랫드에서 수은이 혈장 DNA와 혈액화학치에 미치는 영향

조준형,정상희,강환구,윤효인,Cho, Joon-Hyoung,Jeong, Sang-Hee,Kang, Hwan-Goo,Yun, Hyo-In 대한수의학회 2003 大韓獸醫學會誌 Vol.43 No.4

Changes of plasma DNA contents and serum biochemical values were measured in rats administered with $HgCl_2$ to investigate the in vivo cytotoxic effects of mercury and examine the usefulness of these changes as indicators of mercury exposure and diagnosis of mercury poisoning. Rats were given once intraperitonealy $HgCl_2$(0.13. 0.32. 0.8 and 2 mg/kg b.w) and the changes of plasma DNA contents and serum biochemical values were measured at the time of 2, 4, 8, 24, 48 and 72 hours after the administration of $HgCl_2$. Plasma DNA contents began to increase from 2 hours after the administration of $HgCl_2$ in all the treatment groups significantly compared to control with dose-dependent pattern. The levels of plasma DNA reached to peak at 48 hours as 2.77, 7.60, 15.46 and 16.51 times higher than control in each treatment group of 0.13, 0.32, 0.8 and 2 mg/kgb.w, respectively and remained to be higher until 72 hours after the administration. The values of creatine kinase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, blood urea nitrogen and glucose of serum were increased, however the values of alkaline phosphatase, total protein and triglyceride were decreased. These changes of increase and decrease showed dose-dependent pattern but the starting time, maintenance and magnitude of change were various and characteristic according to serum biochemical indices. Among the changes of serum biochemical values, those of aspartate aminotransferase, lactate dehydrogenase and blood urea nitrogen were apparently and significantly increased compared to control from 2 to 72 hours by the administration of 2 mg/kg $HgCl_2$. This study demonstrates that plasma DNA and serum biochemical values such as aspartate aminotransferase, lactate dehydrogenase, blood urea nitrogen and etc. are valuable as biomarkers for mercury exposure assessment and diagnosis of mercury poisoning.

랫드에서 Diazinon이 혈장 DNA와 혈액화학치에 미치는 영향

조준형 ( Joon Hyoung Cho ),정상희 ( Sang Hee Jeong ),강환구 ( Hwan Goo Kang ) 한국수의공중보건학회 2004 예방수의학회지 Vol.28 No.1

납의 생체내 세포독성 연구: 랫드에서 혈장 DNA와 혈액화학치 변화

조준형(Joon-Hyoung Cho),정상희(Sang-Hee Jeong),강환구(Hwan-Goo Kang),윤효인(Hyo-In Yun) 한국독성학회 2003 Toxicological Research Vol.19 No.3

Changes of plasma DNA contents and serum biochemical values were measured in rats administered with lead acetate to investigate the in vivo cytotoxic effects of lead and examine the usefulness of these in vivo cytotoxicity changes as indicators of lead exposure and diagnosis of lead poisoning. Rats were given once intraperitonealy with lead acetate (1.6, 8, 40 and 200 mg/kg b.w)<br/> and the changes of plasma DNA contents and serum biochemical values were measured at the time of 2, 4, 8, 24, 48 and 72 hours after the administration of lead acetate. Plasma DNA contents began to increase at 2 hours after the administration of lead acetate in the treatment groups of 8, 40 and 200 mg/kg b.w dose-dependently and significantly compared with control group. These DNA increases of each dosage group were continued until 24, 48 and 72 hours and the maximum levels of DNA (4.02, 10.67 and 14.10 times of control) were arrived at 8, 8 and 4 hours after the each treatment, respectively. Among 10 serum biochemical indicators, the activities of creatine kinase were increased to maximum level (6.55 times of control) at 2 hours after the administration and remained to be significantly higher than that of control by 8 hours in the treatment group of 200 mg, however, after 48 hours, the levels in the treatment groups of 40 mg above were lower than that of control. The values<br/> of aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were higher than that of control from 2 to 24 hours in the treatment group of 200 mg. Maximum levels of these enzymes were 3.34, 3.00 and 3.19 times of control, respectively. Both of alkaline phosphatase and triglyceride values in the treatment groups were decreased compared with control. In the case of alkaline phosphatse, the values were significanly decreased from 24 hours and more severely decreased until 72 hours in the treatment groups of 40 mg above (p<0.01). The minimum value was 0.36 times<br/> of control in the 200 mg group. The values of triglyceride were significantly decreased in the tratment groups of 40 mg above (p<0.01), but the values were not different significantly among the treatment groups. This study demonstrates that plasma DNA content and serum biochemical values such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase and triglyceride are valuable as biomarkers for exposure assessment and diagnosis of lead poisoning.

