• Journal of Radiation Protection and Research
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• 제47권3호
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• pp.111-133
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• 2022

The exciting advancement related to the "modeling of digital human" in terms of a computational phantom for radiation dose calculations has to do with the latest hype related to deep learning. The advent of deep learning or artificial intelligence (AI) technology involving convolutional neural networks has brought an unprecedented level of innovation to the field of organ segmentation. In addition, graphics processing units (GPUs) are utilized as boosters for both real-time Monte Carlo simulations and AI-based image segmentation applications. These advancements provide the feasibility of creating three-dimensional (3D) geometric details of the human anatomy from tomographic imaging and performing Monte Carlo radiation transport simulations using increasingly fast and inexpensive computers. This review first introduces the history of three types of computational human phantoms: stylized medical internal radiation dosimetry (MIRD) phantoms, voxelized tomographic phantoms, and boundary representation (BREP) deformable phantoms. Then, the development of a person-specific phantom is demonstrated by introducing AI-based organ autosegmentation technology. Next, a new development in GPU-based Monte Carlo radiation dose calculations is introduced. Examples of applying computational phantoms and a new Monte Carlo code named ARCHER (Accelerated Radiation-transport Computations in Heterogeneous EnviRonments) to problems in radiation protection, imaging, and radiotherapy are presented from research projects performed by students at the Rensselaer Polytechnic Institute (RPI) and University of Science and Technology of China (USTC). Finally, this review discusses challenges and future research opportunities. We found that, owing to the latest computer hardware and AI technology, computational human body models are moving closer to real human anatomy structures for accurate radiation dose calculations.

• Toxicological Research
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• 제13권1_2호
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• pp.71-78
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• 1997

The mutational effects of pentachlorophenol (PCP) on the hypoxanthine phosphoribosyl transf erase (hprt) locus in human T-cell were analysed by T-cell clonal assay in vitro. Cells were exposed for 24 hours at primary culture to 0~100 ppm (W/V) PCP in dimethyl sulfoxide. Treated cells were allowed at the same time to stimulate by phytohemagglutinin (PHA) and T-cell growth factor (TCGF) and then seeded in medium containing 6-thioguanine to select for hprt-negative routants. We have also defined the optimal condition for the determination of mutant frequency. The parameters investigated include survival counting, first and second subculture for clonal efficiency plating and mutant plating. Under the optimal conditions, mutant frequencies of high dose-treated cells were significantly higher than those of non-treated or low dose cells. The results indicated a clear dose-effect relationship and showed that mutant frequency in 50 ppm PCP treated cell was 4.31$\times$$10^{-5}$ (background, 8.32$\times$$10^{-6}$). Above data strongly suggest that hprt mutation assay can be used as a biomarker for the environmental risk assessment.

• 한국환경성돌연변이발암원학회지
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• 제22권3호
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• pp.187-198
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• 2002

Chlorpyrifos is an organophosphate insecticide and one of the most commonly and widely used insecticide. However, a little known about the dermal risk of chlorpyrifos on human being. Therefore, this study was conducted for the dermal risk assessment after exposure to chlorpyrifos in Korean farmers. First, skin irritation by chlorpyrifos (10 mg/$\textrm{cm}^2$, 50 mg/$\textrm{cm}^2$, 100 mg/$\textrm{cm}^2$, 250 mg/$\textrm{cm}^2$ in acetone) was determined in rabbits for 5 days considering the usage of chlorpyrifos short term highly exposure. The index of skin irritation by chlorpyrifos was increased in each dose and length of exposure dependent manners. Next, using benchmark dose (BMD$_{5}$) approach, the dose-response relationship was assessed to calculate the reference dose (RfD). The value of RfD was 2.84 $\mu\textrm{g}$/kg/day from 142.16 $\mu\textrm{g}$/kg/day BMD5 value divided uncertainty factor 50. Finally, we assessed human dermal risk of chlorpyrifos with exposure level and RfD. Skin absorbed levels were assumed with several exposure scenarios encounting the circumstances of exposure that application method, protection equipment and cloth, exposure time and exposure frequency during chlorpyrifos spraying. By the comparison of skin absorbed dose with the reference dose, it was identified that risk values (risk index) to skin chlorpyrifos exposure were 0.958 from the point of above results and it was recommended that the occurrence of hazard effect (skin irritation toxicity) of chlorpyrifos would not be expected. Risk index was smaller than 1 in the case of spraying vehicle mounted application, 1hour exposure time and wearing protective cloth exposure. Whereas, risk index was above 1 in the case of hand-held application, 2hour exposure time and wearing common cloth. Comparing two kinds of application method, total risk index of the hand held application (1.67) was higher than vehicle mounted (0.27). Therefore, chlorpyrifos skin exposure was mainly affected by application equipment and applied form. The results of risk assessment on the human dermal toxicity of chlorpyrifos should be required to control in keeping safety rules, skin surface area available for contact, spraying time ,and spraying frequency.y.

