• Journal of Pharmaceutical Investigation
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• v.39 no.5
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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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• v.21 no.2 s.24
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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.

• The Journal of Korean Society for School & Community Health Education
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• v.18 no.1
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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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• v.30 no.10
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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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• v.20 no.2
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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.

• Research in Community and Public Health Nursing
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• v.26 no.2
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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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• v.15 no.4
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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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• v.9 no.3
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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.

• The Korean Journal of Zoology
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• v.18 no.1
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• pp.41-49
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• 1975

Dose response and time dependence of DNA repair synthesis were investigated to determine the possible relationship between DNA repair synthesis and chromosome exchanges in $\\gamma$-ray irradiated BHK-21 and KB cell lines. DNA repair synthesis induced by $\\gamma$-ray was dose dependent up to 5kR, then leveling off occurred until 50 kR was reached. Time dependence of DNA repair synthesis was continued for up to 1$\\sim$2 hours after irradiation although the initial dose responses were cell line specific. Chromosome exchanges induced by $\\gamma$-ray showed different radiosensitivities in these cell lines and did not show a correlation with the DNA repair synthesis.

• Radiation Oncology Journal
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• v.29 no.2
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• pp.63-70
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• 2011

Purpose: To evaluate the extent of pain response and objective response to palliative radiotherapy (RT) for bone metastases from hepatocellular carcinoma according to RT dose. Materials and Methods: From January 2007 to June 2010, palliative RT was conducted for 103 patients (223 sites) with bone metastases from hepatocellular carcinoma. Treatment sites were divided into the high RT dose and low RT dose groups by biologically effective dose (BED) of 39 $Gy_{10}$. Pain responses were evaluated using the numeric rating scale. Pain scores before and after RT were compared and categorized into 'Decreased', 'No change' and 'Increased'. Radiological objective responses were categorized into complete response, partial response, stable disease and progression using modified RECIST (Response Evaluation Criteria In Solid Tumors) criteria; the factors predicting patients' survival were analyzed. Results: The median follow-up period was 6 months (range, 0 to 46 months), and the radiologic responses existed in 67 RT sites (66.3%) and 44 sites (89.8%) in the high and low RT dose group, respectively. A dose-response relationship was found in relation to RT dose (p=0.02). Pain responses were 75% and 65% in the high and low RT dose groups, respectively. However, no statistical difference in pain response was found between the two groups (p=0.24). There were no differences in the toxicity profiles between the high and low RT dose groups. Median survival from the time of bone metastases diagnosis was 11 months (range, 0 to 46 months). The Child-Pugh classification at the time of palliative RT was the only significant predictive factor for patient survival after RT. Median survival time was 14 months under Child-Pugh A and 2 months under Child-Pugh B and C. Conclusion: The rate of radiologic objective response was higher in the high RT dose group. Palliative AT with a high dose would provide an improvement in patient quality of life through enhanced tumor response, especially in patients with proper liver function.