• Mass Spectrometry Letters
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• v.10 no.1
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• pp.38-42
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• 2019

Damaurone D belongs to the genus Rosa and is a traditional medicinal product used for the treatment of depression, inflammation, and infectious diseases. The purpose of this study was to develop a simple liquid chromatography-tandem mass spectrometry method for the detection of damaurone D in rat plasma and to demonstrate its application in pharmacokinetic studies. Damaurone D and berberine (internal standard) were extracted with acetonitrile using a protein precipitation method. Mass transition was monitored in multiple reaction monitoring mode at m/z $323.2{\rightarrow}267.0$ for damaurone D and m/z $336.1{\rightarrow}320.0$ for berberine in positive ion mode. Analytical validation was conducted by evaluating the specificity, linearity, accuracy, precision, matrix effect, extraction recovery, and stability. The calibration curves were linear over 2-1000 ng/mL. The intra- and inter-day precision and accuracy of quality control samples were 4.79-13.33% and 86.23-102.75%, respectively. The matrix effect and extraction recovery were 96.11-98.47% and 96.11-102.25%, respectively. In the pharmacokinetic study after intravenous administration of damaurone D at a dose of 3 mg/kg in rats, the area under the curve and clearance of damaurone D in rat plasma were $16750.26{\pm}2676.10min{\cdot}ng/mL$ and $182.44{\pm}31.36mL/min/kg$, respectively.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.232-238
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• 2018

Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.

• Imaging Science in Dentistry
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• v.50 no.4
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• pp.291-298
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• 2020

Purpose: The detection and exact localization of penetrating foreign bodies are crucial for the appropriate management of patients with dentoalveolar trauma. This study compared the efficacy of cone-beam computed tomography (CBCT) and spiral computed tomography (CT) scans for the detection of different foreign bodies composed of 5 frequently encountered materials in 2 sizes. The effect of the location of the foreign bodies on their visibility was also analyzed. Materials and Methods: In this in vitro study, metal, tooth, stone, glass, and plastic particles measuring 1×1×1 mm and 2×2×2 mm were prepared. They were implanted in a sheep's head in the tongue muscle, nasal cavity, and at the interface of the mandibular cortex and soft tissue. CBCT and spiral CT scans were taken and the visibility of foreign bodies was scored by 4 skilled maxillofacial radiologists who were blinded to the location and number of foreign bodies. Results: CT and CBCT were equally accurate in visualizing metal, stone, and tooth particles of both sizes. However, CBCT was better for detecting glass particles in the periosteum. Although both imaging modalities visualized plastic particles poorly, CT was slightly better for detecting plastic particles, especially the smaller ones. Conclusion: Considering the lower patient radiation dose and cost, CBCT can be used with almost equal accuracy as CT for detecting foreign bodies of different compositions and sizes in multiple maxillofacial regions. However, CT performed better for detecting plastic particles.

• Advances in environmental research
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• v.10 no.1
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• pp.17-41
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• 2021

Kazakhstan's cities experience high concentrations levels of atmospheric particulate matter (PM), which is well-known for its highly detrimental effect on the human health. A further increase in PM concentrations in the future could lead to a higher air pollution-caused morbidity and mortality, causing an increase in healthcare expenditures by the government. However, to prevent elevated PM concentrations in the future, more stringent standards could be implemented by lowering current maximum allowable PM concentration limit to Organization for Economic Co-operation and Development (OECD)'s limits. Therefore, this study aims to find out what impact this change in environmental policy towards PM has on state economy in the long run. Future PM10 and PM2.5 concentrations were estimated using multiple linear regression based on gross regional product (GRP) and population growth parameters. Dose-response model was based on World Health Organization's approach for the identification of mortality, morbidity and healthcare costs due to air pollution. Analysis of concentrations revealed that only 6 out of 21 cities of Kazakhstan did not exceed the EU limit on PM10 concentration. Changing environmental standards resulted in the 71.7% decrease in mortality and 77% decrease in morbidity cases in all cities compared to the case without changes in environmental policy. Moreover, the cost of morbidity and mortality associated with air pollution decreased by $669 million in 2030 and $2183 million in 2050 in case of implementation of OECD standards. Thus, changing environmental regulations will be beneficial in terms of both of mortality reduction and state budget saving.