• Environmental Analysis Health and Toxicology
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• 제16권2호
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• pp.43-50
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• 2001

A daily newspaper in Korea addressed an controversial issue recently that the concentration of radon measured from the groundwater in Taejon was found out a relatively high level. The cancer risk arising from ingestion of such radon should be derived from calculation of the dose absorbed by the tissues at risk. The study performed by the National Research Council in United States confirmed that the use of a PBPK model for the ingested radon could provide the useful information regarding the distribution of radon among the organs of the body. This study presents an approach for the internal dose assessment of ingested radon for this case. At first, the study develops a PBPK model for ingested radon. However, the important issue is how to simulate a more realistic situation using the model associated with repeated oral doses rather than a single oral dose. The simulations are performed for repeated oral exposures per 8-hour interval using the PBPK model for a male adult. The concentration and cumulative value of radon concentration are calculated and analyzed for lung tissue and adipose group, respectively. The results could be used for the realistic prediction of the internal dose of radon in the human body for repeated oral exposures.

• The Korean Journal of Physiology and Pharmacology
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• 제19권2호
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• pp.99-104
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• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• 한국식품영양과학회:학술대회논문집
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• 한국식품영양과학회 2001년도 International Symposium on Food,Nutrition and Health for 21st Century
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• pp.74-87
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• 2001

Evidence shows that the serum level of cholesterol (CH) is decreased with increasing green tea (GT) consumption. This presentation summarizes our recent findings on the effect of GT extract on intestinal absorption of [$^{14}C$-labeled CH and phosphatidylcholine (PC). Ovariectomized (OX) adult rats were infused intraduodenally with lipid emulsions containing radiolabeled lipids [$^{14}C$-CH or $^{14}C$-phosphatidylcholine (PC)] in the presence of GT extract or catechins to determine the rates and amounts of CH absorption and the intestinal hydrolysis and lymphatic output of PC. During lipid infusion, lymph was collected hourly for 8 h. The lymphatic absorption of $^14C$-CH was drastically lowered by infusion of GT extract at two dosage levels (GTl =5.4 mg catechins/h and GT2 = 15.1mg catechins/h). The cumulative lymphatic absorptions of $^{14}C$-CH in rats infused with GT1 and GT2 were 20.7$\pm$4.3 and $4.8{\pm}4.1{\%}$ dose, respectively, whereas the absorption of $^{14}C$-CH in rats infused with no GT extract (GT0) was $36.3{\pm}1.1{\%}$ dose. GT extracts also significantly lowered the absorption of-tocopherol (TP) in a dose dependent manner ($29.6{\pm}4.9{\%}$ dose in GT0, $20.8{\pm}5.8{\%}$ dose in GTl, and $7.9{\pm}5.4{\%}$ dose in GT2 groups). Both (+)-catechin and EGCG significantly lowered the lymphatic outputs of $^{14}C$-radioactivity after intraduodenal $^{14}C$-PC infusion. A significantly higher amount of $^{14}C$-PC remained unhydrolyzed in the intestinal lumen of the EGCG rats ($22.8{\%}$) compared with the (+)-catechin ($15.8\%$) and control groups ($11.9\%$). GT extracts, (+)-catechin, and EGCG significantly reduced the absorption of TP. The inhibitory effect of GT extract and catechins on lipid absorption may be mediated in part through the inhibition of pancreatic PLAz. The findings provide the first direct evidence that green tea and catechins have a profound inhibitory effect on the intestinal absorption of CH in OX rats. Results suggest that green tea and catechins may be used as a dietary or pharmacological means of lowering cholesterol absorption.

• International Journal of Stem Cells
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• 제16권1호
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• pp.16-26
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• 2023

Despite long-term research achievements, the development of cell therapy (CT) products remains challenging. This is because the risks experienced by the subject and therapeutic effects in the clinical trial stage are unclear due to the various uncertainties of CT when administered to humans. Nevertheless, as autologous cell products for systemic administration have recently been approved for marketing, CT product development is accelerating, particularly in the field of unmet medical needs. The human experience of CT remains insufficient compared with other classes of pharmaceuticals, while there are countless products for clinical development. Therefore, for many sponsors, understanding the rationale of human application of an investigational product based on the consensus and improving the ability to apply it appropriately for CT are necessary. Thus, defining the level of evidence for safety and efficacy fundamentally required for initiating the clinical development and preparing it using a reliable method for CT. Furthermore, the expertise should be strengthened in the design of the first-in-human trial, such as the starting dose and dose-escalation plan, based on a sufficiently acceptable rationale. Cultivating development professionals with these skills will increase the opportunity for more candidates to enter the clinical development phase.