랫드에서 혈액검사에 영향을 미치는 요인들과 경정맥 채혈법의 시술에 관하여

조준형(Joon-Hyoung Cho),정상희(Sang-Hee Jeong),구현옥(Hyun-Ok Ku),강환구(Hwan-Goo Kang),박종명(Jong-Myung Park),윤효인(Hyo-In Yun),이영순(Yong-Soon Lee) 한국실험동물학회 1997 Laboratory Animal Research Vol.13 No.1

Are Payday Loan Service Providers Located in Bank Desert? Applying Spatial Void Hypothesis to Seoul, Korea

Hyoung Jun Kim(김형준),Bo Kyeong Lee(이보경),Joon Hyung Cho(조준형),So Young Sohn(손소영) 대한지리학회 2017 대한지리학회 학술대회논문집 Vol.2017 No.6

카드뮴의 Salmonella typhimurium 변이균주 및 랫드 간장 상피세포에서의 유전독성

정상희,조명행,조준형,Jeong, Sang-hee,Cho, Myung-haing,Cho, Joon-hyoung 대한수의학회 1998 大韓獸醫學會誌 Vol.38 No.3

Cadmium is one of the well-known environmental toxicants and induces cancer in rodents and human, but its carcinogenic mechanism has not been well demonstrated until now. Genotoxic effects of cadmium in Salmonella typhimurium TA98, TA100 and TA1535/pSK1002 or in WB-F344 rat liver epithelial cells were investigated to elucidate the tumor initiating effects of cadmium. TA98, TA100 and TA1535/pSK1002 tester strains were used to detect frameshift mutation, base-pair mutation and SOS repair response, respectively, in Salmonella mutation test. Reverse mutations from histidine to $histidin^+$ of Salmonella typhimurium TA98 and TA100 by $CdCl_2$ were not significantly different from control up to the maximum doses ($100{\mu}M$ and $200{\mu}M$ in TA98 and TA100, respectively) at which non-cytotoxicity was observed. DNA SOS repair responses(${\beta}$-galactosidase activity) generally did not show significant increases compared to control in both of the conditions with or without metabolic activation in Salmonella typhimurium TA1535/pSK1002 by $CdCl_2$. But the activities of ${\beta}$-galactosidase by $400{\mu}M$ of $CdCl_2$ in metabolic activation condition and by 130 and $400{\mu}M$ of $CdCl_2$ in non-metabolic activation condition were more decreased than those of control. DNA single strand breaks for 4hrs were observed only in WB-F344 rat liver epithelial cells treated with $200{\mu}M$ of $CdCl_2$. As a conclusion, $CdCl_2$ did not induce gene mutation in microbials but induce DNA single strand breaks in rat liver epithelial cells.

Rat에서 설파메타진의 대사 및 약물동태학

윤효인,박승춘,박종명,조준형,이문한,Yun, Hyo-in,Park, Seung-chun,Park, Jong-myung,Cho, Joon-hyoung,Lee, Mun-han 대한수의학회 1995 大韓獸醫學會誌 Vol.35 No.4

We used rats as the experimental animal for the elucidation of metabolic patterns and pharmacokinetic profiles of SMZ in the rat, by use of the urine and plasma from predetermined intervals, respectively. Information herefrom would give some insight into species differences and sex differences in the metabolism and pharamcokinetics of drugs, at least SMZ in particular. Results would be summarized as follows: 1. There were two hydorxy metabolites(5-hydroxysulfamethazine and 6-hydroxyethylsulfamethazine) and an acetyl derivative($N_4$-acetyl sulfamethazine) in the 24h-collected urine, on confirmation with each standard materials. There were also two unknown metabolites therein. 2. In the viewpoint of quantitative aspect, $N_4$-acetylsulfamethazine was the largest, hence it is assumed that the acetyl pathway is the major one in the metabolism of SMZ in the rat. 3. As regards sex difference in the rat, the male had more metabolic capacity than the female in metabolism of SMZ. 4. The concenteration-time curves of sulfamethazine(20mg/kg, po) in the plasma compartment were fitted to a one-compartment open model by use of a computer program(NONLIN). 5. There were significant differences(P<0.05) in the pharmacokinetics of sulfamethazine between two sexes in the rat, with higher disposition rate in the male. 6. The emergence of $N_4AcSMZ$ metabolized from SMZ was fast in the plasma of the rat. Half-life of $N_4AcSMZ$ was also. significantly different(P<0.05) between two sexes, suggesting differences in the eliminatory capacity of $N_4AcSMZ$.

돼지와 랫트에서 sulfamethazine의 약물동태학 및 조직분포

윤효인,박승춘,오태광,조준형,박종명,Yun, Hyo-in,Park, Seung-chun,Oh, Tae-kwang,Cho, Joon-hyoung,Park, Jong-myeong 대한수의학회 1997 大韓獸醫學會誌 Vol.37 No.2

In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.