• Journal of Environmental Health Sciences
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• v.48 no.2
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• pp.96-105
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• 2022

Background: Pyrethroid insecticides account for more than 30% of the global insecticide market and are frequently used in agricultural settings and residential and public pest control among the general population. While several animal studies have suggested that exposure to pyrethroids can alter glucose homeostasis, there is only limited evidence of the association between environmental pyrethroid exposure and diabetes in humans. Objectives: This study aimed to report environmental 3-phenoxybenzoic acid (3-PBA) concentrations in urine and evaluate its association with the risk of diabetes in Korean adults. Methods: We analyzed data from the Korean National Environmental Health Survey (KoNEHS) Cycle 2 (2012~2014) and Cycle 3 (2015~2017). A total of 10,123 participants aged ≥19 years were included. Multiple logistic regressions were used to calculate the odds ratios (ORs) for diabetes according to log-transformed urinary 3-PBA levels. We also evaluated age, sex, education, monthly income, marital status, alcohol drinking, physical activity, urinary cotinine, body mass index, and sampling season as potential effect modifiers of these associations. Results: After adjusting for all the covariates, we found significant dose-response relationships between urinary 3-PBA as quartile and the prevalence of diabetes in pooled data of KoNEHS Cycles 2 and 3. In subgroup analyses, the adverse effects of pyrethroid exposure on diabetes were significantly stronger among those aged 19~39 years (p-interaction<0.001) and those who consumed high levels of cotinine (p-interaction=0.020). Conclusions: Our findings highlight the potential diabetes risk of environmental exposure to pyrethroids and should be confirmed in large prospective studies in different populations in the future.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.1
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• pp.27-33
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• 2022

Functional dyspepsia (FD) is a gastrointestinal disorder with diverse symptoms but no structural or organic manifestations. Benachio-F^® (herein named 'BF-1') is an over-the-counter liquid digestive formulated with multiple herbal extracts, which has been reported to improve symptoms of FD. A total two experiments were conducted. First, we examined whether BF-1 can modulate the progression of FD through two experimental rat models. A total of three doses (0.3x, 1x, 3x of the human equivalent dose) were used. In the gastric emptying model, both 1x (standard) or 3x (3-fold-concentrated) BF-1 enhanced gastric emptying was compared with that of vehicle-treated animals. In a feeding inhibition model induced by acute restraint stress, treatment with 1x or 3x BF-1 led to a similar degree of restoration in food intake that was comparable to that of acotiamide-treated animals. Among the constituents of BF, fennel is known for its choleretic effect. Thus, we next investigated whether a novel BF-based formula (named 'BF-2') that contains an increased amount of fennel extract (3.5-fold over BF-1), has greater potency in increasing bile flow. BF-2 showed a superior choleretic effect compared to BF-1. Furthermore, the postprandial concentration of serum secretin was higher in animals pretreated with BF-2 than in those pretreated with BF-1, suggesting that the increased choleretic effect of BF-2 is related to secretin production. Our results demonstrate that BF-1 can modulate the pathophysiological mechanisms of FD by exerting prokinetic and stress-relieving effects, and that BF-2 has a better choleretic effect than BF-1.

• Korean Journal of Head & Neck Oncology
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• v.38 no.2
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• pp.7-13
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• 2022

