• 제목/요약/키워드: dose-response model

검색결과 303건 처리시간 0.03초

흰쥐의 술 후 통증 모델에서 T형 칼슘 통로 차단제인 Ethosuximide와 Mibefradil의 항통각과민 효과 (Antihyperalgesic Effects of Ethosuximide and Mibefradil, T-type Voltage Activated Calcium Channel Blockers, in a Rat Model of Postoperative Pain)

  • 신혜란;차영덕;한정욱;윤정원;김부성;송장호
    • The Korean Journal of Pain
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    • 제20권2호
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    • pp.92-99
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    • 2007
  • Background: A correlation between a T-type voltage activated calcium channel (VACC) and pain mechanism has not yet been established. The purpose of this study is to find out the effect of ethosuximide and mibefradil, representative selective T-type VACC blockers on postoperative pain using an incisional pain model of rats. Methods: After performing a plantar incision, rats were stabilized on plastic mesh for 2 hours. Then, the rats were injected with ethosuximide or mibefradil, intraperitoneally and intrathecally. The level of withdrawal threshold to the von Frey filament near the incision site was determined and the dose response curves were obtained. Results: After an intraperitoneal ethosuximide or mibefradil injection, the dose-response curve showed a dose-dependent increase of the threshold in a withdrawal reaction. After an intrathecal injection of ethosuximide, the threshold of a withdrawal reaction to mechanical stimulation increased and the increase was dose-dependent. After an intrathecal injection of mibefradil, no change occurred in either the threshold of a withdrawal reaction to mechanical stimulation or a dose-response curve. Conclusions: The T-type VACC blockers in a rat model of postoperative pain showed the antihyperalgesic effect. This effect might be due to blockade of T-type VACC, which was distributed in the peripheral nociceptors or at the supraspinal level. Further studies of the effect of T-type VACC on a pain transmission mechanism at the spinal cord level would be needed.

Modelling and packed bed column studies on adsorptive removal of phosphate from aqueous solutions by a mixture of ground burnt patties and red soil

  • Rout, Prangya R.;Dash, Rajesh R.;Bhunia, Puspendu
    • Advances in environmental research
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    • 제3권3호
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    • pp.231-251
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    • 2014
  • The present study examines the phosphate adsorption potential and behavior of mixture of Ground Burnt Patties (GBP), a solid waste generated from cooking fuel used in earthen stoves and Red Soil (RS), a natural substance in fixed bed column mode operation. The characterization of adsorbent was done by Proton Induced X-ray Emission (PIXE), and Proton Induced ${\gamma}$-ray Emission (PIGE) methods. The FTIR spectroscopy of spent adsorbent reveals the presence of absorbance peak at $1127cm^{-1}$ which appears due to P = O stretching, thus confirming phosphate adsorption. The effects of bed height (10, 15 and 20 cm), flow rate (2.5, 5 and 7.5 mL/min) and initial phosphate concentration (5 and 15 mg/L) on breakthrough curves were explored. Both the breakthrough and exhaustion time increased with increase in bed depth, decrease in flow rate and influent concentration. Thomas model, Yoon-Nelson model and Modified Dose Response model were used to fit the column adsorption data using nonlinear regression analysis while Bed Depth Service Time model followed linear regression analysis under different experimental condition to evaluate model parameters that are useful in scale up of the process. The values of correlation coefficient ($R^2$) and the Sum of Square Error (SSE) revealed the Modified Dose Response model as the best fitted model to the experimental data. The adsorbent mixture responded effectively to the desorption and reusability experiment. The results of this finding advocated that mixture of GBP and RS can be used as a low cost, highly efficient adsorbent for phosphate removal from aqueous solution.

