• Title/Summary/Keyword: Dose-response Function

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A Review of Dose-response Models in Microbial Risk Assessment (미생물 위해성 평가의 용량-반응 모델에 대한 고찰)

  • 최은영;박경진
    • Journal of Food Hygiene and Safety
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    • v.19 no.1
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    • pp.19-24
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    • 2004
  • Dose-response models in microbial risk assessment can be divided into biologically plausible models and empirical models. Biologically plausible models are formed by the assumptions in dose distribution of microbes, host sensitivity to microbes, and minimal infectious dose of microbes : there are Exponential model and $\beta$-Poisson model, representatively. Empirical models are mainly used to express the toxicity of chemicals : there are Weibull-Gamma model etc. Deviance function (Y) is used to fit available data to dose-response models, and some dose-response models for food-borne pathogens are developed in humans and experimental animals.

Direct Measurement of Chamber Response Function and Its Application to Radiation Dose Distribution Dosimetry (전리함 반응 함수의 직접 측정과 이를 이용한 방사선의 실제선량 분포측정)

  • Lee Sang Hoon;Cho Byung Chul;Kim Jong Hoon;Choi Eun Kyung;Kwon Soo Il;Chang Hyesook;Yi Byong Yong
    • 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.

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Evaluation of function and disorders of the adrenal gland in neonates (신생아에서의 부신기능 평가와 질환)

  • Hwang, Il Tae
    • Clinical and Experimental Pediatrics
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    • v.50 no.3
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    • pp.236-240
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    • 2007
  • Majority of sick full term newborns have adequate adrenal cortical function in response to stress. Acutely ill neonates with a basal cortisol level less than $15{\mu}g/dL$ (414 nmol/L) suggest adrenal insufficiency and require function testing of adrenal function. In premature infant, immaturity of hypothalamic-pituitary adrenal axis (HPA axis), may limit the ability to increase cortisol production in response to stress. The response to low dose ACTH and CRH appears to be useful as an additional test of adrenal function. CRH stimulation has been used increasingly in neonates. The ACTH and CRH stimulated cortisol response of more than $17{\mu}g/dL$ (469 nmol/L) indicates a normal response.

Pharmacodynamic principles and target concentration intervention

  • Holford, Nick
    • Translational and Clinical Pharmacology
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    • v.26 no.4
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    • pp.150-154
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    • 2018
  • This tutorial reviews the principles of dose individualisation with an emphasis on target concentration intervention (TCI). Once a target effect is chosen then pharmacodynamics can predict the target concentration and pharmacokinetics can predict the target dose to achieve the required response. Dose individualisation can be considered at three levels: population, group and individual. Population dosing, also known as fixed dosing or "one size fits all" is often used but is poor clinical pharmacology; group dosing uses patient features such as weight, organ function and comedication to adjust the dose for a typical patient; individual dosing uses observations of patient response to inform about pharmacokinetic and pharmacodynamics in the individual and use these individual differences to individualise dose.

Simultaneous degradation of nitrogenous heterocyclic compounds by catalytic wet-peroxidation process using box-behnken design

  • Gosu, Vijayalakshmi;Arora, Shivali;Subbaramaiah, Verraboina
    • Environmental Engineering Research
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    • v.25 no.4
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    • pp.488-497
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    • 2020
  • The present study investigates the feasibility of nitrogenous heterocyclic compounds (NHCs) (Pyridine-Quinoline) degradation by catalytic wet peroxidation (CWPO) in the presence of nanoscale zerovalent iron supported on granular activated carbon (nFe0/GAC) using statistical optimization technique. Response surface methodology (RSM) in combination with Box-Behnken design (BBD) was used to optimize the process parameters of CWPO process such as initial pH, catalyst dose, hydrogen peroxide dose, initial concentration of pyridine (Py) and quinolone (Qn) were chosen as the main variables, and total organic carbon (TOC) removal and total Fe leaching were selected as the investigated response. The optimization of process parameters by desirability function showed the ~85% of TOC removal with process condition of initial solution pH 3.5, catalyst dose of 0.55 g/L, hydrogen peroxide concentration of 0.34 mmol, initial concentration of Py 200 mg/L and initial concentration of Qn 200 mg/L. Further, for TOC removal the analysis of variance results of the RSM revealed that all parameter i.e. initial pH, catalyst dose, hydrogen peroxide dose, initial concentration of Py and initial concentration of Qn were highly significant according to the p values (p < 0.05). The quadratic model was found to be the best fit for experimental data. The present study revealed that BBD was reliable and effective for the determination of the optimum conditions for CWPO of NHCs (Py-Qn).

BIOLOGICALLY-BASED DOSE-RESPONSE MODEL FOR NEUROTOXICITY RISK ASSESSMENT

  • Slikker, William Jr.;Gaylor, David W.
    • 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.