Human papillomavirus (HPV) is a causative agent for a subset of oropharyngeal cancer (OPC). The current standard of care (SOC) for locally advanced OPC is 70 Gy definitive radiotherapy (RT) concurrent with cisplatin, which entails significant proportions of acute and late grade 3 or higher toxicities. Accordingly, discovery of favorable prognosis of HPV-related OPC has led to enthusiasm to attenuate subspecialties therapy in multidisciplinary treatment. Diverse deintensification strategies were investigated in multiple phase 2 trials with an assumption that attenuated treatments result in comparable oncologic outcome and less toxicities compared with SOC. Several trials on chemotherapy deintensification revealed that concomitant administration of cisplatin is not to be omitted or substituted for cetuximab without compromising progression-free survival or local control. A transoral robotic surgery (TORS) is investigated as alternative local treatment, but TORS plus SOC or mild deintensified adjuvant RT showed similar toxicities and inferior oncologic outcomes compared with SOC definitive RT or moderately deintensified RT. However, it has been reported that TORS plus deintensified 30-36 Gy adjuvant RT results in excellent outcome and less late toxicity compared with SOC adjuvant RT. Several phase 2 trials reported apparently equivalent progression-free survival and local control and similar adverse effects with moderately deintensified 60 Gy RT compared with SOC 70 Gy RT. Further dose reduction below 60 Gy has been investigated using biology-directed approaches, which use response to induction chemotherapy or metabolic images to triage HPV-positive OPC for deintensified RT. In summary, these trials provide valuable insights for future directions. Available evidence consistently showed that moderately deintensified RT is effective and safe for HPV-positive OPC in both definitive and adjuvant settings. Concurrent cisplatin remains an essential component without which progression-free survival is significantly compromised for advanced HPV-positive OPC. A simple incorporation of TORS to SOC may be detrimental for oncologic outcome without anticipated toxicity reduction. Given the lack of level 1 evidence, it is prudent to curb an unjustified deviation from the current SOC and limit any deintensified strategies to clinical trials and adhere to the current SOC.

• Journal of Veterinary Science
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• v.22 no.5
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• pp.47.1-47.10
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• 2021

Background: Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. Objectives: This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. Methods: The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. Results: The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. Conclusions: Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.

• Journal of Environmental Health Sciences
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• v.48 no.3
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• pp.151-158
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• 2022

Background: Chemical emissions in the environment have rapidly increased with the accelerated industrialization taking place in recent decades. Residents of industrial complexes are concerned about the health risks posed by chemical exposure. Objectives: This study was performed to suggest modeling methods that take into account multimedia and multi-pathways in human exposure and risk assessment. Methods: The concentration of benzene emitted at industrial complexes in Daesan, South Korea and the exposure of local residents was estimated using the Caltox model. The amount of human exposure based on inhalation rate was stochastically predicted for various activity stages such as resting, normal walking, and fast walking. Results: The coefficient of determination (R²) for the CalTOX model efficiency was 0.9676 and the root-mean-square error (RMSE) was 0.0035, indicating good agreement between predictions and measurements. However, the efficiency index (EI) appeared to be a negative value at -1094.4997. This can be explained as the atmospheric concentration being calculated only from the emissions from industrial facilities in the study area. In the human exposure assessment, the higher the inhalation rate percentile value, the higher the inhalation rate and lifetime average daily dose (LADD) at each activity step. Conclusions: Prediction using the Caltox model might be appropriate for comparing with actual measurements. The LADD of females was higher ratio with an increase in inhalation rate than those of males. This finding would imply that females may be more susceptible to benzene as their inhalation rate increases.

• Nuclear Engineering and Technology
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• v.55 no.8
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• pp.3030-3038
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• 2023

Nowadays, mobile robots have been used to search for uncontrolled radioactive source in indoor environments to avoid radiation exposure for technicians. However, in the indoor environments, especially in the presence of obstacles, how to make the robots with limited sensing capabilities automatically search for the radioactive source remains a major challenge. Also, the source search efficiency of robots needs to be further improved to meet practical scenarios such as limited exploration time. This paper proposes an automatic source search strategy, abbreviated as ACA: the location of source is estimated by a convolutional neural network (CNN), and the path is planned by the A-star algorithm. First, the search area is represented as an occupancy grid map. Then, the radiation dose distribution of the radioactive source in the occupancy grid map is obtained by Monte Carlo (MC) method simulation, and multiple sets of radiation data are collected through the eight neighborhood self-avoiding random walk (ENSAW) algorithm as the radiation data set. Further, the radiation data set is fed into the designed CNN architecture to train the network model in advance. When the searcher enters the search area where the radioactive source exists, the location of source is estimated by the network model and the search path is planned by the A-star algorithm, and this process is iterated continuously until the searcher reaches the location of radioactive source. The experimental results show that the average number of radiometric measurements and the average number of moving steps of the ACA algorithm are only 2.1% and 33.2% of those of the gradient search (GS) algorithm in the indoor environment without obstacles. In the indoor environment shielded by concrete walls, the GS algorithm fails to search for the source, while the ACA algorithm successfully searches for the source with fewer moving steps and sparse radiometric data.