Pharmacokinetic profiles of norfloxacin after intravenous and oral administration in the rabbits

박승춘,윤효인,오태광,조준형,Park, Seung-chun,Yun, Hyo-in,Oh, Tae-kwang,Cho, Joon-hyoung The Korean Society of Veterinary Science 1995 大韓獸醫學會誌 Vol.35 No.4

임상적으로 건강한 New Zealand White 종인 수컷 토끼에서 항생제 norfloxacin(NFX)의 체내 동태를 조사하기 위하여 체중 kg당 5mg을 정맥 및 경구 투여하였다. 그 결과 빠른 분포기와 소실기를 갖는 2-콤파트먼트 모델 양상으로 나타났다. 혈장에서의 약물분석은 HPLC로 실시하였는데, 이동상은 acetonitrile/0.01M phosphate buffer/ 10% citric acid 1mM heptane sulfonic acid(10/70/20)이었고, 흡수 파장은 274nm에서 실시하였다. 정맥 투여후, 생물학적 반감기는 3.14시간으로 나타났으며, 분포반감기는 0.38시간으로 빠른 분포를 보여주었다. 최고 혈중농도는 $24.27{\mu}g/ml$로 계산되었으며 청소율은 0.68ml/kg/h로 분석되었다. 경구 투여후, 최고 혈중 농도와 최고 혈중 도달 시간은 $0.86{\mu}g/ml$과 0.43시간으로 각각 계산되었다. 이때의 생물학적 반감기는 3.61시간으로 정맥 투여시와 유의성 있는 차이는 없었으며, 흡수 반감기는 0.17시간으로 빠른 흡수를 보여주었다. 생체이용율은 30%로 나타났으며, 0.2-1.6g/ml인 치료혈중 농도 범위에서 혈장 결합율은 26%로 나타나, 토끼에서 항생요법은 구강 투여시 초기 투여량은 2.71mg/kg이며, 유지 투여량은 12시간마다 2.54mg/kg이 적당한 것으로 분석되었다.

이스라엘잉어 장관 수축에 관여하는 약물수용체에 관한 연구

윤효인,한경호,박승춘,조준형,오태광,Yun, Hyo-in,Han, Kyong-oh,Park, Seung-chun,Cho, Joon-hyoung,Oh, Tae-kwang 대한수의학회 1994 大韓獸醫學會誌 Vol.34 No.3

In order to elucidate the characterization of receptors involved in inestinal motility of Israeli carp, spontaneously contracting Israeli carp intestinal preperations were prepared and mounted in the organ chambers for contraction traicings using a polygraph. Various contractile agonists were treated and their dose-response curves were constructed. $EC_{50}$ values$(pD_2)$ of each agonist on specific receptors, $pA_2$ values of competitive antagonists against some agonists, and $K_1$, values of noncompetitive antagonists against some agonists were analyzed for characterization of receptors related with the intestinal contraction. Results obtained through the experiments were summarized as follows: 1. Acetylcholine(ACh) exhibited biphasic dose-response curves: initial ACh-induced dose dependent contractions were observed in pM levels but followed by decreased response in in-between concentration levels. Dose dependent contractions reappeared in ${\mu}M$ level. The peaks in pM and ${\mu}M$ levels appeared in $10^{-13}M$ and $3{\times}10^{-5}M$, respectvely. 2. Carbachol(CaCh) exhibited dose dependent contractions from $10^{-9}M$ to $10^{-5}M$, and its $pD_2$ values were higher than those of ACh($5.60{\pm}0.11$). ACh and CaCh exhibited equiactive contractions. Nicotine had no effects on contractile responses of Israeli carp intestine. 3. ACh-induced responses were inhibited by atropine($K_1:7{\times}10^{-8}M$), a muscarinic antagonist, in a non-competitive manner. But CaCh-induced responses were inhibited by both antimuscarinic atropine($pA_2:9.52{\pm}0.14$) and selective $M_2$ antagonistic 4-DAMP($pA_2:8.16{\pm}0.09$), in competitive manners. Nicotine receptor antagonistic decamethonium and hexamethonium had no effects on ACh-and CaCh-induced contractions. Therefore, the cholinergic receptor related to intestinal motility of Israeli carp was assumed as $M_2$ type. 4. In Israeli carp intestine, 5-HT (serotonin) exhibited dose dependent contractions in concentration range from $10^{-8}M$ to $10^{-5}M$. The maximal responses, however, were corresponded to about 50% of those of ACh or CaCh. 5-HT induced contractions were inhibited by $5-HT_2$ antagonistic ketanserin ($K_1: 7.8{\times}10^{-4}M$) in a non-competitive manner, but not by both of anti $5-HT_1$, spiperone and anti $5-HT_3$, MDL-72222. Hence, $5-HT_2$ receptors are suggested to be existed in Isreli carp intestine.