• 한국수산과학회지
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• 제54권1호
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• pp.16-22
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• 2021

This study investigated the reduction in human norovirus (HNV) GII. 4 count in pacific oyster Crassostrea gigas using electron beam irradiation. Infectious HNV GII. 4 was detected using RT-qPCR (real time reverse transcription-quantitative polymerase chain reaction) with PMA (propidium monoazide)/sarkosyl. At electron beam doses 1, 5, 7, and 10 kGy, the count of HNV GII. 4 was 2.74, 2.37, 2.06, and 1.55 log copies/μL (control, 3.01 log copy/μL), respectively, confirming that as the irradiation dose increased, norovirus count reduced significantly (P<0.05). After PMA/sarkosyl treatment, the counts further reduced at the same irradiation dose, and 10 kGy showed significant differences between the non-treated and PMA/sarkosyl-treated samples (P<0.05). The Ed (decimal reduction dose of electron beam) value based on the first-order kinetic model was 7.33 kGy (R2=0.98). No significant difference was observed in the pH values of the control (6.2) and electron beam-irradiated samples at all doses (6.1). For sensory evaluation, the non-treated sample scored the highest in all categories (5.25-6.17), while the samples treated with 10 kGy showed the lowest score (4.67-5.33), although without statistical significance (P>0.05). Overall, our results suggest that 7 kGy electron beam is sufficient for the non-thermal sterilization of oysters without causing significant changes in quality.

• Asian Spine Journal
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• 제12권6호
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• pp.1010-1016
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• 2018

Study Design: Retrospective cohort study. Purpose: To report on spinal fusion assessment using computed tomography (CT) after adult spinal deformity (ASD) surgery using ultra-low dose recombinant human bone morphogenetic protein 2 (RhBMP-2). Overview of Literature: The reported dose of RhBMP-2 needed for successful spinal posterolateral fusion in ASD ranges from 10 to 20 mg per spinal level. This study reports the use of ultra-low dose of RhBMP-2 (0.07 mg per facet) to achieve spinal fusion in multilevel ASD surgery. Methods: Consecutive patients who underwent ASD surgery using ultra-low dose RhBMP-2 were recruited. Routine postoperative CT analysis for spinal fusion was performed by two spine surgeons. Inter-observer agreement was calculated for facet fusion (FF) and interbody fusion (IBF) at 6 and 12 months after the procedure. Results: Six consecutive ASD patients with a mean age of 62 years (28-72 years) were examined. Each patient received a total dose of 12 mg with an average dose of $0.69{\pm}0.2mg$ (0.42-1 mg) per single FF and $1.38{\pm}0.44mg$ (0.85-2 mg) for IBF. Total 131 FF and 15 IBF were examined in the study, with 88 FFs and nine IBFs being analyzed specifically at 6 months after the surgery. FF and IBF reported by surgeons A and B at 6 months were 97.7% vs. 91.9% FF, respectively (${\kappa}=0.95$) and 100% vs. 100% IBF, respectively (${\kappa}=1$). Two patients underwent longitudinal follow-up CT at 12 months, and the FF rates reported by surgeons A and B were 100% vs. 95.8%, respectively (${\kappa}=0.96$). Five out of nine facet (56%) non-unions were identified at the cross-links. The remaining four facet pseudarthrosis were noted at 1-2 spinal levels caudal to the cross-links. At the final clinical follow-up, there was no rod breakage, deformity progression, neurological deficit, or symptom recurrence. The Oswestry Disability Index improved by an average of $32.8{\pm}6.3$, while the mental component summary of the 36-item Short-Form Health Survey improved by an average of $4.7{\pm}2.1$, and physical component summary improved by an average of $10.5{\pm}2.1$. Conclusions: To our knowledge, this is the first study to report a CT that defined 92%-98% FF and 100% IBF using the lowest reported dose of RhBMP-2 in multilevel ASD surgery. The use of ultra-low dose RhBMP-2 reduces the RhBMP-2 related complications and healthcare costs.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5727-5731
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• 2015

Background: There is a long standing interest in natural compounds especially those with a high polyphenolic content and high scavenging activity for hazardous free radicals. Cornus mas (CM) fruit is well known for its antioxidant activities; however, its toxicity against human cancers needs to be addressed. Here, we investigated selective anticancer effects of CM on different human cancer cells. Materials and Methods: A hydro-alcoholic extract of CM (HECM) was prepared and total phenolic content (TPC) and total flavonoid content (TFC) were determined by colorimetric assays. Antioxidant activity was assessed with respectto DPPH radical scavenging. MTT assays were used to evaluate the cytotoxicity of different doses of CM (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) towards A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer) and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.05) or very significant (P<0.001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all cancer cells, HECM reduced the cell viability to values below 26%, even at the lowest doses. In all cases, $IC_{50}$ was obtained at doses below $5{\mu}g/ml$. The mean growth inhibition was 81.8%, 81.9%, 81.6% and 79.3% in SKOV3, MCF-7, PC-3 and A549 cells, respectively. Conclusions: Altogether, to our best knowledge, this is a first study that evaluated toxicity of a HECM with high antioxidant activity in different human cancer cells in vitro. Our results indicated that a hydro-alcoholic extract of CM possesses high potency to inhibit proliferation of different tumor cells in a dose independent manner, suggesting that an optimal biological dose is more important and relevant than a maximally tolerated one.