synthetase did not alter in all examined regions after the lead exposure. The specific binding of [³H]MK-801 were significantly increased in the striatum and decreased in the frontal cortex and hippocampus after the chronic lead treatment. These results indicate that the central glutamatergic nervous systems may be affected with the chronic lead-exposure. Furthermore, these results suggest that the toxic effects of lead to the glutamatergic nervous activity are region-dependent and the hippocamus may be the one of the major target site.

클래리시드 정 ( 클래리스로마이신 250mg ) 에 대한 LG 클래리스로마이신 정의 생물학적 동등성

김수진(Soo Jin Kim),심영순(Young Sun Sim),임동구(Dong Koo Lim),오인준(In Joon Oh),신상철(Sang Chul Shin),서순팔(Soon Pal Suh),이용복(Yong Bok Lee) 한국약제학회 1999 Journal of Pharmaceutical Investigation Vol.29 No.3

Bioequivalence of two clarithromycin tablets, the Klaricid^(TM) (Ciba-Geigy Korea Ltd., Seoul, Korea) and the LG clarithromycin (LG Chemical Co., Ltd., Seoul, Korea), was evaluated according to the Korean Guidelines for Bioequivalence Test (KGBT 1998). Sixteen normal male volunteers (20∼26 years old) were randomly divided into two groups and a randomized 2×2 cross-over study was employed. After one tablet containing 250 ㎎ of clarithromycin was orally administered, blood sample was taken at predetermined time intervals, and the concentrations of clarithromycin in serum were determined using HPLC method with electrochemical detector. The pharmacokinetic parameters (AUC_t, C_(max) and T_(max)) were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in AUC_t, C_(max) and T_(max) between two tablets based on Klaricid^(TM) tablet were 4.06%, 2.67% and -9.70%, respectively. The powers (1-β) for AUC_t, C_(max) and T_(max) were 83.53%, 92.34% and 96.64%, respectively. Detectable differences (Δ) and 90 % confidence intervals (α=0.05) were all less than ±20%. All the parameters above met the criteria of KGBT 1998, indicating that LG clarithromycin tablet is bioequivalent to Klaricid^(TM) tablet.

수종 생약의 48시간 동종 수동 피부 아나필락시와 화학적 전달물질에 대한 작용

최수형(Soo Hyung Choi),배은옥(Eun Ok Bae),임동구(Dong Koo Lim),김영란(Young Ran Kim) 대한약학회 1992 약학회지 Vol.36 No.4

Actions for 48-hour homolgous passive cutaneous anaphylaxis (48-hr PCA) and chemical mediators were investgiated in mice and rats. The hyaluronidase activity, which was used in the in vitro screening test of the antiallergic action, was significantly inhibited by Magnoiliae Flos, Achyranthis Radix, Forsythiae Fructus, Alpiniae Fructus, Anemarrhenae Rhizoma and Ponciri Fructus among twelve medicinal plants and tranilast as a comparative drug of the antiallergic action. In the mouse ear, 48-hr PCA was significnatly inhibited by intraperitoneal (i.p.) pretreatment with Magnoliae Flos, Achyranthis Radix, Alpiniae Fructus, Anemarrhenae Rhizoma, Ponciri Fructus, Ledebouriellae Radix and tranilast. And also, the increment of vascular permeability induced by histamine or serotonin was inhibited significantly by i.p. pretreatment with Magnoliae Flos, Achyranthis Radix, Alpiniae Fructus, Anemarrheuae Rhizoma, Zizyphi Fructus and tranilast. In the rat dorsal skin, the increment of vascular permeability induced by histamine or serotonin was significantly inhibited by i.p. pretreatment with Magnoliae Flos, Acyranthis Radix, Alpiniae Fructus, Anemarrhenae Rhizoma and tranilast. And also, the increment of vascular permeability induced by compound 48/80 or calcium ionophore A 23187 was significantly inhibited by i.p. pretreatment with Magnoliae Flos, Achyranthis Radix, Alpiniae Fructus, Amemarrhenae Rhizoma, Zizyphi Fructus, Ledebouriellae Radix, Lithospermi Radix and tranilast. These results suggest that each water extracts of Magnoliae Flos, Achyranthis Radix, Alpiniae Fructus and Anemarrhenae Rhizoma have especially antiallergic activities.