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Effects of the Butanol Fraction of Astragali Radix on the Humoral Immune Function in Mice (황기 부탄올 분획물이 생쥐의 체액성 면역기능에 미치는 영향)

  • 김정훈;문연자;이성원;임숙정;박정숙;우원홍
    • YAKHAK HOEJI
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    • v.45 no.6
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    • pp.670-676
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    • 2001
  • Effect of the butanol fraction of Astragali Radix (BFAR) on the humoral immune response were investigated in ICR mice. Mice were divided into 4 groups and BFAR at doses of 5,25 and 125 mg/kg were administered orally to mice daily for 3 weeks, and the normal animals were given vehicle. The results of this study are summarized as follows; the relative weight of spleen was markedly increased by BFAR treatment, compared with that in normal mice. However, the body weight gain and the relative weight of liver were not affected. Splenic plaque forming cells and hemagglutination titers to sheep red blood cells, and the secondary IgG antibody response to bovine serum albumin were also dose-dependently enhanced by BFAR treatment. In these mice, BFAR did not increase serum alanine aminotransferase total protein, sect albumin and albumin/globulin ratio when compared with those in normal mice. Thus, these findings indicate that BFAR significantly enhances humoral immune response to antigen in concentrations that do not affected liver function.

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Adaptive Response in CHO Cells by Bleomycin, Mitomycin C and Cadmium (Bleomycin, Mitomycin C 및 Cadmium에 의한 CHO 세포의 적응반응)

  • 김양지;한정호;정해원
    • Journal of Environmental Health Sciences
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    • v.18 no.2
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    • pp.117-124
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    • 1992
  • Pretreatment with low concentration of Bleomycin and Cadmium rendered Chinese Hamster Ovary Cells more resistant to the induction of chromosome aberration by subsequent high concentration of same agent, however Mitomycin C did not function in that way. The cells pre-exposed to low dose of Cadmitim did not show cross-resistance to challenge dose of Mitomycin C for the induction of chromosome aberration, but cells pre-exposed to Bleomycin showed cross resistance. And the cells pre-exposed to low dose of Mitomycin C showed cross resistance to challenge of Bleomycin, but Cadmium did not.

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Effects of Low Dose Gamma Irradiation on the Inflammatory Response in Spleen Cells (저선량 감마선 노출에 의한 비장세포의 염증 유발 작용에 대한 연구)

  • Sohn, Eun-Hwa
    • KSBB Journal
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    • v.28 no.6
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    • pp.415-422
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    • 2013
  • Gamma irradiation (${\gamma}IR$) is widely used for radiotherapy as a treatment of cancer cells although it has a risk to damage normal cells. Inflammation is regarded as one of side effects of ${\gamma}IR$ while the effect of low dose of ${\gamma}IR$ on inflammation has not been researched well. Here, we investigated the inflammatory responses of low dose of ${\gamma}IR$ on murine spleen cells. It was evaluated if ${\gamma}IR$ affected the mitogen-induced lymphocyte proliferation, the regulation of various inflammatory cytokines (IFN-${\gamma}$, IL-2, IL-17, IL-4, IL-10), and the involvement of Ikaros and MAPK/NF-${\kappa}B$ medicated mechanism. Exposure of $^{137}Cs-{\gamma}IR$ below 2 Gy decreased the lymphocytes proliferative response to mitogens (LPS, ConA) except at the lowest dose, 0.05 Gy. IL-17, IL-2 and IL-4 mRNA increased at 0.5 and 2 Gy, but not altered at 0.05 Gy. IL-10, anti-inflammatory cytokine, increased only at 0.05 Gy. In regard to intracellular signaling, p-JNK, p-p38 and p-$I{\kappa}B{\alpha}$ were not changed, whereas the activation of ERK and Ikaros increased at the lowest dose. These results suggest that exposure of ${\gamma}IR$ less than 0.5 Gy (or below 0.05 Gy) has beneficial effects as a radiation hormesis on immune function.

Induction of SOS Genes by a Low Dose of Gamma Radiation, 10 Gy, in Salmonella enterica Serovar Typhimurium

  • Lim, Sangyong;Joe, Minho;Seo, Hoseong;Kim, Dongho
    • Journal of Radiation Industry
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    • v.7 no.2_3
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    • pp.109-113
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    • 2013
  • In a previous study, a relatively high dose of gamma radiation (1 kGy) did not fully induce typical SOS genes such as sulA, recA, recN, and din in Salmonella Typhimurium (S. Typhimurium) (Lim et al. 2008, Gene expression profiles following high-dose exposure to gamma radiation in Salmonella enterica serovar Typhimuium. J. Radiat. Ind. 3:111-119). In this study, we examined changes in the transcriptional repertoire of S. Typhimurium after a dose of 10 Gy using DNA microarrays. It was found that more than half (~65%) of the 26 up-regulated genes belong to the SOS regulon: ten genes are typical SOS genes, and seven genes are Salmonella prophage genes, which are known to be activated by LexA cleavage. Among 29 down-regulated genes, the function of five genes with the most decreased expression is associated with carbohydrate transport and energy production. This suggests that upon exposure to gamma radiation cells may cease growing by reducing the metabolic activity, and repair DNA damage using a DNA repair system such as the SOS response system. The difference in expression of the SOS genes between a high (1 kGy) and low (10 Gy) dose of radiation shows the possibility that cells may opt for one of multiple regulatory circuits in response to the specific gamma radiation dose.