Quantitative microbial risk assessment of Campylobacter jejuni in jerky in Korea

  • Ha, Jimyeong;Lee, Heeyoung;Kim, Sejeong;Lee, Jeeyeon;Lee, Soomin;Choi, Yukyung;Oh, Hyemin;Yoon, Yohan
    • Asian-Australasian Journal of Animal Sciences
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    • 제32권2호
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    • pp.274-281
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    • 2019
  • Objective: The objective of this study was to estimate the risk of Campylobacter jejuni (C. jejuni) infection from various jerky products in Korea. Methods: For the exposure assessment, the prevalence and predictive models of C. jejuni in the jerky and the temperature and time of the distribution and storage were investigated. In addition, the consumption amounts and frequencies of the products were also investigated. The data for C. jejuni for the prevalence, distribution temperature, distribution time, consumption amount, and consumption frequency were fitted with the @RISK fitting program to obtain appropriate probabilistic distributions. Subsequently, the dose-response models for Campylobacter were researched in the literature. Eventually, the distributions, predictive model, and dose-response model were used to make a simulation model with @RISK to estimate the risk of C. jejuni foodborne illness from the intake of jerky. Results: Among 275 jerky samples, there were no C. jejuni positive samples, and thus, the initial contamination level was statistically predicted with the RiskUniform distribution [RiskUniform (-2, 0.48)]. To describe the changes in the C. jejuni cell counts during distribution and storage, the developed predictive models with the Weibull model (primary model) and polynomial model (secondary model) were utilized. The appropriate probabilistic distribution was the BetaGeneral distribution, and it showed that the average jerky consumption was 51.83 g/d with a frequency of 0.61%. The developed simulation model from this data series and the dose-response model (Beta Poisson model) showed that the risk of C. jejuni foodborne illness per day per person from jerky consumption was $1.56{\times}10^{-12}$. Conclusion: This result suggests that the risk of C. jejuni in jerky could be considered low in Korea.

환경성 발암물질의 용량-반응모델의 이론적 근거와 응용에 관한 연구 - 음용수 중 chloroform을 중심으로 (Scientific rationale and applicability of dose-response models for environmental carcinogens)

  • 신동천;정용;김종만;이성임;황만식
    • Journal of Preventive Medicine and Public Health
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    • 제29권1호
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    • pp.27-41
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    • 1996
  • This study described methods to predict human health risk associated with exposure to environmental carcinogens using animal bioassay data. Also, biological assumption for various dose-response models were reviewed. To illustrate the process of risk estimate using relevant dose-response models such as Log-normal, Mantel-Bryan, Weibull and Multistage model, we used four animal carcinogenesis bioassy data of chloroform and chloroform concentrations of tap water measured in large cities of Korea from 1987 to 1995. As a result, in the case of using average concentration in exposure data and 95% upper boud unit risk of Multistge model, excess cancer risk(RISK I) was about $1.9\times10^{-6}$, in the case of using probability distribution of cumulative exposure data and unit risks, those risks(RISK II) which were simulated by Monte-Carlo analysis were about $2.4\times10^{-6}\;and\;7.9\times10^{-5}$ at 50 and 95 percentile, respectively. Therefore risk estimated by Monte-Carlo analysis using probability distribution of input variables may be more conservative.

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Occupational Exposure to Knee Loading and the Risk of Osteoarthritis of the Knee: A Systematic Review and a Dose-Response Meta-Analysis

  • Verbeek, Jos;Mischke, Christina;Robinson, Rachel;Ijaz, Sharea;Kuijer, Paul;Kievit, Arthur;Ojajarvi, Anneli;Neuvonen, Kaisa
    • Safety and Health at Work
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    • 제8권2호
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    • pp.130-142
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    • 2017
  • Background: Osteoarthritis of the knee is considered to be related to knee straining activities at work. The objective of this review is to assess the exposure dose-response relation between kneeling or squatting, lifting, and climbing stairs at work, and knee osteoarthritis. Methods: We included cohort and case-control studies. For each study that reported enough data, we calculated the odds ratio (OR) per 5,000 hours of cumulative kneeling and per 100,000 kg of cumulative lifting. We pooled these incremental ORs in a random effects meta-analysis. Results: We included 15 studies (2 cohort and 13 case-control studies) of which nine assessed risks in more than two exposure categories. We considered all but one study at high risk of bias. The incremental OR per 5,000 hours of kneeling was 1.26 (95% confidence interval 1.17-1.35, 5 studies, moderate quality evidence) for a log-linear exposure dose-response model. For lifting, there was no exposure dose-response per 100,000 kg of lifetime lifting (OR 1.00, 95% confidence interval 1.00-1.01). For climbing, an exposure dose-response could not be calculated. Conclusion: There is moderate quality evidence that longer cumulative exposure to kneeling or squatting at work leads to a higher risk of osteoarthritis of the knee. For other exposure, there was no exposure dose-response or there were insufficient data to establish this. More reliable exposure measurements would increase the quality of the evidence.

