Saberi, Alihossein;Khodamoradi, Ehsan;Birgani, Mohammad Javad Tahmasebi;Makvandi, Manoochehr
Asian Pacific Journal of Cancer Prevention
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v.16
no.18
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pp.8553-8557
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2016
Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.
Heparinization is an essential step in extracorporeal circulation for open heart surgery. But wide individual variation to heparin effect sometimes makes it difficult to anticoagulate safely or neutralize appropriately. Because the conventional set protocol of heparinization did not consider this individual variation, a new method of control of heparinization was proposed by Dr. Brian Bull in 1974. We compared the group in which a conventional set protocol was used [Control group] with the other in which a new protocol modified from that of Bull was used [ACT group], on the aspects of the dosages of heparin and protamine administered and postoperative bleeding. Our conventional protocol [Control group] consisted of: 1. Initial heparin was given at dose of 350U/Kg into the right atrium prior to bypass. 2. Additional heparin was given every hour during E.C.C., as much as a half of the Initial dose. 3. 600U of heparin was mixed into every 100ml. of priming solution. 4. The protamine dose was calculated by totalling the units of heparin given to the patient and giving 1 .8mg. of protamine per 100 units of heparin. ACT protocol [ACT group] consisted of: 1. Initial heparinization was same as that of conventional protocol. 2. ACT`s were checked before [A point] and 10 minutes after initial heparinization [B point]. With these 2 points, a dose response curve was drawn. 3. Heparin for the priming solution was same as in control group. 4. Every 30 minutes during E.C.C., ACT`s were checked with Hemochron [International Technidyne Corp.]. ACT between 450 and 600 seconds was regarded as safety zone. If ACT checked at a time was below 450 seconds, heparin dose was calculated on the dose-response curve to lengthen ACT to 480 seconds and was given into the oxygenator. 5. About 10 minutes before the term of E.C.C., ACT was checked to estimate the blood heparin level at the time. Then, protamine dose was calculated at dose of 1.Stag per 100 units of heparin. The calculated dose of protamine was mixed into 50 to lO0ml of 5% Dextrose Water and dripped intravenously during the period of 15 minutes. Compared these two groups mentioned above, results were obtained as follows: 1. Mean value of normal ACT checked with Hemochron on 30 preoperative patients was 124 seconds [range 95-145 sec.]. 2. Doses of heparin and protamine given to the patient were decreased in ACT group as much as 32.2% and 62.2% respectively. 3. Postoperative bleeding and transfusion were also decreased in ACT group in 60.5% and 67.1% respectively. 4. Our modified dose-response curve did not cause any problems in the control of heparinization. 5. Initial heparinization [Heparin 350U/Kg] was sufficient for the most patients until 60 minutes under extracorporeal circulation. 6. We used 1.5mg of protamine to neutralize 100 units of heparin. But smaller dose of protamine may be sufficient for appropriate neutralization.
Abuse liability of ephedrine was investigated by measurement of locomotor activity and self-administration in Sprague-Dawley rats. Locomotor activity was determined in rats treated with 3, 10 and 30 mg/kg ephedrine for 14 days. Self-administration by ephedrine (0.23, 1 and 2.3 mg/kg) was examined in food-trained rats. We also examined effect of dopamine receptor antagonist (spiperone, $30{\;}\mu\textrm{g}/kg$) on the ephedrine-induced response of self-administration. Body weight was not statistically difference between control and ephedrine treatment group, but locomotor activity was dose-dependently increased. Self-administration for ephedrine was decreased in the early response (day 1 and 2) but the response was increased by higher dose of ephedrine. Self-administration was decreased by dopamine receptor antagonist (spiperone). These data showed that ephedrine increased locomotor activity and induced response of self-administration, and the effects of ephedrine were partially related to the dopaminergic system, which suggest the ephedrine may have abuse liability.
Dose response and time dependence of unscheduled DNA synthesis induced by X-rays were measured to determine if any correlation exists between unscheduled DNA synthesis, modal chromosome number, chromosome exchange and mitotic activity in four mammalian cell strains. Unscheduled DNA synthesis occurred in all strains studied. The rate was dose-dependent and strain-specific. Only HeLa $S_3$ showed a staturated dose response after 4, 000 R, other cells were linearly proportional to dose increases. Time dependence of unscheduled DNA synthesis was completed within 2 hours after irradiation regardless of cell strains. Unscheduled DNA synthesis was not directly related to modal chromosome number, total exchange rate and mitotic activity. Mitotic activity and chromosome exchange were both dose-dependent, but the rates of them were inversely related.
