• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.373-379
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• 2009

This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.

• Journal of Preventive Medicine and Public Health
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• 제21권2호
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• pp.295-306
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• 1988

Dose-response relationship among blood cadmium concentrations, catalase and superoxide dismutase activities were studied with acutely intoxicated rats by cadmium. The Sprague-Dawley male rats to which single dose of $1{\sim}32mg/kg\;CdCl_2$ were administered into peritoneal cavity were sacrificed by decapitation at $3{\sim}36$ hours after the administration. Cadmium concentrations in blood increased significantly with dose of $CdCl_2$ administered and reached peak level at 3 hours later. Catalase activities in rats' testes were not correlated with esposure time elapsed after the administration in rats to which $1{\sim}2mg/kg\;of\;CdCl_2$ were administered, but they showed linear relationship with time in groups to which $4{\sim}32mg/kg\;of\;CdCl_2$ were administered. Cu, Zn-SOD activities in testes of acutely intoxicated rats by cadmium were not altered either by dosage or by time elapsed after the administration. Mn-SOD activities in the testes were also not influenced by dosage of $1{\sim}2mg/kg\;CdCl_2$, but remarkably inactivated by dosage of $4{\sim}32mg/kg\;CdCl_2$ with time elapsed after the administration. Neither catalase, Cu, Zn-SOD nor Mn-SOD activities of testes were correlated with blood cadmium concentrations in acutely intoxicated rats by cadmium.

• 한국학교ㆍ지역보건교육학회지
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• 제18권1호
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• pp.1-12
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• 2017

Objectives: This study aimed to analyze sexual experience rates according to socio-demographic factors, health behavioral factors, and internet use time, and to identify sex experience related factors in high school students using the data from the 11th Korean Youth Health Risk Behavior Web-Based Survey. Methods: A total of 33,744 students (17,346 boys and 16,398 girls) in high schools were analyzed using the SPSS WIN version 22 program. SPSS complex samples methods were used for analyses. Socio-demographic factors, health behavioral factors, and internet use time as independents variables were included. The complex samples logistic regression analyses were used to calculate the odds ratio of the sexual experience according to the socio-demographic factors, health behavioral factors and internet use time. Unweighted frequencies and percentages were represented in result tables. Results: 3.6% of girls and 9.9% of boys in high school had sexual experiences. Daily average smoking amount and daily alcohol drinking amount were a dose-response relationship with sexual experience after considering confounding factors. Students who smoke 10-19 cigarettes had 5.74 times higher risk and 20 cigarettes or more had 7.27 times higher risk of sexual experiences, comparing with non-smoking students, relatively. Likewise, students who drink soju less than 1-2 bottles and more than 2 bottles had 3.82- and 4.35 times higher chance of sexual experiences, compared with non drinking students, respectively. Conclusions: We found that there were the dose-response relationship between health behavioral characteristics and sexual experiences. Further research is needed to identify an interaction effect between smoking and drinking alcohol on sexual experiences in high school students.

• Bulletin of the Korean Chemical Society
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• 제30권10호
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• pp.2309-2317
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• 2009

Depurination, the release of purine bases from nucleic acids by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Though cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a replacement for chloroflurocarbons and 1,1,1-trichloroethane as a cleaning solvent in electronics industry. However, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. Owing to the toxicity of 2-BP, there has been a tendency to use 1-BP as an alternative cleaning solvent to 2-BP. However, 1-BP has also been reported to be neurotoxic in rats. Though $N^7$-guanine adduct of 2-BP has been reported previously, massive depurination of the nucleosides and calf thymus DNA was observed in this study. We incubated the nucleosides (ddG, dG, guanosine, ddA, dA and adenosine) with excess amount 2-BP at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and LC-MS/MS. In addition, the time and dose response relationship of depurination in nucleosides induced by 2-bromopropane at the physiological condition was investigated. Similarly, incubation of calf-thymus DNA with the excess amount 2-BP at the physiological condition was also performed. In addition, the time and dose response relationship of depurination in calf-thymus DNA induced by 2-BP at the physiological condition was investigated. Those results suggest that the toxic effect of 2-BP could be both from the depurination of nucleosides and DNA adduct formation.