Novel nomogram-based integrated gonadotropin therapy individualization in in vitro fertilization/intracytoplasmic sperm injection: A modeling approach

  • Ebid, Abdel Hameed IM;Motaleb, Sara M Abdel;Mostafa, Mahmoud I;Soliman, Mahmoud MA
    • Clinical and Experimental Reproductive Medicine
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    • 제48권2호
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    • pp.163-173
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    • 2021
  • Objective: This study aimed to characterize a validated model for predicting oocyte retrieval in controlled ovarian stimulation (COS) and to construct model-based nomograms for assistance in clinical decision-making regarding the gonadotropin protocol and dose. Methods: This observational, retrospective, cohort study included 636 women with primary unexplained infertility and a normal menstrual cycle who were attempting assisted reproductive therapy for the first time. The enrolled women were split into an index group (n=497) for model building and a validation group (n=139). The primary outcome was absolute oocyte count. The dose-response relationship was tested using modified Poisson, negative binomial, hybrid Poisson-Emax, and linear models. The validation group was similarly analyzed, and its results were compared to that of the index group. Results: The Poisson model with the log-link function demonstrated superior predictive performance and precision (Akaike information criterion, 2,704; λ=8.27; relative standard error (λ)=2.02%). The covariate analysis included women's age (p<0.001), antral follicle count (p<0.001), basal follicle-stimulating hormone level (p<0.001), gonadotropin dose (p=0.042), and protocol type (p=0.002 and p<0.001 for short and antagonist protocols, respectively). The estimates from 500 bootstrap samples were close to those of the original model. The validation group showed model assessment metrics comparable to the index model. Based on the fitted model, a static nomogram was built to improve visualization. In addition, a dynamic electronic tool was created for convenience of use. Conclusion: Based on our validated model, nomograms were constructed to help clinicians individualize the stimulation protocol and gonadotropin doses in COS cycles.

Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans

  • Al-Amin, Mohammad;Kawasaki, Ichiro;Gong, Joomi;Shim, Yhong-Hee
    • Molecules and Cells
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    • 제39권2호
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    • pp.163-168
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    • 2016
  • Caffeine has both positive and negative effects on physiological functions in a dose-dependent manner. C. elegans has been used as an animal model to investigate the effects of caffeine on development. Caffeine treatment at a high dose (30 mM) showed detrimental effects and caused early larval arrest. We performed a comparative proteomic analysis to investigate the mode of action of high-dose caffeine treatment in C. elegans and found that the stress response proteins, heat shock protein (HSP)-4 (endoplasmic reticulum [ER] chaperone), HSP-6 (mitochondrial chaperone), and HSP-16 (cytosolic chaperone), were induced and their expression was regulated at the transcriptional level. These findings suggest that high-dose caffeine intake causes a strong stress response and activates all three stress-response pathways in the worms, including the ER-, mitochondrial-, and cytosolic pathways. RNA interference of each hsp gene or in triple combination retarded growth. In addition, caffeine treatment stimulated a food-avoidance behavior (aversion phenotype), which was enhanced by RNAi depletion of the hsp-4 gene. Therefore, up-regulation of hsp genes after caffeine treatment appeared to be the major responses to alleviate stress and protect against developmental arrest.

Genetic radiation risks: a neglected topic in the low dose debate

  • Schmitz-Feuerhake, Inge;Busby, Christopher;Pflugbeil, Sebastian
    • Environmental Analysis Health and Toxicology
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    • 제31권
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    • pp.1.1-1.13
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    • 2016
  • Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (A-bomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down's syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.

동집단 자료의 주의력 결핍 과잉행동 장애를 종점으로 한 납의 벤치마크 용량 하한 도출 (Derivation of benchmark dose lower limit of lead for ADHD based on a longitudinal cohort data set)

  • 김병수;김대희;하미나;권호장
    • Journal of the Korean Data and Information Science Society
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    • 제25권5호
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    • pp.987-998
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    • 2014
  • 본 연구에서는 우리나라 환경부에서 최근에 구축한 아동 동집단 경시적 자료인 아동 건강과 환경 연구 (CHEER) 자료에 기초하여 주의력 결핍 과잉행동 장애 (ADHD)와 혈중 납 농도의 상관을 선형혼합모형을 사용하여 규명하고, CHEER 자료의 경시적 특성으로 나타나는 ADHD 점수의 "평균으로의 회귀" 현상을 보고하고자 한다. 또한 ADHD를 종점으로 한 혈중 납 농도의 용량-반응 곡선을 도출하며, 이렇게 도출된 용량-반응 곡선에 기초하여 몇 가지 상황 하에서 독성기준치인 벤치마크 용량 하한 (BMDL)을 유도한다.

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).