• Title/Summary/Keyword: Dose-response Function

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

  • 최은영;박경진
    • 한국식품위생안전성학회지
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    • 제19권1호
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    • pp.19-24
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    • 2004
  • 미생물 위해성 평가의 용량-반응 모델은 생물학적 모델과 경험적 모델로 나눌 수 있다. 생물학적 모델은 미생물의 분포형태, 미생물에 대한 숙주의 감수성, 감염을 일으킬 수 있는 미생물 수에 대한 가정을 바탕으로 성립된 모델로서, 대표적으로 Exponential model과 $\beta$-Poisson model이 있다. 경험적 모델은 주로 화학물질의 독성을 나타내는데 이용되어 온 모델로, Weibull-Gamma model등이 있다. 여러 용량-반응 모델 중에서 실험 데이터에 적합한 모델을 걱정하는 데에는 deviance function(Y)을 이용하며, 현재 일부 식중독균에 대해서는 사람과 실험동물에서의 용량-반응 모델이 연구되어 있다.

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

  • 이상훈;조병철;김종훈;최은경;권수일;장혜숙;이병용
    • Radiation Oncology Journal
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    • 제15권1호
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    • pp.65-69
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    • 1997
  • 목적 : 전리함의 크기로 인한 공간 분해능의 문제로 나타나는 전리함 반응함수를 제거하여 실제 선량분포를 얻고자 하였다. 대상 및 방법 : 내경 5mm, 6.4mm 등 2개의 서로 다른 크기를 갖는 전리함들과 다이오드, 필름의 반응함수를 구하고, 동일한 방사선 조사면$(10\times20cm^2)$의 선량분포 프로파일을 측정하여, 각각 deconvolution 기법으로 보정한 후, 보절된 격과가 일치하는지 비교하였다. 결과 : 원통형 전리함의 반응함수와 선량분포를 측정하였고, 측정한 선량분포에서 반응 함수의 효과를 deconvolution방법으로 제거하여 실제 선량분포를 찾아내었다. 사용한 에너지는 최대 광자선 에너지 4MV, 6MV, 15MV였으며, 전 에너지 영역에 걸쳐 보정 된 결과가 일치하는 방향으로 변화하였으며, 분해능 증가 효과가 있었다. 결론 : deconvolution 방법으로 전리함 반응 함수의 효과를 제거했을 때, 여러 측정기를 이용하여 측정한 선량 프로파일의 결과가 일치하는 경향을 볼 수 있어서 deconvolution 방법을 통해 얻은 선량 프로파일을 임상적으로 응용할 수 있음을 알았다.

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

  • 황일태
    • Clinical and Experimental Pediatrics
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    • 제50권3호
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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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    • 제26권4호
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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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    • 제25권4호
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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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    • 제6권2호
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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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황기 부탄올 분획물이 생쥐의 체액성 면역기능에 미치는 영향 (Effects of the Butanol Fraction of Astragali Radix on the Humoral Immune Function in Mice)

  • 김정훈;문연자;이성원;임숙정;박정숙;우원홍
    • 약학회지
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    • 제45권6호
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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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Bleomycin, Mitomycin C 및 Cadmium에 의한 CHO 세포의 적응반응 (Adaptive Response in CHO Cells by Bleomycin, Mitomycin C and Cadmium)

  • 김양지;한정호;정해원
    • 한국환경보건학회지
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    • 제18권2호
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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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저선량 감마선 노출에 의한 비장세포의 염증 유발 작용에 대한 연구 (Effects of Low Dose Gamma Irradiation on the Inflammatory Response in Spleen Cells)

  • 손은화
    • KSBB Journal
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    • 제28권6호
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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
    • 방사선산업학회지
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    • 제7권2_3호
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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.