• Archives of Pharmacal Research
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• v.21 no.4
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• pp.370-373
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• 1998

Ten substituted phenacyl derivatives of 4-hydroxypiperidine were synthesized and studied for their effects on the mean arterial blood pressure (MABP) in normotensive anaesthetized rats and smooth muscles contractions of isolated rabbit jejunum. Two derivatives caused fall in blood pressure at the dose of 10-20 mg/kg and one rise in blood pressure at the dose of 20 mg/kg. Two compounds exhibited biphasic response (hypotensive followed by hypertensive) and one gave triphasic response at 10 mg/kg dose. Rest of four derivatives were found devoid of any effect on mean arterial blood pressure up to the dose of 30 mg/kg. All the derivatives except two caused relaxant effect on the spontaneous contraction of rabbit jejunum at the dose range of 0.1 -2 mg/kg.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.301-301
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• 1994

〔$^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

• 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.

• Nuclear Engineering and Technology
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• v.38 no.3
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• pp.285-292
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• 2006

Thermoresistant (TR) clones of radiation-induced fibrosarcoma (RIF) cells have been reported to show an adaptive response to 1cGy of low dose radiation, and HSP25 and inducible HSP70 are involved in this process. In this study, to further elucidate the mechanism by which HSP25 and inducible HSP70 regulate the adaptive response, HSP25 or inducible HSP70 overexpressed RIF cells were irradiated with 1cGy and the cell cycle was analyzed. HSP25 or inducible HSP70 overexpressed cells together with TR cells showed increased G1 phase after 1cGy irradiation, while RIF cells did not. $[^3H]-Thymidine$ and BrdU incorporation also indicated that both HSP25 and inducible HSP70 are involved in G1 arrest after 1cGy irradiation. Molecular analysis revealed upregulation of p27Cip/Kip protein in HSP25 and inducible HSP70 overexpressed cells, and cotransfection of p27Cip/Kip antisense abolished the induction of the adaptive response and 1cGy-mediated G1 arrest. The above results indicate that induction of an adaptive response by HSP25 and inducible HSP70 is mediated by upregulation of p27Cip/Kip protein, resulting in low dose radiation-induced G1 arrest.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.65-69
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• 1997

Purpose : To obtain the actual dose distribution from measured data by doconvolution method using the measured ion chamber response function. Materials and Methods : The chamber response functions for 2 ionization chambers (diameter 5mm, 6.4mm) were measured. and dose Profiles were measured for $10{\times}20cm^2$ field size using two different detectors. The deconvolution of chamber response function from the measured data were performed for these Profiles. The same procedures were repeated for 4MV, 6MV and 1 SMV photon energies. Results : Different dose Profiles were obtained for the same field with the chambers which have the different response functions. Nearly the same results could be obtained with deconvolution for the profiles from various detectors. Conclusion : The effect of the chamber response function can be extracted by deconvolution method. Deconvolved dose profile using various ionization chambers gave better dose distributions. Technical improvements are needed for practical application.

• Journal of Food Hygiene and Safety
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• v.15 no.3
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• pp.267-270
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• 2000

This study was designed to predict the risk of a hazard chemical, vinyl chloride, by applying dose-response assessment that are one of the major process in practicing risk assessment. After extrapolating from the high dose exposure of vinyl chloride based upon animal carcinogenic data to the low dose exposed to human using several mathematical models, we calculated the cancer potency factors as well as virtually safe dose and the resulted values were compared. This process will provide the new insight to assess the risk of a chemical accurately imposed to human in the future.

• Journal of Food Hygiene and Safety
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• v.14 no.4
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• pp.319-326
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• 1999