• Toxicological Research
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• 제20권2호
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• pp.89-100
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• 2004

The comet assay (also called the single-cell gel electrophoresis assay) has been widely used for detecting DNA damage and repair in individual cells. Since the conventional methods of evaluating comet assay data using frequency statistics are unsatisfactory we developed a new quantitative measure of DNA damage/repair that is based on all information residing in the dose/time-response curves of a comet experiment. Blood samples were taken from 25 breast cancer patients before undergoing radiotherapy. The comet assay was performed under alkaline conditions using isolated lymphocytes. Tail DNA, tail length, tail moment and tail inertia of the comet were measured for each patient at four doses of $\gamma$-rays (0, 2, 4 and 8 Gy) and at four time points after irradiation (0, 10, 20 and 30 min) using 100 cells each. The resulting three-dimensional dose-time response surface was modeled by multiple regression, and the second derivative, termed 2D, on dose and time was determined. A software module was programmed in SAS/AF to compute 2D values. We applied the new method successfully to data obtained from cancer patients to be assessed for their radiation sensitivity. We computed the 2D values for the four damage measures, i.e., tail moment, tail length, tail DNA and tail inertia, and examined the pairwise correlation coefficients of 2D both on the log scale and the unlogged scale. 2D values based on tail moment and tail DNA showed a high correlation and, therefore, these two damage measures can be used interchangeably as far as DNA repair is concerned. 2D values based on tail inertia have a correlation profile different from the other 2D values which may reflect different facets of DNA damage/repair. Using the dose-time response surface, other statistical models, e.g., the proportional hazards model, become applicable for data analysis. The 2D approach can be applied to all DNA repair measures, Le., tail moment, tail length, tail DNA and tail inertia, and appears to be superior to conventional evaluation methods as it integrates all data of the dose/time-response curves of a comet assay.

• 지역사회간호학회지
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• 제26권2호
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• pp.169-177
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• 2015

Purpose: Previous studies focused on the negative effects of Internet use such as obesity, depression, and addiction. However, few studies investigated whether the Internet use for an appropriate time has positive effects on adolescents' health. Thus, the purpose of the study was to examine the dose-response relationship between Internet use for non-academic purposes (NAP) and happiness/stress in adolescents. Methods: This study used data from the 2013 Korea Youth Risk Behavior Web-Based Survey. A total of 72,435 adolescents were included. Rao-Scott ${\chi}^2$ and multiple logistic regression were conducted. To test the dose-response relationship, this study examined how happiness/stress changed with increase in the time of Internet use for NAP. Results: After controlling for general characteristics, the odds ratios for being unhappy and stressful were lowest in adolescents using the Internet for NAP for more than 0 hour and less than an hour a day. Interestingly, students who did not use the Internet for NAP had a significantly higher risk of being unhappy/stressful than those using for more than 0 hour and less than an hour a day. Conclusion: Internet use for NAP for more than 0 hour and less than an hour a day has positive effects on happiness/stress in adolescents.

• Biomolecules & Therapeutics
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• 제15권4호
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• pp.224-229
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• 2007

Depurination, the release of purine bases from nucleosides by hydrolysis of the N-glycosidic bond, gives rise to alterations of the cell genome. Although, cells have evolved mechanisms to repair these lesions, unrepaired apurinic sites have been shown to have two biological consequences: lethality and base substitution errors. 2-Bromopropane (2-BP) is used as an intermediate in the synthesis of pharmaceuticals, dyes, and other organics. In addition, 2-BP has been used as a cleaning solvent in electronics industry. But, 2-BP was found to cause reproductive and hematopoietic disorders in local workers exposed to it. We observed massive depurination after incubation of 2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) with the excess amount 2-BP at the physiological condition (pH 7.4, $37^{\circ}C$), which were analyzed by HPLC and LC-MS/MS. In addition, time and dose response relationship of depurination in dA and dG induced by 2-BP at the physiological condition were investigated.