Purpose: We subjected scanning electron microscopic (SEM) images of the active layer of EBT3 film to texture analysis to determine the dose-response curve. Methods: Uncoated Gafchromic EBT3 films were prepared for direct surface SEM scanning. Absorbed doses of 0-20 Gy were delivered to the film's surface using a 6 MV TrueBeam STx photon beam. The film's surface was scanned using a SEM under 100× and 3,000× magnification. Four textural features (Homogeneity, Correlation, Contrast, and Energy) were calculated based on the gray level co-occurrence matrix (GLCM) using the SEM images corresponding to each dose. We used R-square to evaluate the linear relationship between delivered doses and textural features of the film's surface. Results: Correlation resulted in higher linearity and dose-response curve sensitivity than Homogeneity, Contrast, or Energy. The R-square value was 0.964 for correlation using 3,000× magnified SEM images with 9-pixel offsets. Dose verification was used to determine the difference between the prescribed and measured doses for 0, 5, 10, 15, and 20 Gy as 0.09, 1.96, -2.29, 0.17, and 0.08 Gy, respectively. Conclusions: Texture analysis can be used to accurately convert microscopic structural changes to the EBT3 film's surface into absorbed doses. Our proposed method is feasible and may improve the accuracy of film dosimetry used to protect patients from excess radiation exposure.
Heejung Choi;Sungdam Han;Ji Su Kim;Bumhee Park;Min-Jeong Lee;Gyu-Tae Shin;Heungsoo Kim;Kyongmin Kim;A-Young Park;Ho-Joon Shin;Inwhee Park
Clinical and Experimental Vaccine Research
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v.12
no.3
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pp.249-259
/
2023
Purpose: Since patients on hemodialysis (HD) are known to be vulnerable to coronavirus disease 2019 (COVID-19), many studies were conducted regarding the effectiveness of the COVID-19 vaccine in HD patients in Western countries. Here, we assessed antibody response of HD patients for 6 months post-vaccination to identify the duration and effectiveness of the COVID-19 vaccine in the Asian population. Materials and Methods: We compared antibody response of the COVID-19 vaccine in HD patients with healthy volunteers. Patient and control groups had two doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) was measured before vaccination, 2 weeks after the first dose, 2 and 4 weeks, 3 and 6 months after the second dose. Neutralizing antibody was measured before vaccination and at 2 weeks, 3 and 6 months after second dose. Since the third dose was started in the middle of the study, we analyzed the effect of the third dose as well. Results: Although antibody production was weaker than the control group (n=22), the patient group (n=39) showed an increase in IgG and neutralizing antibody after two doses. And, 21/39 patients and 14/22 participants had a third dose (BNT162b2 or mRNA-1273 in the patient group, mRNA-1273 in the control group), and it did not affect antibody response in both group. Trend analysis showed IgG and neutralizing antibody did not decrease over time. Age, sex, and HD vintage did not affect antibody production in HD patients. Patients with higher body mass index displayed better seroresponse, while those on immunosuppressants showed poor seroresponse. Conclusion: Two doses of vaccination led to significant antibody response in HD patients, and the antibody did not wane until 6 months.
In this work, a Gaussian Process (Kriging) approach is proposed to provide efficient dose mapping for complex radiation fields using limited number of responses. Given a few response measurements (or simulation data points), the proposed approach can help the analyst in completing a map of the radiation dose field with a 95% confidence interval, efficiently. Two case studies are used to validate the proposed approach. The First case study is based on experimental dose measurements to build the dose map in a radiation field induced by a D-D neutron generator. The second, is a simulation case study where the proposed approach is used to mimic Monte Carlo dose predictions in the radiation field using a limited number of MCNP simulations. Given the low computational cost of constructing Gaussian Process (GP) models, results indicate that the GP model can reasonably map the dose in the radiation field given a limited number of data measurements. Both case studies are performed on the nuclear engineering radiation laboratories at the University of Sharjah.
Ground-level ozone ($O_3$) can be a menace for vegetation, especially in Asia where $O_3$ levels have been dramatically increased over the past decades. To ensure food security and maintain forest ecosystem services, such as nutrient cycling, carbon sequestration and functional diversity of soil biota, in the over-populated Asia, environmental standards are needed. To set proper standards, dose-response relationships should be established from which critical levels are derived. The predictor of the response in the dose-response relationship is an $O_3$ metric that indicates the dose level to which the plant has been exposed. This study aimed to review the relevant scientific literature and summarize the $O_3$ metrics used worldwide to provide insights for Asia. A variety of $O_3$ metrics have been used, for which we discuss their strengths and weaknesses. The most widely used metrics are based only on $O_3$ levels. Such metrics have been adopted by several regulatory agencies in the global. However, they are biologically irrelevant because they ignore the plant physiological capacity. Adopting AOT40 ($O_3$ mixing ratios Accumulated Over the Threshold of $40nmol\;mol^{-1}$) as the default index for setting critical levels in Asia would be a poor policy with severe consequences at national and Pan-Asian level. Asian studies should focus on flux-based $O_3$ metrics to provide relevant bases for developing proper standards. However, given the technical requirements in calculating flux-based $O_3$ metrics, which can be an important limitation in developing countries, no-threshold cumulative exposure indices like AOT0 should always accompany flux-based indices.
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.
Plato, Nils;Martinsen, Jan I.;Kjaerheim, Kristina;Kyyronen, Pentti;Sparen, Par;Weiderpass, Elisabete
Safety and Health at Work
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v.9
no.3
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pp.290-295
/
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.
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