Recently, it is continuously rising to concern about the health risk being induced by microorganisms in food such as Escherichia coli O157:H7 and Listeria monocytogenes. Various organizations and regulatory agencies including U.S.FPA, U.S.DA and FAO/WHO are preparing the methodology building to apply microbial quantitative risk assessment to risk-based food safety program. Microbial risks are primarily the result of single exposure and its health impacts are immediate and serious. Therefore, the methodology of risk assessment differs from that of chemical risk assessment. Microbial quantitative risk assessment consists of tow steps; hazard identification, exposure assessment, dose-response assessment and risk characterization. Hazard identification is accomplished by observing and defining the types of adverse health effects in humans associated with exposure to foodborne agents. Epidemiological evidence which links the various disease with the particular exposure route is an important component of this identification. Exposure assessment includes the quantification of microbial exposure regarding the dynamics of microbial growth in food processing, transport, packaging and specific time-temperature conditions at various points from animal production to consumption. Dose-response assessment is the process characterizing dose-response correlation between microbial exposure and disease incidence. Unlike chemical carcinogens, the dose-response assessment for microbial pathogens has not focused on animal models for extrapolation to humans. Risk characterization links the exposure assessment and dose-response assessment and involve uncertainty analysis. The methodology of microbial dose-response assessment is classified as nonthreshold and thresh-old approach. The nonthreshold model have assumption that one organism is capable of producing an infection if it arrives at an appropriate site and organism have independence. Recently, the Exponential, Beta-poission, Gompertz, and Gamma-weibull models are using as nonthreshold model. The Log-normal and Log-logistic models are using as threshold model. The threshold has the assumption that a toxicant is produce by interaction of organisms. In this study, it was reviewed detailed process including risk value using model parameter and microbial exposure dose. Also this study suggested model application methodology in field of exposure assessment using assumed food microbial data(NaCl, water activity, temperature, pH, etc.) and the commercially used Food MicroModel. We recognized that human volunteer data to the healthy man are preferred rather than epidemiological data fur obtaining exact dose-response data. But, the foreign agencies are studying the characterization of correlation between human and animal. For the comparison of differences to the population sensitivity: it must be executed domestic study such as the establishment of dose-response data to the Korean volunteer by each microbial and microbial exposure assessment in food.

• Toxicological Research
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• v.6 no.2
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• pp.205-213
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• 1990

The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.

• Korean Journal of Breeding Science
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• v.40 no.1
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• pp.15-21
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• 2008

It was previously pointed out that mutation is the ultimate source of variation. Adequate variation is needed for plant breeding if there is a limitation in natural genetic resources. When the ionizing radiation has been known to cause chromosomal and genomic alternations, it is widely used for inducing mutagenesis. The electron beam as an ionizing radiation is the principal physical mutagens that induces mutation and effectively used in plant breeding. Since dose-response relationships of electron beam in plant species are rarely known, we investigated the seed germination rate and early seedling growth of irradiated seeds of creeping bentgrass (Agrostis palustris Huds., cv Penn-A1) with various electron beam irradiating conditions (1, 1.3, 2 MeV at both 0.03 mA and 0.06 mA with dose of 100 Gy (Gray) and 0.03, 1, 1.3, 2 MeV at 0.03 mA with dose of 200 Gy, respectively) using electron accelerator at Korea Atomic Energy Research Institute. The growth parameters in terms of shoot length, primary root length, and secondary root length showed similar response between 0.06 / 1 (mA / MeV) at 100 Gy and 0.03 / 0.3 (mA / MeV) at 200 Gy. Bentgrass seed germination was mainly affected by the intensity of irradiated dose (Gray). Germination rate was lowered as the irradiated dose increased. On the other hand, early seedling growth was mainly governed not by the dose of radiation but by voltage.

• Nuclear Engineering and Technology
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• v.55 no.6
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• pp.1949-1958
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• 2023

The International Commission on Radiological Protection (ICRP) Publication 116 was released to provide a comprehensive dataset of the dose coefficients (DCs) for external exposures produced with the adult reference voxel phantoms of ICRP Publication 110. Although an advanced skeletal dosimetry method for photons and neutrons using fluence-to-dose response functions (DRFs) was introduced in ICRP Publication 116, the ICRP-116 skeletal DCs were calculated by using the simple method conventionally used (i.e., doses to red bone marrow and endosteum approximated by doses to spongiosa and/or medullary cavities). In the present study, the photon and neutron DRFs were used to produce skeletal DCs of the ICRP-110 reference phantoms, which were then compared with the ICRP-116 DCs. For photons, there were significant differences by up to ~2.8 times especially at energies <0.3 MeV. For neutrons, the differences were generally small over the entire energy region (mostly <20%). The general impact of the DRF-based skeletal DCs on the effective dose calculations was negligibly small, supporting the validity of the ICRP-116 effective DCs despite their skeletal DCs derived from the simple method. Meanwhile, we believe that the DRF-based skeletal DCs could be beneficial in better estimates of skeletal doses of individuals for risk assessments.