• Safety and Health at Work
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• 제9권3호
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• pp.290-295
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• 2018

Background: There is little information on the dose-response relationship between exposure to occupational carcinogenic agents and mesothelioma. This study aimed to investigate this association as well as the existence of agents other than asbestos that might cause mesothelioma. Methods: The Swedish component of the Nordic Occupational Cancer (NOCCA) study consists of 6.78 million individuals with detailed information on occupation. Mesothelioma diagnoses recorded in 1961-2009 were identified through linkage to the Swedish Cancer Registry. We determined cumulative exposure, time of first exposure, and maximum exposure intensity by linking data on occupation to the Swedish NOCCA job-exposure matrix, which includes 29 carcinogenic agents and corresponding exposure for 283 occupations. To assess the risk of mesothelioma, we used conditional logistic regression models to estimate hazard ratios and 95% confidence intervals. Results: 2,757 mesothelioma cases were identified in males, including 1,416 who were exposed to asbestos. Univariate analyses showed not only a significant excess risk for maximum exposure intensity, with a hazard ratio of 4.81 at exposure levels 1.25-2.0 fb/ml but also a clear dose-response effect for cumulative exposure with a 30-, 40-, and 50-year latency time. No convincing excess risk was revealed for any of the other carcinogenic agents included in the Swedish NOCCA job-exposure matrix. Conclusion: When considering asbestos exposure, past exposure, even for short periods, might be enough to cause mesothelioma of the pleura later in life.

• 한국동물학회지
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• 제18권1호
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• pp.41-49
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• 1975

DNA 回復合成과 染色體交換과의 聯關性을 추구하기 위해 감마線을 照射한 BHK-21 과KB 細胞의 DNA 回復合成의 線量反應과 時期를 調査하였다. 감마 線에 의한 DNA 回復合成率은 5kR까지 照射線量에 比例하나 그후 50kR 까지는 變化가 없었다. DNA 回復合成의 初期 線量反應은 細胞에 따라 다르나 照射후 1$\\sim$2時間까지 지속하였다. 감마 線에 의한 染色體交換은 細胞에 따라 다른 感受性을 보였고 DNA 回復合成과의 聯關性을 보여주지 않았다.

• Radiation Oncology Journal
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• 제29권2호
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• pp.63-70
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• 2011

목 적: 간세포암에 의한 뼈전이 환자의 방사선 조사선량에 따른 통증 감소 정도 및 전이성 병소의 영상학적 치료반응을 분석하고 고선량 방사선치료가 도움이 될 수 있는지 알아보고자 하였다. 대상 및 방법: 2007년 1월부터 2010년 6월까지 병리 혹은 임상적으로 간세포암에 의한 뼈전이로 진단받고 증상 완화 목적의 방사선치료를 받은 103명에서 뼈전이 병소 2237개 부위를 대상으로 연구하였다. 조사받은 생물학적 유효선량이 39 $Gy_{10}$이하인 경우 저선량군, 39 $Gy_{10}$를 초과하는 경우 고선량군으로 대상환자를 구분하였다. 통증 감소 정도는 숫자통증등급(numeric rating scale)을 이용하였고 통증이 감소한 경우, 통증 정도에 변화가 없는 경우, 통증이 증가한 경우로 나누었다. 영상학적 반응은 modified Response Evaluation Criteria In Solid Tumors (RECIST) 기준을 이용하였으며 환자의 생존율에 영향을 미치는 인자를 분석하였다. 결 과: 중앙추적 관찰기간은 6개월이었다(범위, 0~46개월). 저선량군에서는 67개 병소(66.3%) 부위에서, 고선량군 에서는 44개 병소(89.8%) 부위에서 영상학적 반응이 있었다 저선량군과 고선량군 사이에 영상학적 치료 반응 정도는 유의하게 차이를 보였다(p=0.02). 저선량군과 고선량군은 각각 65%와 75%의 통증 감소를 보였으나 통계적으로 유의한 차이는 없었다(p=0.24). 저선량군과 고선량군 사이에 급성 및 만성 치료 독성은 통계적으로 유의한 차이가 없었다(p>0.05). 뼈전이 진단 시부터 사망까지 생존기간은 0~46개월(중앙값, 11개월) 범위였고 1년 생존율은 41.6%였다. 잔존 간 기능(Child-Pugh 점수)이 생존율에 유의한 영향을 미치는 인자였고 Child-Pugh 점수에 따른 중앙생존기간은 A 14개월, 8와 C는 2개월로 나타났다. 결 론: 간세포암에 의한 뼈전이는 고선량군에서 영상학적 반응 정도가 더 높았다. 잔존 간 기능이 좋은 환자에게 고선량의 방사선치료 시 높은 치료 반응을 얻음으로써 삶의 질의 향상에 도움을 줄 수 있음을 알 수 있었다.